\ BIP! Finder for COVID-19 - Impact-based ranking

BIP! Finder for COVID-19

This version of BIP! Finder aims to ease the exploration of COVID-19-related literature by enabling ranking articles based on various impact metrics.

Last Update: 18 - 01 - 2023 (628506 entries)

Provided impact measures:
Popularity: Citation-based measure reflecting the current impact.
Influence: Citation-based measure reflecting the total impact.
Reader Attention: The current number of Mendeley readers.
Social Media Attention: The number of recent tweets related to this article.
*More details on these impact measures can be found here.
Score interpretations:
Exceptional score (in top 0.01%).
Substantial score (in top 1%).
Average score (in bottom 99%).
Score not available.
Main data sources:
CORD-19 dataset(1) (list of papers)
LitCovid hub(2) (list of papers)
PMC & PubMed (citations)
Mendeley (number of readers)
COVID-19-TweetIDs(3) (tweets)

Use:  Impact  Relevance & Impact
101Comparative kinetics of SARS-CoV-2 anti-spike protein RBD IgGs and neutralizing antibodies in convalescent and naïve recipients of the BNT162b2 mRNA vaccine vs COVID-19 patients  

BACKGROUND: Coronavirus SARS-CoV-2, the causative agent of COVID-19, has caused a still evolving global pandemic. Given the worldwide vaccination campaign, the understanding of the vaccine-induced versus COVID-19-induced immunity will contribute to adjusting vaccine dosing strategies and speeding-up vaccination efforts. METHODS: Anti-spike-RBD IgGs and neutralizing antibodies (NAbs) titers were measured in BNT162b2 mRNA vaccinated participants (n = 250); we also investigated humoral and cellular immune responses in vaccinated individuals (n = 21) of this cohort 5 months post-vaccination and assayed NAbs levels in COVID-19 hospitalized patients (n = 60) with moderate or severe disease, as well as in COVID-19 recovered patients (n = 34). RESULTS: We found that one (boosting) dose of the BNT162b2 vaccine triggers robust immune (i.e., anti-spike-RBD IgGs and NAbs) responses in COVID-19 convalescent healthy recipients, while naïve recipients require both priming and boosting shots to acquire high antibody titers. Severe COVID-19 triggers an earlier and more intense (versus moderate disease) immune response in hospitalized patients; in all cases, however, antibody titers remain at high levels in COVID-19 recovered patients. Although virus infection promotes an earlier and more intense, versus priming vaccination, immune response, boosting vaccination induces antibody titers significantly higher and likely more durable versus COVID-19. In support, high anti-spike-RBD IgGs/NAbs titers along with spike (vaccine encoded antigen) specific T cell clones were found in the serum and peripheral blood mononuclear cells, respectively, of vaccinated individuals 5 months post-vaccination. CONCLUSIONS: These findings support vaccination efficacy, also suggesting that vaccination likely offers more protection than natural infection. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-021-02090-6.

BMC Med2021       LitCov and CORD-19
102Healthcare Workers in South Korea Maintain a SARS-CoV-2 Antibody Response Six Months After Receiving a Second Dose of the BNT162b2 mRNA Vaccine  

BACKGROUND: Effective vaccines against coronavirus disease 2019 (COVID-19) are available worldwide; however, the longevity of vaccine effectiveness is not known. OBJECTIVE: We performed a prospective observational study to assess the antibody response of healthcare workers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after BNT162b2 mRNA COVID-19 vaccination. METHODS: SARS-CoV-2 neutralizing antibody (nAb) and spike (S) protein-IgG (S-IgG) antibody titers were examined in participants who received two doses of the BNT162b2 mRNA COVID-19 vaccine in a single center between March 1, 2021, and October 11, 2021. Antibody levels were analyzed at four times: before vaccination (visit 1), 4 weeks after the first vaccination (visit 2), 3 months after the second vaccination (visit 3), and 6 months after the second vaccination (visit 4). RESULTS: A total of 249 healthcare workers at Jeju National University Hospital were enrolled in this study, and 982 blood samples were analyzed. The mean age was 38.1 ± 9.5 years, and 145 (58.2%) participants were females. Positive nAbs (inhibition rates ≥ 20%) were measured in 166/249 (66.7%) subjects at visit 2, 237/243 (97.5%) subjects at visit 3, and 150/237 (63.3%) subjects at visit 4. A S-IgG (≥50 AU/mL) positivity was detected in 246/249 (98.8%) subjects at visit 1, and all participants had positive S-IgG antibody levels at visits 3 and 4 after being fully vaccinated. Further analysis of S-IgG levels revealed a median quantitative antibody level of 1275.1 AU/mL (interquartile range [IQR] 755.5–2119.0) at visit 2, 2765.9 AU/mL (IQR 1809.8–4138.4) at visit 3, and 970.1 AU/mL (IQR 606.0–1495.9) at visit 4. Patient characteristics, such as age, body mass index, and comorbidity, had no relationship with nAb or S-IgG levels at any of the visits. Considering the change in antibody levels over time, both nAb and S-IgG levels at visit 4 decreased compared with the corresponding levels at visit 3. No evidence of SARS-CoV-2 infection was found among any of the participants throughout the study. CONCLUSIONS: The BNT162b2 mRNA vaccine was effective in protecting healthcare personnel working in COVID-19-related departments. While the level of S-IgG antibodies was maintained for 6 months after the second vaccination, nAb levels waned over this 6-month period, indicating the need for a booster vaccination in some healthcare workers 6 months after full vaccination. Herein, we suggest that further studies are needed to evaluate the need for an interval of booster vaccination after full vaccination.

Front Immunol2022       LitCov and CORD-19
103Emergency SARS-CoV-2 Variants of Concern: Novel Multiplex Real-Time RT-PCR Assay for Rapid Detection and Surveillance  

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide. Many variants of SARS-CoV-2 have been reported, some of which have increased transmissibility and/or reduced susceptibility to vaccines. There is an urgent need for variant phenotyping for epidemiological surveillance of circulating lineages. Whole-genome sequencing is the gold standard for identifying SARS-CoV-2 variants, which constitutes a major bottleneck in developing countries. Methodological simplification could increase epidemiological surveillance feasibility and efficiency. We designed a novel multiplex real-time reverse transcriptase PCR (RT-PCR) to detect SARS-CoV-2 variants with S gene mutations. This multiplex PCR typing method was established to detect 9 mutations with specific primers and probes (ΔHV 69/70, K417T, K417N, L452R, E484K, E484Q, N501Y, P681H, and P681R) against the receptor-binding domain of the spike protein of SARS-CoV-2 variants. In silico analyses showed high specificity of the assays. Variants of concern (VOC) typing results were found to be highly specific for our intended targets, with no cross-reactivity observed with other upper respiratory viruses. The PCR-based typing methods were further validated using whole-genome sequencing and a commercial kit that was applied to clinical samples of 250 COVID-19 patients from Taiwan. The screening of these samples allowed the identification of epidemic trends by time intervals, including B.1.617.2 in the third Taiwan wave outbreak. This PCR typing strategy allowed the detection of five major variants of concern and also provided an open-source PCR assay which could rapidly be deployed in laboratories around the world to enhance surveillance for the local emergence and spread of B.1.1.7, B.1.351, P.1, and B.1.617.2 variants and of four Omicron mutations on the spike protein (ΔHV 69/70, K417N, N501Y, P681H). IMPORTANCE COVID-19 has spread globally. SARS-CoV-2 variants of concern (VOCs) are leading the next waves of the COVID-19 pandemic. Previous studies have pointed out that these VOCs may have increased infectivity, have reduced vaccine susceptibility, change treatment regimens, and increase the difficulty of epidemic prevention policy. Understanding SARS-CoV-2 variants remains an issue of concern for all local government authorities and is critical for establishing and implementing effective public health measures. A novel SARS-CoV-2 variant identification method based on a multiplex real-time RT-PCR was developed in this study. Five SARS-CoV-2 variants (Alpha, Beta, Gamma, Delta, and Omicron) were identified simultaneously using this method. PCR typing can provide rapid testing results with lower cost and higher feasibility, which is well within the capacity for any diagnostic laboratory. Characterizing these variants and their mutations is important for tracking SAR-CoV-2 evolution and is conducive to public infection control and policy formulation strategies.

Microbiol Spectr2022       LitCov and CORD-19
104Effect of Pfizer/BioNTech and Oxford/AstraZeneca vaccines against COVID-19 morbidity and mortality in real-world settings at countrywide vaccination campaign in Saudi Arabia  


Eur Rev Med Pharmacol Sci2021       LitCov and CORD-19
105Impact of the COVID-19 pandemic on medical education: Medical students' knowledge, attitudes and practices regarding electronic learning  

The Coronavirus Disease 2019 (COVID-19) pandemic has caused an unprecedented disruption in medical education and healthcare systems worldwide. The disease can cause life-threatening conditions and it presents challenges for medical education, as instructors must deliver lectures safely, while ensuring the integrity and continuity of the medical education process. It is therefore important to assess the usability of online learning methods, and to determine their feasibility and adequacy for medical students. We aimed to provide an overview of the situation experienced by medical students during the COVID-19 pandemic, and to determine the knowledge, attitudes, and practices of medical students regarding electronic medical education. A cross-sectional survey was conducted with medical students from more than 13 medical schools in Libya. A paper-based and online survey was conducted using email and social media. The survey requested demographic and socioeconomic information, as well as information related to medical online learning and electronic devices; medical education status during the COVID-19 pandemic; mental health assessments; and e-learning knowledge, attitudes, and practices. A total of 3,348 valid questionnaires were retrieved. Most respondents (64.7%) disagreed that e-learning could be implemented easily in Libya. While 54.1% of the respondents agreed that interactive discussion is achievable by means of e-learning. However, only 21.1% agreed that e-learning could be used for clinical aspects, as compared with 54.8% who disagreed with this statement and 24% who were neutral. Only 27.7% of the respondents had participated in online medical educational programs during the COVID-19 pandemic, while 65% reported using the internet for participating in study groups and discussions. There is no vaccine for COVID-19 yet. As such, the pandemic will undeniably continue to disrupt medical education and training. As we face the prospect of a second wave of virus transmission, we must take certain measures and make changes to minimize the effects of the COVID-19 outbreak on medical education and on the progression of training. The time for change is now, and there should be support and enthusiasm for providing valid solutions to reduce this disruption, such as online training and virtual clinical experience. These measures could then be followed by hands-on experience that is provided in a safe environment.

PLoS One2020       LitCov and CORD-19
106Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions and mortality in older adults in England: test negative case-control study  

OBJECTIVE: To estimate the real world effectiveness of the Pfizer-BioNTech BNT162b2 and Oxford-AstraZeneca ChAdOx1-S vaccines against confirmed covid-19 symptoms (including the UK variant of concern B.1.1.7), admissions to hospital, and deaths. DESIGN: Test negative case-control study. SETTING: Community testing for covid-19 in England. PARTICIPANTS: 156 930 adults aged 70 years and older who reported symptoms of covid-19 between 8 December 2020 and 19 February 2021 and were successfully linked to vaccination data in the National Immunisation Management System. INTERVENTIONS: Vaccination with BNT162b2 or ChAdOx1-S. MAIN OUTCOME MEASURES: Primary outcomes were polymerase chain reaction confirmed symptomatic SARS-CoV-2 infections, admissions to hospital for covid-19, and deaths with covid-19. RESULTS: Participants aged 80 years and older vaccinated with BNT162b2 before 4 January 2021 had a higher odds of testing positive for covid-19 in the first nine days after vaccination (odds ratio up to 1.48, 95% confidence interval 1.23 to 1.77), indicating that those initially targeted had a higher underlying risk of infection. Vaccine effectiveness was therefore compared with the baseline post-vaccination period. Vaccine effects were noted 10 to 13 days after vaccination, reaching a vaccine effectiveness of 70% (95% confidence interval 59% to 78%), then plateauing. From 14 days after the second dose a vaccination effectiveness of 89% (85% to 93%) was found compared with the increased baseline risk. Participants aged 70 years and older vaccinated from 4 January (when ChAdOx1-S delivery commenced) had a similar underlying risk of covid-19 to unvaccinated individuals. With BNT162b2, vaccine effectiveness reached 61% (51% to 69%) from 28 to 34 days after vaccination, then plateaued. With ChAdOx1-S, effects were seen from 14 to 20 days after vaccination, reaching an effectiveness of 60% (41% to 73%) from 28 to 34 days, increasing to 73% (27% to 90%) from day 35 onwards. On top of the protection against symptomatic disease, a further 43% (33% to 52%) reduced risk of emergency hospital admission and 51% (37% to 62%) reduced risk of death was observed in those who had received one dose of BNT162b2. Participants who had received one dose of ChAdOx1-S had a further 37% (3% to 59%) reduced risk of emergency hospital admission. Follow-up was insufficient to assess the effect of ChAdOx1-S on mortality. Combined with the effect against symptomatic disease, a single dose of either vaccine was about 80% effective at preventing admission to hospital with covid-19 and a single dose of BNT162b2 was 85% effective at preventing death with covid-19. CONCLUSION: Vaccination with either one dose of BNT162b2 or ChAdOx1-S was associated with a significant reduction in symptomatic covid-19 in older adults, and with further protection against severe disease. Both vaccines showed similar effects. Protection was maintained for the duration of follow-up (>6 weeks). A second dose of BNT162b2 was associated with further protection against symptomatic disease. A clear effect of the vaccines against the B.1.1.7 variant was found.

BMJ2021       LitCov and CORD-19
107Generation of neutralizing antibodies against Omicron, Gamma and Delta SARS-CoV-2 variants following CoronaVac vaccination  

Vaccination is a fundamental tool to prevent SARS-CoV-2 infection and to limit the COVID-19 pandemic. The emergence of SARS-CoV-2 variants with multiple mutations has raised serious concerns about the ability of neutralizing antibody responses elicited by prior vaccination to effectively combat these variants. The neutralizing capacity against the Gamma, Delta and Omicron variants of sera from individuals immunized with the CoronaVac vaccine remains incompletely determined. The present study evaluated 41 health care workers at the Faculdade de Medicina of the Universidade de Sao Paulo, in Sao Paulo, Brazil, naive to previous SARS- CoV-2 infection, who were vaccinated with two doses of the CoronaVac SARS-CoV-2 vaccine 28 days apart. Neutralizing antibody levels against the Gamma, Delta, and Omicron variants were measured at 32 and 186 days after the second vaccination. We also measured neutralizing antibodies against Omicron in 34 of these individuals following a subsequent booster immunization with the Pfizer vaccine. Quantification of neutralizing antibodies was performed using the Cytopathic Effect-based Virus Neutralization test. Neutralization antibody activity against the Gamma, Delta and Omicron variants was observed in 78.0%, 65.9% and 58.5% of serum samples, respectively, obtained at a mean of 32 days after the second immunization. This decreased to 17.1%, 24.4% and 2.4% of sera having activity against Delta, Gamma and Omicron, respectively, at 186 days post-vaccination. The median neutralizing antibody titers at 32 days were 1:40, 1:20 and 1:20 against Gamma, Delta and Omicron, respectively, and decreased to an undetectable median level against all variants at the later time. A booster immunization with the Pfizer vaccine elicited neutralizing antibodies against Omicron in 85% of subjects tested 60 days after vaccination. We conclude that two doses of the CoronaVac vaccine results in limited protection of short duration against the Gamma, Delta and Omicron SARS-CoV-2 variants. A booster dose with the Pfizer vaccine induced antibody neutralizing activity against Omicron in most patients which was measurable 60 days after the booster.

