\ 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
TitleVenueYearImpactSource
4401Case Series of Multisystem Inflammatory Syndrome in Adults Associated with SARS-CoV-2 Infection-United Kingdom and United States, March-August 2020  

During the course of the coronavirus disease 2019 (COVID-19) pandemic, reports of a new multisystem inflammatory syndrome in children (MIS-C) have been increasing in Europe and the United States (1-3). Clinical features in children have varied but predominantly include shock, cardiac dysfunction, abdominal pain, and elevated inflammatory markers, including C-reactive protein (CRP), ferritin, D-dimer, and interleukin-6 (1). Since June 2020, several case reports have described a similar syndrome in adults; this review describes in detail nine patients reported to CDC, seven from published case reports, and summarizes the findings in 11 patients described in three case series in peer-reviewed journals (4-6). These 27 patients had cardiovascular, gastrointestinal, dermatologic, and neurologic symptoms without severe respiratory illness and concurrently received positive test results for SARS-CoV-2, the virus that causes COVID-19, by polymerase chain reaction (PCR) or antibody assays indicating recent infection. Reports of these patients highlight the recognition of an illness referred to here as multisystem inflammatory syndrome in adults (MIS-A), the heterogeneity of clinical signs and symptoms, and the role for antibody testing in identifying similar cases among adults. Clinicians and health departments should consider MIS-A in adults with compatible signs and symptoms. These patients might not have positive SARS-CoV-2 PCR or antigen test results, and antibody testing might be needed to confirm previous SARS-CoV-2 infection. Because of the temporal association between MIS-A and SARS-CoV-2 infections, interventions that prevent COVID-19 might prevent MIS-A. Further research is needed to understand the pathogenesis and long-term effects of this newly described condition.

MMWR Morb Mortal Wkly Rep2020       LitCov and CORD-19
4402Plant-produced SARS-CoV-2 receptor binding domain (RBD) variants showed differential binding efficiency with anti-spike specific monoclonal antibodies  

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the ongoing coronavirus disease (COVID-19) pandemic which is characterized by respiratory illness and severe pneumonia, and currently accounts for > 2.5 million deaths worldwide. Recently, diverse mutations in the spike protein of SARS-CoV-2 were reported in United Kingdom (Alpha) and South Africa (Beta) strains which raise concerns over the potential increase in binding affinity towards the host cell receptor and diminished host neutralization capabilities. In order to study the effect of mutation in the binding efficiency of SARS-CoV-2 receptor binding domain (RBD) with anti-SARS-CoV/CoV-2 monoclonal antibodies (mAbs), we have produced SARS-CoV-2 RBD and two variants SARS-CoV-2 RBD (Alpha RBD and Beta RBD) in Nicotiana benthamiana by transient expression. Plant-produced SARS-CoV-2 RBD-Fc, Alpha RBD-Fc and Beta RBD-Fc exhibited specific binding to human angiotensin converting enzyme 2 (ACE2) receptor determined by ELISA. Intriguingly, the binding of plant-produced SARS-CoV-2 RBD proteins to plant-produced mAbs CR3022, B38, and H4 was found to be different depending on the variant mutation. In contrary to the plant-produced SARS-CoV-2 RBD-Fc and Alpha RBD-Fc, Beta RBD-Fc variant showed weak binding affinity towards the mAbs. The result suggested that the Beta RBD variant might have acquired partial resistance to neutralizing antibodies compared to other variants. However, further studies with sera from convalescent or vaccinated individuals are required to confirm this finding.

PLoS One2021       LitCov and CORD-19
4403Predictors of intention to vaccinate against COVID-19: Results of a nationwide survey  

Background Public polling indicates that vaccine uptake will be suboptimal when COVID-19 vaccines become available. Formative research seeking an understanding of weak vaccination intentions is urgently needed. Methods Nationwide online survey of 804 U.S. English-speaking adults. Compensated participants were recruited from the U.S. through an internet survey panel of 2.5 million residents developed by a commercial survey firm. Recruitment was based on quota sampling to produce a U.S. Census-matched sample representative of the nation with regard to region of residence, sex, and age. Results COVID-19 vaccination intentions were weak, with 14.8% of respondents being unlikely to get vaccinated and another 23.0% unsure. Intent to vaccinate was highest for men, older people, individuals who identified as white and non-Hispanic, the affluent and college-educated, Democrats, those who were married or partnered, people with pre-existing medical conditions, and those vaccinated against influenza during the 2019-2020 flu season. In a multiple linear regression, significant predictors of vaccination intent were general vaccine knowledge (β=.311, p <.001), rejection of vaccine conspiracies (β=-.117, p =.003), perceived severity of COVID-19 (β=.273, p <.001), influenza vaccine uptake (β=.178, p <.001), having ≥ 5 pre-existing conditions (β=.098, p =.003), being male (β=.119, p <.001), household income of ≥ $120,000 (β=.110, p =.004), identifying as a Democrat (β=.075, p <.029), and not relying upon social media for virus information (β=-.090, p <002). Intent to vaccinate was lower for Fox News (57.3%) than CNN/MSNBC viewers (76.4%) (χ2(1)=12.68, p <.001). Political party differences in threat appraisals and vaccine conspiracy beliefs are described. Conclusions Demographic characteristics, vaccine knowledge, perceived vulnerability to COVID-19, risk factors for COVID-19, and politics likely contribute to vaccination hesitancy.

Vaccine2021       LitCov and CORD-19
4404Rapid and Accurate Identification of SARS-CoV-2 Variants Using Real Time PCR Assays  

BACKGROUND: Genomic surveillance efforts for SARS-CoV-2 are needed to understand the epidemiology of the COVID-19 pandemic. Viral variants may impact routine diagnostic testing, increase viral transmissibility, cause differences in disease severity, have decreased susceptibility to therapeutics, and/or confer the ability to evade host immunity. While viral whole-genome sequencing (WGS) has played a leading role in surveillance programs, many laboratories lack the expertise and resources for performing WGS. This study describes the performance of multiplexed real-time reverse transcription-PCR (RT-PCR) assays for identification of SARS-CoV-2 variants. METHODS: SARS-CoV-2 specimens were tested for spike-gene variants using a combination of allele-specific primer and allele-specific detection technology (PlexPrime(®) and PlexZyme(®)). Targeted detection of spike gene mutations by RT-PCR was compared to variant detection in positive specimens by WGS, including the recently emerged SARS-CoV-2 Omicron variant. RESULTS: A total of 398 SAR-CoV-2 RT-PCR positive and 39 negative specimens previously tested by WGS were re-tested by RT-PCR genotyping. PCR detection of spike gene mutations N501Y, E484K, and S982A correlated 100% with WGS for the 29 lineages represented, including Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P.1). Incorporating the P681R spike gene mutation also allowed screening for the SARS-CoV-2 Delta variant (B.1.617.2 and AY sublineages). Further sampling of 664 specimens that were screened by WGS between June and August 2021 and then re-tested by RT-PCR showed strong agreement for Delta variant positivity: 34.5% for WGS vs 32.9% for RT-PCR in June; 100% vs 97.8% in August. In a blinded panel of 16 Omicron and 16 Delta specimens, results of RT-PCR were 100% concordant with WGS results. CONCLUSIONS: These data demonstrate that multiplexed real-time RT-PCR genotyping has strong agreement with WGS and may provide additional SARS-CoV-2 variant screening capabilities when WGS is unavailable or cost-prohibitive. RT-PCR genotyping assays may also supplement existing sequencing efforts while providing rapid results at or near the time of diagnosis to help guide patient management.

Front Cell Infect Microbiol2022       LitCov and CORD-19
4405SARS-CoV-2 Infection Among Hospitalized Pregnant Women: Reasons for Admission and Pregnancy Characteristics-Eight US Healthcare Centers, March 1-May 30, 2020  

Pregnant women might be at increased risk for severe coronavirus disease 2019 (COVID-19), possibly related to changes in their immune system and respiratory physiology* (1). Further, adverse birth outcomes, such as preterm delivery and stillbirth, might be more common among pregnant women infected with SARS-CoV-2, the virus that causes COVID-19 (2,3). Information about SARS-CoV-2 infection during pregnancy is rapidly growing; however, data on reasons for hospital admission, pregnancy-specific characteristics, and birth outcomes among pregnant women hospitalized with SARS-CoV-2 infections are limited. During March 1-May 30, 2020, as part of Vaccine Safety Datalink (VSD)† surveillance of COVID-19 hospitalizations, 105 hospitalized pregnant women with SARS-CoV-2 infection were identified, including 62 (59%) hospitalized for obstetric reasons (i.e., labor and delivery or another pregnancy-related indication) and 43 (41%) hospitalized for COVID-19 illness without an obstetric reason. Overall, 50 (81%) of 62 pregnant women with SARS-CoV-2 infection who were admitted for obstetric reasons were asymptomatic. Among 43 pregnant women hospitalized for COVID-19, 13 (30%) required intensive care unit (ICU) admission, six (14%) required mechanical ventilation, and one died from COVID-19. Prepregnancy obesity was more common (44%) among pregnant women hospitalized for COVID-19 than that among asymptomatic pregnant women hospitalized for obstetric reasons (31%). Likewise, the rate of gestational diabetes (26%) among pregnant women hospitalized for COVID-19 was higher than it was among women hospitalized for obstetric reasons (8%). Preterm delivery occurred in 15% of pregnancies among 93 women who delivered, and stillbirths (fetal death at ≥20 weeks' gestation) occurred in 3%. Antenatal counseling emphasizing preventive measures (e.g., use of masks, frequent hand washing, and social distancing) might help prevent COVID-19 among pregnant women,§ especially those with prepregnancy obesity and gestational diabetes, which might reduce adverse pregnancy outcomes.

