\ 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
251Assessment of Neutralizing Antibody Response Against SARS-CoV-2 Variants After 2 to 3 Doses of the BNT162b2 mRNA COVID-19 Vaccine  

IMPORTANCE: Although 2 and 3 doses of vaccine have been implemented against the SARS-CoV-2 pandemic, the level of immunity achieved by these additional vaccinations remains unclear. OBJECTIVE: To investigate the induction of neutralizing antibodies against the SARS-CoV-2 Omicron variant after 2 and 3 doses of the BNT162b2 messenger RNA (mRNA) vaccine among recipients of different ages. DESIGN, SETTING, AND PARTICIPANTS: A cohort study was conducted from June 1, 2021, to January 12, 2022, among 82 physicians at Kobe University Hospital who had received 2 doses of the BNT162b2 mRNA vaccine. MAIN OUTCOMES AND MEASURES: The rates of positive test results and the titers of neutralizing antibodies against the Omicron variant after 2 and 3 doses of the vaccine were compared with those against other variants and compared among 3 age groups (≤38 years [younger age group], 39-58 years [intermediate age group], and ≥59 years [older age group]). RESULTS: A total of 82 physicians (71 men [87%]; median age, 44 years [IQR, 33-58 years]) participated; 31 (38%) were in the younger age group, 32 (39%) were in the intermediate age group, and 19 (23%) were in the older age group. At 2 months after 2 doses of the vaccine, 23 participants (28%) had neutralizing antibodies against the Omicron variant, with a titer of 1.3 (95% CI, 1.2-1.4), which was 11.8-fold (95% CI, 9.9-13.9) lower than the titer against the D614G variant and the lowest among the variants tested. Although the titer of the neutralizing antibody against the Delta variant tended to be low among the older age group (2.9 [95% CI, 2.0-4.1]), the titers of the neutralizing antibody against the Omicron variant were low among all age groups (younger age group, 1.3 [95% CI, 1.1-1.6]; intermediate age group, 1.3 (95% CI, [95% CI, 1.1-1.5]; and older age group, 1.2 [95% CI, 1.0-1.4]). At 7 months after 2 doses of the vaccine, 5 participants (6%) had the neutralizing antibody against the Omicron variant, but after the booster (third dose) vaccination, all 72 participants who received the booster had the neutralizing antibody, and the titer was 41 (95% CI, 34-49), much higher than that at 7 months after 2 doses of the vaccine (1.0 [95% CI, 1.0-1.1]). This increase in titers was observed regardless of age groups; the titers were 44 (95% CI, 32-59) among the younger age group, 44 (95% CI, 32-59) among the intermediate age group, and 30 (95% CI, 22-41) among the older age group. CONCLUSIONS AND RELEVANCE: In this cohort study of 82 Japanese participants, 2 doses of the BNT162b2 mRNA vaccine did not induce sufficient neutralizing antibody against the Omicron variant. However, booster vaccination was associated with induction of a high level of neutralizing antibodies against the Omicron variant, irrespective of the recipient’s age.

JAMA Netw Open2022       LitCov and CORD-19
252COVID-19: a conundrum to decipher  


Eur Rev Med Pharmacol Sci2020       LitCov and CORD-19
253Epidemiological characteristics of 17 imported patients infected with SARS-CoV-2 Omicron variant  


Zhong Nan Da Xue Xue Bao Yi Xu2022       LitCov and CORD-19
254Adverse events of special interest and mortality following vaccination with mRNA (BNT162b2) and inactivated (CoronaVac) SARS-CoV-2 vaccines in Hong Kong: A retrospective study  


PLoS Med2022       LitCov
255Psychological impact of COVID-19 pandemic in the Philippines  

BACKGROUND: : The 2019 coronavirus disease (COVID-19) pandemic poses a threat to societies’ mental health. This study examined the prevalence of psychiatric symptoms and identified the factors contributing to psychological impact in the Philippines. METHODS: : A total of 1879 completed online surveys were gathered from March 28-April 12, 2020. Collected data included socio-demographics, health status, contact history, COVID-19 knowledge and concerns, precautionary measures, information needs, the Depression, Anxiety and Stress Scales (DASS-21) and the Impact of Events Scale-Revised (IES-R) ratings. RESULTS: : The IES-R mean score was 19.57 (SD=13.12) while the DASS-21 mean score was 25.94 (SD=20.59). In total, 16.3% of respondents rated the psychological impact of the outbreak as moderate-to-severe; 16.9% reported moderate-to-severe depressive symptoms; 28.8% had moderate-to-severe anxiety levels; and 13.4% had moderate-to-severe stress levels. Female gender; youth age; single status; students; specific symptoms; recent imposed quarantine; prolonged home-stay; and reports of poor health status, unnecessary worry, concerns for family members, and discrimination were significantly associated with greater psychological impact of the pandemic and higher levels of stress, anxiety and depression (p<0.05). Adequate health information, having grown-up children, perception of good health status and confidence in doctors’ abilities were significantly associated with lesser psychological impact of the pandemic and lower levels of stress, anxiety and depression (p<0.05). LIMITATIONS: : An English online survey was used. CONCLUSION: : During the early phase of the pandemic in the Philippines, one-fourth of respondents reported moderate-to-severe anxiety and one-sixth reported moderate-to-severe depression and psychological impact. The factors identified can be used to devise effective psychological support strategies.

J Affect Disord2020       LitCov and CORD-19
256Are SARS-CoV-2 Antibodies Detectable in Human Milk After Vaccination Against COVID-19?  


J Pediatric Infect Dis Soc2022       LitCov and CORD-19
257Outcomes following SARS-CoV-2 infection in liver transplant recipients: an international registry study  

BACKGROUND: Despite concerns that patients with liver transplants might be at increased risk of adverse outcomes from COVID-19 because of coexisting comorbidities and use of immunosuppressants, the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on this patient group remains unclear. We aimed to assess the clinical outcomes in these patients. METHODS: In this multicentre cohort study, we collected data on patients with laboratory-confirmed SARS-CoV-2 infection, who were older than 18 years, who had previously received a liver transplant, and for whom data had been submitted by clinicians to one of two international registries (COVID-Hep and SECURE-Cirrhosis) at the end of the patient's disease course. Patients without a known hospitalisation status or mortality outcome were excluded. For comparison, data from a contemporaneous cohort of consecutive patients with SARS-CoV-2 infection who had not received a liver transplant were collected from the electronic patient records of the Oxford University Hospitals National Health Service Foundation Trust. We compared the cohorts with regard to several outcomes (including death, hospitalisation, intensive care unit [ICU] admission, requirement for intensive care, and need for invasive ventilation). A propensity score-matched analysis was done to test for an association between liver transplant and death. FINDINGS: Between March 25 and June 26, 2020, data were collected for 151 adult liver transplant recipients from 18 countries (median age 60 years [IQR 47–66], 102 [68%] men, 49 [32%] women) and 627 patients who had not undergone liver transplantation (median age 73 years [44–84], 329 [52%] men, 298 [48%] women). The groups did not differ with regard to the proportion of patients hospitalised (124 [82%] patients in the liver transplant cohort vs 474 [76%] in the comparison cohort, p=0·106), or who required intensive care (47 [31%] vs 185 [30%], p=0·837). However, ICU admission (43 [28%] vs 52 [8%], p<0·0001) and invasive ventilation (30 [20%] vs 32 [5%], p<0·0001) were more frequent in the liver transplant cohort. 28 (19%) patients in the liver transplant cohort died, compared with 167 (27%) in the comparison cohort (p=0·046). In the propensity score-matched analysis (adjusting for age, sex, creatinine concentration, obesity, hypertension, diabetes, and ethnicity), liver transplantation did not significantly increase the risk of death in patients with SARS-CoV-2 infection (absolute risk difference 1·4% [95% CI −7·7 to 10·4]). Multivariable logistic regression analysis showed that age (odds ratio 1·06 [95% CI 1·01 to 1·11] per 1 year increase), serum creatinine concentration (1·57 [1·05 to 2·36] per 1 mg/dL increase), and non-liver cancer (18·30 [1·96 to 170·75]) were associated with death among liver transplant recipients. INTERPRETATION: Liver transplantation was not independently associated with death, whereas increased age and presence of comorbidities were. Factors other than transplantation should be preferentially considered in relation to physical distancing and provision of medical care for patients with liver transplants during the COVID-19 pandemic. FUNDING: European Association for the Study of the Liver, US National Institutes of Health, UK National Institute for Health Research.

Lancet Gastroenterol Hepatol2020       LitCov and CORD-19
258Clinical Characteristics and Outcome of Hospitalized COVID-19 Patients in a MERS-CoV Endemic Area  

Background: The Kingdom of Saudi Arabia (KSA) reported 170,639 cases and 1430 deaths from COVID-19 since the first case emerged in the country on March 2 through June 25, 2020. The objective of this report is to describe the characteristics and outcome observed among 99 hospitalized COVID-19 patients in the largest academic hospital in KSA, and assess co-infection with the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Methods: This single-center case series data included select epidemiological, clinical, radiological features and laboratory findings of all confirmed hospitalized cases of COVID-19 in King Saud University Medical City (KSUMC), Riyadh, KSA, from March 22 until May 31, 2020, followed through June 6, 2020. We conducted retrospective analysis of listed data from 99 hospitalized patients and present characteristics and factors associated with severity in percentages and univariate odds ratios. Cases were confirmed using nasopharyngeal or throat swab by real-time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and MERS-CoV by RT-PCR. Results: The 99 hospitalized COVID-19 patients included in this analysis constitute 16% of 632 positive SARS-CoV-2 among 6633 persons who were tested at the KSUMC (positivity rate, 9.4%). MERS-CoV PCR was negative in all 99 patients tested. The majority of these 99 hospitalized patients were males (66%), had a mean age of 44 years (range, 19–87), and a quarter (25.3%) were health care workers. Patients with comorbid conditions accounted for 52.5% of patients including the 8.1% who were asymptomatic; diabetes mellitus being the most frequent (31.3%), followed by hypertension (22.2%). The most common presenting symptoms were fever (67.7%), cough (60.6%), dyspnea (43.4%), upper respiratory symptoms (27.3%), fatigue (26.3%), diarrhea (19.2%) and loss of smell (9.1%). The clinical conditions among these 99 patients included upper respiratory tract infection (47.5%), abnormal chest X-ray, lymphopenia, high inflammatory markers a fifth (21%) of patients had moderate pneumonia, while 7% had severe pneumonia with 22.2% requiring admission to the intensive care unit and 12.1% died. Late presentation with severe disease, an abnormal chest X-ray, lymphopenia, high inflammatory markers (C-reactive protein, ferritin, and procalcitonin), and end organ damage (high creatinine or high aspartate aminotransferase) were predictors for admission to critical care unit or died. Conclusion: We observed no MERS-CoV co-infection in this early cohort of hospitalized COVID-19 patients who were relatively young, more than half had comorbid conditions, presented with fever and/or cough, an abnormal chest X-ray, lymphopenia, and high inflammatory markers. Given MERS-CoV endemicity in the country, co-monitoring of MERS-CoV and SARS-CoV-2 coinfection is critical.

J Epidemiol Glob Health2020       LitCov and CORD-19
259Elicitation of Broadly Neutralizing Antibodies against B.1.1.7, B.1.351 and B.1.617.1 SARS-CoV-2 Variants by Three Prototype Strain-Derived Recombinant Protein Vaccines  

The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Most of the currently approved SARS-CoV-2 vaccines use the prototype strain-derived spike (S) protein or its receptor-binding domain (RBD) as the vaccine antigen. The emergence of several novel SARS-CoV-2 variants has raised concerns about potential immune escape. In this study, we performed an immunogenicity comparison of prototype strain-derived RBD, S1, and S ectodomain trimer (S-trimer) antigens and evaluated their induction of neutralizing antibodies against three circulating SARS-CoV-2 variants, including B.1.1.7, B.1.351, and B.1.617.1. We found that, at the same antigen dose, the RBD and S-trimer vaccines were more potent than the S1 vaccine in eliciting long-lasting, high-titer broadly neutralizing antibodies in mice. The RBD immune sera remained highly effective against the B.1.1.7, B.1.351, and B.1.617.1 variants despite the corresponding neutralizing titers decreasing by 1.2-, 2.8-, and 3.5-fold relative to that against the wild-type strain. Significantly, the S-trimer immune sera exhibited comparable neutralization potency (less than twofold variation in neutralizing GMTs) towards the prototype strain and all three variants tested. These findings provide valuable information for further development of recombinant protein-based SARS-CoV-2 vaccines and support the continued use of currently approved SARS-CoV-2 vaccines in the regions/countries where variant viruses circulate.