Rev Inst Med Trop Sao Paulo2022       LitCov and CORD-19
108Differential Antibody Response to mRNA COVID-19 Vaccines in Healthy Subjects  

Knowledge about development and duration of virus-specific antibodies after COVID-19 vaccination is important for understanding how to limit the pandemic via vaccination in different populations and societies. However, the clinical utility of postvaccination testing of antibody response and selection of targeted SARS-CoV-2 antigen(s) has not been established. The results of such testing from clinical teams independent from vaccine manufacturers are also limited. Here, we report the initial results of an ongoing clinical study on evaluation of antibody response to four different SARS-CoV-2 antigens after first and second dose of Pfizer and Moderna mRNA vaccines and at later time points. We revealed a peak of antibody induction after the vaccine boosting dose with a gradual decline of antibody levels at later time. Anti-nucleocapsid antibody was not induced by spike protein-encoding vaccines and this may continue to serve as a marker of previous SARS-CoV-2 infection. No differences between the two vaccines in terms of antibody response were revealed. Age and gender dependencies were determined to be minimal within the healthy adult (but not aged) population. Our results suggest that postvaccination testing of antibody response is an important and feasible tool for following people after vaccination and selecting individuals who might require a third dose of vaccine at an earlier time point or persons who may not need a second dose due to previous SARS-CoV-2 infection. IMPORTANCE Now that authorized vaccines for COVID-19 have been widely used, it is important to understand how they induce antivirus antibodies, which antigens are targeted, how long antibodies circulate, and how personal health conditions and age may affect this humoral immunity. Here, we report induction and time course of multiple anti-SARS-CoV-2 antibody responses in healthy individuals immunized with Pfizer and Moderna mRNA vaccines. We also determined the age and gender dependence of the antibody response and compared antibody levels to responses seen in those who have recovered from COVID-19. Our results suggest the importance of screening for antibody response to multiple antigens after vaccination in order to reveal individuals who require early and late additional boosting and those who may not need second dose due to prior SARS-CoV-2 infection.

Microbiol Spectr2021       LitCov and CORD-19
109Low immunogenicity to SARS-CoV-2 vaccination among liver transplant recipients  

BACKGROUND AND AIMS: Two SARS-CoV-2 mRNA vaccines were approved to prevent COVID-19 infection, with reported vaccine efficacy of 95%. Liver transplant (LT) recipients are at risk for lower vaccine immunogenicity and were not included in the registration trials. We assessed vaccine immunogenicity and safety in this special population. METHODS: LT recipients followed at the Tel-Aviv Sourasky Medical Center and healthy volunteers were tested for SARS-CoV-2 IgG antibodies directed against the Spike-protein (S) and Nucleocapsid-protein (N) 10-20 days after receiving the second Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine dose. Information regarding vaccine side effects and clinical data was collected from patients and medical records. RESULTS: Eighty LT recipients were enrolled. Mean age was 60 years and 30% were female. Twenty-five healthy volunteer controls were younger (mean age 52.7 years, p=0.013) and mostly female (68%, p=0.002). All participants were negative for IgG N-protein serology, indicating immunity did not result from prior COVID-19 infection. All controls were positive for IgG S-protein serology. Immunogenicity among LT recipients was significantly lower with positive serology in only 47.5% (p<0.001). Antibody titer was also significantly lower in this group (mean 95.41 AU/mL vs. 200.5 AU/mL in controls, p<0.001). Predictors for negative response among LT recipients were older age, lower eGFR, and treatment with high dose steroids and MMF. No serious adverse events were reported in both groups. CONCLUSION: LT recipients developed substantially lower immunological response to Pfizer-BioNTech SARS-CoV-2 mRNA-based vaccine. Factors influencing serological antibodies response include age, renal function and immunosuppressive medications. The findings require re-evaluation of vaccine regimens in this population. LAY SUMMARY: Liver Transplant recipients had a substantially inferior immunity to the Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine. Less than half of the patients developed sufficient levels of antibodies against the virus, and in those who were positive, average antibody levels were two times less compared to healthy controls. Factors predicting non-response were older age, renal function and immunosuppressive medications.

J Hepatol2021       LitCov and CORD-19
110How do you feel during the COVID-19 pandemic? A survey using psychological and linguistic self-report measures and machine learning to investigate mental health, subjective experience, personality and behaviour during the COVID-19 pandemic among university students  

BACKGROUND: The WHO has raised concerns about the psychological consequences of the current COVID-19 pandemic, negatively affecting health across societies, cultures and age-groups. METHODS: This online survey study investigated mental health, subjective experience, and behaviour (health, learning/teaching) among university students studying in Egypt or Germany shortly after the first pandemic lockdown in May 2020. Psychological assessment included stable personality traits, self-concept and state-like psychological variables related to (a) mental health (depression, anxiety), (b) pandemic threat perception (feelings during the pandemic, perceived difficulties in describing, identifying, expressing emotions), (c) health (e.g., worries about health, bodily symptoms) and behaviour including perceived difficulties in learning. Assessment methods comprised self-report questions, standardized psychological scales, psychological questionnaires, and linguistic self-report measures. Data analysis comprised descriptive analysis of mental health, linguistic analysis of self-concept, personality and feelings, as well as correlational analysis and machine learning. N = 220 (107 women, 112 men, 1 = other) studying in Egypt or Germany provided answers to all psychological questionnaires and survey items. RESULTS: Mean state and trait anxiety scores were significantly above the cut off scores that distinguish between high versus low anxious subjects. Depressive symptoms were reported by 51.82% of the student sample, the mean score was significantly above the screening cut off score for risk of depression. Worries about health (mental and physical health) and perceived difficulties in identifying feelings, and difficulties in learning behaviour relative to before the pandemic were also significant. No negative self-concept was found in the linguistic descriptions of the participants, whereas linguistic descriptions of feelings during the pandemic revealed a negativity bias in emotion perception. Machine learning (exploratory) predicted personality from the self-report data suggesting relations between personality and subjective experience that were not captured by descriptive or correlative data analytics alone. CONCLUSION: Despite small sample sizes, this multimethod survey provides important insight into mental health of university students studying in Egypt or Germany and how they perceived the first COVID-19 pandemic lockdown in May 2020. The results should be continued with larger samples to help develop psychological interventions that support university students across countries and cultures to stay psychologically resilient during the pandemic. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40359-021-00574-x.

BMC Psychol2021       LitCov and CORD-19
111A multinational, multicenter study on the psychological outcomes and associated physical symptoms amongst healthcare workers during COVID-19 outbreak  

Abstract Objective Since the declaration of the coronavirus 2019 (COVID-19) outbreak as pandemic, there are reports on the increased prevalence of physical symptoms observed in the general population. We investigated the association between psychological outcomes and physical symptoms among healthcare workers. Methods Healthcare workers from 5 major hospitals, involved in the care for COVID-19 patients, in Singapore and India were invited to participate in a study by performing a self-administered questionnaire within the period of February 19 to April 17, 2020. Healthcare workers included doctors, nurses, allied healthcare workers, administrators, clerical staff and maintenance workers. This questionnaire collected information on demographics, medical history, symptom prevalence in the past month, Depression Anxiety Stress Scales (DASS-21) and the Impact of Events Scale-Revised (IES-R) instrument. The prevalence of physical symptoms displayed by healthcare workers and the associations between physical symptoms and psychological outcomes of depression, anxiety, stress, and post-traumatic stress disorder (PTSD) were evaluated. Results Out of the 906 healthcare workers who participated in the survey, 48 (5.3%) screened positive for moderate to very-severe depression, 79 (8.7%) for moderate to extremely-severe anxiety, 20 (2.2%) for moderate to extremely-severe stress, and 34 (3.8%) for moderate to severe levels of psychological distress. The commonest reported symptom was headache (32.3%), with a large number of participants (33.4%) reporting more than four symptoms. Participants who had experienced symptoms in the preceding month were more likely to be older, have pre-existing comorbidities and a positive screen for depression, anxiety, stress, and PTSD. After adjusting for age, gender and comorbidities, it was found that depression (OR 2.79, 95% CI 1.54–5.07, p = 0.001), anxiety (OR 2.18, 95% CI 1.36–3.48, p = 0.001), stress (OR 3.06, 95% CI 1.27–7.41, p = 0.13), and PTSD (OR 2.20, 95% CI 1.12–4.35, p = 0.023) remained significantly associated with the presence of physical symptoms experienced in the preceding month. Linear regression revealed that the presence of physical symptoms was associated with higher mean scores in the IES-R, DASS Anxiety, Stress and Depression subscales. Conclusions Our study demonstrates a significant association between the prevalence of physical symptoms and psychological outcomes among healthcare workers during the COVID-19 outbreak. We postulate that this association may be bi-directional, and that timely psychological interventions for healthcare workers with physical symptoms should be considered once an infection has been excluded.

Brain Behav Immun2020       LitCov and CORD-19
112SARS-CoV-2 variants and the global pandemic challenged by vaccine uptake during the emergence of the Delta variant: A national survey seeking vaccine hesitancy causes  


J Infect Public Health2022       LitCov
113Mental Health of Children and Adolescents Amidst COVID-19 and Past Pandemics: A Rapid Systematic Review  

Background: The COVID‑19 pandemic and associated public health measures have disrupted the lives of people around the world. It is already evident that the direct and indirect psychological and social effects of the COVID‑19 pandemic are insidious and affect the mental health of young children and adolescents now and will in the future. The aim and objectives of this knowledge-synthesis study were to identify the impact of the pandemic on children’s and adolescent’s mental health and to evaluate the effectiveness of different interventions employed during previous and the current pandemic to promote children’s and adolescents’ mental health. Methodology: We conducted the systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included experimental randomized and nonrandomized controlled trials, observational studies, and qualitative studies. Results: Of the 5828 articles that we retrieved, 18 articles met the inclusion criteria. We thematically analyzed them and put the major findings under the thematic areas of impact of the pandemic on children’s and adolescents’ mental health. These studies reported that pandemics cause stress, worry, helplessness, and social and risky behavioral problems among children and adolescents (e.g., substance abuse, suicide, relationship problems, academic issues, and absenteeism from work). Interventions such as art-based programs, support services, and clinician-led mental health and psychosocial services effectively decrease mental health issues among children and adolescents. Conclusion: Children and adolescents are more likely to experience high rates of depression and anxiety during and after a pandemic. It is critical that future researchers explore effective mental health strategies that are tailored to the needs of children and adolescents. Explorations of effective channels regarding the development and delivery of evidenced-based, age-appropriate services are vital to lessen the effects and improve long-term capacities for mental health services for children and adolescents. Key Practitioner Message: The COVID-19 pandemic’s physical restrictions and social distancing measures have affected each and every domain of life. Although the number of children and adolescents affected by the disease is small, the disease and the containment measures such as social distancing, school closure, and isolation have negatively impacted the mental health and well-being of children and adolescents. The impact of COVID-19 on the mental health of children and adolescents is of great concern. Anxiety, depression, disturbances in sleep and appetite, as well as impairment in social interactions are the most common presentations. It has been indicated that compared to adults, this pandemic may continue to have increased long term adverse consequences on children’s and adolescents’ mental health. As the pandemic continues, it is important to monitor the impact on children’s and adolescents’ mental health status and how to help them to improve their mental health outcomes in the time of the current or future pandemics.

Int J Environ Res Public Healt2021       LitCov and CORD-19
114Lived experiences of frontline healthcare providers offering maternal and newborn services amidst the novel corona virus disease 19 pandemic in Uganda: A qualitative study  

BACKGROUND: The COVID-19 pandemic has brought many health systems in low resource settings to their knees. The pandemic has had crippling effects on the already strained health systems in provision of maternal and newborn healthcare. With the travel restrictions, social distancing associated with the containment of theCOVID-19 pandemic, healthcare providers could be faced with challenges of accessing their work stations, and risked burnout as they offered maternal and newborn services. This study sought to understand the experiences and perceptions of healthcare providers at the frontline during the first phase of the lockdown as they offered maternal and newborn health care services in both public and private health facilities in Uganda with the aim of streamlining patient care in face of the current COVID-19 pandemic and in future disasters. METHODS: Between June 2020 and December 2020, 25 in-depth interviews were conducted among healthcare providers of different cadres in eight Public, Private-Not-for Profit and Private Health facilities in Kampala, Uganda. The interview guide primarily explored the lived experiences of healthcare providers as they offered maternal and newborn healthcare services during the COVID-19 pandemic. All of the in depth interviews were audio recorded and transcribed verbatim. Themes and subthemes were identified using both inductive thematic and phenomenological approaches. RESULTS: The content analysis of the in depth interviews revealed that the facilitators of maternal and newborn care service delivery among the healthcare providers during the COVID-19 pandemic included; salary bonuses, the passion to serve their patients, availability of accommodation during the pandemic, transportation to and from the health facilities by the health facilities, teamwork, fear of losing their jobs and fear of litigation if something went wrong with the mothers or their babies. The barriers to their service delivery included; lack of transport means to access their work stations, fear of contracting COVID-19 and transmitting it to their family members, salary cuts, loss of jobs especially in the private health facilities, closure of the non-essential services to combat high patient numbers, inadequate supply of Personal Protective equipment (PPE), being put in isolation or quarantine for two weeks which meant no earning, brutality from the security personnel during curfew hours and burnout from long hours of work and high patient turnovers. CONCLUSION: The COVID-19 Pandemic has led to a decline in quality of maternal and newborn service delivery by the healthcare providers as evidenced by shorter consultation time and failure to keep appointments to attend to patients. Challenges with transport, fears of losing jobs and fear of contracting COVID-19 with the limited access to personal protective equipment affected majority of the participants. The healthcare providers in Uganda despite the limitations imposed by the COVID-19 pandemic are driven by the inherent passion to serve their patients. Availability of accommodation and transport at the health facilities, provision of PPE, bonuses and inter professional teamwork are critical motivators that needed to be tapped to drive teams during the current and future pandemics.