MMWR Morb Mortal Wkly Rep2020       LitCov and CORD-19
4406Vaccine effectiveness against severe COVID-19 outcomes within the French overseas territories: A cohort study of 2-doses vaccinated individuals matched to unvaccinated ones followed up until September 2021 and based on the National Health Data System  

N/A

PLoS One2022       LitCov
4407Impact of SARS-CoV-2 pandemic among Healthcare workers in a secondary teaching hospital in Spain  

BACKGROUND: The COVID-19 pandemic has posed a huge challenge to healthcare systems and their personnel worldwide. The study of the impact of SARS-CoV-2 infection among healthcare workers (HCW), through prevalence studies, will let us know viral expansion, individuals at most risk and the most exposed areas in healthcare organizations. The aim of this study is to gauge the impact of SARS-CoV-2 pandemic in our hospital workforce and identify groups and areas at increased risk. METHODS AND FINDINGS: This is a cross-sectional and incidence study carried out on healthcare workers based on molecular and serological diagnosis of SARS-CoV-2 infection. Of the 3013 HCW invited to participate, 2439 (80.9%) were recruited, including 674 (22.4%) who had previously consulted at the Occupational Health Service (OHS) for confirmed exposure and/or presenting symptoms suggestive of COVID-19. A total of 411 (16.9%) and 264 (10.8%) healthcare workers were SARS-CoV-2 IgG and rRT-PCR positive, respectively. The cumulative prevalence considering all studies (IgG positive HCW and/or rRT-PCR positive detection) was 485 (19.9%). SARS-CoV-2 IgG-positive patients in whom the virus was not detected were 221 (9.1%); up to 151 of them (68.3%) did not report any compatible symptoms nor consult at the OHS for this reason. Men became more infected than women (25% vs 18.5%, p = 0.0009), including when data were also classified by age. COVID-19 cumulative prevalence among the HCW assigned to medical departments was higher (25.2%) than others, as well as among medical staff (25.4%) compared with other professional categories (p<0.01). CONCLUSIONS: The global impact of the COVID-19 pandemic on HCW of our centre has been 19.9%. Doctors and medical services personnel have had the highest prevalence of SARS-CoV-2 infection, but many of them have not presented compatible symptoms. This emphasizes the performance of continuous surveillance methods of the most exposed health personnel and not only based on the appearance of symptoms.

PLoS One2021       LitCov and CORD-19
4408Autoimmune Hepatitis Following Vaccination for SARS-CoV-2 in Korea: Coincidence or Autoimmunity?  

Autoimmune hepatitis (AIH) is a chronic, autoimmune disease of the liver that occurs when the body’s immune system attacks liver cells, causing the liver to be inflamed. AIH is one of the manifestations of a coronavirus disease 2019 (COVID-19), as well as an adverse event occurring after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Few cases of AIH have been described after vaccination with two messenger RNA (mRNA)-based vaccines—BTN162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)—against SARS-CoV-2. Herein, we report a case of AIH occurring after Pfizer-BioNTech COVID-19 vaccine. A 27-year-old female presented with jaundice and hepatomegaly, appearing 14 days after receiving the second dose of Pfizer-BioNTech vaccine. Her laboratory results showed abnormal liver function with high total immunoglobulin G level. She was diagnosed with AIH with histologic finding and successfully treated with oral prednisolone. We report an AIH case after COVID-19 vaccination in Korea.

J Korean Med Sci2022       LitCov and CORD-19
4409Mental health among head and neck surgeons in Brazil during the COVID-19 pandemic: A national study  

PURPOSE: Head and neck surgeons are among the highest risk for COVID-19 exposure, which also brings great risk to their mental wellbeing. In this study, we aim to evaluate mental health symptoms among head and neck surgeons in Brazil surrounding the time it was declared the epicenter of the virus. MATERIALS AND METHODS: A cross-sectional, survey-based study evaluating burnout, anxiety, distress, and depression among head and neck surgeons in Brazil, assessed through the single-item Mini-Z burnout assessment, 7-item Generalized Anxiety Disorder scale, 22-item Impact of Event Scale-Revised, and 2-item Patient Health Questionnaire, respectively. RESULTS: 163 physicians completed the survey (74.2% males). Anxiety, distress, burnout, and depression symptoms were reported in 74 (45.5%), 43 (26.3%), 24 (14.7%), and 26 (16.0%) physicians, respectively. On multivariable analysis, female physicians were more likely to report a positive screening for burnout compared to males (OR 2.88, CI [1.07–7.74]). Physicians 45 years or older were less likely to experience anxiety symptoms than those younger than 45 years (OR 0.40, CI [0.20–0.81]). Physicians with no self-reported prior psychiatric conditions were less likely to have symptoms of distress compared to those with such history (OR 0.11, CI [0.33–0.38]). CONCLUSION: Head and neck surgeons in Brazil reported symptoms of burnout, anxiety, distress and depression during our study period within the COVID-19 pandemic. Institutions should monitor these symptoms throughout the pandemic. Further study is required to assess the long-term implications for physician wellness.

Am J Otolaryngol2020       LitCov and CORD-19
4410Abnormal immunity of non-survivors with COVID-19: predictors for mortality  

BACKGROUND: The number of coronavirus disease 2019 (COVID-19) cases has rapidly increased all over the world. Specific information about immunity in non-survivors with COVID-19 is scarce. This study aimed to analyse the clinical characteristics and abnormal immunity of the confirmed COVID-19 non-survivors. METHODS: In this single-centered, retrospective, observational study, we enrolled 125 patients with COVID-19 who were died between January 13 and March 4, 2020 in Renmin Hospital of Wuhan University. A total of 414 randomly recruited patients with confirmed COVID-19 who were discharged from the same hospital during the same period served as control. The demographic, clinical characteristics and laboratory findings at admission, and treatment used in these patients were collected. The immunity-related risk factors associated with in-hospital death were tested by logistic regression models and Receiver Operating Characteristic (ROC) curve. RESULTS: Non-survivors (70 years, IQR: 61.5–80) were significantly older than survivors (54 years, IQR: 37–65) (P < 0.001). 56.8% of non-survivors was male. Nearly half of the patients (44.9%) had chronic medical illness. In non-survivors, hypertension (49.6%) was the most common comorbidity, followed by diabetes (20.0%) and coronary heart disease (16.0%). The common signs and symptoms at admission of non-survivors were fever (88%), followed by cough (64.8%), dyspnea (62.4%), fatigue (62.4%) and chest tightness (58.4%). Compared with survivors, non-survivors had higher white blood cell (WBC) count (7.85 vs 5.07 × 10(9)/L), more elevated neutrophil count (6.41 vs 3.08 × 10(9)/L), smaller lymphocyte count (0.69 vs 1.20 × 10(9)/L) and lower platelet count (172 vs 211 × 10(9)/L), raised concentrations of procalcitonin (0.21 vs 0.06 ng/mL) and CRP (70.5 vs 7.2 mg/L) (P < 0.001). This was accompanied with significantly decreased levels of CD3(+) T cells (277 vs 814 cells/μl), CD4(+) T cells (172 vs 473 cells/μl), CD8(+) T cells (84 vs 262.5 cells/μl, P < 0.001), CD19(+) T cells (88 vs 141 cells/μl) and CD16(+) 56(+) T cells (79 vs 128.5 cells/μl) (P < 0.001). The concentrations of immunoglobulins (Ig) G (13.30 vs 11.95 g/L), IgA (2.54 vs 2.21 g/L), and IgE (71.30 vs 42.25 IU/ml) were increased, whereas the levels of complement proteins (C)3 (0.89 vs 0.99 g/L) and C4 (0.22 vs 0.24 g/L) were decreased in non-survivors when compared with survivors (all P < 0.05). The non-survivors presented lower levels of oximetry saturation (90 vs 97%) at rest and lactate (2.40 vs 1.90 mmol/L) (P < 0.001). Old age, comorbidity of malignant tumor, neutrophilia, lymphocytopenia, low CD4(+) T cells, decreased C3, and low oximetry saturation were the risk factors of death in patients with confirmed COVID-19. The frequency of CD4(+) T cells positively correlated with the numbers of lymphocytes (r = 0.787) and the level of oximetry saturation (r = 0.295), Whereas CD4(+) T cells were negatively correlated with age (r =-0.323) and the numbers of neutrophils (r = − 0.244) (all P < 0.001). CONCLUSIONS: Abnormal cellular immunity and humoral immunity were key features of non-survivors with COVID-19. Neutrophilia, lymphocytopenia, low CD4(+) T cells, and decreased C3 were immunity-related risk factors predicting mortality of patients with COVID-19.

Infect Dis Poverty2020       LitCov and CORD-19
4411Parental Perspectives on Immunizations: Impact of the COVID-19 Pandemic on Childhood Vaccine Hesitancy  

Childhood vaccine hesitancy has been studied extensively before the COVID-19 pandemic. The pandemic presented new barriers to pediatric vaccinations. Furthermore, the development of COVID-19 vaccines has complicated factors underlying vaccine hesitancy. We performed a cross-sectional mobile phone-based survey at Children’s Hospital Los Angeles querying parents regarding perspectives on vaccines before and during the pandemic. Our primary aim was to understand the impact of the pandemic on routine childhood vaccine hesitancy. Secondarily, we examined intent to vaccinate, COVID-19 vaccine hesitancy, and key contributing demographic factors. Among 252 participants, we found overall increased childhood vaccine hesitancy (p = 0.006), increased risk perception (p = 0.006), and unchanged vaccine confidence during the COVID-19 pandemic. Increased hesitancy did not translate into decreased intent to vaccinate with routine childhood vaccines or influenza vaccines. During the pandemic, households with higher income (50–99 K, > 100 K) correlated with decreased routine childhood vaccine hesitancy, while Hispanic ethnicity and African American race had increased risk perception. For COVID-19 vaccine hesitancy, households with higher income (> 100 K) correlated with decreased hesitancy, while non-White ethnicity and race had increased risk perception. We found that routine childhood vaccine hesitancy increased during the COVID-19 pandemic, mainly due to increased risk perception. Key contributing demographic factors behind both childhood vaccine hesitancy and COVID-19 vaccine hesitancy included household income and race. Understanding factors behind routine childhood vaccine hesitancy is crucial to maintaining pediatric vaccination rates and promoting vaccine confidence during and after the COVID-19 pandemic.

