\ 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
6301Experience with tocilizumab in severe COVID-19 pneumonia after 80 days of follow-up: A retrospective cohort study  

OBJECTIVES: To describe the clinical characteristics and predictors of major outcomes in patients treated with tocilizumab (TCZ) for severe COVID-19 pneumonia. PATIENTS AND METHODS: Case series of all sequential patients with severe COVID-19 pneumonia treated with TCZ at an Academic Spanish hospital (March 12 - May 2, 2020). Clinical outcomes: death, length of hospital stay. An early clinical response to TCZ (48-72 h after the administration) was assessed by variations in respiratory function markers, Brescia COVID Respiratory Severity Scale (BCRSS), inflammatory parameters, and patients' and physicians' opinion. Associations were tested by multiple logistic regression. RESULTS: From a cohort of 236 patients, 77 patients treated with TCZ were included (median age 62 years (IQR 53.0–72.0), 64.9% were males), 42.9% had Charlson index ≥3; hypertension (41.6%), obesity (34.7%), and diabetes (20.8%). Median follow-up was 83.0 days (78.0–86.5), no patient was readmitted. ICU admission was required for 42 (54.5%), invasive mechanical ventilation in 38 (49.4%) and 10 patients died (12.9% global, 23.8% at ICU admitted). After multivariate adjustment, TCZ response by BCRSS (OR 0.03 (0.01–0.68), p = 0.028), and Charlson index (OR 3.54 (1.20–10.44), p = 0.022) has been identified as independent factors associated with mortality. Median of hospital stay was 16.0 days (11.0–23.0); BCRSS, physician subjective and D-dimer response were associated with shorter hospitalization stay. CONCLUSIONS: In a Mediterranean cohort, use of tocilizumab for severe COVID-19 show 12.9% of mortality. Early TCZ-response by BCRSS and low comorbidity were associated with increased survival. Early TCZ-response was related to shorter median hospital stay.

J Autoimmun2020       LitCov and CORD-19
6302Physical and mental health impacts of COVID-19 on healthcare workers: a scoping review  

BACKGROUND: Coronavirus disease (COVID-19) pandemic has spread to 198 countries, with approximately 2.4 million confirmed cases and 150,000 deaths globally as of April 18. Frontline healthcare workers (HCWs) face a substantially higher risk of infection and death due to excessive COVID-19 exposure. This review aimed at summarizing the evidence of the physical and mental health impacts of COVID-19 pandemic on health-care workers (HCWs). METHODS: We used the Arksey O’Malley framework to conduct a scoping review. A systematic literature search was conducted using two databases: PubMed and Google Scholar. We found 154 studies, and out of which 10 met our criteria. We collected information on the date of publication, first author’s country, the title of the article, study design, study population, intervention and outcome, and key findings, and divided all research articles into two domains: physical and mental health impact. RESULTS: We reviewed a total of 154 articles from PubMed (126) and Google Scholar (28), of which 58 were found to be duplicate articles and were excluded. Of the remaining 96 articles, 82 were excluded after screening for eligibility, and 4 articles did not have available full texts. Ten full-text articles were reviewed and included in this study. Our findings identified the following risk factors for COVID-19-related health impact: working in a high-risk department, diagnosed family member, inadequate hand hygiene, suboptimal hand hygiene before and after contact with patients, improper PPE use, close contact with patients (≥ 12 times/day), long daily contact hours (≥ 15 h), and unprotected exposure. The most common symptoms identified amongst HCWs were fever (85%), cough (70%), and weakness (70%). Prolonged PPE usage led to cutaneous manifestations and skin damage (97%), with the nasal bridge (83%) most commonly affected site. HCWs experienced high levels of depression, anxiety, insomnia, and distress. Female HCWs and nurses were disproportionately affected. CONCLUSION: The frontline healthcare workers are at risk of physical and mental consequences directly as the result of providing care to patients with COVID-19. Even though there are few intervention studies, early data suggest implementation strategies to reduce the chances of infections, shorter shift lengths, and mechanisms for mental health support could reduce the morbidity and mortality amongst HCWs.

Int J Emerg Med2020       LitCov and CORD-19
6303The Impact of Covid-19 on Diabetes Care in Muscat Governorate: A Retrospective Cohort Study in Primary Care  

BACKGROUND: COVID-19 pandemic has led to health service modification and temporary disruption of the routine care provided to patients with diabetes mellitus (DM) in primary care. This was done to minimize outpatient visits, permit physical distancing, and ensure patients’ and healthcare providers safety. There is no evidence that explored or measured the impact of COVID-19 pandemic on diabetes services and patients’ glycemic outcome in Oman. AIM AND OBJECTIVES: To explore the accessibility of DM services in primary care after COVID-19 pandemic announcement, and measure patients’ glycemic outcome. METHODS: Before and after, retrospective cohort study using Al-Shifa healthcare database in primary care. One thousand adult patients with diabetes who attended DM clinic before pandemic announcement in 2019 were randomly selected and followed up until end of 2020. Patients aged ≥18 years and had at least 2 visits in 2019 were included. Access to DM services was identified by number of patients received care, frequency of consultations, mode of consultation, and type of intervention given to patients. Patients’ glycated hemoglobin (HbA1c), and other glycemic parameters after pandemic announcement in 2020 were determined and compared with the same parameters before pandemic in 2019. Association between patients’ HbA1c and mode of consultation was measured using multivariable regression analysis. RESULTS: A total of 937 patients continued to follow and received DM care after pandemic announcement. Median number of consultations was 2 with interquartile range (IQR): 3-2. 57.4% had face-to-face alone, 32.4% had combined face to face and telephone consultation, and 10% had telephone consultation alone. Mean difference in HbA1c (%) before and after pandemic announcement was 0.2 ± 1.4 (95% CI: 0.1 to 0.3), P = .002. With multivariable linear regression, the mean difference in HbA1c was −0.3 (−2.3 to 1.5), P = .734 for telephone consultation alone, −0.5 (−2.4 to 1.4), P = .613 for face-to-face alone, and −0.5 (−2.4 to 1.3), P = .636 for combined consultations, compared to those who did not receive any formal consultation. CONCLUSION: Despite service modification and disruption of comprehensive care in primary care after COVID-19 pandemic announcement, DM services were accessible as majority of patients maintained follow up. There was an overall increase in mean glycated hemoglobin, however, it was a less than 1 unit increase. After adjusting for multivariable, glycated hemoglobin was reduced among those who received consultation including telephone consultation compared to those who did not, however evidence was unconvincing.

J Prim Care Community Health2021       LitCov and CORD-19
6304Structure-based screening of novel lichen compounds against SARS Coronavirus main protease (Mpro) as potentials inhibitors of COVID-19  

ABSTRACT: The outbreak of SARS-CoV-2 and deaths caused by it all over the world have imposed great concern on the scientific community to develop potential drugs to combat Coronavirus disease-19 (COVID-19). In this regard, lichen metabolites may offer a vast reservoir for the discovery of antiviral drug candidates. Therefore, to find novel compounds against COVID-19, we created a library of 412 lichen compounds and subjected to virtual screening against the SARS-CoV-2 Main protease (Mpro). All the ligands were virtually screened, and 27 compounds were found to have high affinity with Mpro. These compounds were assessed for drug-likeness analysis where two compounds were found to fit well for redocking studies. Molecular docking, drug-likeness, X-Score, and toxicity analysis resulting in two lichen compounds, Calycin and Rhizocarpic acid with Mpro-inhibiting activity. These compounds were finally subjected to molecular dynamics simulation to compare the dynamics behavior and stability of the Mpro after ligand binding. The binding energy was calculated by MM-PBSA method to determine the intermolecular protein–ligand interactions. Our results showed that two compounds; Calycin and Rhizocarpic acid had the binding free energy of − 42.42 kJ mol/1 and − 57.85 kJ mol/1 respectively as compared to reference X77 (− 91.78 kJ mol/1). We concluded that Calycin and Rhizocarpic acid show considerable structural and pharmacological properties and they can be used as hit compounds to develop potential antiviral agents against SARS-CoV-2. These lichen compounds may be a suitable candidate for further experimental analysis. GRAPHIC ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11030-020-10118-x) contains supplementary material, which is available to authorized users.