PLoS One2021       LitCov and CORD-19
115The impact of the coronavirus pandemic on elective pediatric otolaryngology outpatient services-An analysis of virtual outpatient clinics in a tertiary referral center using the modified pediatric otolaryngology telemedicine satisfaction survey (POTSS)  

INTRODUCTION: Virtual outpatient clinics (VOPC) have been integrated into both paediatric and based adult outpatient services due to a multitude of factors, including increased demand for services, technological advances and rising morbidity secondary to ageing populations. The novel coronavirus disease (COVID-19) has accentuated pressures on the National Health Service (NHS) infrastructure, particularly elective services, whilst radically altering patterns of practice. AIM: To evaluate the impact of the COVID-19 pandemic on paediatric otolaryngology outpatient services whilst collating patient feedback to elicit long-term sustainability post COVID-19. METHOD: A retrospective analysis of VOPCs was undertaken at a tertiary paediatric referral centre over a 3-month capture period during the COVID-19 pandemic. Demographic, generic clinic (presenting complaint, new vs. follow-up, consultation type), as well as outcome data (medical or surgical intervention, discharge vs. ongoing review, onward referral, investigations, and conversion to face-to-face) was collated. Additionally a modified 15-point patient satisfaction survey was created. The Paediatric Otolaryngology Telemedicine Satisfaction survey (POTSS), was an adaptation of 4 validated patient satisfaction tools including the General Medical Council (GMC) patient questionnaire, the telehealth satisfaction scale (TESS), the telehealth usability questionnaire (TUQ), and the telemedicine satisfaction and usefulness questionnaire (TSUQ). RESULTS: Of 514 patients reviewed virtually over a 3-month period, 225 (45%) were randomly selected to participate, of which 200 met our inclusion criteria. The most common mode of consultation was telephony (92.5%, n=185). Non-attendance rates were reduced when compared to face-to-face clinics during an equivalent period prior to the COVID-19 pandemic. A significant proportion of patients (29% compared to 26% pre-VOPC) were discharged to primary care. Nine percent were listed for surgery compared to 19% pre-VOPC. A subsequent face-to-face appointment was required in 10% of participants. Overall, the satisfaction when assessing the doctor-patient relationship, privacy & trust, as well as consultation domains was high, with the overwhelming majority of parents’ content with the future integration and participation in VOPCs. CONCLUSION: An evolving worldwide pandemic has accelerated the need for healthcare services to reform in order to maintain a steady flow of patients within an elective outpatient setting without compromising patient care. Solutions must be sustainable long-term to account for future disruptions, whilst accounting for evolving patient demographics. Our novel survey has demonstrated the vast potential that the integration of VOPCs can offer paediatric otolaryngology services within a carefully selected cohort of patients.

Int J Pediatr Otorhinolaryngol2020       LitCov and CORD-19
116A Practical Approach to the Management of Cancer Patients During the Novel COVID-19 Pandemic: An International Collaborative Group  

The outbreak of coronavirus disease 2019 (COVID‐19) has rapidly spread globally since being identified as a public health emergency of major international concern and has now been declared a pandemic by the World Health Organization (WHO). In December 2019, an outbreak of atypical pneumonia, known as COVID‐19, was identified in Wuhan, China. The newly identified zoonotic coronavirus, severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), is characterized by rapid human‐to‐human transmission. Many cancer patients frequently visit the hospital for treatment and disease surveillance. They may be immunocompromised due to the underlying malignancy or anticancer therapy and are at higher risk of developing infections. Several factors increase the risk of infection, and cancer patients commonly have multiple risk factors. Cancer patients appear to have an estimated twofold increased risk of contracting SARS‐CoV‐2 than the general population. With the WHO declaring the novel coronavirus outbreak a pandemic, there is an urgent need to address the impact of such a pandemic on cancer patients. This include changes to resource allocation, clinical care, and the consent process during a pandemic. Currently and due to limited data, there are no international guidelines to address the management of cancer patients in any infectious pandemic. In this review, the potential challenges associated with managing cancer patients during the COVID‐19 infection pandemic will be addressed, with suggestions of some practical approaches. IMPLICATIONS FOR PRACTICE: The main management strategies for treating cancer patients during the COVID‐19 epidemic include clear communication and education about hand hygiene, infection control measures, high‐risk exposure, and the signs and symptoms of COVID‐19. Consideration of risk and benefit for active intervention in the cancer population must be individualized. Postponing elective surgery or adjuvant chemotherapy for cancer patients with low risk of progression should be considered on a case‐by‐case basis. Minimizing outpatient visits can help to mitigate exposure and possible further transmission. Telemedicine may be used to support patients to minimize number of visits and risk of exposure. More research is needed to better understand SARS‐CoV‐2 virology and epidemiology.

Oncologist2020       LitCov and CORD-19
117SARS-CoV-2 Infection and Hospitalization Among Adults Aged ≥18 Years, by Vaccination Status, Before and During SARS-CoV-2 B.1.1.529 (Omicron) Variant Predominance-Los Angeles County, California, November 7, 2021-January 8, 2022  

COVID-19 vaccines are effective at preventing infection with SARS-CoV-2, the virus that causes COVID-19, as well as severe COVID-19-associated outcomes in real-world conditions (1,2). The risks for SARS-CoV-2 infection and COVID-19-associated hospitalization are lower among fully vaccinated than among unvaccinated persons; this reduction is even more pronounced among those who have received additional or booster doses (boosters) (3,4). Although the B.1.1.529 (Omicron) variant spreads more rapidly than did earlier SARS-CoV-2 variants, recent studies suggest that disease severity is lower for Omicron compared with that associated with the B.1.617.2 (Delta) variant; but the high volume of infections is straining the health care system more than did previous waves (5).*,† The Los Angeles County (LAC) Department of Public Health (LACDPH) used COVID-19 surveillance and California Immunization Registry 2 (CAIR2) data to describe age-adjusted 14-day cumulative incidence and hospitalization rates during November 7, 2021-January 8, 2022, by COVID-19 vaccination status and variant predominance. For the 14-day period ending December 11, 2021, the last week of Delta predominance, the incidence and hospitalization rates among unvaccinated persons were 12.3 and 83.0 times, respectively, those of fully vaccinated persons with a booster and 3.8 and 12.9 times, respectively, those of fully vaccinated persons without a booster. These rate ratios were lower during Omicron predominance (week ending January 8, 2022), with unvaccinated persons having infection and hospitalization rates 3.6 and 23.0 times, respectively, those of fully vaccinated persons with a booster and 2.0 and 5.3 times, respectively, those of fully vaccinated persons without a booster. In addition, during the entire analytic period, admission to intensive care units (ICUs), intubation for mechanical ventilation, and death were more likely to occur among unvaccinated persons than among fully vaccinated persons without or with a booster (p<0.001). Incidence and hospitalization rates were consistently highest for unvaccinated persons and lowest for fully vaccinated persons with a booster. Being up to date with COVID-19 vaccination is critical to protecting against SARS-CoV-2 infection and associated hospitalization.

MMWR Morb Mortal Wkly Rep2022       LitCov and CORD-19
118Double-blind, randomized, controlled, trial to assess the efficacy of allogenic mesenchymal stromal cells in patients with acute respiratory distress syndrome due to COVID-19 (COVID-AT): A structured summary of a study protocol for a randomised controlled trial  

OBJECTIVES: 1. To assess the efficacy of Mesenchymal Stromal Cells (MSC) versus a control arm as described in the primary endpoint. 2. To evaluate the effects of MSC on the secondary efficacy endpoints. 3. To evaluate the safety and tolerability profiles of MSC. 4. To study soluble and cellular biomarkers that might be involved in the course of the disease and the response to the investigational product. TRIAL DESIGN: A double-blind, randomized, controlled, trial to evaluate the efficacy and safety of MSC intravenous administration in patients with COVID-induced Acute Respiratory Distress Syndrome (ARDS) compared to a control arm. PARTICIPANTS: The trial is being conducted at a third level hospital, Hospital Universitario Puerta de Hierro, in Majadahonda, Madrid (Spain). Inclusion criteria 1. Informed consent prior to performing study procedures (witnessed oral consent with written consent by representatives will be accepted to avoid paper handling). Written consent by patient or representatives will be obtained whenever possible. 2. Adult patients ≥18 years of age at the time of enrolment. 3. Laboratory-confirmed SARS-CoV-2 infection as determined by Polymerase Chain Reaction (PCR), in oropharyngeal swabs or any other relevant specimen obtained during the course of the disease. Alternative tests (e.g., rapid antigen tests) are also acceptable as laboratory confirmation if their specificity has been accepted by the Sponsor. 4. Moderate to severe ARDS (PaO2/FiO2 ratio equal or less than 200 mmHg) for less than 96 hours at the time of randomization. 5. Patients requiring invasive ventilation are eligible within 72 hours from intubation. 6. Eligible for ICU admission, according to the clinical team. Exclusion criteria 1. Imminent and unavoidable progression to death within 24 hours, irrespective of the provision of treatments (in the opinion of the clinical team). 2. “Do Not Attempt Resuscitation” order in place. 3. Any end-stage organ disease or condition, which in the investigator’s opinion, makes the patient an unsuitable candidate for treatment. 4. History of a moderate/severe lung disorder requiring home-based oxygen therapy. 5. Patient requiring Extracorporeal Membrane Oxygenation (ECMO), haemodialysis or hemofiltration at the time of treatment administration. 6. Current diagnosis of pulmonary embolism. 7. Active neoplasm, except carcinoma in situ or basalioma. 8. Known allergy to the products involved in the allogeneic MSC production process. 9. Current pregnancy or lactation (women with childbearing potential should have a negative pregnancy test result at the time of study enrolment). 10. Current participation in a clinical trial with an experimental treatment for COVID-19 (the use of any off-label medicine according to local treatment protocols is not an exclusion criteria). 11. Any circumstances that in the investigator’s opinion compromises the patient’s ability to participate in the clinical trial. INTERVENTION AND COMPARATOR: - Experimental treatment arm: Allogeneic MSC (approximately 1 x 10(6) cells/kg). - Control arm: placebo solution (same composition as the experimental treatment, without the MSC). One single intravenous dose of the assigned treatment will be administered on Day 0 of the study. All trial participants will receive standard of care (SOC). In the context of the current worldwide pandemic, SOC can include medicines that are being used in clinical practice (e.g. lopinavir/ritonavir; hydroxy/chloroquine, tocilizumab, etc.), as well as those authorised for COVID (e.g., remdesivir). MAIN OUTCOMES: Primary endpoint: Change in the PaO2/FiO2 ratio from baseline to day 7 of treatment administration, or to the last available PaO2/FiO2 ratio if death occurs before day 7. Secondary endpoints: - All-cause mortality on days 7, 14, and 28 after treatment. - PaO2/FiO2 ratio at baseline and days 2, 4, 7, 14 and 28 after treatment. - Oxygen saturation (by standardized measurement) at baseline, daily until day 14, and on day 28 after treatment. - Time to PaO2/FiO2 ratio greater than 200 mmHg. - Subjects’ clinical status on the WHO 7-point ordinal scale at baseline, daily until day 14, and on day 28 after treatment. - Time to an improvement of one category from admission on the WHO 7-point ordinal scale. - Percentage of patients that worsen at least one category on the WHO 7-point ordinal scale. - Percentage of patients that improve at least one category (maintained 48h) on the WHO 7-point ordinal scale. - Sequential Organ Failure Assessment (SOFA) scale at baseline and days 2, 4, 7, 14 and 28 after treatment. - Duration of hospitalization (days). - Duration of ICU stay (days). - Oxygen therapy-free days in the first 28 days after treatment. - Duration of supplemental oxygen. - Incidence of and duration of non-invasive and invasive mechanical ventilation in the first 28 days after treatment. - Mechanical ventilation-free days in the first 28 days after treatment. - Ventilation parameters. - Incidence of new onset pulmonary fibrosis at 3 and 12 months after treatment, based on CT scan and pulmonary function tests. - Survival at 3 and 12 months. - Cumulative incidence of Serious Adverse events (SAEs) and Grade 3 and 4 Adverse Events (AEs). - Cumulative incidence of Adverse Drug Reactions (ADR) in the experimental treatment arm. - Cumulative incidence of AEs of special interest. - Levels of analytical markers (C-Reactive Protein, lymphocyte and neutrophil counts, lymphocyte subpopulations, LDH, ferritin, D-dimer, coagulation tests and cytokines...) at baseline and days 2, 4, 7, 14 and 28 after treatment. - Other soluble and cellular biomarkers that might be involved in the course of the disease and the response to MSC. RANDOMISATION: The assignment to treatment will be carried out randomly and blinded, with a 1:1 allocation. Randomization will be done through a centralized system embedded in the electronic Case Report Form (CRF). BLINDING (MASKING): To ensure blinding, treatments will be prepared for administration at the Cell Production Unit and the administration of the treatment will be masked, not allowing the identification of the Investigational Medicinal Product (IMP). NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 20 participants are planned to be randomized, 10 to each treatment group. TRIAL STATUS: Protocol version: 1.2, dated October 14th, 2020 Start of recruitment: 01/10/2020 End of recruitment (estimated): December 2020. TRIAL REGISTRATION: EudraCT Number: 2020-002193-27, registered on July 14(th), 2020. NCT number: NCT04615429, registered on November 4(th), 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-020-04964-1.

Trials2021       LitCov and CORD-19
119COVID-19: consider cytokine storm syndromes and immunosuppression  

Lancet2020       LitCov and CORD-19
120The Rapid Development and Early Success of Covid 19 Vaccines Have Raised Hopes for Accelerating the Cancer Treatment Mechanism  


Arch Razi Inst2021       LitCov and CORD-19
121Structure, Function and Antigenicity of the SARS-CoV-2 Spike Glycoprotein  

The emergence of SARS-CoV-2 has resulted in >90,000 infections and >3,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S(1)/S(2) subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. We determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal antibodies potently inhibited SARS-CoV-2 S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.