J Community Health2021       LitCov and CORD-19
4412Vaccination against SARS-CoV-2 in patients with multiple sclerosis  

N/A

Rev Neurol2021       LitCov and CORD-19
4413Liver injury in COVID-19: management and challenges  

Lancet Gastroenterol Hepatol2020       LitCov and CORD-19
4414Characteristics of COVID-19 infection in Beijing  

BACKGROUND: Since the first case of a novel coronavirus (COVID-19) infection pneumonia was detected in Wuhan, China, a series of confirmed cases of the COVID-19 were found in Beijing. We analyzed the data of 262 confirmed cases to determine the clinical and epidemiological characteristics of COVID-19 in Beijing. METHODS: We collected patients who were transferred by Beijing Emergency Medical Service to the designated hospitals. The information on demographic, epidemiological, clinical, laboratory test for the COVID-19 virus, diagnostic classification, cluster case and outcome were obtained. Furthermore we compared the characteristics between severe and common confirmed cases which including mild cases, no-pneumonia cases and asymptomatic cases, and we also compared the features between COVID-19 and 2003 SARS. FINDINGS: By Feb 10, 2020, 262 patients were transferred from the hospitals across Beijing to the designated hospitals for special treatment of the COVID-19 infected by Beijing emergency medical service. Among of 262 patients, 46 (17.6%) were severe cases, 216 (82.4%) were common cases, which including 192 (73.3%) mild cases, 11(4.2%) non-pneumonia cases and 13 (5.0%) asymptomatic cases respectively. The median age of patients was 47.5 years old and 48.5% were male. 192 (73.3%) patients were residents of Beijing, 50 (26.0%) of which had been to Wuhan, 116 (60.4%) had close contact with confirmed cases, 21 (10.9%) had no contact history. The most common symptoms at the onset of illness were fever (82.1%), cough (45.8%), fatigue (26.3%), dyspnea (6.9%) and headache (6.5%). The median incubation period was 6.7 days, the interval time from between illness onset and seeing a doctor was 4.5 days. As of Feb 10, 17.2% patients have discharged and 81.7% patients remain in hospital in our study, the fatality of COVID-19 infection in Beijing was 0.9%. INTERPRETATION: On the basis of this study, we provided the ratio of the COVID-19 infection on the severe cases to the mild, asymptomatic and non-pneumonia cases in Beijing. Population was generally susceptible, and with a relatively low fatality rate. The measures to prevent transmission was very successful at early stage, the next steps on the COVID-19 infection should be focused on early isolation of patients and quarantine for close contacts in families and communities in Beijing. FUNDING: Beijing Municipal Science and Technology Commission and Ministry of Science and Technology.

J Infect2020       LitCov and CORD-19
4415Nursing students' readiness and coping strategies for the Covid-19 pandemic in Turkey  

BACKGROUND: In the COVID-19 pandemic process, nursing students, who are the nurses of the future, have witnessed a different professional experience. PURPOSE: This study was conducted to examine nursing students' readiness and the coping strategies they used during the COVID-19 pandemic process in Turkey. METHODS: This is a descriptive correlational study using descriptive and inferential analysis. 967 nursing students of two public universities completed the online survey. A socio-demographic form and the Coping Strategies used in Crisis Intervention Scale (CSCIS) were used to collect the data. RESULTS: The mean score for crisis coping of the students was 189.53 ± 27.33 (range 48–240). In case of a state of emergency and an acute pandemic, while 44.1% of the students considered their individual resilience sufficient, 33.6% and 34.6% of them considered their ability to solve problems that may arise and their appropriate coping skills against negative effects, respectively, sufficient. The curriculum of undergraduate nursing education was considered sufficient in terms of readiness by 29.7% of the students, crisis intervention by 25.2% of them, and knowledge/skill level by 30.1% of them. CONCLUSIONS: Nursing students can cope with the crisis during the COVID-19 process.

J Prof Nurs2021       LitCov and CORD-19
4416The role and response of primary healthcare services in the delivery of palliative care in epidemics and pandemics: A rapid review to inform practice and service delivery during the COVID-19 pandemic  

BACKGROUND: The increased number of deaths in the community happening as a result of COVID-19 has caused primary healthcare services to change their traditional service delivery in a short timeframe. Services are quickly adapting to new challenges in the practical delivery of end-of-life care to patients in the community including through virtual consultations and in the provision of timely symptom control. AIM: To synthesise existing evidence related to the delivery of palliative and end-of-life care by primary healthcare professionals in epidemics and pandemics. DESIGN: Rapid systematic review using modified systematic review methods, with narrative synthesis of the evidence. DATA SOURCES: Searches were carried out in Medline, Embase, PsychINFO, CINAHL and Web of Science on 7th March 2020. RESULTS: Only five studies met the inclusion criteria, highlighting a striking lack of evidence base for the response of primary healthcare services in palliative care during epidemics and pandemics. All were observational studies. Findings were synthesised using a pandemic response framework according to ‘systems’ (community providers feeling disadvantaged in terms of receiving timely information and protocols), ‘space’ (recognised need for more care in the community), ‘staff’ (training needs and resilience) and ‘stuff’ (other aspects of managing care in pandemics including personal protective equipment, cleaning care settings and access to investigations). CONCLUSIONS: As the COVID-19 pandemic progresses, there is an urgent need for research to provide increased understanding of the role of primary care and community nursing services in palliative care, alongside hospices and community specialist palliative care providers.

Palliat Med2020       LitCov and CORD-19
4417Workplace factors associated with mental health of healthcare workers during the COVID-19 pandemic: an international cross-sectional study  

BACKGROUND: The association of workplace factors on mental health of healthcare workers (HCWs) during the COVID-19 pandemic needs to be urgently established. This will enable governments and policy-makers to make evidence-based decisions. This international study reports the association between workplace factors and the mental health of HCWs during the pandemic. METHODS: An international, cross-sectional study was conducted in 41 countries. The primary outcome was depressive symptoms, derived from the validated Patient Health Questionnaire-2 (PHQ-2). Multivariable logistic regression identified factors associated with mental health outcomes. Inter-country differences were also evaluated. RESULTS: A total of 2527 responses were received, from 41 countries, including China (n = 1213; 48.0%), UK (n = 891; 35.3%), and USA (n = 252; 10.0%). Of all participants, 1343 (57.1%) were aged 26 to 40 years, and 2021 (80.0%) were female; 874 (34.6%) were doctors, and 1367 (54.1%) were nurses. Factors associated with an increased likelihood of depressive symptoms were: working in the UK (OR = 3.63; CI = [2.90–4.54]; p < 0.001) and USA (OR = 4.10; CI = [3.03–5.54]), p < 0.001); being female (OR = 1.74; CI = [1.42–2.13]; p < 0.001); being a nurse (OR = 1.64; CI = [1.34–2.01]; p < 0.001); and caring for a COVID-19 positive patient who subsequently died (OR = 1.20; CI = [1.01–1.43]; p = 0.040). Workplace factors associated with depressive symptoms were: redeployment to Intensive Care Unit (ICU) (OR = 1.67; CI = [1.14–2.46]; p = 0.009); redeployment with perceived unsatisfactory training (OR = 1.67; CI = [1.32–2.11]; p < 0.001); not being issued with appropriate personal protective equipment (PPE) (OR = 2.49; CI = [2.03–3.04]; p < 0.001); perceived poor workplace support within area/specialty (OR = 2.49; CI = [2.03–3.04]; p < 0.001); and perceived poor mental health support (OR = 1.63; CI = [1.38–1.92]; p < 0.001). CONCLUSION: This is the first international study, demonstrating that workplace factors, including PPE availability, staff training pre-redeployment, and provision of mental health support, are significantly associated with mental health during COVID-19. Governments, policy-makers and other stakeholders need to ensure provision of these to safeguard HCWs’ mental health, for future waves and other pandemics. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12913-021-06279-6.

BMC Health Serv Res2021       LitCov and CORD-19
4418Characterization of Serum and Mucosal SARS-CoV-2-Antibodies in HIV-1-Infected Subjects after BNT162b2 mRNA Vaccination or SARS-CoV-2 Infection  

Only limited data are available regarding the immunogenicity of the BNT162b2 mRNA vaccine in HIV-1(+) patients. Therefore, we investigated the humoral immune response after BNT162b2-mRNA vaccination or SARS-CoV-2 infection in HIV-1(+) patients on antiretroviral therapy compared to HIV-1-uninfected subjects. Serum and saliva samples were analysed by SARS-CoV-2 spike-specific IgG and IgA ELISAs and a surrogate neutralization assay. While all subjects developed anti-spike IgG and IgA and neutralizing antibodies in serum after two doses of BNT162b2 mRNA vaccine, the HIV-1(+) subjects displayed significantly lower neutralizing capacity and anti-spike IgA in serum compared to HIV-1-uninfected subjects. Serum levels of anti-spike IgG and neutralizing activity were significantly higher in vaccinees compared to SARS-CoV-2 convalescents irrespective of HIV-1 status. Among SARS-CoV-2 convalescents, there was no significant difference in spike-specific antibody response between HIV-1(+) and uninfected subjects. In saliva, anti-spike IgG and IgA antibodies were detected both in vaccinees and convalescents, albeit at lower frequencies compared to the serum and only rarely with detectable neutralizing activity. In summary, our study demonstrates that the BNT162b2 mRNA vaccine induces SARS-CoV-2-specific antibodies in HIV-1-infected patients on antiretroviral therapy, however, lower vaccine induced neutralization activity indicates a lower functionality of the humoral vaccine response in HIV-1(+) patients.

Viruses2022       LitCov and CORD-19
4419Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion  

The recent outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 infection in Wuhan, China has posed a serious threat to global public health. To develop specific anti-coronavirus therapeutics and prophylactics, the molecular mechanism that underlies viral infection must first be defined. Therefore, we herein established a SARS-CoV-2 spike (S) protein-mediated cell–cell fusion assay and found that SARS-CoV-2 showed a superior plasma membrane fusion capacity compared to that of SARS-CoV. We solved the X-ray crystal structure of six-helical bundle (6-HB) core of the HR1 and HR2 domains in the SARS-CoV-2 S protein S2 subunit, revealing that several mutated amino acid residues in the HR1 domain may be associated with enhanced interactions with the HR2 domain. We previously developed a pan-coronavirus fusion inhibitor, EK1, which targeted the HR1 domain and could inhibit infection by divergent human coronaviruses tested, including SARS-CoV and MERS-CoV. Here we generated a series of lipopeptides derived from EK1 and found that EK1C4 was the most potent fusion inhibitor against SARS-CoV-2 S protein-mediated membrane fusion and pseudovirus infection with IC50s of 1.3 and 15.8 nM, about 241- and 149-fold more potent than the original EK1 peptide, respectively. EK1C4 was also highly effective against membrane fusion and infection of other human coronavirus pseudoviruses tested, including SARS-CoV and MERS-CoV, as well as SARSr-CoVs, and potently inhibited the replication of 5 live human coronaviruses examined, including SARS-CoV-2. Intranasal application of EK1C4 before or after challenge with HCoV-OC43 protected mice from infection, suggesting that EK1C4 could be used for prevention and treatment of infection by the currently circulating SARS-CoV-2 and other emerging SARSr-CoVs.