Mol Divers2020       LitCov and CORD-19
6305SARS-CoV-2 Vaccine Willingness among Pregnant and Breastfeeding Women during the First Pandemic Wave: A Cross-Sectional Study in Switzerland  

As pregnant women are at high risk of severe SARS-CoV-2 infection and COVID-19 vaccines are available in Switzerland, this study aimed to assess the willingness of Swiss pregnant and breastfeeding women to become vaccinated. Through a cross-sectional online study conducted after the first pandemic wave, vaccination practices and willingness to become vaccinated against SARS-CoV-2 if a vaccine was available were evaluated through binary, multi-choice, and open-ended questions. Factors associated with vaccine willingness were evaluated through univariable and multivariable analysis. A total of 1551 women responded to questions related to the primary outcome. Only 29.7% (153/515) of pregnant and 38.6% (400/1036) of breastfeeding women were willing to get vaccinated against SARS-CoV-2 if a vaccine had been available during the first wave. Positive predictors associated with SARS-CoV-2 vaccine acceptance were an age older than 40 years, a higher educational level, history of influenza vaccination within the previous year, having an obstetrician as the primary healthcare practitioner, and being in their third trimester of pregnancy. After the first pandemic wave, Switzerland had a low SARS-CoV-2 vaccination acceptance rate, emphasizing the need to identify and reduce barriers for immunization in pregnant and breastfeeding women, particularly among the youngest and those with a lower educational level.

Viruses2021       LitCov and CORD-19
6306US Clinicians' Experiences and Perspectives on Resource Limitation and Patient Care During the COVID-19 Pandemic  

IMPORTANCE: Little is known about how US clinicians have responded to resource limitation during the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE: To describe the perspectives and experiences of clinicians involved in institutional planning for resource limitation and/or patient care during the pandemic. DESIGN, SETTING, AND PARTICIPANTS: This qualitative study used inductive thematic analysis of semistructured interviews conducted in April and May 2020 with a national group of clinicians (eg, intensivists, nephrologists, nurses) involved in institutional planning and/or clinical care during the COVID-19 pandemic across the United States. MAIN OUTCOMES AND MEASURES: Emergent themes describing clinicians’ experience providing care in settings of resource limitation. RESULTS: The 61 participants (mean [SD] age, 46 [11] years; 38 [63%] women) included in this study were practicing in 15 US states and were more heavily sampled from areas with the highest rates of COVID-19 infection at the time of interviews (ie, Seattle, New York City, New Orleans). Most participants were White individuals (39 [65%]), were attending physicians (45 [75%]), and were practicing in large academic centers (≥300 beds, 51 [85%]; academic centers, 46 [77%]). Three overlapping and interrelated themes emerged from qualitative analysis, as follows: (1) planning for crisis capacity, (2) adapting to resource limitation, and (3) multiple unprecedented barriers to care delivery. Clinician leaders worked within their institutions to plan a systematic approach for fair allocation of limited resources in crisis settings so that frontline clinicians would not have to make rationing decisions at the bedside. However, even before a declaration of crisis capacity, clinicians encountered varied and sometimes unanticipated forms of resource limitation that could compromise care, require that they make difficult allocation decisions, and contribute to moral distress. Furthermore, unprecedented challenges to caring for patients during the pandemic, including the need to limit in-person interactions, the rapid pace of change, and the dearth of scientific evidence, added to the challenges of caring for patients and communicating with families. CONCLUSIONS AND RELEVANCE: The findings of this qualitative study highlighted the complexity of providing high-quality care for patients during the COVID-19 pandemic. Expanding the scope of institutional planning to address resource limitation challenges that can arise long before declarations of crisis capacity may help to support frontline clinicians, promote equity, and optimize care as the pandemic evolves.

JAMA Netw Open2020       LitCov and CORD-19
6307Global Initiative for the Diagnosis, Management and Prevention of Chronic Obstructive Lung Disease. The 2020 GOLD Science Committee Report on COVID-19 and Chronic Obstructive Pulmonary Disease  

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised many questions about the management of patients with chronic obstructive pulmonary disease (COPD) and whether modifications of their therapy are required. It has raised questions about recognizing and differentiating coronavirus disease (COVID-19) from COPD given the similarity of the symptoms. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) Science Committee used established methods for literature review to present an overview of the management of patients with COPD during the COVID-19 pandemic. It is unclear whether patients with COPD are at increased risk of becoming infected with SARS-CoV-2. During periods of high community prevalence of COVID-19, spirometry should only be used when it is essential for COPD diagnosis and/or to assess lung function status for interventional procedures or surgery. Patients with COPD should follow basic infection control measures, including social distancing, hand washing, and wearing a mask or face covering. Patients should remain up to date with appropriate vaccinations, particularly annual influenza vaccination. Although data are limited, inhaled corticosteroids, long-acting bronchodilators, roflumilast, or chronic macrolides should continue to be used as indicated for stable COPD management. Systemic steroids and antibiotics should be used in COPD exacerbations according to the usual indications. Differentiating symptoms of COVID-19 infection from chronic underlying symptoms or those of an acute COPD exacerbation may be challenging. If there is suspicion for COVID-19, testing for SARS-CoV-2 should be considered. Patients who developed moderate-to-severe COVID-19, including hospitalization and pneumonia, should be treated with evolving pharmacotherapeutic approaches as appropriate, including remdesivir, dexamethasone, and anticoagulation. Managing acute respiratory failure should include appropriate oxygen supplementation, prone positioning, noninvasive ventilation, and protective lung strategy in patients with COPD and severe acute respiratory distress syndrome. Patients who developed asymptomatic or mild COVID-19 should be followed with the usual COPD protocols. Patients who developed moderate or worse COVID-19 should be monitored more frequently and accurately than the usual patients with COPD, with particular attention to the need for oxygen therapy.

Am J Respir Crit Care Med2021       LitCov and CORD-19
6308Impact of household quarantine on SARS-Cov-2 infection in mainland China: A mean-field modelling approach  

N/A

Math Biosci Eng2020       LitCov and CORD-19
6309Comparing Nasopharyngeal Swab and Early Morning Saliva for the Identification of SARS-CoV-2  

BACKGROUND: The ideal SARs-CoV-2 testing method would be accurate and also be patient-performed to reduce exposure to healthcare workers. The aim of this study was to compare patient-performed testing based on a morning saliva sample with the current standard testing method, healthcare worker-collected sampling via a nasopharyngeal swab (NPS). METHODS: This was a prospective single center study which recruited 217 asymptomatic adult male participants in a COVID-19 quarantine center who had tested positive for SARS-CoV-2 8-10 days prior isolation. Paired NPS and saliva specimens were collected and processed within 5 hours of sample collection. Real time reverse transcriptase polymerase chain reaction (RT-PCR) targeting Envelope (E) and RNA-dependent RNA polymerase (RdRp) genes was performed and the results were compared. RESULTS: Overall, 160 of the 217 (74%) participants tested positive for Covid-19 based on saliva, NPS, or both testing methods. The detection rate for SARS-CoV-2 was higher in saliva compared to NPS testing (93.1%, 149/160 vs 52.5%, 84/160, p<0.001). The concordance between the two tests was 45.6% (virus was detected in both saliva and NPS in 73/160), while 47.5% were discordant (87/160 tested positive for one while negative for the other). The Ct values for E and RdRp genes were significantly lower in saliva specimens compared to NP swab specimens. CONCLUSIONS: Our findings demonstrate that saliva is a better alternative specimen for detection of SARS-CoV-2. Taking into consideration, the simplicity of specimen collection, shortage of PPE and the transmissibility of the virus, saliva could enable self-collection for an accurate SARS-CoV-2 surveillance testing.