Cell2020       LitCov and CORD-19
122Experiences, Attitudes and Needs of Users of a Pregnancy and Parenting App (Baby Buddy) During the COVID-19 Pandemic: Mixed Methods Study  

BACKGROUND: The COVID-19 pandemic has impacted the lives of expectant parents and parents of young babies, with disruptions in health care provision and loss of social support. OBJECTIVE: This study investigated the impact of the COVID-19 pandemic and its associated lockdown on this population through the lens of users of the UK National Health Service–approved pregnancy and parenting smartphone app, Baby Buddy. The study aims were threefold: to gain insights into the attitudes and experiences of expectant and recent parents (with babies under 24 weeks of age) during the COVID-19 pandemic; to investigate whether Baby Buddy is meeting users’ needs during this time; and to identify ways to revise the content of Baby Buddy to better support its users now and in future. METHODS: A mixed methods study design combining a web-based survey with semistructured telephone interviews among Baby Buddy users in the United Kingdom was applied. Data were collected from April 15 to mid-June 2020, corresponding to weeks 4-13 of the lockdown in the United Kingdom. RESULTS: A total of 436 expectant (n=244, 56.0%) and recent (n=192, 44.0%) parents responded to the web-based survey, of which 79.1% (n=345) were aged 25-39 years and 17.2% (n=75) spoke English as their second language. Of the 436 respondents, 88.5% (386/436) reported increased levels of anxiety around pregnancy, birth, and being a new parent, and 58.0% (253/436) were concerned about their emotional and mental health. Of the 244 pregnant respondents, 43.4% (n=106) were concerned about their physical health. Telephone interviews with 13 pregnant women and 19 recent parents revealed similarly increased levels of anxiety due to reduced health care provision and loss of support from friends and family. Although a minority of respondents identified some positive outcomes of lockdown, such as family bonding, many telephone interviewees reported feeling isolated, disregarded, and overwhelmed. Recent parents were particularly anxious about the impact of the lockdown on their baby’s development and socialization. Many interviewees were also concerned about their physical health as a consequence of both limited access to face-to-face medical appointments and their own poorer dietary and physical activity behaviors. Across both samples, 97.0% (423/436) of respondents reported that Baby Buddy was currently helping them, with many commenting that its role was even more important given the lack of face-to-face support from health care and parenting organizations. Greater speed in updating digital content to reflect changes due to the pandemic was suggested. CONCLUSIONS: The COVID-19 pandemic has created heightened anxiety and stress among expectant parents and those with a young baby, and for many, lockdown has had an adverse impact on their physical and mental well-being. With reductions in health care and social support, expectant and new parents are increasingly relying on web-based resources. As a free, evidence-based app, Baby Buddy is well positioned to meet this need. The app could support its users even more by actively directing them to the wealth of existing content relevant to their concerns and by adding content to give users the knowledge and confidence to meet new challenges.

JMIR Mhealth Uhealth2020       LitCov and CORD-19
123Differences in IgG Antibody Responses following BNT162b2 and mRNA-1273 SARS-CoV-2 Vaccines  

Studies examining antibody responses by vaccine brand are lacking and may be informative for optimizing vaccine selection, dosage, and regimens. The purpose of this study is to assess IgG antibody responses following immunization with BNT162b2 (30 μg mRNA) and mRNA-1273 (100 μg mRNA) vaccines. A cohort of clinicians at a nonprofit organization is being assessed clinically and serologically following immunization with BNT162b2 or mRNA-1273. IgG responses were measured at the Remington Laboratory by an IgG assay against the SARS-CoV-2 spike protein-receptor binding domain. Mixed-effect linear (MEL) regression modeling was used to examine whether the SARS-CoV-2 IgG level differed by vaccine brand, dosage, or number of days since vaccination. Among 532 SARS-CoV-2 seronegative participants, 530 (99.6%) seroconverted with either vaccine. After adjustments for age and gender, MEL regression modeling revealed that the average IgG antibody level increased after the second dose compared to the first dose (P < 0.001). Overall, titers peaked at week 6 for both vaccines. Titers were significantly higher for the mRNA-1273 vaccine on days 14 to 20 (P < 0.05), 42 to 48 (P < 0.01), 70 to 76 (P < 0.05), and 77 to 83 (P < 0.05) and higher for the BNT162b2 vaccine on days 28 to 34 (P < 0.001). In two participants taking immunosuppressive drugs, the SARS-CoV-2 IgG antibody response remained negative. mRNA-1273 elicited higher IgG antibody responses than BNT162b2, possibly due to the higher S-protein delivery. Prospective clinical and serological follow-up of defined cohorts such as this may prove useful in determining antibody protection and whether differences in antibody kinetics between the vaccines have manufacturing relevance and clinical significance. IMPORTANCE SARS-CoV-2 vaccines using the mRNA platform have become one of the most powerful tools to overcome the COVID-19 pandemic. mRNA vaccines enable human cells to produce and present the virus spike protein to their immune system, leading to protection from severe illness. Two mRNA vaccines have been widely implemented, mRNA-1273 (Moderna) and BNT162b2 (Pfizer/BioNTech). We found that, following the second dose, spike protein antibodies were higher with mRNA-1273 than with BNT162b2. This is biologically plausible, since mRNA-1273 delivers a larger amount of mRNA (100 μg mRNA) than BNT162b2 (30 μg mRNA), which is translated into spike protein. This difference may need to be urgently translated into changes in the manufacturing process and dose regimens of these vaccines.

Microbiol Spectr2021       LitCov and CORD-19
124People's Willingness to Vaccinate Against COVID-19 Despite Their Safety Concerns: Twitter Poll Analysis  

BACKGROUND: On January 30, 2020, the World Health Organization’s Emergency Committee declared the rapid, worldwide spread of COVID-19 a global health emergency. Since then, tireless efforts have been made to mitigate the spread of the disease and its impact, and these efforts have mostly relied on nonpharmaceutical interventions. By December 2020, the safety and efficacy of the first COVID-19 vaccines were demonstrated. The large social media platform Twitter has been used by medical researchers for the analysis of important public health topics, such as the public’s perception on antibiotic use and misuse and human papillomavirus vaccination. The analysis of Twitter-generated data can be further facilitated by using Twitter’s built-in, anonymous polling tool to gain insight into public health issues and obtain rapid feedback on an international scale. During the fast-paced course of the COVID-19 pandemic, the Twitter polling system has provided a viable method for gaining rapid, large-scale, international public health insights on highly relevant and timely SARS-CoV-2–related topics. OBJECTIVE: The purpose of this study was to understand the public’s perception on the safety and acceptance of COVID-19 vaccines in real time by using Twitter polls. METHODS: We developed 2 Twitter polls to explore the public’s views on available COVID-19 vaccines. The surveys were pinned to the Digital Health and Patient Safety Platform Twitter timeline for 1 week in mid-February 2021, and Twitter users and influencers were asked to participate in and retweet the polls to reach the largest possible audience. RESULTS: The adequacy of COVID-19 vaccine safety (ie, the safety of currently available vaccines; poll 1) was agreed upon by 1579 out of 3439 (45.9%) Twitter users. In contrast, almost as many Twitter users (1434/3439, 41.7%) were unsure about the safety of COVID-19 vaccines. Only 5.2% (179/3439) of Twitter users rated the available COVID-19 vaccines as generally unsafe. Poll 2, which addressed the question of whether users would undergo vaccination, was answered affirmatively by 82.8% (2862/3457) of Twitter users, and only 8% (277/3457) categorically rejected vaccination at the time of polling. CONCLUSIONS: In contrast to the perceived high level of uncertainty about the safety of the available COVID-19 vaccines, we observed an elevated willingness to undergo vaccination among our study sample. Since people's perceptions and views are strongly influenced by social media, the snapshots provided by these media platforms represent a static image of a moving target. Thus, the results of this study need to be followed up by long-term surveys to maintain their validity. This is especially relevant due to the circumstances of the fast-paced pandemic and the need to not miss sudden rises in the incidence of vaccine hesitancy, which may have detrimental effects on the pandemic’s course.

J Med Internet Res2021       LitCov and CORD-19
125Multi-centre, three arm, randomized controlled trial on the use of methylprednisolone and unfractionated heparin in critically ill ventilated patients with pneumonia from SARS-CoV-2 infection: A structured summary of a study protocol for a randomised controlled trial  

OBJECTIVES: To assess the hypothesis that an adjunctive therapy with methylprednisolone and unfractionated heparin (UFH) or with methylprednisolone and low molecular weight heparin (LMWH) are more effective in reducing any-cause mortality in critically-ill ventilated patients with pneumonia from SARS-CoV-2 infection compared to LMWH alone. TRIAL DESIGN: The study is designed as a multi-centre, interventional, parallel group, superiority, randomized, investigator sponsored, three arms study. Patients, who satisfy all inclusion criteria and no exclusion criteria, will be randomly assigned to one of the three treatment groups in a ratio 1:1:1. PARTICIPANTS: Inpatients will be recruited from 8 Italian Academic and non-Academic Intensive Care Units INCLUSION CRITERIA (ALL REQUIRED): 1. Positive SARS-CoV-2 diagnostic (on pharyngeal swab of deep airways material) 2. Positive pressure ventilation (either non-invasive or invasive) from > 24 hours 3. Invasive mechanical ventilation from < 96 hours 4. PaO(2)/FiO(2) ratio lower than 150 mmHg 5. D-dimer level > 6 times the upper limit of normal reference range 6. C-reactive Protein > 6-fold upper the limit of normal reference range EXCLUSION CRITERIA: 1. Age < 18 years 2. On-going treatment with anticoagulant drugs 3. Platelet count < 100.000/mm(3) 4. History of heparin-induced thrombocytopenia 5. Allergy to sodium enoxaparin or other LMWH, UFH or methylprednisolone 6. Active bleeding or on-going clinical condition deemed at high risk of bleeding contraindicating anticoagulant treatment 7. Recent (in the last 1 month prior to randomization) brain, spinal or ophthalmic surgery 8. Chronic assumption or oral corticosteroids 9. Pregnancy or breastfeeding or positive pregnancy test. In childbearing age women, before inclusion, a pregnancy test will be performed if not available 10. Clinical decision to withhold life-sustaining treatment or “too sick to benefit” 11. Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition) 12. Lack or withdrawal of informed consent INTERVENTION AND COMPARATOR: • LMWH group: patients in this group will be administered enoxaparin at standard prophylactic dosage. • LMWH + steroid group: patients in this group will receive enoxaparin at standard prophylactic dosage and methylprednisolone. • UFH + steroid group: patients in this group will receive UFH at therapeutic dosages and methylprednisolone. UFH will be administered intravenously in UFH + steroid group at therapeutic doses. The infusion will be started at an infusion rate of 18 UI/kg/hour and then modified to obtain aPTT Ratio in between the range of 1.5-2.0. aPTT will be periodically checked at intervals no longer than 12 hours. The treatment with UFH will be administered up to ICU discharge. After ICU discharge anticoagulant therapy may be interrupted or switched to prophylaxis with LMWH in the destination ward up to clinical judgement of the attending physician. Enoxaparin will be administered in both LMWH group and LMWH + steroid group at standard prophylactic dose (i.e., 4000 UI once day, increased to 6000 UI once day for patients weighting more than 90 kg). The treatment will be administered subcutaneously once a day up to ICU discharge. After ICU discharge it may be continued or interrupted in the destination ward up to clinical judgement of the attending physician. Methylprednisolone will be administered in both LMWH + steroid group and UHF + steroid group intravenously with an initial bolus of 0,5 mg/kg followed by administration of 0,5 mg/kg 4 times daily for 7 days, 0,5 mg/kg 3 times daily from day 8 to day 10, 0,5 mg/kg 2 times daily at days 11 and 12 and 0,5 mg/kg once daily at days 13 and 14. MAIN OUTCOMES: Primary Efficacy Endpoint: All-cause mortality at day 28 Secondary Efficacy Endpoints: - Ventilation free days (VFDs) at day 28, defined as the total number of days that patient is alive and free of ventilation (either invasive or non-invasive) between randomization and day 28 (censored at hospital discharge). - Need of rescue administration of high-dose steroids or immune-modulatory drugs; - Occurrence of switch from non-invasive to invasive mechanical ventilation during ICU stay; - Delay from start of non-invasive ventilation to switch to invasive ventilation; - All-cause mortality at ICU discharge and hospital discharge; - ICU free days (IFDs) at day 28, defined as the total number of days between ICU discharge and day 28. - Occurrence of new infections from randomization to day 28; including infections by Candida, Aspergillus, Adenovirus, Herpes Virus e Cytomegalovirus - Occurrence of new organ dysfunction and grade of dysfunction during ICU stay. - Objectively confirmed venous thromboembolism, stroke or myocardial infarction; Safety endpoints: - Occurrence of major bleeding, defined as transfusion of 2 or more units of packed red blood cells in a day, bleeding that occurs in at least one of the following critical sites [intracranial, intra-spinal, intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, or retroperitoneal], bleeding that necessitates surgical intervention and bleeding that is fatal (defined as a bleeding event that was the primary cause of death or contributed directly to death); - Occurrence of clinically relevant non-major bleeding, defined ad acute clinically overt bleeding that does not meet the criteria for major and consists of any bleeding compromising hemodynamic; spontaneous hematoma larger than 25 cm(2), intramuscular hematoma documented by ultrasonography, haematuria that was macroscopic and was spontaneous or lasted for more than 24 hours after invasive procedures; haemoptysis, hematemesis or spontaneous rectal bleeding requiring endoscopy or other medical intervention or any other bleeding requiring temporary cessation of a study drug. RANDOMIZATION: A block randomisation will be used with variable block sizes (block size 4-6-8), stratified by 3 factors: Centre, BMI (<30/≥30) and Age (<75/≥75). Central randomisation will be performed using a secure, web-based, randomisation system with an allocation ratio of 1:1:1. The allocation sequence will be generated by the study statistician using computer generated random numbers. BLINDING (MASKING): Participants to the study will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The target sample size is based on the hypothesis that the combined use of UHF and steroid versus the LMWH group will significantly reduce the risk of death at day 28. The overall sample size in this study is expected to be 210 with a randomization 1:1:1 and seventy patients in each group. Assuming an alpha of 2.5% (two tailed) and mortality rate in LMWH group of 50%, as indicated from initial studies of ICU patients, the study will have an 80% power to detect at least a 25 % absolute reduction in the risk of death between: a) LMHW + steroid group and LMWH group or b) UHF + steroid group and LMWH group. The study has not been sized to assess the difference between LMHW + steroid group and UHF + steroid group, therefore the results obtained from this comparison will need to be interpreted with caution and will need further adequately sized studies confirm the effect. On the basis of a conservative estimation, that 8 participating sites admit an average of 3 eligible patients per month per centre (24 patients/month). Assuming that 80 % of eligible patients are enrolled, recruitment of 210 participants will be completed in approximately 10 months. TRIAL STATUS: Protocol version 1.1 of April 26(th), 2020. Recruitment start (expected): September 1(st), 2020 Recruitment finish (expected): June 30(th), 2021 TRIAL REGISTRATION: EudraCT number 2020-001921-30, registered on April 15(th), 2020 AIFA approval on May 4(th), 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Trials2020       LitCov and CORD-19
126The impact of COVID-19 pandemic on mental health & wellbeing among home-quarantined Bangladeshi students: A cross-sectional pilot study  

BACKGROUND: COVID-19 is imposing threat both on physical and mental health since its outbreak. Bangladesh adopted lockdown strategy with potential consequences on day to day life, mental and physical health and this study aims to explore the impact of COVID-19 on mental health and wellbeing among Bangladeshi students. METHODS: A cross-sectional study was conducted between 9th and 23rd April 2020 among 505 college and university students. Data was collected by using online questionnaire including DASS 21 and IES. Descriptive analysis and bivariate linear regression were performed to examine the association of variables. RESULTS: 28.5 % of the respondents had stress, 33.3% anxiety, 46.92% depression from mild to extremely severe, according to DASS 21 and 69.31% had event-specific distress from mild to severe in terms of severity according to IES. Perceiving physical symptoms as COVID-19 was significantly associated with DASS stress subscale (B=3.71, 95% CI: 1.01 to 6.40), DASS anxiety subscale (B= 3.95, 95% CI: 1.95 to 5.96), DASS depression subscale (B=3.82, 95% CI: 0.97 to 6.67) and IES scale (B=7.52, 95% CI: 3.58 to 11.45). Additionally, fear of infection, financial uncertainty, inadequate food supply, absence of physical exercise and limited or no recreational activity had significant association with stress, anxiety, depression and post-traumatic symptoms. CONCLUSION: This COVID-19 outbreak imposes psychological consequences on people to a great extent which requires attention from the concerned authorities to cope with this situation mentally. The perception about the outbreak can also play a big role in psychological impact.