Cell Res2020       LitCov and CORD-19
4420Knowledge and Information Sources About COVID-19 Among University Students in Jordan: A Cross-Sectional Study  

Background: Coronavirus disease 2019 (COVID-19) has rapidly spread worldwide, and it was officially declared to be a pandemic by the World Health Organization (WHO) on March 11, 2020. Most countries over the entire globe have reported some COVID-19 cases. The current study aimed to assess student knowledge about COVID-19 at different Jordanian universities and determine where they sourced their information. Methods:A cross-sectional study was conducted among 2,083 undergraduate or postgraduate students from different governmental and private universities during the initial stage of the disease in Jordan (March 19–21, 2020) using a validated, structured, self-administered, online questionnaire. The survey was structured to assess their knowledge about viral sources, incubation period, mortality rate, transmission, symptoms and complications as well as the source of information about COVID-19. Results:Overall, 56.5% of the respondents showed good knowledge and almost 40.5% showed moderate knowledge. On the other hand, 3.0% of the participants showed poor knowledge about COVID-19. The average knowledge score of students was 80.1%, which is considered to be within the scale of good knowledge. Both the college of study and educational level significantly (P < 0.05) associated with student knowledge. Students who majored in medical sciences showed the highest mean score of 82.8%, with 69.0% displaying a good knowledge level. Postgraduate students had significantly higher knowledge scores compared to undergraduate students. The majority of students used the internet, social media and mass media as sources of information about COVID-19. Scientific websites and articles were used more commonly by medical and postgraduate students. Conclusions:The COVID-19 pandemic is a major challenge to the health of the world population; therefore, these results assessing students' knowledge provide an important baseline for planning required educational interventions such as contact tracing and self-quarantine. These results may also help public health authorities by engaging communities in implementation of protective health measures, including positive hygienic practices such as hand washing to reduce the risk of COVID-19.

Front Public Health2020       LitCov and CORD-19
4421Rapid Quantitative Point-Of-Care Diagnostic Test for post-COVID-19 Vaccination Antibody Monitoring  

Point-of-care (POC) quantification of antibody responses against SARS-CoV-2 spike protein can enable decentralized monitoring of immune responses after infection or vaccination. We evaluated a novel POC microfluidic cartridge-based device (ViroTrack Sero COVID-19 Total Ab) for quantitative detection of total antibodies against SARS-CoV-2 spike trimeric spike protein compared to standard laboratory chemiluminescence (CLIA)-based tests. Antibody responses of 101 individuals were measured on capillary blood, venous whole blood, plasma, and diluted plasma samples directly on the POC. Results were available within 7 min. As the reference, plasma samples were analyzed on DiaSorin LIAISON XL CLIA analyzer using LIAISON SARS-CoV-2 IgM, LIAISON SARS-CoV-2 S1/S2 IgG, and LIAISON SARS-CoV-2 TrimericS IgG assays. The Spearman rank’s correlation coefficient between ViroTrack Sero COVID-19 Total Ab and LIAISON SARS-CoV-2 S1/S2 IgG and LIAISON SARS-CoV-2 TrimericS IgG assays was found to be 0.83 and 0.89, respectively. ViroTrack Sero COVID-19 Total Ab showed high correlation between the different matrixes. Agreement for determination of samples of >230 binding antibody units (BAU)/mL on POC and CLIA methods is estimated to be around 90%. ViroTrack Sero Covid Total Ab is a rapid and simple-to-use POC test with high sensitivity and correlation of numerical results expressed in BAU/mL compared to those of a commercial CLIA assay. IMPORTANCE Serological testing is an important diagnostic support tool in the fight against COVID-19. So far, serological testing has been performed on either lateral flow assays, which perform only qualitatively and can be difficult for the individual to read, or standard laboratory assays, which are time- and resource-consuming. The purpose of the study was to evaluate the performance of a new POC microfluidic cartridge-based device based on immunomagnetic agglutination assay that can provide an accurate numerical quantification of the total antibodies within only 7 min from a single drop of capillary blood. We demonstrated a high level of correlation between the POC and the two CLIA laboratory-based immunoassays from Diasorin, thus allowing a potentially wider use of quantitative serology tests in the COVID-19 pandemic.

Microbiol Spectr2022       LitCov and CORD-19
4422Direct Activation of Endothelial Cells by SARS-CoV-2 Nucleocapsid Protein Is Blocked by Simvastatin  

Emerging evidence suggests that endothelial activation plays a central role in the pathogenesis of acute respiratory distress syndrome (ARDS) and multiorgan failure in patients with coronavirus disease 2019 (COVID-19). However, the molecular mechanisms underlying endothelial activation in COVID-19 patients remain unclear. In this study, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins that potently activate human endothelial cells were screened to elucidate the molecular mechanisms involved in endothelial activation. It was found that nucleocapsid protein (NP) of SARS-CoV-2 significantly activated human endothelial cells through Toll-like receptor 2 (TLR2)/NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways. Moreover, by screening a natural microbial compound library containing 154 natural compounds, simvastatin was identified as a potent inhibitor of NP-induced endothelial activation. Remarkably, though the protein sequences of N proteins from coronaviruses are highly conserved, only NP from SARS-CoV-2 induced endothelial activation. The NPs from other coronaviruses such as SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), HUB1-CoV, and influenza virus H1N1 did not activate endothelial cells. These findings are consistent with the results from clinical investigations showing broad endotheliitis and organ injury in severe COVID-19 patients. In conclusion, the study provides insights on SARS-CoV-2-induced vasculopathy and coagulopathy and suggests that simvastatin, an FDA-approved lipid-lowering drug, may help prevent the pathogenesis and improve the outcome of COVID-19 patients. IMPORTANCE Coronavirus disease 2019 (COVID-19), caused by the betacoronavirus SARS-CoV-2, is a worldwide challenge for health care systems. The leading cause of mortality in patients with COVID-19 is hypoxic respiratory failure from acute respiratory distress syndrome (ARDS). To date, pulmonary endothelial cells (ECs) have been largely overlooked as a therapeutic target in COVID-19, yet emerging evidence suggests that these cells contribute to the initiation and propagation of ARDS by altering vessel barrier integrity, promoting a procoagulative state, inducing vascular inflammation and mediating inflammatory cell infiltration. Therefore, a better mechanistic understanding of the vasculature is of utmost importance. In this study, we screened the SARS-CoV-2 viral proteins that potently activate human endothelial cells and found that nucleocapsid protein (NP) significantly activated human endothelial cells through TLR2/NF-κB and MAPK signaling pathways. Moreover, by screening a natural microbial compound library containing 154 natural compounds, simvastatin was identified as a potent inhibitor of NP-induced endothelial activation. Our results provide insights on SARS-CoV-2-induced vasculopathy and coagulopathy, and suggests that simvastatin, an FDA-approved lipid-lowering drug, may benefit to prevent the pathogenesis and improve the outcome of COVID-19 patients.

J Virol2021       LitCov and CORD-19
4423Outcomes of the SARS-CoV-2 omicron (B.1.1.529) variant outbreak among vaccinated and unvaccinated patients with cancer in Europe: results from the retrospective, multicentre, OnCovid registry study  

N/A

Lancet Oncol2022       LitCov
4424Use of the variplex™ SARS-CoV-2 RT-LAMP as a rapid molecular assay to complement RT-PCR for COVID-19 diagnosis  

BACKGROUND: Molecular assays based on reverse transcription-loop-mediated isothermal amplification (RT-LAMP) may be useful for rapid diagnosis of the severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) because of the easy performance and the option to bypass RNA extraction. OBJECTIVES: This study was designed to evaluate the clinical performance of the CE-labeled variplexTM real time SARS-CoV-2 RT-LAMP assay in comparison to commercial RT-PCRs. STUDY DESIGN: RNA extracted from pharyngeal swabs was tested by variplex™ RT-LAMP and Corman’s LightMix™ E gene RT-PCR as reference. Samples of respiratory secretions from Coronavirus infection disease (COVID-19) and negative control patients were analyzed by variplex™ without RNA extraction and tested in parallel with the Allplex™ and VIASURE BD MAX RT-PCRs. RESULTS: Using isolated RNA variplex™ RT-LAMP showed a sensitivity of 75% compared to LightMix E gene RT-PCR but contrary to the latter it produced no false-positive results. For the evaluation of samples from respiratory secretions concordance analysis showed only a moderate agreement between the variplex™ RT-LAMP conducted on unprocessed samples and Allplex™ and VIASURE RT-PCRs (Cohen’s κ ranging from 0.52-0.56). Using the approach to define a sample as true-positive when at least two assays gave a positive result the clinical sensitivities were as follows: 76.3% for variplex™, 84.2% for Allplex™ and 68.4% for VIASURE. However, when results of RT-PCR and RT-LAMP were combined diagnostic sensitivity was increased to 92-100%. CONCLUSION: The variplex RT-LAMP may serve as a rapid test to be combined with a RT-PCR assay to increase the diagnostic accuracy in patients with suspected COVID-19 infection.

J Clin Virol2020       LitCov and CORD-19
4425SARS-CoV-2/ACE2 Interaction Suppresses IRAK-M Expression and Promotes Pro-Inflammatory Cytokine Production in Macrophages  

The major cause of death in SARS-CoV-2 infected patients is due to de-regulation of the innate immune system and development of cytokine storm. SARS-CoV-2 infects multiple cell types in the lung, including macrophages, by engagement of its spike (S) protein on angiotensin converting enzyme 2 (ACE2) receptor. ACE2 receptor initiates signals in macrophages that modulate their activation, including production of cytokines and chemokines. IL-1R-associated kinase (IRAK)-M is a central regulator of inflammatory responses regulating the magnitude of TLR responsiveness. Aim of the work was to investigate whether SARS-CoV-2 S protein-initiated signals modulate pro-inflammatory cytokine production in macrophages. For this purpose, we treated PMA-differentiated THP-1 human macrophages with SARS-CoV-2 S protein and measured the induction of inflammatory mediators including IL6, TNFα, IL8, CXCL5, and MIP1a. The results showed that SARS-CoV-2 S protein induced IL6, MIP1a and TNFα mRNA expression, while it had no effect on IL8 and CXCL5 mRNA levels. We further examined whether SARS-CoV-2 S protein altered the responsiveness of macrophages to TLR signals. Treatment of LPS-activated macrophages with SARS-CoV-2 S protein augmented IL6 and MIP1a mRNA, an effect that was evident at the protein level only for IL6. Similarly, treatment of PAM3csk4 stimulated macrophages with SARS-CoV-2 S protein resulted in increased mRNA of IL6, while TNFα and MIP1a were unaffected. The results were confirmed in primary human peripheral monocytic cells (PBMCs) and isolated CD14+ monocytes. Macrophage responsiveness to TLR ligands is regulated by IRAK-M, an inactive IRAK kinase isoform. Indeed, we found that SARS-CoV-2 S protein suppressed IRAK-M mRNA and protein expression both in THP1 macrophages and primary human PBMCs and CD14+ monocytes. Engagement of SARS-CoV-2 S protein with ACE2 results in internalization of ACE2 and suppression of its activity. Activation of ACE2 has been previously shown to induce anti-inflammatory responses in macrophages. Treatment of macrophages with the ACE2 activator DIZE suppressed the pro-inflammatory action of SARS-CoV-2. Our results demonstrated that SARS-CoV-2/ACE2 interaction rendered macrophages hyper-responsive to TLR signals, suppressed IRAK-M and promoted pro-inflammatory cytokine expression. Thus, activation of ACE2 may be a potential anti-inflammatory therapeutic strategy to eliminate the development of cytokine storm observed in COVID-19 patients.