Clin Infect Dis2020       LitCov and CORD-19
6310Virtual screening, ADME/T and binding free energy analysis of anti-viral, anti-protease and anti-infectious compounds against NSP10/NSP16 methyltransferase and main protease of SARS CoV-2  

Recently, a pathogen has been identified as a novel coronavirus (SARS-CoV-2) and found to trigger novel pneumonia (COVID-19) in human beings and some other mammals. The uncontrolled release of cytokines is seen from the primary stages of symptoms to last acute respiratory distress syndrome (ARDS). Thus, it is necessary to find out safe and effective drugs against this deadly coronavirus as soon as possible. Here, we downloaded the three-dimensional model of NSP10/NSP16 methyltransferase (PDB-ID: 6w6l) and main protease (PDB-ID: 6lu7) of COVID-19. Using these molecular models, we performed virtual screening with our anti-viral, inti-infectious, and anti-protease compounds, which are attractive therapeutics to prevent infection of the COVID-19. We found that top screened compound binds with protein molecules with good dock score with the help of hydrophobic interactions and hydrogen bonding. We observed that protease complexed with Cyclocytidine hydrochloride (anti-viral and anti-cancer), Trifluridine (anti-viral), Adonitol, and Meropenem (anti-bacterial), and Penciclovir (anti-viral) bound with a good docking score ranging from −6.8 to −5.1 (Kcal/mol). Further, NSP10/NSP16 methyltransferase complexed with Telbivudine, Oxytetracycline dihydrate (anti-viral), Methylgallate (anti-malarial), 2-deoxyglucose and Daphnetin (anti-cancer) from the docking score of −7.0 to −5.7 (Kcal/mol). In conclusion, the selected compounds may be used as a novel therapeutic agent to combat this deadly pandemic disease, SARS-CoV-2 infection, but needs further experimental research. HIGHLIGHTS: NSP10/NSP16 methyltransferase and main protease complex of SARS CoV-2 bind with selected drugs. NSP10/NSP16 methyltransferase and protease interacted with drugs by hydrophobic interactions. Compounds show good DG binging free energy with protein complexes. Ligands were found to follow the Lipinski rule of five.

J Recept Signal Transduct Res2020       LitCov and CORD-19
6311Comparative effectiveness of ChAdOx1 vs BNT162b2 covid-19 vaccines in health and social care workers in England: cohort study using OpenSAFELY  

N/A

BMJ2022       LitCov
6312Virtual adaptation of traditional healthcare quality improvement training in response to COVID-19: a rapid narrative review  

BACKGROUND: Information and communication technology are playing a major role in ensuring continuity of healthcare services during the COVID-19 pandemic. The pandemic has also disrupted healthcare quality improvement (QI) training and education for healthcare professionals and there is a need to rethink the way QI training and education is delivered. The purpose of this rapid evidence review is to quickly, but comprehensively collate studies to identify what works and what does not in delivering QI training and education using distance learning modalities. METHODS: Three healthcare databases were searched along with grey literature sources for studies published between 2015 and 2020. Studies with QI training programmes or courses targeting healthcare professionals and students with at least one component of the programme being delivered online were included. RESULTS: A total of 19 studies were included in the review. Most studies had a mixed methods design and used blended learning methods, combining online and in-person delivery modes. Most of the included studies reported achieving desired outcomes, including improved QI knowledge, skills and attitudes of participants and improved clinical outcomes for patients. Some benefits of online QI training delivery include fewer required resources, reduced need for on-site instructors, increased programme reach, and more control and flexibility over learning time for participants. Some limitations of online delivery modes include limited learning and networking opportunities, functional and technical problems and long lead time for content adaptation and customisation. DISCUSSION: The review highlights that distance learning approaches to QI help in overcoming barriers to traditional QI training. Some important considerations for those looking to adapt traditional programmes to virtual environments include balancing virtual and non-virtual methods, using suitable technological solutions, customising coaching support, and using multiple criteria for programme evaluation. CONCLUSION: Virtual QI and training of healthcare professionals and students is a viable, efficient, and effective alternative to traditional QI education that will play a vital role in building their competence and confidence to improve the healthcare system in post-COVID environment.

Hum Resour Health2020       LitCov and CORD-19
6313Potential effects of vaccinations on the prevention of COVID-19: rationale, clinical evidence, risks and public health considerations  

N/A

Expert Rev Vaccines2020       LitCov and CORD-19
6314Existence of SARS-CoV-2 Entry Molecules in the Oral Cavity  

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and furin, which promote entry of the virus into the host cell, have been identified as determinants of SARS-CoV-2 infection. Dorsal tongue and gingiva, saliva, and tongue coating samples were examined to determine the presence of these molecules in the oral cavity. Immunohistochemical analyses showed that ACE2 was expressed in the stratified squamous epithelium of the dorsal tongue and gingiva. TMPRSS2 was strongly expressed in stratified squamous epithelium in the keratinized surface layer and detected in the saliva and tongue coating samples via Western blot. Furin was localized mainly in the lower layer of stratified squamous epithelium and detected in the saliva but not tongue coating. ACE2, TMPRSS2, and furin mRNA expression was observed in taste bud-derived cultured cells, which was similar to the immunofluorescence observations. These data showed that essential molecules for SARS-CoV-2 infection were abundant in the oral cavity. However, the database analysis showed that saliva also contains many protease inhibitors. Therefore, although the oral cavity may be the entry route for SARS-CoV-2, other factors including protease inhibitors in the saliva that inhibit viral entry should be considered.

Int J Mol Sci2020       LitCov and CORD-19
6315Prognostic factors for severity and mortality in patients infected with COVID-19: A systematic review  

BACKGROUND AND PURPOSE: The objective of our systematic review is to identify prognostic factors that may be used in decision-making related to the care of patients infected with COVID-19. DATA SOURCES: We conducted highly sensitive searches in PubMed/MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL) and Embase. The searches covered the period from the inception date of each database until April 28, 2020. No study design, publication status or language restriction were applied. STUDY SELECTION AND DATA EXTRACTION: We included studies that assessed patients with confirmed or suspected SARS-CoV-2 infectious disease and examined one or more prognostic factors for mortality or disease severity. Reviewers working in pairs independently screened studies for eligibility, extracted data and assessed the risk of bias. We performed meta-analyses and used GRADE to assess the certainty of the evidence for each prognostic factor and outcome. RESULTS: We included 207 studies and found high or moderate certainty that the following 49 variables provide valuable prognostic information on mortality and/or severe disease in patients with COVID-19 infectious disease: Demographic factors (age, male sex, smoking), patient history factors (comorbidities, cerebrovascular disease, chronic obstructive pulmonary disease, chronic kidney disease, cardiovascular disease, cardiac arrhythmia, arterial hypertension, diabetes, dementia, cancer and dyslipidemia), physical examination factors (respiratory failure, low blood pressure, hypoxemia, tachycardia, dyspnea, anorexia, tachypnea, haemoptysis, abdominal pain, fatigue, fever and myalgia or arthralgia), laboratory factors (high blood procalcitonin, myocardial injury markers, high blood White Blood Cell count (WBC), high blood lactate, low blood platelet count, plasma creatinine increase, high blood D-dimer, high blood lactate dehydrogenase (LDH), high blood C-reactive protein (CRP), decrease in lymphocyte count, high blood aspartate aminotransferase (AST), decrease in blood albumin, high blood interleukin-6 (IL-6), high blood neutrophil count, high blood B-type natriuretic peptide (BNP), high blood urea nitrogen (BUN), high blood creatine kinase (CK), high blood bilirubin and high erythrocyte sedimentation rate (ESR)), radiological factors (consolidative infiltrate and pleural effusion) and high SOFA score (sequential organ failure assessment score). CONCLUSION: Identified prognostic factors can help clinicians and policy makers in tailoring management strategies for patients with COVID-19 infectious disease while researchers can utilise our findings to develop multivariable prognostic models that could eventually facilitate decision-making and improve patient important outcomes. SYSTEMATIC REVIEW REGISTRATION: Prospero registration number: CRD42020178802. Protocol available at: https://www.medrxiv.org/content/10.1101/2020.04.08.20056598v1.