Viruses2021       LitCov and CORD-19
260Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19  

BACKGROUND: The clinical implications of SARS‐CoV‐2 infection are highly variable. Some people with SARS‐CoV‐2 infection remain asymptomatic, whilst the infection can cause mild to moderate COVID‐19 and COVID‐19 pneumonia in others. This can lead to some people requiring intensive care support and, in some cases, to death, especially in older adults. Symptoms such as fever, cough, or loss of smell or taste, and signs such as oxygen saturation are the first and most readily available diagnostic information. Such information could be used to either rule out COVID‐19, or select patients for further testing. This is an update of this review, the first version of which published in July 2020. OBJECTIVES: To assess the diagnostic accuracy of signs and symptoms to determine if a person presenting in primary care or to hospital outpatient settings, such as the emergency department or dedicated COVID‐19 clinics, has COVID‐19. SEARCH METHODS: For this review iteration we undertook electronic searches up to 15 July 2020 in the Cochrane COVID‐19 Study Register and the University of Bern living search database. In addition, we checked repositories of COVID‐19 publications. We did not apply any language restrictions. SELECTION CRITERIA: Studies were eligible if they included patients with clinically suspected COVID‐19, or if they recruited known cases with COVID‐19 and controls without COVID‐19. Studies were eligible when they recruited patients presenting to primary care or hospital outpatient settings. Studies in hospitalised patients were only included if symptoms and signs were recorded on admission or at presentation. Studies including patients who contracted SARS‐CoV‐2 infection while admitted to hospital were not eligible. The minimum eligible sample size of studies was 10 participants. All signs and symptoms were eligible for this review, including individual signs and symptoms or combinations. We accepted a range of reference standards. DATA COLLECTION AND ANALYSIS: Pairs of review authors independently selected all studies, at both title and abstract stage and full‐text stage. They resolved any disagreements by discussion with a third review author. Two review authors independently extracted data and resolved disagreements by discussion with a third review author. Two review authors independently assessed risk of bias using the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS‐2) checklist. We presented sensitivity and specificity in paired forest plots, in receiver operating characteristic space and in dumbbell plots. We estimated summary parameters using a bivariate random‐effects meta‐analysis whenever five or more primary studies were available, and whenever heterogeneity across studies was deemed acceptable. MAIN RESULTS: We identified 44 studies including 26,884 participants in total. Prevalence of COVID‐19 varied from 3% to 71% with a median of 21%. There were three studies from primary care settings (1824 participants), nine studies from outpatient testing centres (10,717 participants), 12 studies performed in hospital outpatient wards (5061 participants), seven studies in hospitalised patients (1048 participants), 10 studies in the emergency department (3173 participants), and three studies in which the setting was not specified (5061 participants). The studies did not clearly distinguish mild from severe COVID‐19, so we present the results for all disease severities together. Fifteen studies had a high risk of bias for selection of participants because inclusion in the studies depended on the applicable testing and referral protocols, which included many of the signs and symptoms under study in this review. This may have especially influenced the sensitivity of those features used in referral protocols, such as fever and cough. Five studies only included participants with pneumonia on imaging, suggesting that this is a highly selected population. In an additional 12 studies, we were unable to assess the risk for selection bias. This makes it very difficult to judge the validity of the diagnostic accuracy of the signs and symptoms from these included studies. The applicability of the results of this review update improved in comparison with the original review. A greater proportion of studies included participants who presented to outpatient settings, which is where the majority of clinical assessments for COVID‐19 take place. However, still none of the studies presented any data on children separately, and only one focused specifically on older adults. We found data on 84 signs and symptoms. Results were highly variable across studies. Most had very low sensitivity and high specificity. Only cough (25 studies) and fever (7 studies) had a pooled sensitivity of at least 50% but specificities were moderate to low. Cough had a sensitivity of 67.4% (95% confidence interval (CI) 59.8% to 74.1%) and specificity of 35.0% (95% CI 28.7% to 41.9%). Fever had a sensitivity of 53.8% (95% CI 35.0% to 71.7%) and a specificity of 67.4% (95% CI 53.3% to 78.9%). The pooled positive likelihood ratio of cough was only 1.04 (95% CI 0.97 to 1.11) and that of fever 1.65 (95% CI 1.41 to 1.93). Anosmia alone (11 studies), ageusia alone (6 studies), and anosmia or ageusia (6 studies) had sensitivities below 50% but specificities over 90%. Anosmia had a pooled sensitivity of 28.0% (95% CI 17.7% to 41.3%) and a specificity of 93.4% (95% CI 88.3% to 96.4%). Ageusia had a pooled sensitivity of 24.8% (95% CI 12.4% to 43.5%) and a specificity of 91.4% (95% CI 81.3% to 96.3%). Anosmia or ageusia had a pooled sensitivity of 41.0% (95% CI 27.0% to 56.6%) and a specificity of 90.5% (95% CI 81.2% to 95.4%). The pooled positive likelihood ratios of anosmia alone and anosmia or ageusia were 4.25 (95% CI 3.17 to 5.71) and 4.31 (95% CI 3.00 to 6.18) respectively, which is just below our arbitrary definition of a 'red flag', that is, a positive likelihood ratio of at least 5. The pooled positive likelihood ratio of ageusia alone was only 2.88 (95% CI 2.02 to 4.09). Only two studies assessed combinations of different signs and symptoms, mostly combining fever and cough with other symptoms. These combinations had a specificity above 80%, but at the cost of very low sensitivity (< 30%). AUTHORS' CONCLUSIONS: The majority of individual signs and symptoms included in this review appear to have very poor diagnostic accuracy, although this should be interpreted in the context of selection bias and heterogeneity between studies. Based on currently available data, neither absence nor presence of signs or symptoms are accurate enough to rule in or rule out COVID‐19. The presence of anosmia or ageusia may be useful as a red flag for COVID‐19. The presence of fever or cough, given their high sensitivities, may also be useful to identify people for further testing. Prospective studies in an unselected population presenting to primary care or hospital outpatient settings, examining combinations of signs and symptoms to evaluate the syndromic presentation of COVID‐19, are still urgently needed. Results from such studies could inform subsequent management decisions.

Cochrane Database Syst Rev2021       LitCov and CORD-19
261The Technological Impact of COVID-19 on the Future of Education and Healthcare Delivery  


Pain Physician2020       LitCov and CORD-19
262Did social isolation during the SARS-CoV-2 epidemic have an impact on the lifestyles of citizens?  


Epidemiol Prev2020       LitCov and CORD-19
263Emotions of COVID-19: Content Analysis of Self-Reported Information Using Artificial Intelligence  

BACKGROUND: The COVID-19 pandemic has disrupted human societies around the world. This public health emergency was followed by a significant loss of human life; the ensuing social restrictions led to loss of employment, lack of interactions, and burgeoning psychological distress. As physical distancing regulations were introduced to manage outbreaks, individuals, groups, and communities engaged extensively on social media to express their thoughts and emotions. This internet-mediated communication of self-reported information encapsulates the emotional health and mental well-being of all individuals impacted by the pandemic. OBJECTIVE: This research aims to investigate the human emotions related to the COVID-19 pandemic expressed on social media over time, using an artificial intelligence (AI) framework. METHODS: Our study explores emotion classifications, intensities, transitions, and profiles, as well as alignment to key themes and topics, across the four stages of the pandemic: declaration of a global health crisis (ie, prepandemic), the first lockdown, easing of restrictions, and the second lockdown. This study employs an AI framework comprised of natural language processing, word embeddings, Markov models, and the growing self-organizing map algorithm, which are collectively used to investigate social media conversations. The investigation was carried out using 73,000 public Twitter conversations posted by users in Australia from January to September 2020. RESULTS: The outcomes of this study enabled us to analyze and visualize different emotions and related concerns that were expressed and reflected on social media during the COVID-19 pandemic, which could be used to gain insights into citizens’ mental health. First, the topic analysis showed the diverse as well as common concerns people had expressed during the four stages of the pandemic. It was noted that personal-level concerns expressed on social media had escalated to broader concerns over time. Second, the emotion intensity and emotion state transitions showed that fear and sadness emotions were more prominently expressed at first; however, emotions transitioned into anger and disgust over time. Negative emotions, except for sadness, were significantly higher (P<.05) in the second lockdown, showing increased frustration. Temporal emotion analysis was conducted by modeling the emotion state changes across the four stages of the pandemic, which demonstrated how different emotions emerged and shifted over time. Third, the concerns expressed by social media users were categorized into profiles, where differences could be seen between the first and second lockdown profiles. CONCLUSIONS: This study showed that the diverse emotions and concerns that were expressed and recorded on social media during the COVID-19 pandemic reflected the mental health of the general public. While this study established the use of social media to discover informed insights during a time when physical communication was impossible, the outcomes could also contribute toward postpandemic recovery and understanding psychological impact via emotion changes, and they could potentially inform health care decision making. This study exploited AI and social media to enhance our understanding of human behaviors in global emergencies, which could lead to improved planning and policy making for future crises.

J Med Internet Res2021       LitCov and CORD-19
264Practice-Level Variation in Telemedicine Use in a Pediatric Primary Care Network During the COVID-19 Pandemic: Retrospective Analysis and Survey Study  

BACKGROUND: Telehealth, the delivery of health care through telecommunication technology, has potential to address multiple health system concerns. Despite this potential, only 15% of pediatric primary care clinicians reported using telemedicine as of 2016, with the majority identifying inadequate payment for these services as the largest barrier to their adoption. The COVID-19 pandemic led to rapid changes in payment and regulations surrounding telehealth, enabling its integration into primary care pediatrics. OBJECTIVE: Due to limited use of telemedicine in primary care pediatrics prior to the COVID-19 pandemic, much is unknown about the role of telemedicine in pediatric primary care. To address this gap in knowledge, we examined the association between practice-level telemedicine use within a large pediatric primary care network and practice characteristics, telemedicine visit diagnoses, in-person visit volumes, child-level variations in telemedicine use, and clinician attitudes toward telemedicine. METHODS: We analyzed electronic health record data from 45 primary care practices and administered a clinician survey to practice clinicians. Practices were stratified into tertiles based on rates of telemedicine use (low, intermediate, high) per 1000 patients per week during a two-week period (April 19 to May 2, 2020). By practice tertile, we compared (1) practice characteristics, (2) telemedicine visit diagnoses, (3) rates of in-person visits to the office, urgent care, and the emergency department, (4) child-level variation in telemedicine use, and (5) clinician attitudes toward telemedicine across these practices. RESULTS: Across pediatric primary care practices, telemedicine visit rates ranged from 5 to 23 telemedicine visits per 1000 patients per week. Across all tertiles, the most frequent telemedicine visit diagnoses were mental health (28%-36% of visits) and dermatologic (15%-28%). Compared to low telemedicine use practices, high telemedicine use practices had fewer in-person office visits (10 vs 16 visits per 1000 patients per week, P=.005) but more total encounters overall (in-office and telemedicine: 28 vs 22 visits per 1000 patients per week, P=.006). Telemedicine use varied with child age, race and ethnicity, and recent preventive care; however, no significant interactions existed between these characteristics and practice-level telemedicine use. Finally, clinician attitudes regarding the usability and impact of telemedicine did not vary significantly across tertiles. CONCLUSIONS: Across a network of pediatric practices, we identified significant practice-level variation in telemedicine use, with increased use associated with more varied telemedicine diagnoses, fewer in-person office visits, and increased overall primary care encounter volume. Thus, in the context of the pandemic, when underutilization of primary care was prevalent, higher practice-level telemedicine use supported pediatric primary care encounter volume closer to usual rates. Child-level telemedicine use differed by child age, race and ethnicity, and recent preventive care, building upon prior concerns about differences in access to telemedicine. However, increased practice-level use of telemedicine services was not associated with reduced or increased differences in use, suggesting that further work is needed to promote equitable access to primary care telemedicine.