Front Immunol2021       LitCov and CORD-19
4426Association of prior metabolic and bariatric surgery with severity of COVID-19 in patients with obesity  

BACKGROUND: Obesity is a risk factor for poor clinical outcomes in patients with coronavirus disease 2019 (COVID-19). OBJECTIVES: To investigate the relationship between prior metabolic surgery and the severity of COVID-19 in patients with severe obesity. SETTING: Cleveland Clinic Health System in the United States. METHODS: Among 4365 patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between March 8, 2020 and July 22, 2020 in the Cleveland Clinic Health System, 33 patients were identified who had a prior history of metabolic surgery. The surgical patients were propensity matched 1:10 to nonsurgical patients to assemble a cohort of control patients (n = 330) with a body mass index (BMI) ≥ 40 kg/m(2) at the time of SARS-CoV-2 testing. The primary endpoint was the rate of hospital admission. The exploratory endpoints included admission to the intensive care unit (ICU), need for mechanical ventilation and dialysis during index hospitalization, and mortality. After propensity score matching, outcomes were compared in univariate and multivariate regression models. RESULTS: The average BMI of the surgical group was 49.1 ± 8.8 kg/m(2) before metabolic surgery and was down to 37.2 ± 7.1 at the time of SARS-CoV-2 testing, compared with the control group’s BMI of 46.7 ± 6.4 kg/m(2). In the univariate analysis, 6 (18.2%) patients in the metabolic surgery group and 139 (42.1%) patients in the control group were admitted to the hospital (P = .013). In the multivariate analysis, a prior history of metabolic surgery was associated with a lower hospital admission rate compared with control patients with obesity (odds ratio, 0.31; 95% confidence interval, 0.11−0.88; P = .028). While none of the 4 exploratory outcomes occurred in the metabolic surgery group, 43 (13.0%) patients in the control group required ICU admission (P = .021), 22 (6.7%) required mechanical ventilation, 5 (1.5%) required dialysis, and 8 (2.4%) patients died. CONCLUSION: Prior metabolic surgery with subsequent weight loss and improvement of metabolic abnormalities was associated with lower rates of hospital and ICU admission in patients with obesity who became infected with SARS-CoV-2. Confirmation of these findings will require larger studies.

Surg Obes Relat Dis2020       LitCov and CORD-19
4427Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates  

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of COVID-19. The main receptor of SARS-CoV-2, angiotensin I converting enzyme 2 (ACE2), is now undergoing extensive scrutiny to understand the routes of transmission and sensitivity in different species. Here, we utilized a unique dataset of ACE2 sequences from 410 vertebrate species, including 252 mammals, to study the conservation of ACE2 and its potential to be used as a receptor by SARS-CoV-2. We designed a five-category binding score based on the conservation properties of 25 amino acids important for the binding between ACE2 and the SARS-CoV-2 spike protein. Only mammals fell into the medium to very high categories and only catarrhine primates into the very high category, suggesting that they are at high risk for SARS-CoV-2 infection. We employed a protein structural analysis to qualitatively assess whether amino acid changes at variable residues would be likely to disrupt ACE2/SARS-CoV-2 spike protein binding and found the number of predicted unfavorable changes significantly correlated with the binding score. Extending this analysis to human population data, we found only rare (frequency <0.001) variants in 10/25 binding sites. In addition, we found significant signals of selection and accelerated evolution in the ACE2 coding sequence across all mammals, and specific to the bat lineage. Our results, if confirmed by additional experimental data, may lead to the identification of intermediate host species for SARS-CoV-2, guide the selection of animal models of COVID-19, and assist the conservation of animals both in native habitats and in human care.

Proc Natl Acad Sci U S A2020       LitCov and CORD-19
4428Factors of parental COVID-19 vaccine hesitancy: A cross sectional study in Japan  

The eligibility of COVID-19 vaccines has been expanded to children aged 12 and above in several countries including Japan, and there is a plan to further lower the age. This study aimed to assess factors related to parental COVID-19 vaccine hesitancy. A nationwide internet-based cross-sectional study was conducted between May 25 and June 3, 2021 in Japan. The target population was parents of children aged 3–14 years who resided in Japan, and agreed to answer the online questionnaire. Parental COVID-19 vaccine hesitancy (their intention to vaccinate their child) and related factors were analyzed using logistic regression models. Interaction effects of gender of parents and their level of social relationship satisfaction related to parental vaccine hesitancy was tested using log likelihood ratio test (LRT). Social media as the most trusted information source increased parental vaccine hesitancy compared to those who trusted official information (Adjusted Odds Ratio: aOR 2.80, 95% CI 1.53–5.12). Being a mother and low perceived risk of infection also increased parental vaccine hesitancy compared to father (aOR 2.43, 95% CI 1.57–3.74) and those with higher perceived risk of infection (aOR 1.55, 95% CI 1.04–2.32) respectively. People with lower satisfaction to social relationships tended to be more hesitant to vaccinate their child among mothers in contrast to fathers who showed constant intention to vaccinate their child regardless of the level of satisfaction to social relationship (LRT p = 0.021). Our findings suggest that dissemination of targeted information about COVID-19 vaccine by considering means of communication, gender and people who are isolated during measures of social distancing may help to increase parental vaccine acceptance.

PLoS One2021       LitCov and CORD-19
4429Racial and Ethnic Disparities in Postpartum Care in the Greater Boston Area During the COVID-19 Pandemic  

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JAMA Netw Open2022       LitCov
4430Host-Virus Chimeric Events in SARS-CoV-2-Infected Cells Are Infrequent and Artifactual  

N/A

J Virol2021       LitCov and CORD-19
4431Letter to the editor: efficacy of different methods of combination regimen administrations including dexamethasone, intravenous immunoglobulin and interferon-beta to treat critically ill COVID-19 patients: a structured summary of a study protocol for a randomized controlled trial  

OBJECTIVES: There is little information about Coronavirus Disease 2019 (COVID-19) management for critically ill patients. Most of these patients develop acute respiratory distress syndrome (ARDS) due to excessive inflammatory response and the ensuing cytokine storm. Anti-inflammatory drugs including corticosteroids can be used to effectively reduce the effect of this cytokine storm and lung damage. However, corticosteroids can have side effects, so simultaneous administration of immunoglobulin (IV-IG) and interferon-beta can help manage treatment using corticosteroids. Therefore, we designed a trial to test our hypothesis that early administration of dexamethasone in combination with IV-IG and interferon-beta can reduce the effect of the cytokine storm in critically ill patients COVID-19. TRIAL DESIGN: A phase two multi-center randomized controlled trial (RCT) with three parallel arms (1:1:1 ratio). PARTICIPANTS: They will be hospitalized patients with severe COVID-19 who have positive RT-PCR test and have blood oxygen saturation levels (SpO(2)) less than 90% and respiratory rate higher than 24 per minute or have involvement of more than 50% of their lung when viewed using computed tomography (CT)-scan. The age range of patients will be 18-70 years old. Exclusion criteria: the need for intubation; allergy, intolerance, or contraindication to any study drug including dexamethasone, IV-IG, and interferon-beta; pregnancy or lactation; known HIV positive or active hepatitis B or C. The study will be conducted in several hospitals of the Golestan province, Iran. INTERVENTION AND COMPARATOR: The study subjects will be randomly allocated to three treatment arms: two experimental groups (two arms: Intervention 1 and Intervention 2) and one Control Group, which will be matched for age and sex using frequency matching method. Each eligible patient in the control arm will receive the standard treatment for COVID-19 based on WHO guidelines and the Ministry of the Health and Medical Education (MOHME) of Iran. Each patient in the Intervention Group 1 will receive the standard treatment for COVID-19 and dexamethasone, at the first 24 hours’ time of admission. The intervention begins with the administration of dexamethasone based on the SpO(2) levels. If the level of SpO(2) does not improve after 24 hours, IV-IG (400 mg/kg once daily for 5 days) and interferon-beta (7 doses every other day) will be prescribed along with dexamethasone administration. In Intervention Group 2, the administration of dexamethasone will be started within the first 24 hours’ time of admission and will be continued for 48-72 hours and then the SpO(2) level will be checked. Then, if the level of SpO(2) has not improved after that time, IV-IG and interferon-beta will be prescribed as the same dosage as Group 1. If the percentages of the SpO(2) level are between 85 and 90/ 80 and 85/ 75 and 80/ less than 75, the dosages will be 4 mg every 12 hours/ 4 mg every 8 hours/ 8 mg every 12 hours/ 8 mg every 8 hours, respectively. According to the WHO recommendation, all participants will have the best available supportive care with full monitoring. MAIN OUTCOMES: Primary: An increase in the SpO(2) level to reach more than 90% in each case, which will be assessed by the oximeter. Secondary: The duration of hospital stays; intubation status and the percentage of patients who are free of mechanical ventilation; the mortality rates during hospitalization and one month after the admission time. RANDOMISATION: Participants will be allocated into either control or intervention groups with a 1:1:1 allocation ratio using a computer random number generator to generate a table of random numbers for simple randomization. BLINDING (MASKING): The project's principal investigator (PI) is unblinded. However, the PI will not analyse the data and interpret the results. An unblinded researcher (a pharmacist) will cover the drug’s bottles with aluminium foil and prepare them interventions and control drugs in a syringe with a code so that patients are blinded. This person will have no patients contact. The staff and nurses, caring for the patients, will be unblinded for each study group due to the nature of this study. The staff that take outcome measurements will be blinded. The laboratory technicians will also be blinded as well as the statistical team. These study statisticians will have access to coded data and will analyse the data labelled as group X, group Y, and group Z. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The target sample size will be 105 critically ill COVID-19 patients, who will be allocated randomly to the three trial arms with 35 patients in each group. TRIAL STATUS: Recruitment is ongoing. The study began on April 18 2020 and will be completed June 19 2020. This summary describes protocol version 1; April 2 2020. TRIAL REGISTRATION: https://www.irct.ir/. Identifier: IRCT20120225009124N4 version 1; Registration date: April 2 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the 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 full protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.