J Affect Disord2020       LitCov and CORD-19
127Anti-SARS-CoV-2 Immunoglobulin Isotypes and Neutralization Activity Against Viral Variants, According to BNT162b2-Vaccination and Infection History  

PURPOSE: To compare SARS-CoV-2 antigen-specific antibody production and plasma neutralizing capacity against B.1 wild-type-like strain, and Gamma/P.1 and Delta/B.1.617.2 variants-of-concern, in subjects with different Covid-19 disease and vaccination histories. METHODS: Adult subjects were: 1) Unvaccinated/hospitalized for Covid-19; 2) Covid-19-recovered followed by one BNT162b2 vaccine dose; and 3) Covid-19-naïve/2-dose BNT162b2 vaccinated. Multiplex Luminex(®) immunoassays measured IgG, IgA, and IgM plasma levels against SARS-CoV-2 receptor-binding domain (RBD), spike-1 (S), and nucleocapsid proteins. Neutralizing activity was determined in Vero E6 cytopathic assays. RESULTS: Maximum anti-RBD IgG levels were similar in Covid(-)19‑recovered individuals 8‒10 days after single-dose vaccination and in Covid-19-naïve subjects 7 days after 2(nd) vaccine dosing; both groups had ≈2‑fold higher anti-RBD IgG levels than Unvaccinated/Covid-19 subjects tracked through 2 weeks post-symptom onset. Anti-S IgG expression patterns were similar to RBD within each group, but with lower signal strengths. Viral antigen-specific IgA and IgM levels were more variable than IgG patterns. Anti-nucleocapsid immunoglobulins were not detected in Covid-19-naïve subjects. Neutralizing activity against the B.1 strain, and Gamma/P.1 and Delta/B.1.617.2 variants, was highest in Covid‑19-recovered/single-dose vaccinated subjects; although neutralization against the Delta variant in this group was only 26% compared to B.1 neutralization, absolute anti-Delta titers suggested maintained protection. Neutralizing titers against the Gamma and Delta variants were 33‒77% and 26‒67%, respectively, versus neutralization against the B.1 strain (100%) in the three groups. CONCLUSION: These findings support SARS-CoV-2 mRNA vaccine usefulness regardless of Covid-19 history, and confirm remarkable protection provided by a single vaccine dose in people who have recovered from Covid-19.

Front Immunol2021       LitCov and CORD-19
128Immunogenicity of COVID-19 Tozinameran Vaccination in Patients on Chronic Dialysis  

Patients with kidney failure have notoriously weak responses to common vaccines. Thus, immunogenicity of novel SARS-CoV-2 vaccines might be impaired in this group. To determine immunogenicity of SARS-CoV-2 vaccination in patients with chronic dialysis, we analyzed the humoral and T-cell response after two doses of mRNA vaccine Tozinameran (BNT162b2 BioNTech/Pfizer). This observational study included 43 patients on dialysis before vaccination with two doses of Tozinameran 21 days apart. Overall, 36 patients completed the observation period until three weeks after the second dose and 32 patients were further analyzed at week 10. Serum samples were analyzed by SARS-CoV-2 specific IgG and IgA antibodies ~1, ~3–4 and ~10 weeks after the second vaccination. In addition, SARS-CoV-2-specific T-cell responses were assessed at ~3–4 weeks by an interferon-gamma release assay (IGRA). Antibody and T cell outcomes at this timepoint were compared to a group of 44 elderly patients not on dialysis, after immunization with Tozinameran. Median age of patients on chronic dialysis was 74.0 years (IQR 66.0, 82.0). The proportion of males was higher (69.4%) than females. Only 20/36 patients (55.6%, 95%CI: 38.29–71.67) developed SARS-CoV-2-IgG antibodies at the first sampling, whereas 32/36 patients (88.9%, 95%CI: 73.00–96.38) demonstrated IgG detection at the second sampling. In a longitudinal follow-up at ~10 weeks after the second dose, the proportion of dialysis patients reactive for anti-SARS-CoV-2-IgG decreased to 27/32 (84.37%, 95%CI: 66.46–94.10) The proportion of anti-SARS-CoV-2 S1 IgA decreased from 33/36 (91.67%; 95%CI: 76.41–97.82) at weeks 3–4 down to 19/32 (59.38; 95%CI: 40.79–75.78). Compared to a cohort of vaccinees with similar age but not on chronic dialysis seroconversion rates and antibody titers were significantly lower. SARS-CoV-2-specific T-cell responses 3 weeks after second vaccination were detected in 21/31 vaccinated dialysis patients (67.7%, 95%CI: 48.53–82.68) compared to 42/44 (93.3%, 95%CI: 76.49–98.84) in controls of similar age. Patients on dialysis demonstrate a delayed, but robust immune response three to four weeks after the second dose, which indicates effective vaccination of this vulnerable group. However, the lower immunogenicity of Tozinameran in these patients needs further attention to develop potential countermeasures such as an additional booster vaccination.

Front Immunol2021       LitCov and CORD-19
129Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study  

Summary Background Coronavirus disease 2019 (COVID-19) causes severe community and nosocomial outbreaks. Comprehensive data for serial respiratory viral load and serum antibody responses from patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not yet available. Nasopharyngeal and throat swabs are usually obtained for serial viral load monitoring of respiratory infections but gathering these specimens can cause discomfort for patients and put health-care workers at risk. We aimed to ascertain the serial respiratory viral load of SARS-CoV-2 in posterior oropharyngeal (deep throat) saliva samples from patients with COVID-19, and serum antibody responses. Methods We did a cohort study at two hospitals in Hong Kong. We included patients with laboratory-confirmed COVID-19. We obtained samples of blood, urine, posterior oropharyngeal saliva, and rectal swabs. Serial viral load was ascertained by reverse transcriptase quantitative PCR (RT-qPCR). Antibody levels against the SARS-CoV-2 internal nucleoprotein (NP) and surface spike protein receptor binding domain (RBD) were measured using EIA. Whole-genome sequencing was done to identify possible mutations arising during infection. Findings Between Jan 22, 2020, and Feb 12, 2020, 30 patients were screened for inclusion, of whom 23 were included (median age 62 years [range 37–75]). The median viral load in posterior oropharyngeal saliva or other respiratory specimens at presentation was 5·2 log10 copies per mL (IQR 4·1–7·0). Salivary viral load was highest during the first week after symptom onset and subsequently declined with time (slope −0·15, 95% CI −0·19 to −0·11; R 2=0·71). In one patient, viral RNA was detected 25 days after symptom onset. Older age was correlated with higher viral load (Spearman's ρ=0·48, 95% CI 0·074–0·75; p=0·020). For 16 patients with serum samples available 14 days or longer after symptom onset, rates of seropositivity were 94% for anti-NP IgG (n=15), 88% for anti-NP IgM (n=14), 100% for anti-RBD IgG (n=16), and 94% for anti-RBD IgM (n=15). Anti-SARS-CoV-2-NP or anti-SARS-CoV-2-RBD IgG levels correlated with virus neutralisation titre (R 2>0·9). No genome mutations were detected on serial samples. Interpretation Posterior oropharyngeal saliva samples are a non-invasive specimen more acceptable to patients and health-care workers. Unlike severe acute respiratory syndrome, patients with COVID-19 had the highest viral load near presentation, which could account for the fast-spreading nature of this epidemic. This finding emphasises the importance of stringent infection control and early use of potent antiviral agents, alone or in combination, for high-risk individuals. Serological assay can complement RT-qPCR for diagnosis. Funding Richard and Carol Yu, May Tam Mak Mei Yin, The Shaw Foundation Hong Kong, Michael Tong, Marina Lee, Government Consultancy Service, and Sanming Project of Medicine.

Lancet Infect Dis2020       LitCov and CORD-19
130Humoral and Cellular Responses to mRNA-1273 and BNT162b2 SARS-CoV-2 Vaccines Administered to Hemodialysis Patients  

RATIONALE AND OBJECTIVE: Patients with kidney failure requiring maintenance dialysis have a higher risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and worse clinical outcomes after coronavirus disease 2019 (COVID-19) than the general population. Therefore, immunization against SARS-CoV-2 with effective vaccines is an important component of health-maintenance strategies for these patients. This study evaluated the humoral and cellular responses to messenger RNA (mRNA) SARS-CoV-2 vaccines in this population. STUDY DESIGN: Observational prospective, multi-center cohort study. SETTING AND PARTICIPANTS: Two hundred five patients treated at three dialysis units at the Hospital Clínic of Barcelona (Spain) were vaccinated from February 3 to April 4, 2021 and followed until April 23, 2021. EXPOSURE: Immunization with either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 mRNA vaccine. OUTCOMES: Seroconversion, defined as the detection of IgG antibodies to the receptor-binding domain of the S1 spike antigen of SARS-CoV-2 (anti–S1-RBD IgG), and the identification of activated CD4(+) T cells 3 weeks after completing vaccination. Anti-S1-RBD IgG levels were also analyzed as a secondary outcome. ANALYTICAL APPROACH: Univariate and multivariable logistic and multiple linear regression models were used to evaluate the associations between vaccination and study outcomes. RESULTS: 97.7% of 175 vaccinated patients who were seronegative at baseline developed a response (humoral, cellular, or both). 95.4% of these patients seroconverted, while 62% of those tested for a cellular immunity had a positive response. Greater age and immunosuppressive treatment were associated with lower antibody levels. LIMITATIONS: Mandatory vaccine administration by health authorities. Anti-S1-RBD IgG levels were reported up to 150 U/mL and cellular immune responses were characterized qualitatively. Antibody assay and cellular response assessment may not be comparable with previously published laboratory approaches. CONCLUSIONS: Immunization with mRNA vaccines generated a humoral and cellular immune response in a high proportion of patients with kidney failure receiving maintenance dialysis. These findings as well as the high risk of infection and poor clinical outcomes among these patients make their vaccination a health priority.

Am J Kidney Dis2021       LitCov and CORD-19
131Impact of COVID-19 pandemic on mental health in the general population: A systematic review  

Background: As a major virus outbreak in the 21(st) century, the Coronavirus disease 2019 (COVID-19) pandemic has led to unprecedented hazards to mental health globally. While psychological support is being provided to patients and healthcare workers, the general public's mental health requires significant attention as well. This systematic review aims to synthesize extant literature that reports on the effects of COVID-19 on psychological outcomes of the general population and its associated risk factors. Methods: A systematic search was conducted on PubMed, Embase, Medline, Web of Science, and Scopus from inception to 17 May 2020 following the PRISMA guidelines. A manual search on Google Scholar was performed to identify additional relevant studies. Articles were selected based on the predetermined eligibility criteria. Results: Relatively high rates of symptoms of anxiety (6.33% to 50.9%), depression (14.6% to 48.3%), post-traumatic stress disorder (7% to 53.8%), psychological distress (34.43% to 38%), and stress (8.1% to 81.9%) are reported in the general population during the COVID-19 pandemic in China, Spain, Italy, Iran, the US, Turkey, Nepal, and Denmark. Risk factors associated with distress measures include female gender, younger age group (≤40 years), presence of chronic/psychiatric illnesses, unemployment, student status, and frequent exposure to social media/news concerning COVID-19. Limitations: A significant degree of heterogeneity was noted across studies. Conclusions: The COVID-19 pandemic is associated with highly significant levels of psychological distress that, in many cases, would meet the threshold for clinical relevance. Mitigating the hazardous effects of COVID-19 on mental health is an international public health priority.