J Med Internet Res2020       LitCov and CORD-19
265Evaluation of the safety and immunogenicity of different COVID-19 vaccine combinations in healthy individuals: study protocol for a randomized, subject-blinded, controlled phase 3 trial [PRIBIVAC]  


Trials2022       LitCov
266The impact of COVID-19 on subthreshold depressive symptoms: a longitudinal study  

AIMS: The coronavirus disease 2019 (COVID-19) pandemic represents an unprecedented threat to mental health. Herein, we assessed the impact of COVID-19 on subthreshold depressive symptoms and identified potential mitigating factors. METHODS: Participants were from Depression Cohort in China (ChiCTR registry number 1900022145). Adults (n = 1722) with subthreshold depressive symptoms were enrolled between March and October 2019 in a 6-month, community-based interventional study that aimed to prevent clinical depression using psychoeducation. A total of 1506 participants completed the study in Shenzhen, China: 726 participants, who completed the study between March 2019 and January 2020 (i.e. before COVID-19), comprised the ‘wave 1’ group; 780 participants, who were enrolled before COVID-19 and completed the 6-month endpoint assessment during COVID-19, comprised ‘wave 2’. Symptoms of depression, anxiety and insomnia were assessed at baseline and endpoint (i.e. 6-month follow-up) using the Patient Health Questionnaire-9 (PHQ-9), Generalised Anxiety Disorder-7 (GAD-7) and Insomnia Severity Index (ISI), respectively. Measures of resilience and regular exercise were assessed at baseline. We compared the mental health outcomes between wave 1 and wave 2 groups. We additionally investigated how mental health outcomes changed across disparate stages of the COVID-19 pandemic in China, i.e. peak (7–13 February), post-peak (14–27 February), remission plateau (28 February−present). RESULTS: COVID-19 increased the risk for three mental outcomes: (1) depression (odds ratio [OR] = 1.30, 95% confidence interval [CI]: 1.04–1.62); (2) anxiety (OR = 1.47, 95% CI: 1.16–1.88) and (3) insomnia (OR = 1.37, 95% CI: 1.07–1.77). The highest proportion of probable depression and anxiety was observed post-peak, with 52.9% and 41.4%, respectively. Greater baseline resilience scores had a protective effect on the three main outcomes (depression: OR = 0.26, 95% CI: 0.19–0.37; anxiety: OR = 1.22, 95% CI: 0.14–0.33 and insomnia: OR = 0.18, 95% CI: 0.11–0.28). Furthermore, regular physical activity mitigated the risk for depression (OR = 0.79, 95% CI: 0.79–0.99). CONCLUSIONS: The COVID-19 pandemic exerted a highly significant and negative impact on symptoms of depression, anxiety and insomnia. Mental health outcomes fluctuated as a function of the duration of the pandemic and were alleviated to some extent with the observed decline in community-based transmission. Augmenting resiliency and regular exercise provide an opportunity to mitigate the risk for mental health symptoms during this severe public health crisis.

Epidemiol Psychiatr Sci2021       LitCov and CORD-19
267Early public adherence with and support for stay-at-home COVID-19 mitigation strategies despite adverse life impact: a transnational cross-sectional survey study in the United States and Australia  

BACKGROUND: Governments worldwide recommended unprecedented measures to contain the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As pressure mounted to scale back measures, understanding public priorities was critical. We assessed initial public adherence with and support for stay-at-home orders in nations and cities with different SARS-CoV-2 infection and COVID-19 death rates. METHODS: Cross-sectional surveys were administered to representative samples of adults aged ≥18 years from regions with different SARS-CoV-2 prevalences from April 2–8, 2020. Regions included two nations [the United States (US—high prevalence) and Australia (AU—low prevalence)] and two US cities [New York City (NY—high prevalence) and Los Angeles (LA—low prevalence)]. Regional SARS-CoV-2 and COVID-19 prevalence (cumulative SARS-CoV-2 infections, COVID-19 deaths) as of April 8, 2020: US (363,321, 10,845), AU (5956, 45), NY (81,803, 4571), LA (7530, 198). Of 8718 eligible potential respondents, 5573 (response rate, 63.9%) completed surveys. Median age was 47 years (range, 18–89); 3039 (54.5%) were female. RESULTS: Of 5573 total respondents, 4560 (81.8%) reported adherence with recommended quarantine or stay-at-home policies (range of samples, 75.5–88.2%). Additionally, 29.1% of respondents screened positive for anxiety or depression symptoms (range of samples, 28.6–32.0%), with higher prevalences among those of younger age, female gender, and those in quarantine or staying at home most of the time versus those who did not report these behaviours. Despite elevated prevalences of adverse mental health symptoms and significant life disruptions, 5022 respondents (90.1%) supported government-imposed stay-at-home orders (range of samples, 88.9–93.1%). Of these, 90.8% believed orders should last at least three more weeks or until public health or government officials recommended, with support spanning the political spectrum. CONCLUSIONS: Public adherence with COVID-19 mitigation policies was highly prevalent, in both highly-affected (US, NY) and minimally-affected regions (AU, LA). Despite disruption of respondents’ lives, the vast majority supported continuation of extended stay-at-home orders. Despite common support, these two countries diverged in stringent mitigation implementation, which may have contributed to subsequent outcomes. These results reveal the importance of surveillance of public support for and adherence with such policies during the COVID-19 pandemic and for future infectious disease outbreaks. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-021-10410-x.

BMC Public Health2021       LitCov and CORD-19
268Concerns Expressed by Chinese Social Media Users During the COVID-19 Pandemic: Content Analysis of Sina Weibo Microblogging Data  

BACKGROUND: The COVID-19 pandemic has created a global health crisis that is affecting economies and societies worldwide. During times of uncertainty and unexpected change, people have turned to social media platforms as communication tools and primary information sources. Platforms such as Twitter and Sina Weibo have allowed communities to share discussion and emotional support; they also play important roles for individuals, governments, and organizations in exchanging information and expressing opinions. However, research that studies the main concerns expressed by social media users during the pandemic is limited. OBJECTIVE: The aim of this study was to examine the main concerns raised and discussed by citizens on Sina Weibo, the largest social media platform in China, during the COVID-19 pandemic. METHODS: We used a web crawler tool and a set of predefined search terms (New Coronavirus Pneumonia, New Coronavirus, and COVID-19) to investigate concerns raised by Sina Weibo users. Textual information and metadata (number of likes, comments, retweets, publishing time, and publishing location) of microblog posts published between December 1, 2019, and July 32, 2020, were collected. After segmenting the words of the collected text, we used a topic modeling technique, latent Dirichlet allocation (LDA), to identify the most common topics posted by users. We analyzed the emotional tendencies of the topics, calculated the proportional distribution of the topics, performed user behavior analysis on the topics using data collected from the number of likes, comments, and retweets, and studied the changes in user concerns and differences in participation between citizens living in different regions of mainland China. RESULTS: Based on the 203,191 eligible microblog posts collected, we identified 17 topics and grouped them into 8 themes. These topics were pandemic statistics, domestic epidemic, epidemics in other countries worldwide, COVID-19 treatments, medical resources, economic shock, quarantine and investigation, patients’ outcry for help, work and production resumption, psychological influence, joint prevention and control, material donation, epidemics in neighboring countries, vaccine development, fueling and saluting antiepidemic action, detection, and study resumption. The mean sentiment was positive for 11 topics and negative for 6 topics. The topic with the highest mean of retweets was domestic epidemic, while the topic with the highest mean of likes was quarantine and investigation. CONCLUSIONS: Concerns expressed by social media users are highly correlated with the evolution of the global pandemic. During the COVID-19 pandemic, social media has provided a platform for Chinese government departments and organizations to better understand public concerns and demands. Similarly, social media has provided channels to disseminate information about epidemic prevention and has influenced public attitudes and behaviors. Government departments, especially those related to health, can create appropriate policies in a timely manner through monitoring social media platforms to guide public opinion and behavior during epidemics.

J Med Internet Res2020       LitCov and CORD-19
269Pulmonary Vascular Endothelialitis, Thrombosis and Angiogenesis in Covid-19  


N Engl J Med2020       LitCov and CORD-19
270COVID-19 vaccine acceptance, hesitancy and determinants among physicians in a university-based teaching hospital in Thailand  

BACKGROUND: The COVID-19 vaccines provide renewed hope in the fight against the recent pandemic. To ensure widespread vaccination, it is crucial to analyze vaccine willingness and its determinants among physicians, key health care influencers. This study aimed to assess acceptance rate and identify factors associated with vaccine hesitancy among Thai physicians. METHODS: A cross-sectional online-based questionnaire was distributed to all physicians at King Chulalongkorn Memorial Hospital during March 31, 2021 to April 30, 2021 in order to assess their attitudes toward receiving the COVID-19 vaccine. Reasons for vaccine acceptance and refusal as well as predictors of vaccine hesitancy were analyzed by bivariate and multivariable analysis. RESULTS: A total of 705 complete responses were received with 95.6% (n = 675) of physicians expressing willingness to receive a COVID-19 vaccine. Only one of the 31 physicians (4.4%) who expressed a hesitancy or unwillingness to be vaccinated was a faculty member; the others were physicians-in-training. Approximately one-fifths of physicians surveyed were also not willing to recommend the vaccine to their family members (21.4%, n = 151) or patients (18.7%, n = 132). Using multivariable logistic regression, vaccine hesitancy was independently associated with preference for particular vaccines over the government allocated option, especially for mRNA vaccine (aOR 8.86; 95% CI 1.1–71.54; p = 0.041). Vaccine literacy showed an inverse relationship (aOR 0.34; 95% CI 0.13–0.9; p = 0.029) with vaccine hesitancy. Uncertainty of the vaccine efficacy (83.9%) and fear of adverse events (48.4%) were major concerns contributing to vaccine hesitancy. CONCLUSION: This study revealed a high rate of physician willingness to take the COVID-19 vaccine especially among staffs; however, a significant proportion would not currently suggest vaccination to their families or patients. Restrictions on vaccine choice and vaccine illiteracy, together with concerns over adverse effects and uncertainty of efficacy, were associated with negative attitudes toward vaccination. To raise acceptance of the vaccination program, efforts should be made to balance individual preference for vaccine type in addition to increasing the availability of accurate data on safety and efficacy for each vaccine. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-021-06863-5.

BMC Infect Dis2021       LitCov and CORD-19
271Association of Age With Likelihood of Developing Symptoms and Critical Disease Among Close Contacts Exposed to Patients With Confirmed SARS-CoV-2 Infection in Italy  

We quantified the probability of developing symptoms (respiratory or fever geq 37.5 {deg}C) and critical disease (requiring intensive care or resulting in death) of SARS-CoV-2 positive subjects. 5,484 contacts of SARS-CoV-2 index cases detected in Lombardy, Italy were analyzed, and positive subjects were ascertained via nasal swabs and serological assays. 73.9% of all infected individuals aged less than 60 years did not develop symptoms (95% confidence interval: 71.8-75.9%). The risk of symptoms increased with age. 6.6% of infected subjects older than 60 years had critical disease, with males at significantly higher risk.

JAMA Netw Open2021       LitCov and CORD-19
272Update on SARS-CoV-2 Omicron Variant of Concern and Its Peculiar Mutational Profile  

The process of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic diversification is still ongoing and has very recently led to the emergence of a new variant of concern (VOC), defined as Omicron or B.1.1.529. Omicron VOC is the most divergent variant identified so far and has generated immediate concern for its potential capability to increase SARS-CoV-2 transmissibility and, more worryingly, to escape therapeutic and vaccine-induced antibodies. Nevertheless, a clear definition of the Omicron VOC mutational spectrum is still missing. Herein, we provide a comprehensive definition and functional characterization (in terms of infectivity and/or antigenicity) of mutations characterizing the Omicron VOC. In particular, 887,475 SARS-CoV-2 Omicron VOC whole-genome sequences were retrieved from the GISAID database and used to precisely define its specific patterns of mutations across the different viral proteins. In addition, the functional characterization of Omicron VOC spike mutations was finely discussed according to published manuscripts. Lastly, residues characterizing the Omicron VOC and the previous four VOCs (Alpha, Beta, Gamma, and Delta) were mapped on the three-dimensional structure of the SARS-CoV-2 spike protein to assess their localization in the different spike domains. Overall, our study will assist with deciphering the Omicron VOC mutational profile and will shed more light on its clinical implications. This is critical considering that Omicron VOC is currently the predominant variant worldwide. IMPORTANCE The Omicron variant of concern (VOC) has a peculiar spectrum of mutations characterized by the acquisition of mutations or deletions rarely detected in previously identified variants, particularly in the spike glycoprotein. Such mutations, mostly residing in the receptor-binding domain, could play a pivotal role in enhancing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity (by increasing binding affinity for ACE2), jeopardizing spike recognition by therapeutic and vaccine-induced antibodies and causing diagnostic assay failure. To our knowledge, this is one of the first exhaustive descriptions of newly emerged mutations underlying the Omicron VOC and its biological and clinical implications.