Trials2020       LitCov and CORD-19
4432Acceptance of a COVID-19 Vaccine in Southeast Asia: A Cross-Sectional Study in Indonesia  

Introduction: Several vaccine candidates are being clinically tested in response to the 2019 coronavirus disease (COVID-19) pandemic. This study was conducted to assess the acceptance of a 50 or 95% effective COVID-19 vaccine, when it becomes available in southeast Asia, among the general population in Indonesia. Methods: A cross-sectional online survey was conducted between March 25 and April 6, 2020. Participants were asked if they would accept a free vaccine which was 95 or 50% effective. Using a logistic regression model, we assessed the associations between sociodemographic characteristics, exposure to COVID-19 information, or perceived risk of infection with acceptance of a hypothetical COVID-19 vaccine. Results: Among 1,359 respondents, 93.3% of respondents (1,268/1,359) would like to be vaccinated for a 95% effective vaccine, but this acceptance decreased to 67.0% (911/1,359) for a vaccine with 50% effectiveness. For a 95% effective vaccine, being a healthcare worker and having a higher perceived risk of COVID-19 infection were associated with higher acceptance, adjusted odds ratio (aOR): 2.01; 95%CI: 1.01, 4.00 and aOR: 2.21; 95%CI: 1.07, 4.59, respectively; compared to civil servants, being retired was associated with less acceptance (aOR: 0.15; 95%CI: 0.04, 0.63). For a 50% effective vaccine, being a healthcare worker was also associated with greater acceptance, aOR: 1.57; 95%CI: 1.12, 2.20. Conclusion: Acceptance of a COVID-19 vaccine was highly influenced by the baseline effectiveness of the vaccine. Preparing the general population to accept a vaccine with relatively low effectiveness may be difficult.

Front Public Health2020       LitCov and CORD-19
4433Stress Perceived by University Health Sciences Students, 1 Year after COVID-19 Pandemic  

Today’s COVID-19 situation can affect university Health Sciences students’ psychological health. This study aimed to analyze the stress caused by the impact of the COVID-19 pandemic on Health Sciences students from the University of Zaragoza (Spain) almost 1 year after the pandemic began. This cross-sectional descriptive study was conducted with a sample of 252 university students who completed a self-administered online questionnaire. It evaluated the impact of perceived stress with a modified scale (PSS-10-C), and assessed anxiety and depression on the Goldberg scale. Students presented stress (13.1%), anxiety (71.4%) and depression (81%). Females (81.7%) and the third-year Occupational Therapy students (p = 0.010) reported perceived stress. Nursing students perceived less stress (OR: 0.148; 95% CI: 0.026 to 0.842). University students developed stress and anxiety due to COVID-19 almost 1 year after the pandemic began. Psychological support measures for these groups should be prioritized.

Int J Environ Res Public Healt2021       LitCov and CORD-19
4434Pregnant women's experiences of social distancing behavioural guidelines during the Covid-19 pandemic 'lockdown' in the UK, a qualitative interview study  

BACKGROUND: Covid-19 triggered the rapid roll-out of mass social distancing behavioural measures for infection control. Pregnant women were categorised as ‘at risk’ requiring extra vigilance with behavioural guidelines. Their understanding and ability to adhere to recommendations was unknown. OBJECTIVES: To complete a behavioural analysis of the determinants of recommended social distancing behaviour in pregnant women, according to the ‘capability, opportunity, motivation and behaviour’ (‘COM-B’) model to inform the development of recommendations/materials to support pregnant women in understanding and adhering to behavioural guidelines. DESIGN: Qualitative interview study with pregnant women in the Bristol area (UK). METHODS: Semi-structured telephone/videoconference interviews were conducted following a topic guide informed by the COM-B model, transcribed verbatim and subjected to framework analysis. Infographic materials were iteratively produced with stakeholder consultation, to support pregnant women. RESULTS: Thirty-one women participated (selected for demographic range). Women reported adhering to social distancing recommendations and intended to continue. COM-B analysis identified gaps in understanding around risk, vulnerability, and the extent of required social distancing, as well as facilitators of social distancing behaviour (e.g. social support, motivation to stay safe, home environment/resources). Additional themes around detrimental mental health effects and changes to maternity healthcare from the social distancing measures were identified. Infographic resources (plus midwife report) addressing women’s key concerns were produced and disseminated. CONCLUSIONS: The COM-B model provided useful details of determinants of pregnant women’s adherence to social distancing behaviours. The confusion of what being ‘at risk’ meant and varying interpretation of what was expected indicates a need for greater clarity around categories and guidance. The loss of maternity care and negative mental health effects of social distancing suggest a growing area of unmet health needs to be addressed in future. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-021-11202-z.

BMC Public Health2021       LitCov and CORD-19
4435Safety and immunogenicity of COVID-19 vaccination in patients with non-alcoholic fatty liver disease (CHESS2101): A multicenter study  

BACKGROUND & AIMS: The development of COVID-19 vaccines has progressed with encouraging safety and efficacy data. Concerns have been raised about SARS-CoV-2 vaccine responses in the large population of patients with non-alcoholic fatty liver disease (NAFLD). The study aimed to explore the safety and immunogenicity of COVID-19 vaccination in NAFLD. METHODS: This multicenter study included patients with NAFLD without a history of SARS-CoV-2 infection. All patients were vaccinated with 2 doses of inactivated vaccine against SARS-CoV-2. The primary safety outcome was the incidence of adverse reactions within 7 days after each injection and overall incidence of adverse reactions within 28 days, and the primary immunogenicity outcome was neutralizing antibody response at least 14 days after the whole-course vaccination. RESULTS: A total of 381 patients with pre-existing NAFLD were included from 11 designated centers in China. The median age was 39.0 years (IQR 33.0–48.0 years) and 179 (47.0%) were male. The median BMI was 26.1 kg/m(2) (IQR 23.8–28.1 kg/m(2)). The number of adverse reactions within 7 days after each injection and adverse reactions within 28 days totaled 95 (24.9%) and 112 (29.4%), respectively. The most common adverse reactions were injection site pain in 70 (18.4%), followed by muscle pain in 21 (5.5%), and headache in 20 (5.2%). All adverse reactions were mild and self-limiting, and no grade 3 adverse reactions were recorded. Notably, neutralizing antibodies against SARS-CoV-2 were detected in 364 (95.5%) patients with NAFLD. The median neutralizing antibody titer was 32 (IQR 8-64), and the neutralizing antibody titers were maintained. CONCLUSIONS: The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in patients with NAFLD. LAY SUMMARY: The development of vaccines against coronavirus disease 2019 (COVID-19) has progressed rapidly, with encouraging safety and efficacy data. This study now shows that the inactivated COVID-19 vaccine appears to be safe with good immunogenicity in the large population of patients with non-alcoholic fatty liver disease.

J Hepatol2021       LitCov and CORD-19
4436SARS-CoV-2 D614G spike mutation increases entry efficiency with enhanced ACE2-binding affinity  

The causative agent of the COVID-19 pandemic, SARS-CoV-2, is steadily mutating during continuous transmission among humans. Such mutations can occur in the spike (S) protein that binds to the ACE2 receptor and is cleaved by TMPRSS2. However, whether S mutations affect SARS-CoV-2 cell entry remains unknown. Here, we show that naturally occurring S mutations can reduce or enhance cell entry via ACE2 and TMPRSS2. A SARS-CoV-2 S-pseudotyped lentivirus exhibits substantially lower entry than that of SARS-CoV S. Among S variants, the D614G mutant shows the highest cell entry, as supported by structural and binding analyses. Nevertheless, the D614G mutation does not affect neutralization by antisera against prototypic viruses. Taken together, we conclude that the D614G mutation increases cell entry by acquiring higher affinity to ACE2 while maintaining neutralization susceptibility. Based on these findings, further worldwide surveillance is required to understand SARS-CoV-2 transmissibility among humans.

Nat Commun2021       LitCov and CORD-19
4437Chinese Public's Attention to the COVID-19 Epidemic on Social Media: Observational Descriptive Study  

BACKGROUND: Since the coronavirus disease (COVID-19) epidemic in China in December 2019, information and discussions about COVID-19 have spread rapidly on the internet and have quickly become the focus of worldwide attention, especially on social media. OBJECTIVE: This study aims to investigate and analyze the public’s attention to events related to COVID-19 in China at the beginning of the COVID-19 epidemic (December 31, 2019, to February 20, 2020) through the Sina Microblog hot search list. METHODS: We collected topics related to the COVID-19 epidemic on the Sina Microblog hot search list from December 31, 2019, to February 20, 2020, and described the trend of public attention on COVID-19 epidemic-related topics. ROST Content Mining System version 6.0 was used to analyze the collected text for word segmentation, word frequency, and sentiment analysis. We further described the hot topic keywords and sentiment trends of public attention. We used VOSviewer to implement a visual cluster analysis of hot keywords and build a social network of public opinion content. RESULTS: The study has four main findings. First, we analyzed the changing trend of the public’s attention to the COVID-19 epidemic, which can be divided into three stages. Second, the hot topic keywords of public attention at each stage were slightly different. Third, the emotional tendency of the public toward the COVID-19 epidemic-related hot topics changed from negative to neutral, with negative emotions weakening and positive emotions increasing as a whole. Fourth, we divided the COVID-19 topics with the most public concern into five categories: the situation of the new cases of COVID-19 and its impact, frontline reporting of the epidemic and the measures of prevention and control, expert interpretation and discussion on the source of infection, medical services on the frontline of the epidemic, and focus on the worldwide epidemic and the search for suspected cases. CONCLUSIONS: Our study found that social media (eg, Sina Microblog) can be used to measure public attention toward public health emergencies. During the epidemic of the novel coronavirus, a large amount of information about the COVID-19 epidemic was disseminated on Sina Microblog and received widespread public attention. We have learned about the hotspots of public concern regarding the COVID-19 epidemic. These findings can help the government and health departments better communicate with the public on health and translate public health needs into practice to create targeted measures to prevent and control the spread of COVID-19.