J Affect Disord2020       LitCov and CORD-19
132Humoral immunity against SARS-CoV-2 in workers of social Healthcare centers of Castilla y León after vaccination with the BNT162b2 mRNA vaccine from Pfizer/Biontech  


Rev Esp Salud Publica2021       LitCov and CORD-19
133The effects of the COVID-19 pandemic on the use of the performance-enhancing drugs  

The coronavirus disease (COVID-19) pandemic has been impacting the whole society in every aspect of the daily life, comprising the sport field. Several restrictive strategies have been implemented by governments in an effort to stem the spread of the disease and salvage public health. Such efforts have severely constrained access to non-essential services, leading to the closure of non-essential points of gathering and business and the enforcement of rigorous social distancing and prolonged lockdowns, in addition to masking and stay-at-home mandates. However necessary, there is no denying that such extremely rigorous, and to most people unprecedented, measures have adversely affected the global economy and the daily lives of everyone of us, including professional and amateur athletes (1). The most important sport events were postponed or cancelled, including the 2020 Tokyo Olympic Games. But how was the phenomenon of performance-enhancing drug (PED) use impacted and how was the most concerning issue affecting the integrity of sport affected by the pandemic control restrictions? The World Anti-doping Agency (WADA) was established in 1999, whereas its code was implemented in 2004 in order to articulate and enforce doping control initiatives and provide educational strategies aimed at preventing PED use (2). Nonetheless, it is worth noting that the prevalence of PED use among athletes is mostly unchanged since the foundation of WADA. Unfortunately, the use of the performance-enhancing drugs is not limited to athletic performances, but it concerns other settings as well. Nowadays, several strategies for doping control are adopted such as education, deterrence, detection, enforcement and rule of law (3), but the most important anti-dissemination strategy is constituted by information campaigns, especially addressed to youngsters, meant to raise awareness as to the serious health risks involved in PED use. Currently, the primary drivers of anabolic androgenic steroids (ASA) use are 1) the determination to improve performances and prevail no matter what the cost may be; 2) the economic benefits, popularity and fame; 3) greater stamina and resistance. This public health issue has raised particular concerns due to the recent ASA market developments, which is somewhat similar to the illicit market of narcotic drugs. Moreover, it has to be considered that the higher stress and psychosocial condition related to pandemic social restrictions has fueled and exacerbated substance use disorders (4). The prevalence of doping in sport causes unfairness and damages the very fabric of our society, especially insofar as it involves children and young adults who look up to athletes as role models. In this concern, the impact of the COVD-19 pandemic may have led to substantial modifications in substance use patterns and an increased risk of substitution, adulteration, contamination, and dilution with a potentially harmful substance (5, 6). During the COVID-19 lockdown, WADA and stakeholders suspended or scaled down doping control programs, testing and other activities. As a consequence, athletes have seen the unexpected opportunity to misuse AAS without the possible risk of testing positive (7). This has been controversial, considering the measures taken by governments to flatten the pandemic curve in order to safeguard public health. Indeed, all the technologies implemented for teleworking, such as teaching students on-line, telehealth applications, prescriptions and referrals, and treating patients in hospitals/care homes via video links can also be applied to enhance and uphold sport integrity. Conversely, anti-doping testing for professional competitive athletes has increased, due to the lockdown raising suspicion about doping opportunities. The U.S. Anti-doping Agency has put in place novel measures to combat the lack of anti-doping testing during the pandemic: these include a in-home self-test that requires athletes to provide urine and small blood samples at home to be tested in the anti-doping laboratory, under supervision provided by video-conference (8). As such, reports from forensic science and toxicology laboratories are crucial for the early detection and response to such events. Furthermore, toxicology laboratories should assure their continue effort in providing new methods and technologies designed to tackle the consumption of illicit substances and to monitor the constantly changing illegal drug markets (9). The most recent WADA code revision has certainly brought about important progress in the ongoing fight against PED abuse. Indeed, it has introduced the possibility to store the samples for 10 years after the first analysis, maintaining the same legal value if re-tested and use for prosecution purposes (10). In that regard, the prospect of re-testing the same sample with newly developed analytical methods based on innovative technologies may represent a strong deterrent for doping users, since anti-doping research rapidly evolves (6), largely by implementing the same approaches used to fight new psychoactive substances (NPS) use (11,12). It is worth noting that the NPS phenomenon bears several similarities with doping, especially due to the constant emergence of new substances and methods aimed at circumventing current legal restrictions. In Italy, the National Antidoping Organization (NADO-Italia) is in charge of guaranteeing compliance with WADA rules and the transposition of the List of Prohibited Substances and Methods. However, the gap between elite athletes and amateur athletes is still broad and unaddressed, since non-professional sport competitions are not adequately overseen, and neither are the competing athletes . This difference may give rise to an important public health issue, on account of the adverse effects of uncontrolled doping agents consumption. In this concern, the Italian anti-doping law created the Section of the Technical Health Committee for Supervision and Control on Doping and for Health Protection in Sport Activities, that carries out, among its other tasks, the following activities on amateur sport: 1) updating each year the list of banned substances and practices, adapting it to the WADA list; 2) determining cases, criteria and methodologies for anti-doping controls; 3) promoting research projects and information/training campaigns meant to protect health in sports and tackle doping (13). In conclusion, regarding the highly complex dynamics triggered by the pandemic, new and unexpected challenges have come to the fore in the ongoing fight against substance abuse in its every aspect, such as NPS (14), ASA consumption by amateur athletes, or other substance abuse settings, e.g. driving under the influence of psychotropic substances (15). The current Italian antidoping approach for amateur athletes seems to be a promising strategy to bridge the gap between professional sports and amateur sports. Moreover, youngsters should be thoroughly educated as to the threats posed by such substances, so that they can realize how profoundly and severely drug abuse can affect not only their sport career, but their health and well-being overall.

Acta Biomed2022       LitCov and CORD-19
134Pre-exposure prophylaxis with hydroxychloroquine for high-risk healthcare workers during the COVID-19 pandemic: A structured summary of a study protocol for a multicentre, double-blind randomized controlled trial  

OBJECTIVES: The aim of this study is to assess the efficacy of the use of pre-exposure prophylaxis (PrEP) with hydroxychloroquine against placebo in healthcare workers with high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in reducing their risk of coronavirus disease 2019 (COVID-19) disease during an epidemic period. As secondary objectives, we would like to: i) assess the efficacy of the use of PrEP with hydroxychloroquine against placebo in healthcare workers with high risk of SARS-CoV-2 infection in reducing their risk of exposure to SARS-CoV-2 (defined by seroconversion) during an epidemic period, ii) evaluate the safety of PrEP with hydroxychloroquine in adults, iii) describe the incidence of SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 infection, iv) identify clinical, analytical and microbiological predictors of COVID-19 among healthcare workers at high risk of SARS-CoV-2 infection, v) set up a repository of serum samples obtained from healthcare workers at high risk of SARS-CoV-2 infection for future research on blood markers to predict SARS-CoV-2 infection. TRIAL DESIGN: Multicentre double-blind parallel design (ratio 1:1) randomized controlled clinical trial. PARTICIPANTS: Approximately 440 healthcare workers of four Spanish hospitals (Hospital Clínic of Barcelona, Hospital de la Santa Creu i Sant Pau of Barcelona, Hospital Plató of Barcelona, Hospital General de Granollers, Barcelona) will be recruited. Participants are considered to be at high-risk of SARS-CoV-2 infection due to their frequent contact with suspected and confirmed cases of COVID-19. For eligibility, healthcare workers with 18 years old or older working at least 3 days a week in a hospital with both negative SARS-CoV-2 polymerase chain reaction (PCR) assays and serological COVID-19 rapid diagnostic tests (RDT) are invited to participate. Participants with any of the following conditions are excluded: pregnancy, breastfeeding, ongoing antiviral, antiretroviral or corticosteroids treatment, chloroquine or hydroxychloroquine uptake the last month or any contraindication to hydroxychloroquine treatment. INTERVENTION AND COMPARATOR: Intervention group (PrEP): participants will receive the standard of care and will take 400mg of hydroxychloroquine (2 tablets of 200 mg per Dolquine® tablet) daily the first four consecutive days, followed by 400 mg weekly for a period of 6 months. Control group: participants will receive placebo tablets with identical physical appearance to hydroxychloroquine 200 mg (Dolquine®) tablets following the same treatment schedule of the intervention group. Both groups will be encouraged to use the personal protection equipment (PPE) for COVID-19 prevention according to current hospital guidelines. MAIN OUTCOMES: The primary endpoint will be the number of confirmed cases of a COVID-19 (defined by a positive PCR for SARS-CoV-2 or symptoms compatible with COVID-19 with seroconversion) in the PrEP group compared to the placebo group at any time during the 6 months of the follow-up in healthcare workers with negative SARS-CoV-2 PCR and serology at day 0. As secondary endpoints, we will obtain: i) the SARS-CoV-2 seroconversion in the PrEP group compared to placebo during the 6 months of follow-up in healthcare workers with negative serology at day 0; ii) the occurrence of any adverse event related with hydroxychloroquine treatment; iii) the incidence of SARS-CoV-2 infection and COVID-19 among healthcare workers in the non-PrEP group, among the total of healthcare workers included in the non-PrEP group during the study period; iv) the risk ratio for the different clinical, analytical and microbiological conditions to develop COVID-19; v) a repository of serum samples obtained from healthcare workers confirmed COVID-19 cases for future research on blood markers to predict SARS-CoV-2 infection. RANDOMISATION: Participants meeting all eligibility requirements will be allocated to one of the two study arms (PrEP with hydroxychloroquine or non-PrEP control group) in a 1:1 ratio using simple randomisation with computer generated random numbers. BLINDING (MASKING): Participants, doctors and nurses caring for participants, and investigators assessing the outcomes will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Each intervention group will have 220 participants, giving a total of 440 participants. TRIAL STATUS: The current protocol version is 1.5, 2(nd) of June 2020. Two hundred and seventy-fiveparticipants were recruited and completed first month follow-up until date. The estimated sample size could not be reached yet due to the declining national epidemic curve. Thus, 275 is the total number of participants included until date. The study has been suspended (26(th) of June) until new epidemic curve occurs. TRIAL REGISTRATION: This trial was registered on April 2(nd) 2020 at clinicaltrials.gov with the number NCT04331834. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Trials2020       LitCov and CORD-19
135Insights into COVID-19 Vaccine Development Based on Immunogenic Structural Proteins of SARS-CoV-2, Host Immune Responses and Herd Immunity  

The first quarter of the 21st century has remarkably been characterized by a multitude of challenges confronting human society as a whole in terms of several outbreaks of infectious viral diseases, such as the 2003 severe acute respiratory syndrome (SARS), China; the 2009 influenza H1N1, Mexico; the 2012 Middle East respiratory syndrome (MERS), Saudi Arabia; and the ongoing coronavirus disease 19 (COVID-19), China. COVID-19, caused by SARS-CoV-2, reportedly broke out in December 2019, Wuhan, the capital of China’s Hubei province, and continues unabated, leading to considerable devastation and death worldwide. The most common target organ of SARS-CoV-2 is the lungs, especially the bronchial and alveolar epithelial cells, culminating in acute respiratory distress syndrome (ARDS) in severe patients. Nevertheless, other tissues and organs are also known to be critically affected following infection, thereby complicating the overall aetiology and prognosis. Excluding H1N1, the SARS-CoV (also referred as SARS-CoV-1), MERS, and SARS-CoV-2 are collectively referred to as coronaviruses, and taxonomically placed under the realm Riboviria, order Nidovirales, suborder Cornidovirineae, family Coronaviridae, subfamily Orthocoronavirinae, genus Betacoronavirus, and subgenus Sarbecovirus. As of 23 September 2021, the ongoing SARS-CoV-2 pandemic has globally resulted in around 229 million and 4.7 million reported infections and deaths, respectively, apart from causing huge psychosomatic debilitation, academic loss, and deep economic recession. Such an unprecedented pandemic has compelled researchers, especially epidemiologists and immunologists, to search for SARS-CoV-2-associated potential immunogenic molecules to develop a vaccine as an immediate prophylactic measure. Amongst multiple structural and non-structural proteins, the homotrimeric spike (S) glycoprotein has been empirically found as the most suitable candidate for vaccine development owing to its immense immunogenic potential, which makes it capable of eliciting both humoral and cell-mediated immune responses. As a consequence, it has become possible to design appropriate, safe, and effective vaccines, apart from related therapeutic agents, to reduce both morbidity and mortality. As of 23 September 2021, four vaccines, namely, Comirnaty, COVID-19 vaccine Janssen, Spikevax, and Vaxzevria, have received the European Medicines Agency’s (EMA) approval, and around thirty are under the phase three clinical trial with emergency authorization by the vaccine-developing country-specific National Regulatory Authority (NRA). In addition, 100–150 vaccines are under various phases of pre-clinical and clinical trials. The mainstay of global vaccination is to introduce herd immunity, which would protect the majority of the population, including immunocompromised individuals, from infection and disease. Here, we primarily discuss category-wise vaccine development, their respective advantages and disadvantages, associated efficiency and potential safety aspects, antigenicity of SARS-CoV-2 structural proteins and immune responses to them along with the emergence of SARS-CoV-2 VOC, and the urgent need of achieving herd immunity to contain the pandemic.

Cells2021       LitCov and CORD-19
136Citizens' Adherence to COVID-19 Mitigation Recommendations by the Government: A 3-Country Comparative Evaluation Using Web-Based Cross-Sectional Survey Data  

BACKGROUND: Social distancing is an effective preventative policy for the coronavirus disease (COVID-19) that is enforced by governments worldwide. However, significant variations are observed in following the policy across individuals and countries. Arguably, differences in citizens’ adherence actions will be influenced by their perceptions about government’s plans and the information available to guide their behaviors—more so in the digital age in the realm of mass influence of social media on citizens. Insights into the underlying factors and dynamics involved with citizens’ adherence process will inform the policy makers to follow appropriate communication and messaging approaches to influence citizens’ willingness to adhere to the recommendations. OBJECTIVE: The aim of this study is a comparative evaluation of citizens’ adherence process to COVID-19–relevant recommendations by the government. The focus is on how three different countries’ (United States, Kuwait, and South Korea) citizens, randomly sampled, respond to governments’ pandemic guidance efforts. We draw insights into two categories of perceived government roles in managing the pandemic: (1) citizens’ perceptions of government’s role in responding to the pandemic and (2) citizens’ perceptions of government’s business reopening efforts. Undoubtedly, the internet and social media have burgeoned, with differing effects on shaping individuals’ views and assessments of the COVID-19 situation; we argue and test for the effects of information sources, social media use, and knowledge on the adherence actions. METHODS: We randomly sampled web-based survey data collected by a global firm in May 2020 from citizens of the United States, Kuwait, and South Korea. A nonlinear ordered probit regression, controlling for several counterfactuals, was used for analysis. The focal estimated effects of the study were compared across countries using the weighted distance between the parameter estimates. RESULTS: The total sample size was 482 respondents, of which 207 (43%) lived in the United States, 181 (38%) lived in Kuwait, and 94 (20%) lived in South Korea. The ordered probit estimation results suggest that overall, perception of government response efforts positively influenced self-adherence (P<.001) and others’ adherence (P<.001) to social distancing and sheltering. Perception of government business reopening efforts positively influenced others’ adherence (P<.001). A higher intensity of general health information source for COVID-19 had a positive effect on self-adherence (P=.003). A higher intensity of social media source use for COVID-19 positively influenced others’ adherence (P=.002). A higher intensity of knowledge on COVID-19 positively influenced self-adherence (P=.008) and negatively influenced others’ adherence (P<.001). There were country-level variations—broadly, the United States and Kuwait had better effects than South Korea. CONCLUSIONS: As the COVID-19 global pandemic continues to grow and governmental restrictions are ongoing, it is critical to understand people’s frustration to reduce panic and promote social distancing to facilitate the control of the pandemic. This study finds that the government plays a central role in terms of adherence to restrictions. Governments need to enhance their efforts on publicizing information on the pandemic, as well as employ strategies for improved communication management to citizens through social media as well as mainstream information sources.