Microbiol Spectr2022       LitCov and CORD-19
273Investigating the Prevalence of Reactive Online Searching in the COVID-19 Pandemic: Infoveillance Study  

BACKGROUND: The ongoing pandemic has placed an unprecedented strain on global society, health care, governments, and mass media. Public dissemination of government policies, medical interventions, and misinformation has been remarkably rapid and largely unregulated during the COVID-19 pandemic, resulting in increased misinterpretations, miscommunication, and public panic. Being the first full-scale global pandemic of the digital age, COVID-19 has presented novel challenges pertinent to government advice, the spread of news and misinformation, and the trade-off between the accessibility of science and the premature public use of unproven medical interventions. OBJECTIVE: This study aims to assess the use of internet search terms relating to COVID-19 information and misinformation during the global pandemic, identify which were most used in six affected countries, investigate any temporal trends and the likely propagators of key search terms, and determine any correlation between the per capita cases and deaths with the adoption of these search terms in each of the six countries. METHODS: This study uses relative search volume data extracted from Google Trends for search terms linked to the COVID-19 pandemic alongside per capita case and mortality data extracted from the European Open Data Portal to identify the temporal dynamics of the spread of news and misinformation during the global pandemic in six affected countries (Australia, Germany, Italy, Spain, the United Kingdom, and the United States). A correlation analysis was carried out to ascertain any correlation between the temporal trends of search term use and the rise of per capita mortality and disease cases. RESULTS: Of the selected search terms, most were searched immediately following promotion by governments, public figures, or viral circulation of information, but also in relation to the publication of scientific resources, which were sometimes misinterpreted before further dissemination. Strong correlations were identified between the volume of these COVID-19–related search terms (overall mean Spearman rho 0.753, SD 0.158), and per capita mortality (mean per capita deaths Spearman rho 0.690, SD 0.168) and cases (mean per capita cases Spearman rho 0.800, SD 0.112). CONCLUSIONS: These findings illustrate the increased rate and volume of the public consumption of novel information during a global health care crisis. The positive correlation between mortality and online searching, particularly in countries with lower COVID-19 testing rates, may demonstrate the imperative to safeguard official communications and dispel misinformation in these countries. Online news, government briefings, and social media provide a powerful tool for the dissemination of important information to the public during pandemics, but their misuse and the presentation of misrepresented medical information should be monitored, minimized, and addressed to safeguard public safety. Ultimately, governments, public health authorities, and scientists have a moral imperative to safeguard the truth and maintain an accessible discourse with the public to limit fear.

J Med Internet Res2020       LitCov and CORD-19
274Parental Mental Health and Children's Behaviors and Media Usage during COVID-19-Related School Closures  

BACKGROUND: Coronavirus disease 2019 (COVID-19) is different from previous disasters in that it continues to the present and has affected all aspects of family life. During epidemics, psychosocial support is not less important than infection control. During COVID-19-related school closures, prolonged partial closures of schools could have detrimental social and health consequences for children and may increase the burden on the family. Based on a community sample in Korea, this study identified parental concerns, children's media usage, other various factors and examined whether parental stress level or depression were positively associated with problem behaviors, media exposure, and sleep problems of the primary school children during school closure under COVID-19. METHODS: Participants were 217 parents residing in Suwon, South Korea, who had primary school children and responded to a web-based questionnaire on parental concerns from school closure under COVID-19, subjective stress, depression, whether having received mental health services, and family characteristics; children's sleep patterns, problem behaviors, media usage during the online-only class period, and changes in activity level following the pandemic. RESULTS: During school closure, children gained body weight, spent less time in physical activities and more in media usage. Besides online learning content (97.2%), YouTube was highly used content (87.6%), and games followed (78.3%). Parental subjective stress index was highly associated with parental depression (Pearson correlation 0.439, P < 0.001), children's sleep problems (0.283, P < 0.001), tablet time (0.171, P = 0.012) and behavior problems (0.413, P < 0.001). Parental depression was associated with children's sleep problems (0.355, P < 0.001), TV time (0.153, P = 0.024), tablet time (0.159, P = 0.019), and behavior problems (0.524, P < 0.001). Parents who previously received mental services seemed to be more concerned about the problems their children already have getting worse because of COVID-19 than the disease itself. Children's sleep problem was associated with tablet (0.172, P = 0.011) and smartphone time (0.298, P < 0.001), but not its frequency. CONCLUSION: During COVID-19-related school closures, many parents and children had various difficulties relating to mental health. Ongoing monitoring of mental health of high-risk groups and multiple support systems may need to be expanded to cover those parents having difficulty in caring for their children.

J Korean Med Sci2021       LitCov and CORD-19
275Clinical and Epidemiological Features of SARS-CoV-2 Patients in SARI Ward of a Tertiary Care Centre in New Delhi  


J Assoc Physicians India2020       LitCov and CORD-19
2766-month consequences of COVID-19 in patients discharged from hospital: a cohort study  

BACKGROUND: The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity. METHODS: We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7, 2020, and May 29, 2020. Patients who died before follow-up, patients for whom follow-up would be difficult because of psychotic disorders, dementia, or re-admission to hospital, those who were unable to move freely due to concomitant osteoarthropathy or immobile before or after discharge due to diseases such as stroke or pulmonary embolism, those who declined to participate, those who could not be contacted, and those living outside of Wuhan or in nursing or welfare homes were all excluded. All patients were interviewed with a series of questionnaires for evaluation of symptoms and health-related quality of life, underwent physical examinations and a 6-min walking test, and received blood tests. A stratified sampling procedure was used to sample patients according to their highest seven-category scale during their hospital stay as 3, 4, and 5–6, to receive pulmonary function test, high resolution CT of the chest, and ultrasonography. Enrolled patients who had participated in the Lopinavir Trial for Suppression of SARS-CoV-2 in China received severe acute respiratory syndrome coronavirus 2 antibody tests. Multivariable adjusted linear or logistic regression models were used to evaluate the association between disease severity and long-term health consequences. FINDINGS: In total, 1733 of 2469 discharged patients with COVID-19 were enrolled after 736 were excluded. Patients had a median age of 57·0 (IQR 47·0–65·0) years and 897 (52%) were men. The follow-up study was done from June 16, to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 (175·0–199·0) days. Fatigue or muscle weakness (63%, 1038 of 1655) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1617) of patients. The proportions of median 6-min walking distance less than the lower limit of the normal range were 24% for those at severity scale 3, 22% for severity scale 4, and 29% for severity scale 5–6. The corresponding proportions of patients with diffusion impairment were 22% for severity scale 3, 29% for scale 4, and 56% for scale 5–6, and median CT scores were 3·0 (IQR 2·0–5·0) for severity scale 3, 4·0 (3·0–5·0) for scale 4, and 5·0 (4·0–6·0) for scale 5–6. After multivariable adjustment, patients showed an odds ratio (OR) 1·61 (95% CI 0·80–3·25) for scale 4 versus scale 3 and 4·60 (1·85–11·48) for scale 5–6 versus scale 3 for diffusion impairment; OR 0·88 (0·66–1·17) for scale 4 versus scale 3 and OR 1·77 (1·05–2·97) for scale 5–6 versus scale 3 for anxiety or depression, and OR 0·74 (0·58–0·96) for scale 4 versus scale 3 and 2·69 (1·46–4·96) for scale 5–6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% vs 58·5%) and median titres (19·0 vs 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with estimated glomerular filtration rate (eGFR) 90 mL/min per 1·73 m(2) or more at acute phase had eGFR less than 90 mL/min per 1·73 m(2) at follow-up. INTERPRETATION: At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery. FUNDING: National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, and Peking Union Medical College Foundation.

Lancet2021       LitCov and CORD-19
277A single mRNA vaccine dose in COVID-19 patients boosts neutralizing antibodies against SARS-CoV-2 and variants of concern  

The urgent need for, but limited availability of, SARS-CoV-2 vaccines worldwide has led to widespread consideration of dose sparing strategies. Here, we evaluate the SARS-CoV-2 specific antibody responses following BNT162b2 vaccination in 150 previously SARS-CoV-2-infected individuals from a population-based cohort. One week after first vaccine dose, spike protein antibody levels are 27-fold higher and neutralizing antibody titers 12-fold higher, exceeding titers of fully vaccinated SARS-CoV-2-naive controls, with minimal additional boosting after the second dose. Neutralizing antibody titers against four variants of concern increase after vaccination, however overall neutralization breadth does not improve. Pre-vaccination neutralizing antibody titers and time since infection have the largest positive effect on titers following vaccination. COVID-19 severity and the presence of comorbidities have no discernible impact on vaccine response. In conclusion, a single dose of BNT162b2 vaccine up to 15 months after SARS-CoV-2 infection offers higher neutralizing antibody titers than two vaccine doses in SARS-CoV-2-naive individuals.

Cell Rep Med2021       LitCov and CORD-19
278Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T-cell reactivity against prevalent SARS-CoV-2 variants  

BACKGROUND: Heterologous COVID-19 vaccination regimens combining vector- and mRNA-based vaccines are already administered, but data on solicited adverse reactions, immunological responses and elicited protection are limited. METHODS: To evaluate the reactogenicity and humoral as well as cellular immune responses towards most prevalent SARS-CoV-2 variants after a heterologous ChAdOx1 nCoV-19 BNT162b2 prime-boost vaccination, we analysed a cohort of 26 clinic employees aged 25-46 (median 30.5) years who received a ChAdOx1 nCoV-19 prime followed by a BNT162b2 boost after an 8-week interval. Serological data were compared to a cohort which received homologous BNT162b2 vaccination with a 3-week interval (14 individuals aged 25-65, median 42). FINDINGS: Self-reported solicited symptoms after ChAdOx1 nCoV-19 prime were in line with previous reports and more severe than after the BNT162b2 boost. Antibody titres increased significantly over time resulting in strong neutralization titres two weeks after the BNT162b2 boost and subsequently slightly decreased over the course of 17 weeks. At the latest time point measured, all analysed sera retained neutralizing activity against the currently dominant Delta (B.1.617.2) variant. Two weeks post boost, neutralizing activity against the Alpha (B.1.1.7) and immune-evading Beta (B.1.351) variant was ∼4-fold higher than in individuals receiving homologous BNT162b2 vaccination. No difference was observed in neutralization of Kappa (B.1.617.1). In addition, heterologous vaccination induced CD4(+) and CD8(+) T cells reactive to SARS-CoV-2 spike peptides of all analysed variants; Wuhan-Hu-1, Alpha, Beta, Gamma (P.1), and Delta. INTERPRETATION: In conclusion, heterologous ChAdOx1 nCoV-19 / BNT162b2 prime-boost vaccination is not associated with serious adverse events and induces potent humoral and cellular immune responses. The Alpha, Beta, Delta, and Kappa variants of spike are potently neutralized by sera from all participants and reactive T cells recognize spike peptides of all tested variants. These results suggest that this heterologous vaccination regimen is at least as immunogenic and protective as homologous vaccinations and also offers protection against current variants of concern. FUNDING: This project has received funding from the European Union's Horizon 2020 research and innovation programme, the German Research Foundation, the BMBF, the Robert Koch Institute (RKI), the Baden-Württemberg Stiftung, the county of Lower Saxony, the Ministry for Science, Research and the Arts of Baden-Württemberg, Germany, and the National Institutes of Health.

EBioMedicine2021       LitCov and CORD-19
279Psychosocial factors associated with postpartum psychological distress during the Covid-19 pandemic: a cross-sectional study  

BACKGROUND: Trauma, natural and man-made catastrophic events can be predictors of postpartum psychological distress. In a public health response due to coronavirus disease 2019 outbreak, the Italian government imposed a lockdown from March 9 to May 3. This extraordinary situation may have been challenging for maternal psychological health. The aim of this study was to investigate the prevalence of depressive and post-traumatic stress symptoms in women giving birth during the Covid-19 pandemic and its associations with quarantine measures, obstetrical factors, and relational attachment style. METHODS: Women who gave birth in a high-volume obstetric/gynaecological medical centre located in an epidemic area during the Covid-19 pandemic (March 8 to June 15) were asked to complete an online survey about their childbirth experience and the perceived effect of the pandemic. The Edinburgh Postnatal Depression Scale (EPDS), the Impact of Event Scale-Revised (IES-R), and the Relationship Questionnaire (RQ) were administered to assess levels of postpartum depressive and post-traumatic stress symptoms (PTSS) and relational style of attachment, respectively. Multivariate analysis was applied to identify associations between quarantine measures, childbirth experience, attachment style, and EPDS and IES-R scores. RESULTS: The survey was completed by 163 women (response rate 60.8%). The prevalence of depressive symptoms was 44.2% (EPDS cut-off score ≥ 11) and the PTSS rate was 42.9% (IES-R cut-off score ≥ 24). Dismissive and fearful avoidant attachment styles were significantly associated with the risk of depression and PTSS, respectively. Perceived pain during birth was a risk factor for postpartum depression. Perceived support provided by healthcare staff was a protective factor against depression and PTSS. Another protective factor against PTSS was quiet on the ward due to the absence of hospital visitors. CONCLUSION: This study reports a high prevalence of postpartum depressive and PTSS in women who gave birth during the Covid-19 pandemic. Postnatal psychological distress seemed to be associated more with the prenatal experience and other individual factors than with the pandemic hospital restrictions. Early detection during pregnancy of an insecure attachment style is fundamental to provide targeted preventive and therapeutic psychological interventions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12884-020-03399-5.