PLoS One2020       LitCov and CORD-19
6316The Prevalence of Olfactory and Gustatory Dysfunction in COVID-19 Patients: A Systematic Review and Meta-analysis  

N/A

Otolaryngol Head Neck Surg2020       LitCov and CORD-19
6317Is remote near-peer anatomy teaching an effective teaching strategy? Lessons learned from the transition to online learning during the Covid-19 pandemic  

In response to the Covid‐19 pandemic, medical educators have transformed pre‐clerkship anatomy curricula into online formats. The purpose of this study was to evaluate the effectiveness and student perceptions of an online near‐peer anatomy curriculum. The classes of 2022 and 2023 completed identical foundational anatomy curricula in‐person, whereas the class of 2024 completed an adapted curriculum for remote online learning. Quantitative and qualitative responses were used to compare attitudes between instructional methods. Assessment scores and evaluation survey responses were collected from the classes of 2022 (n = 185), 2023 (n = 184), and 2024 (n = 183). Mean assessment scores (±SD) for the classes of 2022, 2023, and 2024 were 93.64% (±5.86), 93.75% (±4.09), and 92.04% (±4.83), respectively. Post hoc group comparisons showed the class of 2024 scored significantly lower than the two previous classes [2022: (H(1) = 18.58, P < 0.001), 2023: (H(1) = 18.65, P < 0.001)]. Mean survey results concerning curriculum quality were 4.06/5.00 for the class of 2023 and 3.57/5.0 for the class of 2024 (t(365) = 2.67, P = 0.008). Considering a small effect size (η (2) = 0.034), there was no meaningful difference in student assessment scores. A potential drawback of online near‐peer anatomy teaching remains in student perceptions of course quality; qualitative feedback suggested technological limitations and perceptions of online course instructors were partly responsible for lower student satisfaction. Following the Covid‐19 pandemic, medical educators should incorporate the lessons learned from this unique educational inflection point to improve curricula moving forward.

Anat Sci Educ2021       LitCov and CORD-19
6318Intranasal ChAdOx1 nCoV-19/AZD1222 vaccination reduces viral shedding after SARS-CoV-2 D614G challenge in preclinical models  

N/A

Sci Transl Med2021       LitCov and CORD-19
6319Burnout syndrome among healthcare workers during COVID-19 Pandemic in Accra, Ghana  

N/A

PLoS One2022       LitCov
6320Establishing clinical pharmacist telehealth services during the COVID-19 pandemic  

DISCLAIMER: In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: After community transmission of the novel virus that causes coronavirus disease 2019 (COVID-19) was detected in the State of Washington in February 2020, innovative measures, such as telehealth appointments, were needed to safely continue to provide optimal pharmaceutical care for patients with chronic conditions and cancer. SUMMARY: Prior to the COVID-19 pandemic, federal regulations limited the scope of telehealth pharmacist services. However, enactment of the Coronavirus Preparedness and Response Supplemental Appropriations Act, followed by guidance by the Centers for Medicare and Medicaid Services and the Department of Health and Human Services, allowed currently credentialed providers (including pharmacists) to continue to provide patient care services via telehealth with fewer restrictions. Our health system has numerous credentialed pharmacists across multiple ambulatory care clinics. In this article, we highlight our process of expediting the implementation of telehealth services. This process included obtaining authorization for the credentialed pharmacists to provide telehealth services, completion of training modules, implementation of new technology platforms, development of new workflows, and utilization of resources for providers and patients to facilitate successful completion of telehealth visits. We also highlight the consent and documentation components crucially important to the telehealth visit and share some of our successes, as well as identified limitations, in providing pharmacist services via telehealth. CONCLUSION: In the setting of the COVID-19 pandemic, our institution was able to swiftly implement clinical pharmacist telehealth services for many patients, offering a safe and effective way to continue providing a high level of care. This article discusses our experience with and potential limitations of telehealth to assist other pharmacists seeking to implement and/or expand their telehealth services.

Am J Health Syst Pharm2020       LitCov and CORD-19
6321Interferon-Lambda Intranasal Protection and Differential Sex Pathology in a Murine Model of SARS-CoV-2 Infection  

Outbreaks of emerging viral pathogens like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are a major medical challenge. There is a pressing need for antivirals that can be rapidly deployed to curb infection and dissemination. We determined the efficacy of interferon lambda-1 (IFN-λ) as a broad-spectrum antiviral agent to inhibit SARS-CoV-2 infection and reduce pathology in a mouse model of disease. IFN-λ significantly limited SARS-CoV-2 production in primary human bronchial epithelial cells in culture. Pretreatment of human lung cells with IFN-λ completely blocked infectious virus production, and treatment with IFN-λ at the time of infection inhibited virus production more than 10-fold. To interrogate the protective effects of IFN-λ in response to SARS-CoV-2 infection, transgenic mice expressing the human angiotensin-converting enzyme 2 (ACE-2) were tested. One dose of IFN-λ administered intranasally was found to reduce animal morbidity and mortality. Our study with SARS-CoV-2 also revealed a sex differential in disease outcome. Male mice had higher mortality, reflecting the more severe symptoms and mortality found in male patients infected with SARS-CoV-2. The results indicate that IFN-λ potentially can treat early stages of SARS-CoV-2 infection and decrease pathology, and this murine model can be used to investigate the sex differential documented in COVID-19.

mBio2021       LitCov and CORD-19
6322Seroprevalence of SARS-CoV-2 antibodies in vaccinated healthcare workers in Marrakech (Morocco)  

N/A

Int J Immunopathol Pharmacol2022       LitCov
6323Coronavirus Pseudotypes for All Circulating Human Coronaviruses for Quantification of Cross-Neutralizing Antibody Responses  

The novel coronavirus SARS-CoV-2 is the seventh identified human coronavirus. Understanding the extent of pre-existing immunity induced by seropositivity to endemic seasonal coronaviruses and the impact of cross-reactivity on COVID-19 disease progression remains a key research question in immunity to SARS-CoV-2 and the immunopathology of COVID-2019 disease. This paper describes a panel of lentiviral pseudotypes bearing the spike (S) proteins for each of the seven human coronaviruses (HCoVs), generated under similar conditions optimized for high titre production allowing a high-throughput investigation of antibody neutralization breadth. Optimal production conditions and most readily available permissive target cell lines were determined for spike-mediated entry by each HCoV pseudotype: SARS-CoV-1, SARS-CoV-2 and HCoV-NL63 best transduced HEK293T/17 cells transfected with ACE2 and TMPRSS2, HCoV-229E and MERS-CoV preferentially entered HUH7 cells, and CHO cells were most permissive for the seasonal betacoronavirus HCoV-HKU1. Entry of ACE2 using pseudotypes was enhanced by ACE2 and TMPRSS2 expression in target cells, whilst TMPRSS2 transfection rendered HEK293T/17 cells permissive for HCoV-HKU1 and HCoV-OC43 entry. Additionally, pseudotype viruses were produced bearing additional coronavirus surface proteins, including the SARS-CoV-2 Envelope (E) and Membrane (M) proteins and HCoV-OC43/HCoV-HKU1 Haemagglutinin-Esterase (HE) proteins. This panel of lentiviral pseudotypes provides a safe, rapidly quantifiable and high-throughput tool for serological comparison of pan-coronavirus neutralizing responses; this can be used to elucidate antibody dynamics against individual coronaviruses and the effects of antibody cross-reactivity on clinical outcome following natural infection or vaccination.