J Med Internet Res2020       LitCov and CORD-19
137Vaccine effectiveness against SARS-CoV-2 infection or COVID-19 hospitalization with the Alpha, Delta, or Omicron SARS-CoV-2 variant: A nationwide Danish cohort study  


PLoS Med2022       LitCov
138Factors Associated With US Adults' Likelihood of Accepting COVID-19 Vaccination  

IMPORTANCE: The development of a coronavirus disease 2019 (COVID-19) vaccine has progressed at unprecedented speed. Widespread public uptake of the vaccine is crucial to stem the pandemic. OBJECTIVE: To examine the factors associated with survey participants’ self-reported likelihood of selecting and receiving a hypothetical COVID-19 vaccine. DESIGN, SETTING, AND PARTICIPANTS: A survey study of a nonprobability convenience sample of 2000 recruited participants including a choice-based conjoint analysis was conducted to estimate respondents’ probability of choosing a vaccine and willingness to receive vaccination. Participants were asked to evaluate their willingness to receive each hypothetical vaccine individually. The survey presented respondents with 5 choice tasks. In each, participants evaluated 2 hypothetical COVID-19 vaccines and were asked whether they would choose vaccine A, vaccine B, or neither vaccine. Vaccine attributes included efficacy, protection duration, major adverse effects, minor adverse effects, US Food and Drug Administration (FDA) approval process, national origin of vaccine, and endorsement. Levels of each attribute for each vaccine were randomly assigned, and attribute order was randomized across participants. Survey data were collected on July 9, 2020. MAIN OUTCOMES AND MEASURES: Average marginal component effect sizes and marginal means were calculated to estimate the relationship between each vaccine attribute level and the probability of the respondent choosing a vaccine and self-reported willingness to receive vaccination. RESULTS: A total of 1971 US adults responded to the survey (median age, 43 [interquartile range, 30-58] years); 999 (51%) were women, 1432 (73%) White, 277 (14%) were Black, and 190 (10%) were Latinx. An increase in efficacy from 50% to 70% was associated with a higher probability of choosing a vaccine (coefficient, 0.07; 95% CI, 0.06-0.09), and an increase from 50% to 90% was associated with a higher probability of choosing a vaccine (coefficient, 0.16; 95% CI, 0.15-0.18). An increase in protection duration from 1 to 5 years was associated with a higher probability of choosing a vaccine (coefficient, 0.05 95% CI, 0.04-0.07). A decrease in the incidence of major adverse effects from 1 in 10 000 to 1 in 1 000 000 was associated with a higher probability of choosing a vaccine (coefficient, 0.07; 95% CI, 0.05-0.08). An FDA emergency use authorization was associated with a lower probability of choosing a vaccine (coefficient, −0.03; 95% CI, −0.04 to −0.01) compared with full FDA approval. A vaccine that originated from a non-US country was associated with a lower probability of choosing a vaccine (China: −0.13 [95% CI, −0.15 to −0.11]; UK: −0.04 [95% CI, −0.06 to −0.02]). Endorsements from the US Centers for Disease Control and Prevention (coefficient, 0.09; 95% CI, 0.07-0.11) and the World Health Organization (coefficient, 0.06; 95% CI, 0.04-0.08), compared with an endorsement from President Trump were associated with higher probabilities of choosing a vaccine. Analyses of participants’ willingness to receive each vaccine when assessed individually yielded similar results. An increase in efficacy from 50% to 90% was associated with a 10% higher marginal mean willingness to receive a vaccine (from 0.51 to 0.61). A reduction in the incidence of major side effects was associated with a 4% higher marginal mean willingness to receive a vaccine (from 0.54 to 0.58). A vaccine originating in China was associated with a 10% lower willingness to receive a vaccine vs one developed in the US (from 0.60 to 0.50) Endorsements from the Centers for Disease Control and Prevention and World Health Organization were associated with increases in willingness to receive a vaccine (7% and 6%, respectively) from a baseline endorsement by President Trump (from 0.52 to 0.59 and from 0.52 to 0.58, respectively). CONCLUSIONS AND RELEVANCE: In this survey study of US adults, vaccine-related attributes and political characteristics were associated with self-reported preferences for choosing a hypothetical COVID-19 vaccine and self-reported willingness to receive vaccination. These results may help inform public health campaigns to address vaccine hesitancy when a COVID-19 vaccine becomes available.

JAMA Netw Open2020       LitCov and CORD-19
139Digital Approaches to Remote Pediatric Healthcare Delivery During the COVID-19 Pandemic: Existing Evidence and a Call for Further Research  

The global spread of the coronavirus disease (COVID-19) outbreak poses a public health threat and has affected people worldwide in various unprecedented ways, both personally and professionally. There is no question that the current global COVID-19 crisis, now more than ever, is underscoring the importance of leveraging digital approaches to optimize pediatric health care delivery in the era of this pandemic. In this perspective piece, we highlight some of the available digital approaches that have been and can continue to be used to streamline remote pediatric patient care in the era of the COVID-19 pandemic, including but not limited to telemedicine. JMIR Pediatrics and Parenting is currently publishing a COVID-19 special theme issue in which investigators can share their interim and final research data related to digital approaches to remote pediatric health care delivery in different settings. The COVID-19 pandemic has rapidly transformed health care systems worldwide, with significant variations and innovations in adaptation. There has been rapid expansion of the leveraging and optimization of digital approaches to health care delivery, particularly integrated telemedicine and virtual health. Digital approaches have played and will play major roles as invaluable and reliable resources to overcome restrictions and challenges imposed during the COVID-19 pandemic and to increase access to effective, accessible, and consumer-friendly care for more patients and families. However, a number of challenges remain to be addressed, and further research is needed. Optimizing digital approaches to health care delivery and integrating them into the public health response will be an ongoing process during the current COVID-19 outbreak and during other possible future pandemics. Regulatory changes are essential to support the safe and wide adoption of these approaches. Involving all relevant stakeholders in addressing current and future challenges as well as logistical, technological, and financial barriers will be key for success. Future studies should consider evaluating the following research areas related to telemedicine and other digital approaches: cost-effectiveness and return on investment; impact on quality of care; balance in use and number of visits needed for the management of both acute illness and chronic health conditions; system readiness for further adoption in other settings, such as inpatient services, subspecialist consultations, and rural areas; ongoing user-centered evaluations, with feedback from patients, families, and health care providers; strategies to optimize health equity and address disparities in access to care related to race and ethnicity, socioeconomic status, immigration status, and rural communities; privacy and security concerns for protected health information with Health Insurance Portability and Accountability Act (HIPAA)–secured programs; confidentiality issues for some specific populations, especially adolescents and those in need of mental health services; early detection of exposure to violence and child neglect; and integration of training into undergraduate and graduate medical education and subspecialty fellowships. Addressing these research areas is essential to understanding the benefits, sustainability, safety, and optimization strategies of telemedicine and other digital approaches as key parts of modern health care delivery. These efforts will inform long-term adoption of these approaches with expanded dissemination and implementation efforts.

JMIR Pediatr Parent2020       LitCov and CORD-19
140Patient experiences of fertility clinic closure during the COVID-19 pandemic: appraisals, coping and emotions  

STUDY QUESTION: What are appraisals, coping strategies and emotional reactions of patients to coronavirus disease 2019 (COVID-19) fertility clinic closures? SUMMARY ANSWER: Clinic closure was appraised as stressful due to uncertainty and threat to the attainability of the parenthood goal but patients were able to cope using strategies that fit the uncertainty of the situation. WHAT IS KNOWN ALREADY: Psychological research on COVID-19 suggests that people are more anxious than historical norms and moderately to extremely upset about fertility treatment cancellation owing to COVID-19. STUDY DESIGN, SIZE, DURATION: The study was of cross-sectional design, comprising a mixed-methods, English language, anonymous, online survey posted from April 09 to April 21 to social media. Eligibility criteria were being affected by COVID-19 fertility clinic closure, 18 years of age or older and able to complete the survey in English. In total, 946 people clicked on the survey link, 76 did not consent, 420 started but did not complete survey, and 450 completed (48% completion, 446 women, four men). PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall 74.7% (n = 336) of respondents were residents in the UK with an average age of 33.6 years (SD = 4.4) and average years trying to conceive, 3.5 years (SD = 2.22). The survey comprised quantitative questions about the intensity of cognitive appraisals and emotions about clinic closure, and ability to cope with clinic closure. Open-text questions covered their understanding of COVID-19 and its effect on reproductive health and fertility plans, concerns and perceived benefits of clinic closure, and knowledge about closure. Sociodemographic information was collected. Descriptive and inferential statistics were used on quantitative data. Thematic qualitative analysis (inductive coding) was performed on the textual data from each question. Deductive coding grouped themes from each question into meta-themes related to cognitive stress and coping theory. MAIN RESULTS AND THE ROLE OF CHANCE: Most patients (81.6%, n = 367) had tests or treatments postponed, with these being self (41.3%, n = 186) or publicly (46.4%, n = 209) funded. Patients appraised fertility clinic closure as having potential for a more negative than positive impact on their lives, and to be very or extremely uncontrollable and stressful (p ≤ .001). Most reported a slight to moderate ability to cope with closure. Data saturation was achieved with all open-text questions, with 33 broad themes identified and four meta-themes linked to components of the cognitive stress and coping theory. First, participants understood clinic closure was precautionary due to unknown effects of COVID-19 but some felt clinic closure was unfair relative to advice about getting pregnant given to the public. Second, closure was appraised as a threat to attainability of the parenthood goal largely due to uncertainty of the situation (e.g., re-opening, effect of delay) and intensification of pre-existing hardships of fertility problems (e.g., long time waiting for treatment, history of failed treatment). Third, closure taxed personal coping resources but most were able to cope using thought-management (e.g., distraction, focusing on positives), getting mentally and physically fit for next treatments, strengthening their social network, and keeping up-to-date. Finally, participants reported more negative than positive emotions (p ≤ .001) and almost all participants reported stress, worry and frustration at the situation, while some expressed anger and resentment at the unfairness of the situation. Overall, 11.9% were not at all able to cope, with reports of intense feelings of hopelessness and deteriorating wellbeing and mental health. LIMITATIONS, REASONS FOR CAUTION: The survey captures patient reactions at a specific point in time, during lockdown and before clinics announced re-opening. Participants were self-selected (e.g., UK residents, women, 48% starting but not completing the survey), which may affect generalisability. WIDER IMPLICATIONS OF THE FINDINGS: Fertility stakeholders (e.g., clinics, patient support groups, regulators, professional societies) need to work together to address the great uncertainty from COVID-19. This goal can be met proactively by setting up transparent processes for COVID-19 eventualities and signposting to information and coping resources. Future psychological research priorities should be on identifying patients at risk of distress with standardised measures and developing digital technologies appropriate for the realities of fertility care under COVID-19. STUDY FUNDING/COMPETING INTEREST(S): University funded research. Outside of the submitted work, Professor Boivin reports personal fees from Merck KGaA, Merck AB, Theramex, Ferring Pharmaceuticals A/S; grants from Merck Serono Ltd; and that she is co-developer of the Fertility Quality of Life (FertiQoL) and MediEmo apps. Outside of the submitted work, Dr. Mathur reports personal or consultancy fees from Manchester Fertility, Gedeon Richter, Ferring and Merck. Outside of the submitted work, Dr. Gameiro reports consultancy fees from Ferring Pharmaceuticals A/S, Access Fertility and SONA-Pharm LLC, and grants from Merck Serono Ltd. The other authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A

Hum Reprod2020       LitCov and CORD-19
141Effectiveness of a Third Dose of mRNA Vaccines Against COVID-19 Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults During Periods of Delta and Omicron Variant Predominance-VISION Network, 10 States, August 2021-January 2022  


MMWR Morb Mortal Wkly Rep2022       LitCov and CORD-19
142Mitigating the Psychological Impact of COVID-19 on Healthcare Workers: A Digital Learning Package  

The coronavirus pandemic (COVID-19) will undoubtedly have psychological impacts for healthcare workers, which could be sustained; frontline workers will be particularly at risk. Actions are needed to mitigate the impacts of COVID-19 on mental health by protecting and promoting the psychological wellbeing of healthcare workers during and after the outbreak. We developed and evaluated a digital learning package using Agile methodology within the first three weeks of UK outbreak. This e-package includes evidence-based guidance, support and signposting relating to psychological wellbeing for all UK healthcare employees. A three-step rapid development process included public involvement activities (PPIs) (STEP 1), content and technical development with iterative peer review (STEP 2), and delivery and evaluation (STEP 3). The package outlines the actions that team leaders can take to provide psychologically safe spaces for staff, together with guidance on communication and reducing social stigma, peer and family support, signposting others through psychological first aid (PFA), self-care strategies (e.g., rest, work breaks, sleep, shift work, fatigue, healthy lifestyle behaviours), and managing emotions (e.g., moral injury, coping, guilt, grief, fear, anxiety, depression, preventing burnout and psychological trauma). The e-package includes advice from experts in mental wellbeing as well as those with direct pandemic experiences from the frontline, as well as signposting to public mental health guidance. Rapid delivery in STEP 3 was achieved via direct emails through professional networks and social media. Evaluation included assessment of fidelity and implementation qualities. Essential content was identified through PPIs (n = 97) and peer review (n = 10) in STEPS 1 and 2. The most important messages to convey were deemed to be normalisation of psychological responses during a crisis, and encouragement of self-care and help-seeking behaviour. Within 7 days of completion, the package had been accessed 17,633 times, and healthcare providers had confirmed immediate adoption within their health and wellbeing provisions. Evaluation (STEP 3, n = 55) indicated high user satisfaction with content, usability and utility. Assessment of implementation qualities indicated that the package was perceived to be usable, practical, low cost and low burden. Our digital support package on ‘psychological wellbeing for healthcare workers’ is free to use, has been positively evaluated and was highly accessed within one week of release. It is available here: Supplementary Materials. This package was deemed to be appropriate, meaningful and useful for the needs of UK healthcare workers. We recommend provision of this e-package to healthcare workers alongside wider strategies to support their psychological wellbeing during and after the COVID-19 pandemic.