BMC Pregnancy Childbirth2020       LitCov and CORD-19
280New York Inner City Hospital COVID-19 Experience and Current Data: Retrospective Analysis at the Epicenter of the American Coronavirus Outbreak  

BACKGROUND: In the midst of the coronavirus disease pandemic, emerging clinical data across the world has equipped frontline health care workers, policy makers, and researchers to better understand and combat the illness. OBJECTIVE: The aim of this study is to report the correlation of clinical and laboratory parameters with patients requiring mechanical ventilation and the mortality in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We did a review of patients with SARS-CoV-2 confirmed infection admitted and managed by our institution during the last month. Patients were grouped into intubated and nonintubated, and subgrouped to alive and deceased. A comprehensive analysis using the following parameters were performed: age, sex, ethnicity, BMI, comorbidities, inflammatory markers, laboratory values, cardiac and renal function, electrocardiogram (EKG), chest x-ray findings, temperature, treatment groups, and hospital-acquired patients with SARS-CoV-2. RESULTS: A total of 184 patients were included in our study with ages ranging from 28-97 years (mean 64.72 years) and including 73 females (39.67%) and 111 males (60.33%) with a mean BMI of 29.10. We had 114 African Americans (61.96%), 58 Hispanics (31.52%), 11 Asians (5.98%), and 1 Caucasian (0.54%), with a mean of 1.70 comorbidities. Overall, the mortality rate was 17.39% (n=32), 16.30% (n=30) of our patients required mechanical ventilation, and 11.41% (n=21) had hospital-acquired SARS-CoV-2 infection. Pertinent and statistically significant results were found in the intubated versus nonintubated patients with confirmed SARS-CoV-2 for the following parameters: age (P=.01), BMI (P=.07), African American ethnicity (P<.001), Hispanic ethnicity (P=.02), diabetes mellitus (P=.001), creatinine (P=.29), blood urea nitrogen (BUN; P=.001), procalcitonin (P=.03), C-reactive protein (CRP; P=.007), lactate dehydrogenase (LDH; P=.001), glucose (P=.01), temperature (P=.004), bilateral pulmonary infiltrates in chest x-rays (P<.001), and bilateral patchy opacity (P=.02). The results between the living and deceased subgroups of patients with confirmed SARS-CoV-2 (linking to or against mortality) were BMI (P=.04), length of stay (P<.001), hypertension (P=.02), multiple comorbidity (P=.045), BUN (P=.04), and EKG findings with arrhythmias or blocks (P=.02). CONCLUSIONS: We arrived at the following conclusions based on a comprehensive review of our study group, data collection, and statistical analysis. Parameters that were strongly correlated with the need for mechanical ventilation were younger age group, overweight, Hispanic ethnicity, higher core body temperature, EKG findings with sinus tachycardia, and bilateral diffuse pulmonary infiltrates on the chest x-rays. Those intubated exhibited increased disease severity with significantly elevated levels of serum procalcitonin, CRP, LDH, mean glucose, creatinine, and BUN. Mortality was strongly correlated with BMI, African American ethnicity, hypertension, presence of multiple comorbidities (with a mean of 2.32), worsening renal function with acute kidney injury or acute chronic kidney injury, and EKG findings of arrhythmias and heart blocks.

J Med Internet Res2020       LitCov and CORD-19
281The outbreak of the novel SARS-CoV-2: A review of the current global status  

There is currently an ongoing worldwide pandemic of a novel virus belonging to the family of Coronaviruses (CoVs) which are large, enveloped, plus-stranded RNA viruses. Coronaviruses belong to the order of Nidovirales, family of Coronavirinae and are divided into four genera: alphacoronavirus, betacoronavirus, gammacoronavirus and deltacoronavirus. CoVs cause diseases in a wide variety of birds and mammals and have been found in humans since 1960. To date, seven human CoVs were identified including the alpha-CoVs HCoVs-NL63 and HCoVs-229E and the beta-CoVs HCoVs-OC43, HCoVs-HKU1, the severe acute respiratory syndrome-CoV (SARS-CoV), the Middle East respiratory syndrome-CoV (MERS-CoV) and the novel virus that first appeared in December 2019 in Wuhan, China, and rapidly spread to 213 countries as of the writing this paper. It was officially named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the international committee on taxonomy of viruses (ICTV) and the disease’s name is COVID-19 for coronavirus disease 2019. SARS-CoV-2 is very contagious and is capable of spreading from human to human. Infection routes include droplet and contact, and aerosol transmission is currently under investigation. It is associated with a respiratory illness that may cause severe pneumonia and acute respiratory distress syndrome (ARDS). SARS-CoV-2 became an emergency of international concern. As of July 12, 2020, the virus has been responsible for 12,698,995 confirmed cases and 564,924 deaths worldwide and the number is still increasing. Up until now, no specific treatment has yet been proven effective against SARS-CoV-2. Since the beginning of this outbreak, several interesting papers on SARS-CoV-2 and COVID-19 have been published to report on the phylogenetic evolution, epidemiology, pathogenesis, transmission as well as clinical characteristics of COVID-19 and possible treatments agents. This paper is a systematic review of the available literature on SARS-CoV-2. It was performed in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and aims to help readers access the latest knowledge surrounding this new infectious disease and to provide a reference for future studies.

J Infect Public Health2020       LitCov and CORD-19
282Function Is More Reliable than Quantity to Follow Up the Humoral Response to the Receptor-Binding Domain of SARS-CoV-2-Spike Protein after Natural Infection or COVID-19 Vaccination  

Both the SARS-CoV-2 pandemic and emergence of variants of concern have highlighted the need for functional antibody assays to monitor the humoral response over time. Antibodies directed against the spike (S) protein of SARS-CoV-2 are an important component of the neutralizing antibody response. In this work, we report that in a subset of patients—despite a decline in total S-specific antibodies—neutralizing antibody titers remain at a similar level for an average of 98 days in longitudinal sampling of a cohort of 59 Hispanic/Latino patients exposed to SARS-CoV-2. Our data suggest that 100% of seroconverting patients make detectable neutralizing antibody responses which can be quantified by a surrogate viral neutralization test. Examination of sera from ten out of the 59 subjects which received mRNA-based vaccination revealed that both IgG titers and neutralizing activity of sera were higher after vaccination compared to a cohort of 21 SARS-CoV-2 naïve subjects. One dose was sufficient for the induction of a neutralizing antibody, but two doses were necessary to reach 100% surrogate virus neutralization in subjects irrespective of previous SARS-CoV-2 natural infection status. Like the pattern observed after natural infection, the total anti-S antibodies titers declined after the second vaccine dose; however, neutralizing activity remained relatively constant for more than 80 days after the first vaccine dose. Furthermore, our data indicates that—compared with mRNA vaccination—natural infection induces a more robust humoral immune response in unexposed subjects. This work is an important contribution to understanding the natural immune response to the novel coronavirus in a population severely impacted by SARS-CoV-2. Furthermore, by comparing the dynamics of the immune response after the natural infection vs. the vaccination, these findings suggest that functional neutralizing antibody tests are more relevant indicators than the presence or absence of binding antibodies.

Viruses2021       LitCov and CORD-19
283Optimized Pseudotyping Conditions for the SARS-COV-2 Spike Glycoprotein  

The severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) Spike glycoprotein is solely responsible for binding to the host cell receptor and facilitating fusion between the viral and host membranes. The ability to generate viral particles pseudotyped with SARS-COV-2 Spike is useful for many types of studies, such as characterization of neutralizing antibodies or development of fusion-inhibiting small molecules. Here, we characterized the use of a codon-optimized SARS-COV-2 Spike glycoprotein for the generation of pseudotyped HIV-1, murine leukemia virus (MLV), and vesicular stomatitis virus (VSV) particles. The full-length Spike protein functioned inefficiently with all three systems but was enhanced over 10-fold by deleting the last 19 amino acids of the cytoplasmic tail. Infection of 293FT target cells was possible only if the cells were engineered to stably express the human angiotensin-converting enzyme 2 (ACE2) receptor, but stably introducing an additional copy of this receptor did not further enhance susceptibility. Stable introduction of the Spike-activating protease TMPRSS2 further enhanced susceptibility to infection by 5- to 10-fold. Replacement of the signal peptide of the Spike protein with an optimal signal peptide did not enhance or reduce infectious particle production. However, modifications D614G and R682Q further enhanced infectious particle production. With all enhancing elements combined, the titer of pseudotyped HIV-1 particles reached almost 10(6) infectious particles/ml. Finally, HIV-1 particles pseudotyped with SARS-COV-2 Spike were successfully used to detect neutralizing antibodies in plasma from coronavirus disease 2019 (COVID-19) patients, but not in plasma from uninfected individuals. IMPORTANCE In work with pathogenic viruses, it is useful to have rapid quantitative tests for viral infectivity that can be performed without strict biocontainment restrictions. A common way of accomplishing this is to generate viral pseudoparticles that contain the surface glycoprotein from the pathogenic virus incorporated into a replication-defective viral particle that contains a sensitive reporter system. These pseudoparticles enter cells using the glycoprotein from the pathogenic virus, leading to a readout for infection. Conditions that block entry of the pathogenic virus, such as neutralizing antibodies, will also block entry of the viral pseudoparticles. However, viral glycoproteins often are not readily suited for generating pseudoparticles. Here, we describe a series of modifications that result in the production of relatively high-titer SARS-COV-2 pseudoparticles that are suitable for the detection of neutralizing antibodies from COVID-19 patients.

J Virol2020       LitCov and CORD-19
284Exploring the use and challenges of implementing virtual visits during COVID-19 in primary care and lessons for sustained use  

BACKGROUND: The COVID-19 pandemic has rapidly transformed how healthcare is delivered to limit the transmission of the virus. This descriptive cross-sectional study explored the current use of virtual visits in providing care among primary care providers in southwestern Ontario during the first wave of the COVID-19 pandemic and the anticipated level of utilization post-pandemic. It also explored clinicians’ perceptions of the available support tools and resources and challenges to incorporating virtual visits within primary care practices. METHODS: Primary care physicians and nurse practitioners currently practicing in the southwestern part of Ontario were invited to participate in an online survey. The survey invite was distributed via email, different social media platforms, and newsletters. The survey questions gathered clinicians’ demographic information and assessed their experience with virtual visits, including the proportion of visits conducted virtually (before, during the pandemic, and expected volume post-pandemic), overall satisfaction and comfort level with offering virtual visits using modalities, challenges experienced, as well as useful resources and tools to support them in using virtual visits in their practice. RESULTS: We received 207 responses, with 96.6% of respondents offering virtual visits in their practice. Participants used different modalities to conduct virtual visits, with the vast majority offering visits via phone calls (99.5%). Since the COVID-19 pandemic, clinicians who offered virtual visits have conducted an average of 66.4% of their visits virtually, compared to an average of 6.5% pre-pandemic. Participants anticipated continuing use of virtual visits with an average of 43.9% post-pandemic. Overall, 74.5% of participants were satisfied with their experience using virtual visits, and 88% believed they could incorporate virtual visits well within the usual workflow. Participants highlighted some challenges in offering virtual care. For example, 58% were concerned about patients’ limited access to technology, 55% about patients’ knowledge of technology, and 41% about the lack of integration with their current EMR, the increase in demand over time, and the connectivity issues such as inconsistent Wi-Fi/Internet connection. There were significant differences in perception of some challenges between clinicians in urban vs, rural areas. Clinicians in rural areas were more likely to consider the inconsistent Wi-Fi and limited connectivity as barriers to incorporating virtual visits within the practice setting (58.8% vs. 40.2%, P = 0.030). In comparison, clinicians in urban areas were significantly more concerned about patients overusing virtual care services (39.4% vs. 21.6%, P = 0.024). As for support tools, 47% of clinicians advocated for virtual care standards outlined by their profession’s college. About 32% identified change management support and technical training as supportive tools. Moreover, 39% and 28% thought local colleagues and in-house organizational support are helpful resources, respectively. CONCLUSION: Our study shows that the adoption of virtual visits has exponentially increased during the pandemic, with a significant interest in continuing to use virtual care options in the delivery of primary care post-pandemic. The study sheds light on tools and resources that could enhance operational efficiencies in adopting virtual visits in primary care settings and highlights challenges that, when addressed, can expand the health system capacity and sustained use of virtual care.