Viruses2021       LitCov and CORD-19
6324Diagnostic Value of a SARS-CoV-2 Rapid Test Kit for Detection of Neutralizing Antibodies as a Point-of-Care Surveillance Test  

Detection and tracking of antibodies play an increasingly prominent role in population surveillance and implementation of public health measures to combat the current coronavirus disease 2019 (COVID-19) pandemic, with much attention placed on developing commercial serological assays as point-of-care diagnostic tools. While many rapid diagnostic tests (RDTs) that detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG and IgM antibodies have been evaluated, there is currently limited insight into detection of neutralizing antibodies (nAbs) by such modalities. Here, we evaluate performance characteristics of an RDT that detects SARS-CoV-2 IgG antibodies and, importantly, nAbs based on both infection- and vaccine-immunized cohorts by direct comparison to known antibody titers obtained from live virus microneutralization (VMN) assays. We further contextualize interpretations of band intensity of the RDT with reference to the World Health Organization (WHO) International Standard. We report a sensitivity of 94.37% and specificity of 92.50% for SARS-CoV-2 IgG detection and a sensitivity of 94.37% and specificity of 92.68% for nAbs. A limit of detection was determined as 3.125 IU/mL and 25.00 IU/mL, respectively, with reference to the WHO International Standard. We confirm that indication of nAb concentration, as elucidated by band intensity on the RDT, correlated with nAb titers defined by VMN assays and surrogate nAb assays. We additionally observe no cross-reactivity of the nAb test line to SARS-CoV-1 but report display of weak seropositivity for one sample on the SARS-CoV-2 IgG test line. Our study reveals promising performance characteristics of the assessed RDT, which implicates its usefulness in a wide range of diagnostic and epidemiological settings. IMPORTANCE In the ongoing coronavirus disease 2019 (COVID-19) pandemic, antibody tests play an increasingly important role in detecting previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and monitoring of response to vaccinations. In particular, neutralizing antibodies have recently been demonstrated to be highly predictive of immune protection against symptomatic infection. Our study is the first to evaluate a rapid diagnostic test based on samples acquired from both recovered COVID-19 patients and individuals vaccinated for SARS-CoV-2, which detects neutralizing antibodies in addition to SARS-CoV-2 IgG. We report promising sensitivity, specificity, and cross-reactivity profiles, which implicate its usefulness in a wide range of settings as a diagnostic point-of-care tool to aid in curbing transmission and reducing mortality caused by COVID-19 symptoms.

Microbiol Spectr2022       LitCov and CORD-19
6325Addressing challenges for clinical research responses to emerging epidemics and pandemics: a scoping review  

BACKGROUND: Major infectious disease outbreaks are a constant threat to human health. Clinical research responses to outbreaks generate evidence to improve outcomes and outbreak control. Experiences from previous epidemics have identified multiple challenges to undertaking timely clinical research responses. This scoping review is a systematic appraisal of political, economic, administrative, regulatory, logistical, ethical and social (PEARLES) challenges to clinical research responses to emergency epidemics and solutions identified to address these. METHODS: A scoping review. We searched six databases (MEDLINE, Embase, Global Health, PsycINFO, Scopus and Epistemonikos) for articles published from 2008 to July 2018. We included publications reporting PEARLES challenges to clinical research responses to emerging epidemics and pandemics and solutions identified to address these. Two reviewers screened articles for inclusion, extracted and analysed the data. RESULTS: Of 2678 articles screened, 76 were included. Most presented data relating to the 2014–2016 Ebola virus outbreak or the H1N1 outbreak in 2009. The articles related to clinical research responses in Africa (n = 37), Europe (n = 8), North America (n = 5), Latin America and the Caribbean (n = 3) and Asia (n = 1) and/or globally (n = 22). A wide range of solutions to PEARLES challenges was presented, including a need to strengthen global collaborations and coordination at all levels and develop pre-approved protocols and equitable frameworks, protocols and standards for emergencies. Clinical trial networks and expedited funding and approvals were some solutions implemented. National ownership and community engagement from the outset were a key enabler for delivery. Despite the wide range of recommended solutions, none had been formally evaluated. CONCLUSIONS: To strengthen global preparedness and response to the COVID-19 pandemic and future epidemics, identified solutions for rapid clinical research deployment, delivery, and dissemination must be implemented. Improvements are urgently needed to strengthen collaborations, funding mechanisms, global and national research capacity and capability, targeting regions vulnerable to epidemics and pandemics. Solutions need to be flexible to allow timely adaptations to context, and research led by governments of affected regions. Research communities globally need to evaluate their activities and incorporate lessons learnt to refine and rehearse collaborative outbreak response plans in between epidemics.

BMC Med2020       LitCov and CORD-19
6326Psychological distress among frontline workers during the COVID-19 pandemic: A mixed-methods study  

BACKGROUND: Novel virus outbreaks, such as the COVID-19 pandemic, may increase psychological distress among frontline workers. Psychological distress may lead to reduced performance, reduced employability or even burnout. In the present study, we assessed experienced psychological distress during the COVID-19 pandemic from a self-determination theory perspective. METHODS: This mixed-methods study, with repeated measures, used surveys (quantitative data) combined with audio diaries (qualitative data) to assess work-related COVID-19 experiences, psychological need satisfaction and frustration, and psychological distress over time. Forty-six participants (nurses, junior doctors, and consultants) completed 259 surveys and shared 60 audio diaries. Surveys and audio diaries were analysed separately. RESULTS: Quantitative results indicated that perceived psychological distress during COVID-19 was higher than pre-COVID-19 and fluctuated over time. Need frustration, specifically autonomy and competence, was positively associated with psychological distress, while need satisfaction, especially relatedness, was negatively associated with psychological distress. In the qualitative, thematic analysis, we observed that especially organisational logistics (rostering, work-life balance, and internal communication) frustrated autonomy, and unfamiliarity with COVID-19 frustrated competence. Despite many need frustrating experiences, a strong connection with colleagues and patients were important sources of relatedness support (i.e. need satisfaction) that seemed to mitigate psychological distress. CONCLUSION: The COVID-19 pandemic resulted in an increase of psychological distress among frontline workers. Both need frustration and need satisfaction explained unique variance of psychological distress, but seemed to originate from different sources. Challenging times require healthcare organisations to better support their professionals by tailored formal and informal support. We propose to address both indirect (e.g. organisation) and direct (e.g. colleagues) elements of the clinical and social environment in order to reduce need frustration and enhance need satisfaction.