Int J Environ Res Public Healt2020       LitCov and CORD-19
143Short-term outcome of pregnant women vaccinated with BNT162b2 mRNA COVID-19 vaccine  

OBJECTIVES: To determine the immunogenicity and reactogenicity of the Pfizer/BioNTech BNT162b2 mRNA coronavirus disease 2019 (COVID‐19) vaccine among pregnant women compared with non‐pregnant women, and to evaluate obstetric outcome following vaccination. METHODS: This was an observational case–control study of pregnant women who were vaccinated with a two‐dose regimen of the BNT162b2 vaccine during gestation between January and February 2021 (study group) and age‐matched non‐pregnant women who received the vaccine during the same time period (control group). Participants received a digital questionnaire 1–4 weeks after the second dose and were asked to provide information regarding demographics, medication, medical history, history of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, timing of COVID‐19 vaccine doses and side effects after each vaccine dose. A second digital questionnaire, regarding current pregnancy and delivery outcomes, was sent to patients in the study group after the calculated due date. All recruited women were offered a serology blood test for SARS‐CoV‐2 immunoglobulin G (IgG) following the second vaccination dose and SARS‐CoV‐2 IgG levels were compared between the two groups. RESULTS: Of 539 pregnant women who were recruited after completion of the two‐dose regimen of the vaccine, 390 returned the digital questionnaire and were included in the study group and compared to 260 age‐matched non‐pregnant vaccinated women. The rates of rash, fever and severe fatigue following vaccination among pregnant women were comparable to those in non‐pregnant women. Myalgia, arthralgia and headache were significantly less common among pregnant women after each dose, local pain or swelling and axillary lymphadenopathy were significantly less common among pregnant women after the first and second doses, respectively, while paresthesia was significantly more common among the pregnant population after the second dose. Among pregnant women, there were no significant differences in the rates of side effects according to whether the vaccine was administered during the first, second or third trimester of pregnancy, except for local pain/swelling, which was significantly less common after the first dose when administered during the third trimester, and uterine contractions, which were significantly more common after the second dose when administered during the third trimester. The rates of obstetric complications, including uterine contractions (1.3% after the first dose and 6.4% after the second dose), vaginal bleeding (0.3% after the first dose and 1.5% after the second dose) and prelabor rupture of membranes (0% after the first dose and 0.8% after the second dose), were very low following vaccination. All serum samples in both groups were positive for SARS‐CoV‐2 IgG. However, pregnant women had significantly lower serum SARS‐CoV‐2 IgG levels compared to non‐pregnant women (signal‐to‐cut‐off ratio, 27.03 vs 34.35, respectively; P < 0.001). Among the 57 pregnant women who delivered during the study period and who completed the second questionnaire, median gestational age at delivery was 39.5 (interquartile range, 38.7–40.0) weeks, with no cases of preterm birth < 37 weeks, no cases of fetal or neonatal death and two (3.5%) cases of admission to the neonatal intensive care unit for respiratory support. CONCLUSIONS: The adverse‐effect profile and short‐term obstetric and neonatal outcomes among pregnant women who were vaccinated with the BNT162b2 vaccine at any stage of pregnancy do not indicate any safety concerns. The vaccine is effective in generating a humoral immune response in pregnant women, although SARS‐CoV‐2 IgG levels were lower than those observed in non‐pregnant vaccinated women. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Ultrasound Obstet Gynecol2021       LitCov and CORD-19
144Protecting the front line: a cross-sectional survey analysis of the occupational factors contributing to healthcare workers' infection and psychological distress during the COVID-19 pandemic in the USA  

OBJECTIVE: The COVID-19 pandemic has been associated with significant occupational stressors and challenges for front-line healthcare workers (HCWs), including COVID-19 exposure risk. Our study sought to assess factors contributing to HCW infection and psychological distress during the COVID-19 pandemic in the USA. DESIGN: We conducted a cross sectional survey of HCWs (physicians, nurses, emergency medical technicians (EMTs), non-clinical staff) during May 2020. Participants completed a 42-item survey assessing disease transmission risk (clinical role, work environment, availability of personal protective equipment) and mental health (anxiety, depression and burn-out). SETTING: The questionnaire was disseminated over various social media platforms. 3083 respondents from 48 states, the District of Columbia and US territories accessed the survey. PARTICIPANTS: Using a convenience sample of HCWs who worked during the pandemic, 3083 respondents accessed the survey and 2040 participants completed at least 80% of the survey. PRIMARY OUTCOME: Prevalence of self-reported COVID-19 infection, in addition to burn-out, depression and anxiety symptoms. RESULTS: Participants were largely from the Northeast and Southern USA, with attending physicians (31.12%), nurses (26.80%), EMTs (13.04%) with emergency medicine department (38.30%) being the most common department and specialty represented. Twenty-nine per cent of respondents met the criteria for being a probable case due to reported COVID-19 symptoms or a positive test. HCWs in the emergency department (31.64%) were more likely to contract COVID-19 compared with HCWs in the ICU (23.17%) and inpatient settings (25.53%). HCWs that contracted COVID-19 also reported higher levels of depressive symptoms (mean diff.=0.31; 95% CI 0.16 to 0.47), anxiety symptoms (mean diff.=0.34; 95% CI 0.17 to 0.52) and burn-out (mean diff.=0.54; 95% CI 0.36 to 0.71). CONCLUSION: HCWs have experienced significant physical and psychological risk while working during the COVID-19 pandemic. These findings highlight the urgent need for increased support for provider physical and mental health well-being.

BMJ Open2020       LitCov and CORD-19
145Use of Rapid Online Surveys to Assess People's Perceptions During Infectious Disease Outbreaks: A Cross-sectional Survey on COVID-19  

BACKGROUND: Given the extensive time needed to conduct a nationally representative household survey and the commonly low response rate of phone surveys, rapid online surveys may be a promising method to assess and track knowledge and perceptions among the general public during fast-moving infectious disease outbreaks. OBJECTIVE: This study aimed to apply rapid online surveying to determine knowledge and perceptions of coronavirus disease 2019 (COVID-19) among the general public in the United States and the United Kingdom. METHODS: An online questionnaire was administered to 3000 adults residing in the United States and 3000 adults residing in the United Kingdom who had registered with Prolific Academic to participate in online research. Prolific Academic established strata by age (18-27, 28-37, 38-47, 48-57, or ≥58 years), sex (male or female), and ethnicity (white, black or African American, Asian or Asian Indian, mixed, or “other”), as well as all permutations of these strata. The number of participants who could enroll in each of these strata was calculated to reflect the distribution in the US and UK general population. Enrollment into the survey within each stratum was on a first-come, first-served basis. Participants completed the questionnaire between February 23 and March 2, 2020. RESULTS: A total of 2986 and 2988 adults residing in the United States and the United Kingdom, respectively, completed the questionnaire. Of those, 64.4% (1924/2986) of US participants and 51.5% (1540/2988) of UK participants had a tertiary education degree, 67.5% (2015/2986) of US participants had a total household income between US $20,000 and US $99,999, and 74.4% (2223/2988) of UK participants had a total household income between £15,000 and £74,999. US and UK participants’ median estimate for the probability of a fatal disease course among those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was 5.0% (IQR 2.0%-15.0%) and 3.0% (IQR 2.0%-10.0%), respectively. Participants generally had good knowledge of the main mode of disease transmission and common symptoms of COVID-19. However, a substantial proportion of participants had misconceptions about how to prevent an infection and the recommended care-seeking behavior. For instance, 37.8% (95% CI 36.1%-39.6%) of US participants and 29.7% (95% CI 28.1%-31.4%) of UK participants thought that wearing a common surgical mask was “highly effective” in protecting them from acquiring COVID-19, and 25.6% (95% CI 24.1%-27.2%) of US participants and 29.6% (95% CI 28.0%-31.3%) of UK participants thought it was prudent to refrain from eating at Chinese restaurants. Around half (53.8%, 95% CI 52.1%-55.6%) of US participants and 39.1% (95% CI 37.4%-40.9%) of UK participants thought that children were at an especially high risk of death when infected with SARS-CoV-2. CONCLUSIONS: The distribution of participants by total household income and education followed approximately that of the US and UK general population. The findings from this online survey could guide information campaigns by public health authorities, clinicians, and the media. More broadly, rapid online surveys could be an important tool in tracking the public’s knowledge and misperceptions during rapidly moving infectious disease outbreaks.

J Med Internet Res2020       LitCov and CORD-19
146Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With COVID-19 Pneumonia in Wuhan, China  


JAMA Intern Med2020       LitCov and CORD-19
147Exposure to COVID-19-Related Information and its Association With Mental Health Problems in Thailand: Nationwide, Cross-sectional Survey Study  

BACKGROUND: The COVID-19 pandemic has had a negative impact on both the physical and mental health of individuals worldwide. Evidence regarding the association between mental health problems and information exposure among Thai citizens during the COVID-19 outbreak is limited. OBJECTIVE: This study aimed to explore the relationship between information exposure and mental health problems during the COVID-19 pandemic in Thailand. METHODS: Between April 21 and May 4, 2020, we conducted a cross-sectional, nationwide online survey of the general population in Thailand. We categorized the duration of exposure to COVID-19-related information as follows: <1 h/day (reference group), 1-2 h/day, and ≥3 h/day. Mental health outcomes were assessed using the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7 scale, the Perceived Stress Scale-10, and the Insomnia Severity Index for symptoms of depression, anxiety, perceived stress, and insomnia, respectively. Multivariable logistic regression models were used to evaluate the relationship between information exposure and the risk of developing the aforementioned symptoms. An ancillary analysis using multivariable multinomial logistic regression models was also conducted to assess the possible dose-response relationship across the severity strata of mental health problems. RESULTS: Of the 4322 eligible participants, 4004 (92.6%) completed the online survey. Of them, 1481 (37.0%), 1644 (41.1%), and 879 (22.0%) participants were exposed to COVID-19-related information for less than 1 hour per day, 1 to 2 hours per day, or 3 or more hours per day, respectively. The major source of information related to the COVID-19 pandemic was social media (95.3%), followed by traditional media (68.7%) and family members (34.9%). Those exposed to information for 3 or more hours per day had a higher risk of developing symptoms of depression (adjusted odds ratio [OR] 1.35, 95% CI 1.03-1.76; P=.03), anxiety (adjusted OR 1.88, 95% CI 1.43-2.46; P<.001), and insomnia (adjusted OR 1.52, 95% CI 1.17-1.97; P=.001) than people exposed to information for less than 1 hour per day. Meanwhile, people exposed to information for 1 to 2 hours per day were only at risk of developing symptoms of anxiety (adjusted OR 1.35, 95% CI 1.08-1.69; P=.008). However, no association was found between information exposure and the risk of perceived stress. In the ancillary analysis, a dose-response relationship was observed between information exposure of 3 or more hours per day and the severity of mental health problems. CONCLUSIONS: These findings suggest that social media is the main source of COVID-19-related information. Moreover, people who are exposed to information for 3 or more hours per day are more likely to develop psychological problems, including depression, anxiety, and insomnia. Longitudinal studies investigating the long-term effects of COVID-19-related information exposure on mental health are warranted.

J Med Internet Res2021       LitCov and CORD-19
148What Was the Change in Telehealth Usage and Proportion of No-show Visits for an Orthopaedic Trauma Clinic During the COVID-19 Pandemic?  


Clin Orthop Relat Res2020       LitCov and CORD-19
149Determinants of COVID-19 Vaccine Hesitancy: A Cross-Sectional Study on a Mexican Population Using an Online Questionnaire (COV-AHQ)  

Mexico has become one of the most highly affected countries by coronavirus disease 2019 (COVID-19) pandemic in Latin America. Therefore, efficient vaccination programs are needed to address COVID-19 pandemic. Although recent advances around the world have made it possible to develop vaccines in record time, there has been increasing fear and misinformation around the vaccines. Hence, understanding vaccine hesitancy is imperative for modeling successful vaccination strategies. In this study, we analyzed the attitude and perceptions toward COVID-19 vaccination, in a Mexican population (n = 1,512), using the proposed COVID-19 Vaccine Acceptance and Hesitancy Questionnaire (COV-AHQ) (Cronbach's alpha > 0.8), which evaluates a mild perception of danger and contamination with respect to COVID-19, a moderate perception of xenophobia generated throughout COVID-19 quarantine, fear of adverse effects of COVID-19 vaccination, and hesitancy of parent toward vaccination of children; furthermore, a section including sociodemographic variables was included. According to the results of this study, the statistical correlation analysis of the general vaccination posture seems to correlate significantly (p < 0.05) with a mild perception of danger and contamination with respect to COVID-19, a moderate perception of xenophobia generated throughout COVID-19 quarantine, hesitancy of parent toward vaccination of children, willingness to get COVID-19 vaccine, previous influenza vaccination, perception of the vaccine that could help the economy of country, occupation, gender, age, and participants actively researching COVID-19 vaccine information. An in-depth analysis assisted by binary logistic regression concluded that the young adult population around ages 18–34 years are the most likely to get vaccinated. This posture seems to be highly influenced by a mild perception of danger and contamination with respect to COVID-19, a moderate perception of xenophobia generated throughout COVID-19 quarantine, fear of adverse effects of COVID-19 vaccination, and hesitancy of parents toward vaccination of children. While their own personal religious beliefs and economic status, the level of education does not seem to have an effect on the willingness to get vaccinated neither did having a previous COVID-19 diagnosis or even knowing someone with a positive COVID-19 diagnosis. Health authorities and policymakers could use the results of this study to aid in modeling vaccination programs and strategies and identify population groups with high vaccine hesitancy prevalence and assess significant public health issues.

Front Public Health2021       LitCov and CORD-19
150The mRNA-1273 Vaccine Induces Cross-Variant Antibody Responses to SARS-CoV-2 With Distinct Profiles in Individuals With or Without Pre-Existing Immunity  

mRNA-based vaccines effectively induce protective neutralizing antibodies against SARS-CoV-2, the etiological agent of COVID-19. Yet, the kinetics and compositional patterns of vaccine-induced antibody responses to the original strain and emerging variants of concern remain largely unknown. Here we characterized serum antibody classes and subclasses targeting the spike receptor-binding domain of SARS-CoV-2 wild type and α, β, γ and δ variants in a longitudinal cohort of SARS-CoV-2 naïve and COVID-19 recovered individuals receiving the mRNA-1273 vaccine. We found that mRNA-1273 vaccine recipients developed a SARS-CoV-2-specific antibody response with a subclass profile comparable to that induced by natural infection. Importantly, these antibody responses targeted both wild type SARS-CoV-2 as well as its α, β, γ and δ variants. Following primary vaccination, individuals with pre-existing immunity showed higher induction of all antibodies but IgG3 compared to SARS-CoV-2-naïve subjects. Unlike naïve individuals, COVID-19 recovered subjects did not mount a recall antibody response upon the second vaccine dose. In these individuals, secondary immunization resulted in a slight reduction of IgG1 against the receptor-binding domain of β and γ variants. Despite the lack of recall humoral response, vaccinees with pre-existing immunity still showed higher titers of IgG1 and IgA to all variants analyzed compared to fully vaccinated naïve individuals. Our findings indicate that mRNA-1273 vaccine triggered cross-variant antibody responses with distinct profiles in vaccinees with or without pre-existing immunity and suggest that individuals with prior history of SARS-CoV-2 infection may not benefit from the second mRNA vaccine dose with the current standard regimen.

Front Immunol2021       LitCov and CORD-19

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(3) Currently tweets of June 23rd to June 29th 2022 have been considered.

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