PLoS One2021       LitCov and CORD-19
285Direct and Indirect Associations of Media Use With COVID-19 Vaccine Hesitancy in South Korea: Cross-sectional Web-Based Survey  

BACKGROUND: The battle against the 2019 novel coronavirus (COVID-19) has not concluded. Despite the availability of vaccines, the high prevalence of vaccine hesitancy represents a significant challenge to public health, and raising vaccine acceptance among the public is critical. Although media has become an increasingly popular source of COVID-19 vaccine-related information, the question of whether and how media use is related to the public’s vaccine hesitancy warrants exploration. OBJECTIVE: This study aimed to (1) examine the level of COVID-19 vaccine hesitancy, (2) identify factors associated with COVID-19 vaccine hesitancy, and (3) explore the direct and indirect relationship between media use and vaccine hesitancy through psychological factors. METHODS: A month before COVID-19 vaccination was initiated in South Korea, we conducted a cross-sectional web-based survey over 6 days (January 20-25, 2021). This study included 1016 participants, and a logit model for regression analyzed associations between sociodemographic factors, health-related factors, psychological factors, and media use toward one’s COVID-19 vaccine hesitancy. Additionally, we conducted a path analysis to examine the indirect effects of media use on vaccine hesitancy by using psychological factors (ie, perceived risk of COVID-19 infection, perceived benefits, and perceived barriers of COVID-19 vaccination). RESULTS: Among the participants (N=1016), 53.3% (541/1016) hesitated to take the COVID-19 vaccine, while 46.7% (475/1016) agreed to accept the vaccine. Of the sociodemographic factors, female gender (odds ratio [OR] 1.967, 95% CI 1.36-2.86; P<.001), age in 50s (OR 0.47, 95% CI 0.23-0.96; P=.004), and age over 60s (OR 0.49, 95% CI 0.24-0.99; P=.04) were significant individual predictors of COVID-19 vaccine hesitancy. Perceived susceptibility of infection (OR 0.69, 95% CI 0.52-0.91; P=.01) and perceived benefits of vaccination (OR 0.69, 95% CI 0.52-0.91; P=.01) were associated with lower vaccine hesitancy. Perceived barriers of vaccination (OR 1.63, 95% CI 1.29-2.07; P<.001) and lower trust in government (OR 0.72, 95% CI 0.53-0.98; P=.04) were related to vaccine hesitancy. The use of offline and online media as sources for the perceived benefits of vaccination was associated with vaccine hesitancy, resulting in lower vaccine hesitancy. Moreover, perceived susceptibility of the disease and perceived barriers of vaccination mediated the association between social media use and vaccine hesitancy. CONCLUSIONS: Our findings revealed a considerable level of COVID-19 vaccine hesitancy in South Korea. Gender-based and generation-based public health policies and communication are recommended. Efforts to lower the perceived risk of vaccine side effects and heighten perceived benefits of the vaccine are required. Although the use of media has a positive and negative effect on the population’s vaccine hesitancy, efforts should be made to disseminate reliable and timely information on media while confronting misinformation or disinformation for successive implementation of vaccine programs during pandemics.

J Med Internet Res2022       LitCov and CORD-19
286Providing Access To Monoclonal Antibody Treatment Of Coronavirus Patients In Rural And Underserved Areas  


N/A2022       LitCov
287Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates  

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease, coronavirus disease 2019 (Covid-19), have spread to millions of persons worldwide. Multiple vaccine candidates are under development, but no vaccine is currently available. Interim safety and immunogenicity data about the vaccine candidate BNT162b1 in younger adults have been reported previously from trials in Germany and the United States. METHODS: In an ongoing, placebo-controlled, observer-blinded, dose-escalation, phase 1 trial conducted in the United States, we randomly assigned healthy adults 18 to 55 years of age and those 65 to 85 years of age to receive either placebo or one of two lipid nanoparticle–formulated, nucleoside-modified RNA vaccine candidates: BNT162b1, which encodes a secreted trimerized SARS-CoV-2 receptor–binding domain; or BNT162b2, which encodes a membrane-anchored SARS-CoV-2 full-length spike, stabilized in the prefusion conformation. The primary outcome was safety (e.g., local and systemic reactions and adverse events); immunogenicity was a secondary outcome. Trial groups were defined according to vaccine candidate, age of the participants, and vaccine dose level (10 μg, 20 μg, 30 μg, and 100 μg). In all groups but one, participants received two doses, with a 21-day interval between doses; in one group (100 μg of BNT162b1), participants received one dose. RESULTS: A total of 195 participants underwent randomization. In each of 13 groups of 15 participants, 12 participants received vaccine and 3 received placebo. BNT162b2 was associated with a lower incidence and severity of systemic reactions than BNT162b1, particularly in older adults. In both younger and older adults, the two vaccine candidates elicited similar dose-dependent SARS-CoV-2–neutralizing geometric mean titers, which were similar to or higher than the geometric mean titer of a panel of SARS-CoV-2 convalescent serum samples. CONCLUSIONS: The safety and immunogenicity data from this U.S. phase 1 trial of two vaccine candidates in younger and older adults, added to earlier interim safety and immunogenicity data regarding BNT162b1 in younger adults from trials in Germany and the United States, support the selection of BNT162b2 for advancement to a pivotal phase 2–3 safety and efficacy evaluation. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)

N Engl J Med2020       LitCov and CORD-19
288COVID-19 Vaccine Hesitancy Among Chinese Population: A Large-Scale National Study  

Globally, vaccine hesitancy is a growing public health problem. It is detrimental to the consolidation of immunization program achievements and elimination of vaccine-targeted diseases. The objective of this study was to estimate the prevalence of COVID-19 vaccine hesitancy in China and explore its contributing factors. A national cross-sectional online survey among Chinese adults (≥18 years old) was conducted between August 6, 2021 and August 9 via a market research company. We collected sociodemographic information; lifestyle behavior; quality of life; the knowledge, awareness, and behavior of COVID-19; the knowledge, awareness, and behavior of COVID-19 vaccine; willingness of COVID-19 vaccination; accessibility of COVID-19 vaccination services; skepticism about COVID-19 and COVID-19 vaccine; doctor and vaccine developer scale; and so on. Odds ratios (OR) with 95% confidence intervals (CI) were used to estimate the associations by using logistic regression models. A total of 29,925 residents (48.64% men) were enrolled in our study with mean age of 30.99 years. We found an overall prevalence of COVID-19 vaccine hesitancy at 8.40% (95% CI, 8.09–8.72) in primary vaccination and 8.39% (95% CI, 8.07–8.70) in booster vaccination. In addition, after adjusting for potential confounders, we found that women, higher educational level, married residents, higher score of health condition, never smoked, increased washing hands, increased wearing mask, increased social distance, lower level of vaccine conspiracy beliefs, disease risks outweigh vaccine risk, higher level of convenient vaccination, and higher level of trust in doctor and developer were more willing to vaccinate than all others (all p < 0.05). Age, sex, educational level, marital status, chronic disease condition, smoking, healthy behaviors, the curability of COVID-19, the channel of accessing information of COVID-19 vaccine, endorsement of vaccine conspiracy beliefs, weigh risks of vaccination against risks of the disease, making a positive influence on the health of others around you, and lower trust in healthcare system may affect the variation of willingness to take a COVID-19 vaccine (all p < 0.05). The prevalence of COVID-19 vaccine hesitancy was modest in China, even with the slight resulting cascade of changing vaccination rates between the primary and booster vaccination. Urgent action to address vaccine hesitancy is needed in building trust in medical personnel and vaccine producers, promoting the convenience of vaccination services, and spreading reliable information of COVID-19 vaccination via the Internet and other media.

Front Immunol2021       LitCov and CORD-19
289Risk of Myocarditis After Sequential Doses of COVID-19 Vaccine and SARS-CoV-2 Infection by Age and Sex  


Circulation2022       LitCov
290Impact of the COVID-19 Pandemic on Healthcare Utilization in a Large Integrated Healthcare System: Retrospective Cohort Study  

BACKGROUND: The COVID-19 pandemic has caused an abrupt reduction in the use of in-person health care, accompanied by a corresponding surge in the use of telehealth services. However, the extent and nature of changes in health care utilization during the pandemic may differ by care setting. Knowledge of the impact of the pandemic on health care utilization is important to health care organizations and policy makers. OBJECTIVE: The aims of this study are (1) to evaluate changes in in-person health care utilization and telehealth visits during the COVID-19 pandemic and (2) to assess the difference in changes in health care utilization between the pandemic year 2020 and the prepandemic year 2019. METHODS: We retrospectively assembled a cohort consisting of members of a large integrated health care organization, who were enrolled between January 6 and November 2, 2019 (prepandemic year), and between January 5 and October 31, 2020 (pandemic year). The rates of visits were calculated weekly for four settings: inpatient, emergency department (ED), outpatient, and telehealth. Using Poisson models, we assessed the impact of the pandemic on health care utilization during the early days of the pandemic and conducted difference-in-deference (DID) analyses to measure the changes in health care utilization, adjusting for the trend of health care utilization in the prepandemic year. RESULTS: In the early days of the pandemic, we observed significant reductions in inpatient, ED, and outpatient utilization (by 30.2%, 37.0%, and 80.9%, respectively). By contrast, there was a 4-fold increase in telehealth visits between weeks 8 (February 23) and 12 (March 22) in 2020. DID analyses revealed that after adjusting for prepandemic secular trends, the reductions in inpatient, ED, and outpatient visit rates in the early days of the pandemic were 1.6, 8.9, and 367.2 visits per 100 person-years (P<.001), respectively, while the increase in telehealth visits was 272.9 visits per 100 person-years (P<.001). Further analyses suggested that the increase in telehealth visits offset the reduction in outpatient visits by week 26 (June 28, 2020). CONCLUSIONS: In-person health care utilization decreased drastically during the early period of the pandemic, but there was a corresponding increase in telehealth visits during the same period. By end-June 2020, the combined outpatient and telehealth visits had recovered to prepandemic levels.

J Med Internet Res2021       LitCov and CORD-19
291Multidisciplinary research priorities for the COVID-19 pandemic: a call for action for mental health science  

Summary The coronavirus disease 2019 (COVID-19) pandemic is having a profound effect on all aspects of society, including mental health and physical health. We explore the psychological, social, and neuroscientific effects of COVID-19 and set out the immediate priorities and longer-term strategies for mental health science research. These priorities were informed by surveys of the public and an expert panel convened by the UK Academy of Medical Sciences and the mental health research charity, MQ: Transforming Mental Health, in the first weeks of the pandemic in the UK in March, 2020. We urge UK research funding agencies to work with researchers, people with lived experience, and others to establish a high level coordination group to ensure that these research priorities are addressed, and to allow new ones to be identified over time. The need to maintain high-quality research standards is imperative. International collaboration and a global perspective will be beneficial. An immediate priority is collecting high-quality data on the mental health effects of the COVID-19 pandemic across the whole population and vulnerable groups, and on brain function, cognition, and mental health of patients with COVID-19. There is an urgent need for research to address how mental health consequences for vulnerable groups can be mitigated under pandemic conditions, and on the impact of repeated media consumption and health messaging around COVID-19. Discovery, evaluation, and refinement of mechanistically driven interventions to address the psychological, social, and neuroscientific aspects of the pandemic are required. Rising to this challenge will require integration across disciplines and sectors, and should be done together with people with lived experience. New funding will be required to meet these priorities, and it can be efficiently leveraged by the UK's world-leading infrastructure. This Position Paper provides a strategy that may be both adapted for, and integrated with, research efforts in other countries.

Lancet Psychiatry2020       LitCov and CORD-19
292Do psychiatric patients experience more psychiatric symptoms during COVID-19 pandemic and lockdown? A case-control study with service and research implications for immunopsychiatry  

Abstract This study aimed to assess and compare the immediate stress and psychological impact experienced by people with and without psychiatric illnesses during the peak of 2019 coronavirus disease (COVID-19) epidemic with strict lockdown measures. Seventy-six psychiatric patients and 109 healthy control subjects were recruited from Chongqing, China and completed a survey on demographic data, physical symptoms during the past 14 days and a range of psychiatric symptoms using the Impact of Event Scale- Revised (IES-R), Depression, Anxiety and Stress Scale (DASS-21) and Insomnia Severity Index (ISI). IES-R measures PTSD symptoms in survivorship after an event. DASS -21 is based on tripartite model of psychopathology that comprise a general distress construct with distinct characteristics. The mean IES-R, DASS-21 anxiety, depression and stress subscale and ISI scores were higher in psychiatric patients than healthy controls (p<0.001). Serious worries about their physical health, anger and impulsivity and intense suicidal ideation were significantly higher in psychiatric patients than healthy controls (p<0.05). More than one-third of psychiatric patients might fulfil the diagnostic criteria post-traumatic stress disorder (PTSD). More than one-quarter of psychiatric patients suffered from moderately severe to severe insomnia. Respondents who reported no change, poor or worse physical health status and had a psychiatric illness were significantly more likely to have higher mean IES-R, DASS depression, anxiety and stress subscale scores and ISI scores (p<0.05). This study confirms the severity of negative psychological impact on psychiatric patients during the COVID-19 epidemic with strict lockdown measures. Understanding the psychological impact on psychiatric patients during the COVID-19 pandemic has the potential to provide insight into how to develop a new immunopsychiatry service. Further research is required to compare pro-inflammatory cytokines between psychiatric patients and healthy controls during the pandemic.