PLoS One2021       LitCov and CORD-19
6327Point-of-care serological assays for delayed SARS-CoV-2 case identification among health-care workers in the UK: a prospective multicenter cohort study  

BACKGROUND: Health-care workers constitute a high-risk population for acquisition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Capacity for acute diagnosis via PCR testing was limited for individuals with mild to moderate SARS-CoV-2 infection in the early phase of the COVID-19 pandemic and a substantial proportion of health-care workers with suspected infection were not tested. We aimed to investigate the performance of point-of-care and laboratory serology assays and their utility in late case identification, and to estimate SARS-CoV-2 seroprevalence. METHODS: We did a prospective multicentre cohort study between April 8 and June 12, 2020, in two phases. Symptomatic health-care workers with mild to moderate symptoms were eligible to participate 14 days after onset of COVID-19 symptoms, as per the Public Health England (PHE) case definition. Health-care workers were recruited to the asymptomatic cohort if they had not developed PHE-defined COVID-19 symptoms since Dec 1, 2019. In phase 1, two point-of-care lateral flow serological assays, the Onsite CTK Biotech COVID-19 split IgG/IgM Rapid Test (CTK Bitotech, Poway, CA, USA) and the Encode SARS-CoV-2 split IgM/IgG One Step Rapid Test Device (Zhuhai Encode Medical Engineering, Zhuhai, China), were evaluated for performance against a laboratory immunoassay (EDI Novel Coronavirus COVID-19 IgG ELISA kit [Epitope Diagnostics, San Diego, CA, USA]) in 300 samples from health-care workers and 100 pre-COVID-19 negative control samples. In phase 2 (n=6440), serosurveillance was done among 1299 (93·4%) of 1391 health-care workers reporting symptoms, and in a subset of asymptomatic health-care workers (405 [8·0%] of 5049). FINDINGS: There was variation in test performance between the lateral flow serological assays; however, the Encode assay displayed reasonable IgG sensitivity (127 of 136; 93·4% [95% CI 87·8–96·9]) and specificity (99 of 100; 99·0% [94·6–100·0]) among PCR-proven cases and good agreement (282 of 300; 94·0% [91·3–96·7]) with the laboratory immunoassay. By contrast, the Onsite assay had reduced sensitivity (120 of 136; 88·2% [95% CI 81·6–93·1]) and specificity (94 of 100; 94·0% [87·4–97·8]) and agreement (254 of 300; 84·7% [80·6–88·7]). Five (7%) of 70 PCR-positive cases were negative across all assays. Late changes in lateral flow serological assay bands were recorded in 74 (9·3%) of 800 cassettes (35 [8·8%] of 400 Encode assays; 39 [9·8%] of 400 Onsite assays), but only seven (all Onsite assays) of these changes were concordant with the laboratory immunoassay. In phase 2, seroprevalence among the workforce was estimated to be 10·6% (95% CI 7·6–13·6) in asymptomatic health-care workers and 44·7% (42·0–47·4) in symptomatic health-care workers. Seroprevalence across the entire workforce was estimated at 18·0% (95% CI 17·0–18·9). INTERPRETATION: Although a good positive predictive value was observed with both lateral flow serological assays and ELISA, this agreement only occurred if the pre-test probability was modified by a strict clinical case definition. Late development of lateral flow serological assay bands would preclude postal strategies and potentially home testing. Identification of false-negative results among health-care workers across all assays suggest caution in interpretation of IgG results at this stage; for now, testing is perhaps best delivered in a clinical setting, supported by government advice about physical distancing. FUNDING: None.

Lancet Respir Med2020       LitCov and CORD-19
6328Multi-System Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Review of Clinical Presentation, Hypothetical Pathogenesis and Proposed Management  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may result in the multisystem inflammatory syndrome in children (MIS-C). The clinical presentation of MIS-C includes fever, severe illness, and the involvement of two or more organ systems, in combination with laboratory evidence of inflammation and laboratory or epidemiologic evidence of SARS-CoV-2 infection. Some features of MIS-C resemble Kawasaki Disease, toxic shock syndrome, and secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome. The relationship of MIS-C to SARS-CoV-2 infection suggests that the pathogenesis involves post-infectious immune dysregulation. Patients with MIS-C should ideally be managed in a pediatric intensive care environment since rapid clinical deterioration may occur. Specific immunomodulatory therapy depends on the clinical presentation. The relationship between the immune response to SARS-CoV-2 vaccines in development and MIS-C requires further study.

Children (Basel)2020       LitCov and CORD-19
6329Panbio antigen rapid test is reliable to diagnose SARS-CoV-2 infection in the first 7 days after the onset of symptoms  

BACKGROUND: RT-qPCR is the current recommended laboratory method to diagnose SARS-CoV-2 acute infection, several factors such as requirement of special equipment, time consuming, high cost and skilled staff limit the use of these techniques. A more rapid and high-throughput method is essential. METHODS: We analyzed clinical data and nasopharyngeal samples, collected during September 2020, from patients attended at the emergency department of a secondary hospital and in two primary healthcare centers in Madrid. The performance of the Panbio™ COVID-19 AG Rapid Test Device for the detection of SARS-CoV-2 antigen was compared to RT-qPCR. RESULTS: 255 nasopharyngeal swabs, including 150 from the emergency department and 105 from primary helthcare centers, were tested. 184 patients were symptomatic (72.1 %). Amongst the 60 positive RT-qPCR samples, 40 were detected by the rapid antigen test, given an overall sensitivity of 73.3 %. All the samples detected positive with the rapid antigen test were also positive with RT-qPCR. The median cycle threshold was 23.28 (IQR 18.5–30.16). Patients with less than seven days onset of symptoms showed a higher viral load, and sensitivity for rapid antigen test (86.5 %), compared to those with more days (sensitivity of 53.8 %)(p < 0.004). CONCLUSIONS: The rapid antigen test evaluated in this study showed a high sensitivity and specificity in samples obtained during the first week of symptoms and with high viral loads. This assay seems to be an effective strategy for controlling the COVID-19 pandemic for the rapid identification and isolation of SARS-CoV-2 infected patients.

J Clin Virol2020       LitCov and CORD-19
6330Epidemiological characteristics of COVID-19 patients in IRAN: A single center study  

• The majority of cases were in the age group of 50 to 60 years of old. • A total of 2964 cases of COVID-19 were investigated. • The male-to-female ratio was 1.93:1. • A significant effect of age, gender and comorbidities on the mortality. • The Case Fatality Rate among understudy cases was 8.06%.

J Clin Virol2020       LitCov and CORD-19
6331Multicenter Study of Temporal Changes and Prognostic Value of a CT Visual Severity Score in Hospitalized Patients With Coronavirus Disease  

N/A

AJR Am J Roentgenol2021       LitCov and CORD-19
6332Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation  

During the current coronavirus disease 2019 (COVID-19) pandemic, a variety of mutations have accumulated in the viral genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and, at the time of writing, four variants of concern are considered to be potentially hazardous to human society(1). The recently emerged B.1.617.2/Delta variant of concern is closely associated with the COVID-19 surge that occurred in India in the spring of 2021 (ref. (2)). However, the virological properties of B.1.617.2/Delta remain unclear. Here we show that the B.1.617.2/Delta variant is highly fusogenic and notably more pathogenic than prototypic SARS-CoV-2 in infected hamsters. The P681R mutation in the spike protein, which is highly conserved in this lineage, facilitates cleavage of the spike protein and enhances viral fusogenicity. Moreover, we demonstrate that the P681R-bearing virus exhibits higher pathogenicity compared with its parental virus. Our data suggest that the P681R mutation is a hallmark of the virological phenotype of the B.1.617.2/Delta variant and is associated with enhanced pathogenicity.