J Med Internet Res2020       LitCov and CORD-19
4438COVID-19 vaccination intention in the first year of the pandemic: A systematic review  

AIMS AND OBJECTIVES: To synthesise evidence regarding vaccination intention, identify factors contributing to vaccine hesitancy among healthcare professionals and the general populations globally. BACKGROUND: As COVID‐19 vaccine becomes available worldwide, attention is being directed to community vaccine uptake, to achieve population‐wide immunity. A number of factors have been reported to influence vaccine intention. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines, a systematic search of COVID‐19 vaccination intention related literature published on or before 31 December 2020 from seven databases was undertaken. RESULTS: Thirty articles were included in this systematic review. Overall COVID‐19 vaccination intention during the first year of the pandemic ranged from 27.7% to 93.3%. Findings highlighted that socio‐demographic differences, perceptions of risk and susceptibility to COVID‐19 and vaccine attributes influenced vaccination intention. Healthcare professionals particularly, nurses have higher vaccine hesitancy reportedly due to concerns regarding vaccine safety and efficacy and mistrust of health authorities. Negative information about COVID‐19 vaccines in the social media and low confidence in the health system were associated with lower acceptability among the community. Interestingly, cumulative increase in COVID‐19 caseloads of countries over time was not associated with vaccination intention. CONCLUSIONS: The significant variability in vaccine intention rates worldwide would hamper efforts to achieve immunity against COVID‐19. Nurses’ concerns about vaccine safety and efficacy need to be addressed to increase vaccine acceptance and maximise their influence on vaccination decision in the community. As misinformation through social media negatively impacts vaccination uptake, authoritative and reliable information on vaccine attributes, disease risks and vaccination benefits are needed. RELEVANCE TO CLINICAL PRACTICE: Concerns about vaccine safety and efficacy including misinformation are important contributors to vaccine hesitancy. Addressing these factors, particularly among nurses who are considered trusted influencers of vaccination decisions in the community is an important strategy for pandemic preparedness.

J Clin Nurs2021       LitCov and CORD-19
4439Diarrhea During COVID-19 Infection: Pathogenesis, Epidemiology, Prevention and Management  

Abstract Background and aims The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 / COVID-19) pandemic is a worldwide emergency. An increasing number of diarrhea cases is reported. Here we investigate the epidemiology, clinical presentation, molecular mechanisms, management, and prevention of SARS-CoV-2 associated diarrhea. Methods We searched on PubMed, EMBASE, and Web of Science up to March 2020 to identify studies documenting diarrhea and mechansism of intestinal inflammation in patients with confirmed diagnosis of SARS-CoV-2 infection. Results Clinical studies show an incidence rate of diarrhea ranging from 2% to 50% of cases. It may precede or trail respiratory symptoms. A pooled analysis revealed an overall percentage of diarrhea onset of 10.4%. SARS-CoV uses the the angiotensin-converting enzyme 2 (ACE2) and the serine protease TMPRSS2 for S protein priming. ACE2 and TMPRSS2 are not only expressed in lung, but also in the small intestinal epithelia. ACE2 is expressed furthermore in the upper esophagus, liver, and colon. SARS-CoV-2 binding affinity to ACE2 is significantly higher (10-20 times) compared with SARS-CoV. Several reports indicate viral RNA shedding in stool detectable longer time period than in nasopharyngeal swabs. Current treatment is supportive, but several options appear promising and are the subject of investigation. Conclusion Diarrhea is a frequent presenting symptom in patients infected with SARS-CoV-2. Increasing evidence indicates possible fecal oral transmission, indicating the need for a rapid and effective modification of the screening and diagnostic algorithms. The optimal methods to prevent, manage, and treat diarrhea in COVID-19 infected patients are subjects of intensive research.

Clin Gastroenterol Hepatol2020       LitCov and CORD-19
4440Technology, Privacy and User Opinions of COVID-19 Mobile Apps for Contact Tracing: Systematic Search and Content Analysis  

BACKGROUND: Many countries across the globe have released their own COVID-19 contact tracing apps. This has resulted in the proliferation of several apps that used a variety of technologies. With the absence of a standardized approach used by the authorities, policy makers, and developers, many of these apps were unique. Therefore, they varied by function and the underlying technology used for contact tracing and infection reporting. OBJECTIVE: The goal of this study was to analyze most of the COVID-19 contact tracing apps in use today. Beyond investigating the privacy features, design, and implications of these apps, this research examined the underlying technologies used in contact tracing apps. It also attempted to provide some insights into their level of penetration and to gauge their public reception. This research also investigated the data collection, reporting, retention, and destruction procedures used by each of the apps under review. METHODS: This research study evaluated 13 apps corresponding to 10 countries based on the underlying technology used. The inclusion criteria ensured that most COVID-19-declared epicenters (ie, countries) were included in the sample, such as Italy. The evaluated apps also included countries that did relatively well in controlling the outbreak of COVID-19, such as Singapore. Informational and unofficial contact tracing apps were excluded from this study. A total of 30,000 reviews corresponding to the 13 apps were scraped from app store webpages and analyzed. RESULTS: This study identified seven distinct technologies used by COVID-19 tracing apps and 13 distinct apps. The United States was reported to have released the most contact tracing apps, followed by Italy. Bluetooth was the most frequently used underlying technology, employed by seven apps, whereas three apps used GPS. The Norwegian, Singaporean, Georgian, and New Zealand apps were among those that collected the most personal information from users, whereas some apps, such as the Swiss app and the Italian (Immuni) app, did not collect any user information. The observed minimum amount of time implemented for most of the apps with regard to data destruction was 14 days, while the Georgian app retained records for 3 years. No significant battery drainage issue was reported for most of the apps. Interestingly, only about 2% of the reviewers expressed concerns about their privacy across all apps. The number and frequency of technical issues reported on the Apple App Store were significantly more than those reported on Google Play; the highest was with the New Zealand app, with 27% of the reviewers reporting technical difficulties (ie, 10% out of 27% scraped reviews reported that the app did not work). The Norwegian, Swiss, and US (PathCheck) apps had the least reported technical issues, sitting at just below 10%. In terms of usability, many apps, such as those from Singapore, Australia, and Switzerland, did not provide the users with an option to sign out from their apps. CONCLUSIONS: This article highlighted the fact that COVID-19 contact tracing apps are still facing many obstacles toward their widespread and public acceptance. The main challenges are related to the technical, usability, and privacy issues or to the requirements reported by some users.

J Med Internet Res2021       LitCov and CORD-19
4441The relationship of nurses' psychological well-being with their coronaphobia and work-life balance during the COVID-19 pandemic: A cross-sectional study  

AIMS AND OBJECTIVES: This study aimed to determine the relationship of nurses’ psychological well‐being with their coronaphobia and work–life balance during the COVID‐19 pandemic. BACKGROUND: COVID‐19 is a global life‐threatening disease. The COVID‐19 pandemic negatively affects nurses’ mental health. No studies have been conducted to determine the factors that affect nurses’ psychological well‐being during the COVID‐19 pandemic in Turkey. If nurses’ psychological well‐being is impaired during the COVID‐19 pandemic, the quality of nursing care and the nurses’ performance may be negatively affected. DESIGN: This is a descriptive, correlational and cross‐sectional study. The Strengthening the Reporting of Observational studies in Epidemiology (STROBE) reporting guideline checklist for cross‐sectional studies was used for reporting in this study. METHODS: The study population consisted of the nurses working in a Health Application and Research Center in Turkey. Data were collected using Google forms between June–August 2020. The study sample consisted of 295 nurses who voluntarily agreed to participate in the study and used social media tools. The data were collected using a Sociodemographic Characteristics Form, the COVID‐19 Phobia Scale (C19P‐S), the Work–Life Balance (WLB) Scale and the Psychological Well‐Being (PWB) Scale. The factors that affect psychological well‐being were determined using the stepwise multiple linear regression analysis. RESULTS: The nurses’ work–life balance and psychological well‐being were negatively affected during the COVID‐19 pandemic. Their COVID‐19 phobia was mild‐to‐moderate level. The nurses’ psychological well‐being was significantly affected by the variable of neglecting life the most, followed by coronaphobia and work–life balance, which explain 75% of the variance. CONCLUSIONS: This study shows that coronaphobia experienced by nurses and work–life balance was related to their psychological well‐being during the COVID‐19 pandemic. Managers should take measures (regulating the working hours) to decrease nurses’ COVID‐19 phobia (education, counselling or psychotherapy) and work–life imbalance. RELEVANCE TO CLINICAL PRACTICE: Nurses’ peers, managers and organisations need to take into account nurses’ negative emotions and behaviours and organise training programmes to help them overcome their fears, communicate clearly and provide for their basic needs. Organisations, including managers and nurses, must recognise the distress being experienced by their nurses and create safe environments in which to have significant conversations. Nurses’ mental health can be screened regularly by multidisciplinary teams, psychological support can be provided when required, and working hours can be regulated through appropriate shifts and breaks that will ensure work–life balance during and after the COVID‐19 pandemic. Nurses receiving emotional support from their families and friends (via chatting and sharing troubles) can also contribute positively. These measures and regulations will positively affect nurses’ psychological well‐being and contribute to an increase in the quality of care and nurses’ performance.

J Clin Nurs2021       LitCov and CORD-19
4442Evaluating immunity to SARS-CoV-2 in nursing home residents using saliva IgG  

N/A

J Am Geriatr Soc2022       LitCov and CORD-19
4443Virtual Trauma-Focused Therapy for Military Members, Veterans and Public Safety Personnel With Posttraumatic Stress Injury: Systematic Scoping Review  

BACKGROUND: A necessary shift from in-person to remote delivery of psychotherapy (eg, teletherapy, eHealth, videoconferencing) has occurred because of the COVID-19 pandemic. A corollary benefit is a potential fit in terms of the need for equitable and timely access to mental health services in remote and rural locations. Owing to COVID-19, there may be an increase in the demand for timely, virtual delivery of services among trauma-affected populations, including public safety personnel (PSP; eg, paramedics, police, fire, correctional officers), military members, and veterans. There is a lack of evidence on the question of whether digital delivery of trauma-therapies for military members, veterans, and PSP leads to similar outcomes to in-person delivery. Information on barriers and facilitators and recommendations regarding digital-delivery is also scarce. OBJECTIVE: This study aims to evaluate the scope and quality of peer-reviewed literature on psychotherapeutic digital health interventions delivered remotely to military members, veterans, and PSP and synthesize the knowledge of needs, gaps, barriers to, and facilitators for virtual assessment of and virtual interventions for posttraumatic stress injury. METHODS: Relevant studies were identified using MEDLINE (Medical Literature Analysis and Retrieval System Online), EMBASE (Excerpta Medica dataBASE), APA (American Psychological Association) PsycINFO, CINAHL (Cumulative Index of Nursing and Allied Health Literature) Plus with Full Text, and Military & Government Collection. For collation, analysis, summarizing, and reporting of results, we used the CASP (Critical Skills Appraisal Program) qualitative checklist, PEDro (Physiotherapy Evidence Database) scale, level of evidence hierarchy, PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews), and narrative synthesis. RESULTS: A total of 38 studies were included in this review. Evidence for the effectiveness of digital delivery of prolonged exposure therapy, cognitive processing therapy, behavioral activation treatment with therapeutic exposure to military members, veterans, and PSP was rated level 1a, whereas evidence for cognitive behavioral therapy was conflicting. The narrative synthesis indicated that virtual delivery of these therapies can be as effective as in-person delivery but may reduce stigma and cost while increasing access to therapy. Issues of risk, safety, potential harm (ie, suicidality, enabling avoidance), privacy, security, and the match among the therapist, modality, and patient warrant further consideration. There is a lack of studies on the influences of gender, racial, and cultural factors that may result in differential outcomes, preferences, and/or needs. An investigation into other therapies that may be suitable for digital delivery is needed. CONCLUSIONS: Digital delivery of trauma therapies for military members, veterans, and PSP is a critical area for further research. Although promising evidence exists regarding the effectiveness of digital health within these populations, many questions remain, and a cautious approach to more widespread implementation is warranted.