Brain Behav Immun2020       LitCov and CORD-19
293Quantitative SARS-CoV-2 anti-spike responses to Pfizer-BioNTech and Oxford-AstraZeneca vaccines by previous infection status  

OBJECTIVES: We investigate determinants of SARS-CoV-2 anti-spike IgG responses in healthcare workers (HCWs) following one or two doses of Pfizer-BioNTech or Oxford-AstraZeneca vaccines. METHODS: HCWs participating in regular SARS-CoV-2 PCR and antibody testing were invited for serological testing prior to first and second vaccination, and 4 weeks post-vaccination if receiving a 12-week dosing interval. Quantitative post-vaccination anti-spike antibody responses were measured using the Abbott SARS-CoV-2 IgG II Quant assay (detection threshold: ≥50 AU/ml). We used multivariable logistic regression to identify predictors of seropositivity and generalised additive models to track antibody responses over time. RESULTS: 3570/3610(98.9%) HCWs were seropositive >14 days post-first vaccination and prior to second vaccination, 2706/2720(99.5%) after Pfizer-BioNTech and 864/890(97.1%) following Oxford-AstraZeneca vaccines. Previously infected and younger HCWs were more likely to test seropositive post-first vaccination, with no evidence of differences by sex or ethnicity. All 470 HCWs tested >14 days after second vaccine were seropositive. Quantitative antibody responses were higher after previous infection: median(IQR) >21 days post-first Pfizer-BioNTech 14,604(7644-22,291) AU/ml vs. 1028(564-1985) AU/ml without prior infection (p<0.001). Oxford-AstraZeneca vaccine recipients had lower readings post-first dose compared to Pfizer-BioNTech, with and without previous infection, 10,095(5354-17,096) and 435(203-962) AU/ml respectively (both p<0.001 vs. Pfizer-BioNTech). Antibody responses >21 days post-second Pfizer vaccination in those not previously infected, 10,058 (6408-15,582) AU/ml, were similar to those after prior infection and one vaccine dose. CONCLUSIONS: SARS-CoV-2 vaccination leads to detectable anti-spike antibodies in nearly all adult HCWs. Whether differences in response impact vaccine efficacy needs further study.

Clin Microbiol Infect2021       LitCov and CORD-19
294SPIKE-1: A Randomised Phase II/III trial in a community setting, assessing use of camostat in reducing the clinical progression of COVID-19 by blocking SARS-CoV-2 Spike protein-initiated membrane fusion  

OBJECTIVES: The primary objective is to evaluate the efficacy of camostat to prevent respiratory deterioration in patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Secondary objectives include assessment of the ability of camostat to reduce the requirement for Coronavirus disease 2019 (COVID-19) related hospital admission and to reduce the requirement for supplementary oxygen and ventilation as treatment for SARS-CoV-2 infection, to evaluate overall mortality related to COVID-19 and to evaluate the efficacy of camostat by effect on clinical improvement. Research objectives include to assess change in COVID-19 symptom severity, to evaluate the ability of camostat to reduce viral load throughout duration of illness as well as translational research on host and viral genomics, serum antibody production, COVID-19 diagnostics, and validation of laboratory testing methods and biomarkers. TRIAL DESIGN: SPIKE-1 is a randomised, multicentre, prospective, open label, community-based clinical trial. Eligible patients will be randomised 1:1 to the camostat treatment arm and control arm (best supportive care). The trial is designed to include a pilot phase recruiting up to 50 patients in each arm. An initial review at the end of the pilot phase will allow assessment of available data and inform the requirement for any protocol adaptations to include refinement of eligibility criteria to enrich the patient population and sample size calculations. Up to 289 additional patients will be randomised in the continuation phase of the trial. A formal interim analysis will be performed once 50% of the maximum sample size has been recruited PARTICIPANTS: The trial will recruit adults (≥ 18 years) who score moderate to very high risk according to COVID-age risk calculation, with typical symptoms of COVID-19 infection as per Public Health England guidance or equivalent organisations in the UK, Health Protection Scotland, Public Health Wales, Public Health Agency (Northern Ireland) and with evidence of current COVID-19 infection from a validated assay. The trial is being conducted in the UK and patients are recruited through primary care and hospital settings. INTERVENTION AND COMPARATOR: Eligible patients with be randomised to receive either camostat tablets, 200 mg four times daily (qds) for 14 days (treatment arm) or best supportive care (control arm). MAIN OUTCOMES: Primary outcome measure: the rate of hospital admissions requiring supplemental oxygen. Secondary outcome measures include: the rate of COVID-19 related hospital admission in patients with SARS-CoV-2 infection; the number of supplementary oxygen-free days and ventilator-free days measured at 28 days from randomisation; the rate of mortality related to COVID-19 one year from randomisation; the time to worst point on the nine-point category ordinal scale (recommended by the World Health Organization: Coronavirus disease (COVID-2019)) or deterioration of two points or more, within 28 days from randomisation. Research outcomes include the assessment of change in COVID-19 symptom severity on days 1-14 as measured by (1) time to apyrexia (maintained for 48 hrs) by daily self-assessment of temperature, time to improvement (by two points) in peripheral oxygenation saturation defined by daily self-assessment of fingertip peripheral oxygenation saturation levels, (3) assessment of COVID-19 symptoms using the Flu-iiQ questionnaire (determined by app recording and/or daily video call (or phone) consultation and (4) assessment of functional score (where possible) at screening, day 7 and 14. The ability of camostat to reduce viral load throughout duration of illness will be assessed by (1) change in respiratory (oropharyngeal/nasopharyngeal swab RT-PCR) log10 viral load from baseline to Days 7 and 14, (2) change in respiratory (saliva RT-PCR) log10 viral load from baseline to Days 1-14 and (3) change in upper respiratory viral shedding at Day 1 -14 measured as time to clearance of nasal SARS-CoV-2, defined as 2 consecutive negative swabs by qPCR. Additional translational research outcomes include assessment of host and viral genomics, serum antibody production and COVID-19 diagnostics at baseline and on Days 7 and 14. RANDOMISATION: Eligible patients will be randomised using an interactive web response system (IWRS) in a 1:1 ratio to one of two arms: (1) treatment arm or (2) control arm. BLINDING (MASKING): The trial is open-label. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The trial is designed to include a pilot and a continuation phase. Up to 100 patients (randomised 1:1 treatment and control arm) will be recruited in the pilot phase and a maximum of 289 patients (randomised 1:1 treatment and control) will be recruited as part of the continuation phase. The total number of patients recruited will not exceed 389. TRIAL STATUS: Protocol version number v3 25 September 2020. Trial opened to recruitment on 04 August 2020. The authors anticipate recruitment to be completed by October 2021. TRIAL REGISTRATION: EudraCT 2020-002110-41; 18 June 2020 ClinicalTrials.gov NCT04455815; 02 July 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). Unpublished PK data provided under confidentiality agreement to the trial Sponsor has been removed from the background section of the protocol to allow for publication of the trial protocol. 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/s13063-021-05461-9.

Trials2021       LitCov and CORD-19
295Factors Influencing COVID-19 Vaccination Intentions Among College Students: A Cross-Sectional Study in India  

Background: Students act as messengers in delivering effective messages for better uptake of health-promoting behavior. Understanding their knowledge about coronavirus disease 2019 (COVID-19), intentions to use the COVID-19 vaccine, and its associated factors will help develop promising strategies in vaccine promotion concerning the current COVID-19 pandemic. Methods: A cross-sectional online survey was carried out among students in the healthcare and non-healthcare sectors to assess their intentions to get vaccinated against the COVID-19. A non-probability snowball sampling technique was used to recruit study participants (N = 655) through social media platforms and emails. Study participants were recruited across the country, including six major geographical regions (Eastern, Western, Northern, Southern, North-east, and Central) in India between November 2020 and January 2021 before the introduction of the COVID-19 vaccine. Descriptive statistics were used to present the sociodemographic, and vaccine-related behaviors of the study participants. Key determinants that likely predict vaccine acceptance among students were modeled using logistic regression analysis. For each analysis, p < 0.05 was considered significant. Results: A total of 655 students were recruited, 323 from healthcare and 332 from non-healthcare sectors, to assess their intentions to receive the COVID-19 vaccine. Of the 655 students, 63.8% expressed intentions to receive the COVID-19 vaccine. The acceptance was higher among non-healthcare students (54.07 vs. 45.93%). At the time of the study, 27.8% of the students indicated that they had been exposed to a confirmed COVID-19 patient. A vast majority (93.4%) of the students knew about the COVID-19 virus, and most (89.3%) of them were aware of the development of a COVID-19 vaccine. The history of vaccine hesitancy was found to be low (17.1%). Only one-third (33.4%) of the students showed concern about contracting COVID-19. Trust in the healthcare system [adjusted odds ratio (aOR): 4.13; (95% CI: 2.83–6.04), p < 0.00] and trust in domestic vaccines [aOR: 1.46; (95% CI: 1.02–2.08), p < 0.05] emerged as the significant predictors of student's intention to get vaccinated. Higher acceptance for vaccine was observed among students in the non-healthcare [aOR: 1.982; 95% CI: 1.334–2.946, p < 0.00]. Conclusion: This study shows that the Indian college students had relatively high levels of positive intentions to receive COVID-19 vaccines, although about one-third were not sure or unwilling to receive the vaccine, highlighting possible vaccine hesitancy. Informational campaigns and other strategies to address vaccine hesitancy are needed to promote uptake of COVID-19 vaccines.

Front Public Health2021       LitCov and CORD-19
296Geographic Distribution of Mental Health Problems Among Chinese College Students During the COVID-19 Pandemic: Nationwide, Web-Based Survey Study  

BACKGROUND: Since the COVID-19 outbreak was first reported, considerable attention has been drawn to mental health problems among college students. OBJECTIVE: We aimed to estimate the prevalence of anxiety and depressive symptoms among college students in different geographical areas of China during the early stage of the COVID-19 outbreak. METHODS: A nationwide cross-sectional survey was conducted among Chinese college students of 16 provinces or municipalities from February 4 to 12, 2020. A web-based survey was adopted to collect information from these college students, including demographics, perceived risk of infection, attitudes toward the epidemic and its control, and mental health status. Anxiety symptoms were assessed using the Generalized Anxiety Disorder scale, and depressive symptoms were assessed using the Patient Health Questionnaire. Chi-square test was used to compare the percentage of perceived risk of infection and attitude toward COVID-19 among college students in different geographic locations. Binary logistic models were used to identify associations between geographic locations and mental health problems after controlling for covariates. RESULTS: A total of 11,787 participants were analyzed in this study (response rate: 79.7%). The prevalence of anxiety and depressive symptoms among college students was 17.8% (95% CI 17.1%-18.5%) and 25.9% (95% CI 25.1%-26.7%), respectively. After controlling for covariates, current residence area in Wuhan city was found to have a positive association with anxiety symptoms (odds ratio [OR] 1.37, 95% CI 1.11-1.68) and depressive symptoms (OR 1.32, 95% CI 1.09-1.59). Similarly, college location in Wuhan city was found to have a positive association with anxiety symptoms (OR 1.20, 95% CI 1.07-1.35) and depressive symptoms (OR 1.22, 95% CI 1.10-1.36). History of residence in or travel to Wuhan city in the past month was also positively associated with anxiety symptoms (OR 1.62, 95% CI 1.46-1.80) and depressive symptoms (OR 1.48, 95% CI 1.35-1.63). Furthermore, the perceived risk of COVID-19 was higher among students whose college location and current residence area were in Wuhan city, and it was positively associated with anxiety and depressive symptoms. CONCLUSIONS: During the COVID-19 pandemic, mental health problems among Chinese college students were widespread and geographically diverse. Our study results provide further insight for policymakers to develop targeted intervention strategies.