Nature2021       LitCov and CORD-19
6333Examining telehealth use among primary care patients, providers and clinics during the COVID-19 pandemic  

N/A

BMC Prim Care2022       LitCov
6334Coronavirus Infections in Children Including COVID-19: An Overview of the Epidemiology, Clinical Features, Diagnosis, Treatment and Prevention Options in Children  

Coronaviruses (CoVs) are a large family of enveloped, single-stranded, zoonotic RNA viruses. Four CoVs commonly circulate among humans: HCoV2-229E, -HKU1, -NL63 and -OC43. However, CoVs can rapidly mutate and recombine leading to novel CoVs that can spread from animals to humans. The novel CoVs severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. The 2019 novel coronavirus (SARS-CoV-2) is currently causing a severe outbreak of disease (termed COVID-19) in China and multiple other countries, threatening to cause a global pandemic. In humans, CoVs mostly cause respiratory and gastrointestinal symptoms. Clinical manifestations range from a common cold to more severe disease such as bronchitis, pneumonia, severe acute respiratory distress syndrome, multi-organ failure and even death. SARS-CoV, MERS-CoV and SARS-CoV-2 seem to less commonly affect children and to cause fewer symptoms and less severe disease in this age group compared with adults, and are associated with much lower case-fatality rates. Preliminary evidence suggests children are just as likely as adults to become infected with SARS-CoV-2 but are less likely to be symptomatic or develop severe symptoms. However, the importance of children in transmitting the virus remains uncertain. Children more often have gastrointestinal symptoms compared with adults. Most children with SARS-CoV present with fever, but this is not the case for the other novel CoVs. Many children affected by MERS-CoV are asymptomatic. The majority of children infected by novel CoVs have a documented household contact, often showing symptoms before them. In contrast, adults more often have a nosocomial exposure. In this review, we summarize epidemiologic, clinical and diagnostic findings, as well as treatment and prevention options for common circulating and novel CoVs infections in humans with a focus on infections in children.

Pediatr Infect Dis J2020       LitCov and CORD-19
6335Post-COVID-19 Tachycardia Syndrome: A Distinct Phenotype of Post-Acute COVID-19 Syndrome  

In this paper we highlight the presence of tachycardia in Post-acute Covid-19 Syndrome by introducing a new label for this phenomenon: Post-covid-19 tachycardia syndrome and argue that this constitutes a phenotype or sub-syndrome in PACS. We also discuss epidemiology, putative mechanisms, treatment options and future research directions in this novel clinical syndrome.

Am J Med2021       LitCov and CORD-19
6336A whole blood test to measure SARS-CoV-2-specific response in COVID-19 patients  

OBJECTIVES: To examine whether specific T-cell-responses to SARS-CoV-2 peptides can be detected in COVID-19 using a whole-blood experimental setting, which may be further explored as potential diagnostic tool. METHODS: We evaluated IFN-γ levels after stimulating whole-blood with spike and remainder-antigens peptides megapools (MP) derived from SARS-CoV-2 sequences; IL-1β, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17A, eotaxin, basic FGF, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF, RANTES, TNF-α, VEGF were also evaluated. RESULTS: IFN-γ-response to spike and remainder-antigens MPs was significantly increased in 35 COVID-19-patients compared to 29 “NO COVID-19”-individuals (medians spike-MP: 0.26 vs 0, p=0.0002; medians remainder-antigens-MP: 0.07 vs 0.02; p=0.02). This response was detected independently of patients’ clinical parameters. IFN-γ-response to SARS-CoV-2-unrelated antigens CMV and SEB was similar in COVID-19 compared to NO-COVID-19-invididuals (median CMV: 3.46 versus 5.28, p=0.16; median SEB: 12.68 versus 15.05; p=0.1). In response to spike-MPs in COVID-19- compared to “NO COVID-19”-individuals, we found significant higher median of IL-2 (50.08 vs 0, p=0.0018), IFN-γ (90.16 vs 0, p=0.01), IL-4 (0.52 vs 0, p=0.03), IL-13 (0.84 vs 0, p=0.007) and MCP-1 (4602 vs 359.2, p=0.05). CONCLUSIONS: Immune response to SARS-CoV-2 peptides in a whole-blood assay is associated to COVID-19 and it is characterized by both Th1 and Th2 profile. This experimental approach may be useful for developing new T-cell based diagnostic tests for disease and vaccine settings.

Clin Microbiol Infect2020       LitCov and CORD-19
6337COVID-19 in Nursing Homes: Calming the Perfect Storm  

N/A

J Am Geriatr Soc2020       LitCov and CORD-19
6338Impact of the societal response to COVID-19 on access to healthcare for non-COVID-19 health issues in slum communities of Bangladesh, Kenya, Nigeria and Pakistan: results of pre-COVID and COVID-19 lockdown stakeholder engagements  

INTRODUCTION: With COVID-19, there is urgency for policymakers to understand and respond to the health needs of slum communities. Lockdowns for pandemic control have health, social and economic consequences. We consider access to healthcare before and during COVID-19 with those working and living in slum communities. METHODS: In seven slums in Bangladesh, Kenya, Nigeria and Pakistan, we explored stakeholder perspectives and experiences of healthcare access for non-COVID-19 conditions in two periods: pre-COVID-19 and during COVID-19 lockdowns. RESULTS: Between March 2018 and May 2020, we engaged with 860 community leaders, residents, health workers and local authority representatives. Perceived common illnesses in all sites included respiratory, gastric, waterborne and mosquitoborne illnesses and hypertension. Pre-COVID, stakeholders described various preventive, diagnostic and treatment services, including well-used antenatal and immunisation programmes and some screening for hypertension, tuberculosis, HIV and vectorborne disease. In all sites, pharmacists and patent medicine vendors were key providers of treatment and advice for minor illnesses. Mental health services and those addressing gender-based violence were perceived to be limited or unavailable. With COVID-19, a reduction in access to healthcare services was reported in all sites, including preventive services. Cost of healthcare increased while household income reduced. Residents had difficulty reaching healthcare facilities. Fear of being diagnosed with COVID-19 discouraged healthcare seeking. Alleviators included provision of healthcare by phone, pharmacists/drug vendors extending credit and residents receiving philanthropic or government support; these were inconsistent and inadequate. CONCLUSION: Slum residents’ ability to seek healthcare for non-COVID-19 conditions has been reduced during lockdowns. To encourage healthcare seeking, clear communication is needed about what is available and whether infection control is in place. Policymakers need to ensure that costs do not escalate and unfairly disadvantage slum communities. Remote consulting to reduce face-to-face contact and provision of mental health and gender-based violence services should be considered.

BMJ Glob Health2020       LitCov and CORD-19
6339A case report of rhino-facial mucormycosis in a non-diabetic patient with COVID-19: a systematic review of literature and current update  

BACKGROUND: COVID-19 disease may be associated with a wide range of bacterial and fungal infections. We report a patient with COVID-19 infection who developed rhino-facial mucormycosis during treatment with corticosteroids. CASE PRESENTATION: A 59-year-old non-diabetic male patient was admitted with a diagnosis of COVID-19 based on positive RT-PCR and CT of the lungs. Due to sever lung involvement, he was treated with methylprednisolone. The patient was re-admitted to hospital, due to nasal obstruction and left side facial and orbital swelling, several days after discharge. In sinus endoscopic surgery, debridement was performed and the specimens were sent to pathology and mycology laboratories. A nasal biopsy showed wide hyphae without septa. The sequenced PCR product revealed Rhizopus oryzae. Despite all medical and surgical treatment, the patient died. In addition, the characteristics of patients with COVID-19-associated mucormycosis were reviewed in 44 available literatures. In most studies, diabetes mellitus was the most common predisposing factor for mucormycosis. CONCLUSION: Our report highlights the need for assessing the presence of mucormycosis in patients with COVID-19 and also it shows that physicians should consider the potential for secondary invasive fungal infections in COVID-19 cases.