JMIR Mhealth Uhealth2020       LitCov and CORD-19
4444Real-time tracking of self-reported symptoms to predict potential COVID-19  

N/A

Nat Med2020       LitCov and CORD-19
4445SARS-CoV-2 Infection of Rhesus Macaques Treated Early with Human COVID-19 Convalescent Plasma  

Human clinical studies investigating use of convalescent plasma (CP) for treatment of coronavirus disease 2019 (COVID-19) have produced conflicting results. Outcomes in these studies may vary at least partly due to different timing of CP administration relative to symptom onset. The mechanisms of action of CP include neutralizing antibodies but may extend beyond virus neutralization to include normalization of blood clotting and dampening of inflammation. Unresolved questions include the minimum therapeutic titer in the CP units or CP recipient as well as the optimal timing of administration. Here, we show that treatment of macaques with CP within 24 h of infection does not reduce viral shedding in nasal or lung secretions compared to controls and does not detectably improve any clinical endpoint. We also demonstrate that CP administration does not impact viral sequence diversity in vivo, although the selection of a viral sequence variant in both macaques receiving normal human plasma was suggestive of immune pressure. Our results suggest that CP, administered to medium titers, has limited efficacy, even when given very early after infection. Our findings also contribute information important for the continued development of the nonhuman primate model of COVID-19. These results should inform interpretation of clinical studies of CP in addition to providing insights useful for developing other passive immunotherapies and vaccine strategies. IMPORTANCE Antiviral treatment options for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain very limited. One treatment that was explored beginning early in the pandemic (and that is likely to be tested early in future pandemics) is plasma collected from people who have recovered from coronavirus disease 2019 (COVID-19), known as convalescent plasma (CP). We tested if CP reduces viral shedding or disease in a nonhuman primate model. Our results demonstrate that administration of CP 1 day after SARS-CoV-2 infection had no significant impact on viral loads, clinical disease, or sequence diversity, although treatment with normal human plasma resulted in selection of a specific viral variant. Our results demonstrate that passive immunization with CP, even during early infection, provided no significant benefit in a nonhuman primate model of SARS-CoV-2 infection.

Microbiol Spectr2021       LitCov and CORD-19
4446Early postmortem mapping of SARS-CoV-2 RNA in patients with COVID-19 and the correlation with tissue damage  

Clinical observations indicate that COVID-19 is a systemic disease. An investigation of the viral distribution within the human body and its correlation with tissue damage can aid in understanding the pathophysiology of SARS-CoV-2 infection. We present a detailed mapping of the viral RNA in 61 tissues and organs of 11 deceased patients with COVID-19. The autopsies were performed within the early postmortem interval (between 1.5 and 15 hr, mean: 5.6 hr) to minimize the bias due to viral RNA and tissue degradation. Very high viral loads (>10(4)copies/ml) were detected in most patients' lungs, and the presence of intact viral particles in the lung tissue could be verified by transmission electron microscopy. Interestingly, viral RNA was detected throughout various extrapulmonary tissues and organs without visible tissue damage. The dissemination of SARS-CoV-2-RNA throughout the body supports the hypothesis that there is a maladaptive host response with viremia and multiorgan dysfunction.

Elife2021       LitCov and CORD-19
4447Identification of nsp1 gene as the target of SARS-CoV-2 real-time RT-PCR using nanopore whole-genome sequencing  

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has caused the COVID‐19 pandemic. Accurate detection of SARS‐CoV‐2 using molecular assays is critical for patient management and the control of the COVID‐19 pandemic. However, there is an increasing number of SARS‐CoV‐2 viruses with mutations at the primer or probe binding sites, and these mutations may affect the sensitivity of currently available real‐time reverse transcription–polymerase chain reaction (RT‐PCR) assays targeting the N, E, and ORF1a/b genes. Using sequence‐independent single‐primer amplification (SISPA) and nanopore whole‐genome sequencing, we have found that the nsp1 gene, located at the 5’ end of the SARS‐CoV‐2 genome, was highly expressed in the nasopharyngeal or saliva specimens of 9 COVID‐19 patients of different clinical severity. Based on this finding, we have developed a novel nsp1 real‐time RT‐PCR assay. The primers and probes are highly specific for SARS‐CoV‐2. Validation with 101 clinical specimens showed that our nsp1 RT‐PCR assay has a sensitivity of 93.1% (95% confidence interval, 86.2‐97.2%), which was similar to those of N and E gene RT‐PCR assays. The diagnostic specificity was 100% (95% CI, 92.9‐100%). The addition of nsp1 for multi‐target detection of SARS‐CoV‐2 can avoid false negative results due to mutations at the primers/probes binding sites of currently available RT‐PCR assays. This article is protected by copyright. All rights reserved.

J Med Virol2020       LitCov and CORD-19
4448Psychosocial burden in nurses working in nursing homes during the Covid-19 pandemic: a cross-sectional study with quantitative and qualitative data  

N/A

BMC Health Serv Res2022       LitCov
4449Chest Computed Tomography and Clinical Follow-Up of Discharged Patients with COVID-19 in Wenzhou City, Zhejiang, China  

Rationale: Many clinical studies have focused on the epidemiological and clinical characteristics of inpatients with coronavirus disease (COVID-19). However, there are few reports about the clinical follow-up of discharged patients. Objectives: To describe the follow-up of patients with COVID-19 in Wenzhou City, Zhejiang, China. Methods: We retrospectively reviewed 4-week follow-ups in patients with COVID-19, including computed tomographic (CT) chest scanning, blood testing, and oropharyngeal-swab testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ribonucleic acid. The chest CT scans and blood tests were performed on the last day before discharge and 2 weeks and 4 weeks after discharge. The oropharyngeal-swab tests were performed at both 1 week and 2 weeks after discharge. Fifty-one patients with common COVID-19 were enrolled in the study. All the CT and clinical data were collected between January 23 and March 28, 2020. Results: Compared with the abnormalities found on the the last CT scans before discharge, the abnormalities in the lungs at the first and second follow-ups after discharge had been gradually absorbed. The cases with focal ground-glass opacity were reduced from 17.7% to 9.8% of cases. The cases with multiple ground-glass opacities decreased from 80.4% to 23.5%. The cases with consolidation were reduced from 49.0% to 2.0%. The cases with interlobular septal thickening were reduced from 80.4% to 35.3%. The cases with subpleural lines were reduced from 29.4% to 7.8%. The cases with irregular lines were reduced from 41.2% to 15.7%. The lung lesions of 25.5% patients were shown to be fully absorbed on the first CT scans after discharge, and the rate of lung recovery increased to 64.7% after the second follow-up. Nucleic-acid test results became recurrently positive in 17.6% of discharged patients, of whom only 33.3% complained of clinical symptoms. There were no differences in the characteristics of the last CT scans before discharge between the patients with recurrently positive test results and the patients with negative test results. The lung damage was fully absorbed in 55.6% of discharged patients with recurrence of positive test results for SARS-CoV-2 ribonucleic acid. Conclusions: The lung damage due to COVID-19 could be reversible for patients with common COVID-19. A few cases showed recurring positive results of nucleic-acid tests after discharge.

Ann Am Thorac Soc2020       LitCov and CORD-19
4450Isolation and Characterization of Mouse Monoclonal Antibodies That Neutralize SARS-CoV-2 and Its Variants of Concern Alpha, Beta, Gamma and Delta by Binding Conformational Epitopes of Glycosylated RBD With High Potency  

Antibodies targeting Receptor Binding Domain (RBD) of SARS-CoV-2 have been suggested to account for the majority of neutralizing activity in COVID-19 convalescent sera and several neutralizing antibodies (nAbs) have been isolated, characterized and proposed as emergency therapeutics in the form of monoclonal antibodies (mAbs). However, SARS-CoV-2 variants are rapidly spreading worldwide from the sites of initial identification. The variants of concern (VOC) B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma) and B.1.167.2 (Delta) showed mutations in the SARS-CoV-2 spike protein potentially able to cause escape from nAb responses with a consequent reduction of efficacy of vaccines and mAbs-based therapy. We produced the recombinant RBD (rRBD) of SARS-CoV-2 spike glycoprotein from the Wuhan-Hu 1 reference sequence in a mammalian system, for mice immunization to isolate new mAbs with neutralizing activity. Here we describe four mAbs that were able to bind the rRBD in Enzyme-Linked Immunosorbent Assay and the transmembrane full-length spike protein expressed in HEK293T cells by flow cytometry assay. Moreover, the mAbs recognized the RBD in supernatants of SARS-CoV-2 infected VERO E6 cells by Western Blot under non-reducing condition or in supernatants of cells infected with lentivirus pseudotyped for spike protein, by immunoprecipitation assay. Three out of four mAbs lost their binding efficiency to completely N-deglycosylated rRBD and none was able to bind the same recombinant protein expressed in Escherichia coli, suggesting that the epitopes recognized by three mAbs are generated by the conformational structure of the glycosylated native protein. Of particular relevance, three mAbs were able to inhibit Wuhan SARS-CoV-2 infection of VERO E6 cells in a plaque-reduction neutralization test and the Wuhan SARS-CoV-2 as well as the Alpha, Beta, Gamma and Delta VOC in a pseudoviruses-based neutralization test. These mAbs represent important additional tools for diagnosis and therapy of COVID-19 and may contribute to the understanding of the functional structure of SARS-CoV-2 RBD.

Front Immunol2021       LitCov and CORD-19

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

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