J Med Internet Res2021       LitCov and CORD-19
297Supporting Parents & Kids Through Lockdown Experiences (SPARKLE): A digital parenting support app implemented in an ongoing general population cohort study during the COVID-19 pandemic: A structured summary of a study protocol for a randomised controlled trial  

OBJECTIVES: The COVID-19 related lockdowns and distancing measures have presented families with unprecedented challenges. A UK-wide cohort study tracking changes in families’ mental health since early lockdown (Co-SPACE) found a significant rise in primary school-aged children’s behaviour problems and associated family-related stress. Three-quarters of parents in Co-SPACE also reported wanting extra support. In SPARKLE, we will examine whether providing Co-SPACE families with a smartphone application delivering information and parenting support, Parent Positive, can reverse the negative effects of the pandemic on children and parents. The efficacy on child and parent outcomes and cost-effectiveness of Parent Positive will be examined. We will also test whether the effects are moderated by pre-existing levels of child conduct problems and usage of Parent Positive. Exploratory analyses will examine whether other baseline characteristics or lockdown circumstances moderate the effects of Parent Positive. TRIAL DESIGN: SPARKLE is a two-arm superiority parallel group randomised controlled trial embedded in an existing large UK-wide self-selected community cohort – Co-SPACE. Those who consent to SPARKLE will be randomised 1:1 to either Parent Positive or Follow-up As Usual (FAU). PARTICIPANTS: Co-SPACE (a UK-wide longitudinal cohort study) parents aged ≥18 who have children aged 4-10 years will be eligible for SPARKLE. INTERVENTION AND COMPARATOR: Parent Positive: is a digital public health intervention that can be delivered rapidly at scale to support parents in managing their children’s behaviour to reduce conduct problems and levels of family conflict, which were exacerbated during the first lockdown, and which may increase further in future months as families need to cope with continuous uncertainty and further disruption to their daily lives. Co-designed with parents and based on decades of parenting research, Parent Positive consists of three elements: (i) Parenting Boosters: where advice, delivered in the form of narrated animations, videos, graphics and text is provided to help parents with eight common parenting challenges; (ii) Parenting Exchange: a facilitated parent-to-parent communication and peer support platform and; (iii) Parent Resources: giving access to carefully selected high-quality, evidence-based online parenting resources. Follow-up as Usual: FAU was selected as a comparator because the public health nature meant that an active comparator was not appropriate due to the pragmatic, rapid implementation of the trial. Individuals randomised to FAU will receive no intervention for the first two months while the data for baseline (T1), T2 and T3 are collected. They will then be given full access to the app until 30th November 2021. MAIN OUTCOMES: Outcome measures will be collected remotely through Qualtrics according to the Co-SPACE schedule at baseline (T1), which will be the Co-SPACE survey data obtained immediately prior to randomisation, and then at one month (T2) and two months (T3) post-randomisation. Measures will be collected to assess group differences in child and parent outcomes, costs and service utilisation, and adverse events. Usage of Parent Positive will also be tracked. The primary outcome is parent-reported child conduct problems at one-month post-randomisation measured using the Strengths and Difficulties Questionnaire conduct problems subscale. RANDOMISATION: Enrolled participants will be allocated to Parent Positive or FAU at the ratio of 1:1 by simple randomisation using the Randomizer function within the Qualtrics programme. Neither blocking nor stratification will be used. BLINDING (MASKING): It is not possible to blind parents enrolled in the study and Qualtrics will automatically inform parents of their group allocation. Blinded members of the research team and the senior statistician will not be given access to the Qualtrics system or the data in order to remain blinded until after the analysis is complete. We do not anticipate any serious harms associated with taking part in the intervention, therefore there will be no need to unblind any blinded staff during the study. The junior statistician will be unblinded throughout. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 616 will be recruited into the trial with 308 consenting parents randomised to each treatment arm. TRIAL STATUS: V1.0; 15.03.2021. Not yet recruiting. Anticipated start date: 1(st) April 2021. Anticipated end date for recruitment: 31(st) July 2021. TRIAL REGISTRATION: Clinicaltrial.gov: NCT04786080. The trial was prospectively registered on 8 March 2021. 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. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-021-05226-4.

Trials2021       LitCov and CORD-19
298Effect of dexamethasone in patients with ARDS and COVID-19-prospective, multi-centre, open-label, parallel-group, randomised controlled trial (REMED trial): A structured summary of a study protocol for a randomised controlled trial  

OBJECTIVES: The primary objective of this study is to test the hypothesis that administration of dexamethasone 20 mg is superior to a 6 mg dose in adult patients with moderate or severe ARDS due to confirmed COVID-19. The secondary objective is to investigate the efficacy and safety of dexamethasone 20 mg versus dexamethasone 6 mg. The exploratory objective of this study is to assess long-term consequences on mortality and quality of life at 180 and 360 days. TRIAL DESIGN: REMED is a prospective, phase II, open-label, randomised controlled trial testing superiority of dexamethasone 20 mg vs 6 mg. The trial aims to be pragmatic, i.e. designed to evaluate the effectiveness of the intervention in conditions that are close to real-life routine clinical practice. PARTICIPANTS: The study is multi-centre and will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic. INCLUSION CRITERIA: Subjects will be eligible for the trial if they meet all of the following criteria: 1. Adult (≥18 years of age) at time of enrolment; 2. Present COVID-19 (infection confirmed by RT-PCR or antigen testing); 3. Intubation/mechanical ventilation or ongoing high-flow nasal cannula (HFNC) oxygen therapy; 4. Moderate or severe ARDS according to Berlin criteria: • Moderate – PaO(2)/FiO(2) 100–200 mmHg; • Severe – PaO(2)/FiO(2) < 100 mmHg; 5. Admission to ICU in the last 24 hours. EXCLUSION CRITERIA: Subjects will not be eligible for the trial if they meet any of the following criteria: 1. Known allergy/hypersensitivity to dexamethasone or excipients of the investigational medicinal product (e.g. parabens, benzyl alcohol); 2. Fulfilled criteria for ARDS for ≥14 days at enrolment; 3. Pregnancy or breastfeeding; 4. Unwillingness to comply with contraception measurements from enrolment until at least 1 week after the last dose of dexamethasone (sexual abstinence is considered an adequate contraception method); 5. End-of-life decision or patient is expected to die within next 24 hours; 6. Decision not to intubate or ceilings of care in place; 7. Immunosuppression and/or immunosuppressive drugs in medical history: a) Systemic immunosuppressive drugs or chemotherapy in the past 30 days; b) Systemic corticosteroid use before hospitalization; c) Any dose of dexamethasone during the present hospital stay for COVID-19 for ≥5 days before enrolment; d) Systemic corticosteroids during present hospital stay for conditions other than COVID-19 (e.g. septic shock); 8. Current haematological or generalized solid malignancy; 9. Any contraindication for corticosteroid administration, e.g. • intractable hyperglycaemia; • active gastrointestinal bleeding; • adrenal gland disorders; • presence of superinfection diagnosed with locally established clinical and laboratory criteria without adequate antimicrobial treatment; 10. Cardiac arrest before ICU admission; 11. Participation in another interventional trial in the last 30 days. INTERVENTION AND COMPARATOR: Dexamethasone solution for injection/infusion is the investigational medicinal product as well as the comparator. The trial will assess two doses, 20 mg (investigational) vs 6 mg (comparator). Patients in the intervention group will receive dexamethasone 20 mg intravenously once daily on day 1–5, followed by dexamethasone 10 mg intravenously once daily on day 6–10. Patients in the control group will receive dexamethasone 6 mg day 1–10. All authorized medicinal products containing dexamethasone in the form of solution for i.v. injection/infusion can be used. MAIN OUTCOMES: Primary endpoint: Number of ventilator-free days (VFDs) at 28 days after randomisation, defined as being alive and free from mechanical ventilation. SECONDARY ENDPOINTS: a) Mortality from any cause at 60 days after randomisation; b) Dynamics of inflammatory marker (C-Reactive Protein, CRP) change from Day 1 to Day 14; c) WHO Clinical Progression Scale at Day 14; d) Adverse events related to corticosteroids (new infections, new thrombotic complications) until Day 28 or hospital discharge; e) Independence at 90 days after randomisation assessed by Barthel Index. The long-term outcomes of this study are to assess long-term consequences on mortality and quality of life at 180 and 360 days through telephone structured interviews using the Barthel Index. RANDOMISATION: Randomisation will be carried out within the electronic case report form (eCRF) by the stratified permuted block randomisation method. Allocation sequences will be prepared by a statistician independent of the study team. Allocation to the treatment arm of an individual patient will not be available to the investigators before completion of the whole randomisation process. The following stratification factors will be applied: • Age <65 and ≥ 65; • Charlson Comorbidity index (CCI) <3 and ≥3; • CRP <150 mg/L and ≥150 mg/L • Trial centre. Patients will be randomised in a 1 : 1 ratio into one of the two treatment arms. Randomisation through the eCRF will be available 24 hours every day. BLINDING (MASKING): This is an open-label trial in which the participants and the study staff will be aware of the allocated intervention. Blinded pre-planned statistical analysis will be performed. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size is calculated to detect the difference of 3 VFDs at 28 days (primary efficacy endpoint) between the two treatment arms with a two-sided type I error of 0.05 and power of 80%. Based on data from a multi-centre randomised controlled trial in COVID-19 ARDS patients in Brazil and a multi-centre observational study from French and Belgian ICUs regarding moderate to severe ARDS related to COVID-19, investigators assumed a standard deviation of VFD at 28 days as 9. Using these assumptions, a total of 142 patients per treatment arm would be needed. After adjustment for a drop-out rate, 150 per treatment arm (300 patients per study) will be enrolled. TRIAL STATUS: This is protocol version 1.1, 15.01.2021. The trial is due to start on 2 February 2021 and recruitment is expected to be completed by December 2021. TRIAL REGISTRATION: The study protocol was registered on EudraCT No.:2020-005887-70, and on December 11, 2020 on ClinicalTrials.gov (Title: Effect of Two Different Doses of Dexamethasone in Patients With ARDS and COVID-19 (REMED)) Identifier: NCT04663555 with a last update posted on February 1, 2021. FULL PROTOCOL: The full protocol (version 1.1) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the standard 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/s13063-021-05116-9.

Trials2021       LitCov and CORD-19
299Omicron and Delta variant of SARS-CoV-2: A comparative computational study of spike protein  


J Med Virol2022       LitCov and CORD-19
300Application of telemedicine video visits in a maternal-fetal medicine practice at the epicenter of the COVID-19 pandemic  

BACKGROUND: Telemedicine in obstetrics has mostly been described in the rural areas that have limited access to subspecialties. During the COVID-19 pandemic, health systems rapidly expanded telemedicine services for urgent and nonurgent healthcare delivery, even in urban settings. The New York University health system implemented a prompt systemwide expansion of video-enabled telemedicine visits, increasing telemedicine to >8000 visits daily within 6 weeks of the beginning of the pandemic. There are limited studies that explore patient and provider satisfaction of telemedicine visits in obstetrical patients during the COVID-19 epidemic, particularly in the United States. OBJECTIVE: This study aimed to evaluate both the patients’ and the providers’ satisfaction with the administration of maternal-fetal medicine services through telemedicine and to identify the factors that drive the patients’ desire for future obstetrical telemedicine services. STUDY DESIGN: A cross-sectional survey was administered to patients who completed a telemedicine video visit with the Division of Maternal-Fetal Medicine at the New York University Langone Hospital—Long Island from March 19, 2020, to May 26, 2020. A 10-question survey assessing the patients’ digital experience and desire for future use was either administered by telephone or self-administered by the patients via a link after obtaining verbal consent. The survey responses were scored from 1—strongly disagree to 5—strongly agree. We analyzed the demographics and survey responses of the patients who agreed to vs those who answered neutral or disagree to the question “I would like telehealth to be an option for future obstetric visits.” The providers also answered a similar 10-question survey. The median scores were compared using appropriate tests. A P value of <.05 was considered significant. RESULTS: A total of 253 patients participated in 433 telemedicine visits, and 165 patients completed the survey, resulting in a 65% survey response rate. Overall, there were high rates of patient satisfaction in all areas assessed. Those who desired future telemedicine had significantly greater agreeability that they were able to see and hear their provider easily (5 [4.5, 5] vs 5 [4, 5]; P=.014) and that the lack of physical activity was not an issue (5 [4, 5] vs 5 [4, 5]; P=.032). They were also more likely to agree that the telemedicine visits were as good as in-person visits (4 [3, 5] vs 3 [2, 3]; P<.001) and that telehealth made it easier for them to see doctors or specialists (5 [4, 5] vs 3 [2, 3]; P<.001). The patients seeking consults for poor obstetrical history were more likely to desire future telemedicine compared with other visit types (19 (90%) vs 2 (10%); P=.05). Provider survey responses also demonstrated high levels of satisfaction, with 83% agreeing that they would like telemedicine to be an option for future obstetrical visits. CONCLUSION: We demonstrated that maternal-fetal medicine obstetrical patients and providers were highly satisfied with the implementation of telemedicine during the initial wave of the COVID-19 pandemic and a majority of them desire telemedicine as an option for future visits. A patient's desire for future telemedicine visits was significantly affected by their digital experience, the perception of a lack of need for physical contact, perceived time saved on travel, and access to healthcare providers. Health systems need to continue to improve healthcare delivery and invest in innovative solutions to conduct physical examinations remotely.

Am J Obstet Gynecol MFM2021       LitCov and CORD-19

(1) COVID-19 Open Research Dataset (CORD-19). 2020. Version 2022-06-02. Retrieved from https://ai2-semanticscholar-cord-19.s3-us-west-2.amazonaws.com/historical_releases.html. Accessed 2022-06-05. doi:10.5281/zenodo.3715506
(2) Chen Q, Allot A, & Lu Z. (2020) Keep up with the latest coronavirus research, Nature 579:193 and Chen Q, Allot A, Lu Z. LitCovid: an open database of COVID-19 literature. Nucleic Acids Research. 2020. (version 2023-01-10)
(3) Currently tweets of June 23rd to June 29th 2022 have been considered.

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