BMC Infect Dis2021       LitCov and CORD-19
6340Investigation on the mental health status of pregnant women in China during the Pandemic of COVID-19  

PURPOSE: To evaluate the anxiety and depression in pregnant women in China, and its influencing factors during the corona virus disease 2019 (COVID-19) pandemic. METHODS: From February 22 to February 27, a questionnaire survey was conducted on 156 pregnant women, including demographic characteristics, a self-rating anxiety scale (SAS), and a self-depression rating scale (SDS). RESULTS: A total of 13 non-homologous end-joining (8.3%, 13/156) patients were anxious, 79 patients (50.6%, 79/156) were depressed, and 13 patients (8.3%, 13/156) suffered from both anxiety and depression. The SAS score of pregnant women was 40.55 ± 6.09, and the SDS score was 50.42 ± 11.64. For the SAS score, only 8.3% of all patients (13/156) were in a light anxiety state. For the SDS score, 46.79% (73/156) of patients was normal, 23.72% of patients (37/156) showed mild depression, 22.44% (35/156) showed moderate depression, and 4.49% (7/156) showed severe depression. No significant changes were observed in SAS and SDS scores between patients from different regions within China, health state, gestational week, educational background, and living condition (P > 0.05). Moreover, no significant differences were observed between diagnosed/suspected patients and the normal control group (P > 0.05), and between pregnant women in Wuhan compared to other regions (P > 0.05). CONCLUSION: During the COVID-19 epidemic, the anxiety level of pregnant women was the same as that before the epidemic, while the level of depression was significantly higher. Pregnant women who lived in Wuhan, the epicenter of the epidemic, were not more anxious or depressed compared to pregnant women in other regions during the COVID-19 epidemic. Furthermore, the mental health status of pregnant women with COVID-19 was not more severe. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00404-020-05805-x) contains supplementary material, which is available to authorized users.

Arch Gynecol Obstet2020       LitCov and CORD-19
6341Immune response to the third COVID-19 vaccine dose is related to lymphocyte count in multiple sclerosis patients treated with fingolimod  

BACKGROUND: The majority of multiple sclerosis [MS] patients treated with fingolimod fail to develop a protective level of IgG humoral and adaptive cellular immune responses following full BNT162b2 SARS-CoV-2 vaccination. OBJECTIVE: To compare the efficacy of the third COVID-19 vaccine dose in vaccine non-responders fingolimod-treated MS patients. STUDY DESIGN: This is a prospective 3-month, single-center, randomized clinical trial. METHODS: Twenty relapsing MS patients who had been on fingolimod therapy ≥ 12 months and failed to develop humoral IgG immune response to 2-dose Pfizer BNT162b2 COVID-19 vaccination were randomized into two groups: fingolimod-continuation group and fingolimod-discontinuation group. Humoral and memory cellular immune responses were assessed within 1 and 3 months following the third Pfizer BNT162b2 vaccine dose and compared between the groups. RESULTS: A higher rate of patients in the fingolimod-discontinuation group [n = 8/10] compared to fingolimod-continuation group [n = 2/10] developed positive SARS-COV-2 IgG. Median IgG titer 1 month following the third dose was 202.3 BAU/ml vs. 26.4 BAU/ml, respectively, p = 0.022. The development of IgG humoral response correlated with absolute lymphocyte count. Specific SARS-COV-2 memory B cell and T cell immune responses were not detected in both groups, either at 1 month or 3 months following the third COVID-19 vaccine dose. CONCLUSIONS: Short period of fingolimod treatment discontinuation was associated with the development of humoral protection but not with adaptive cellular immunity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00415-022-11030-0.

J Neurol2022       LitCov and CORD-19
6342UV Inactivation of SARS-CoV-2 across the UVC Spectrum: KrCl* Excimer, Mercury-Vapor and Light-Emitting-Diode (LED) Sources  

Effective disinfection technology to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can help reduce viral transmission during the ongoing COVID-19 global pandemic and in the future. UV devices emitting UVC irradiation (200 to 280 nm) have proven to be effective for virus disinfection, but limited information is available for SARS-CoV-2 due to the safety requirements of testing, which is limited to biosafety level 3 (BSL3) laboratories. In this study, inactivation of SARS-CoV-2 in thin-film buffered aqueous solution (pH 7.4) was determined across UVC irradiation wavelengths of 222 to 282 nm from krypton chloride (KrCl*) excimers, a low-pressure mercury-vapor lamp, and two UVC light-emitting diodes. Our results show that all tested UVC devices can effectively inactivate SARS-CoV-2, among which the KrCl* excimer had the best disinfection performance (i.e., highest inactivation rate). The inactivation rate constants of SARS-CoV-2 across wavelengths are similar to those for murine hepatitis virus (MHV) from our previous investigation, suggesting that MHV can serve as a reliable surrogate of SARS-CoV-2 with a lower BSL requirement (BSL2) during UV disinfection tests. This study provides fundamental information on UVC’s action on SARS-CoV-2 and guidance for achieving reliable disinfection performance with UVC devices. IMPORTANCE UV light is an effective tool to help stem the spread of respiratory viruses and protect public health in commercial, public, transportation, and health care settings. For effective use of UV, there is a need to determine the efficiency of different UV wavelengths in killing pathogens, specifically SARS-CoV-2, to support efforts to control the ongoing COVID-19 global pandemic and future coronavirus-caused respiratory virus pandemics. We found that SARS-CoV-2 can be inactivated effectively using a broad range of UVC wavelengths, and 222 nm provided the best disinfection performance. Interestingly, 222-nm irradiation has been found to be safe for human exposure up to thresholds that are beyond those effective for inactivating viruses. Therefore, applying UV light from KrCl* excimers in public spaces can effectively help reduce viral aerosol or surface-based transmissions.

Appl Environ Microbiol2021       LitCov and CORD-19
6343Factors influencing likelihood of COVID-19 vaccination: A survey of Tennessee adults  

DISCLAIMER: In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: To examine the vaccine-related beliefs and behaviors associated with likely hesitancy toward vaccination against coronavirus disease 2019 (COVID-19) among nonelderly adults. METHODS: A cross-sectional survey was conducted in June 2020. Responses were sought from Tennessee adults 18 to 64 years of age who were not healthcare providers. The survey instrument focused on vaccine-related beliefs, prior and planned influenza and pneumococcal vaccine use, and attitudes toward receiving a COVID-19 vaccination. Inferential statistics assessed survey responses, and logistic regression determined predictors of the likelihood of COVID-19 vaccination. RESULTS: A total of 1,000 completed responses were analyzed (a 62.9% response rate), and respondents were mostly White (80.1%), insured (79.6%), and/or actively working (64.2%); the sample was well balanced by gender, age, income, and political leaning. Approximately one-third (34.4%) of respondents indicated some historical vaccine hesitancy, and only 21.4% indicated always getting a seasonal influenza vaccination. More than half (54.1%) indicated at least some hesitancy toward vaccination against COVID-19, with 32.1% citing lack of evidence of vaccine effectiveness as the leading reason. COVID-19 vaccine hesitancy was more likely among those with more moderate (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.749-3.607) or conservative (OR, 3.01; 95% CI, 2.048-4.421) political leanings, Black Americans (OR, 1.80; 95% CI, 1.182-2.742), and residents of nonmetropolitan areas (OR, 1.99; 95% CI, 1.386-2.865). CONCLUSION: Subgroups of the population may prove more challenging to vaccinate against COVID-19, requiring targeted approaches to addressing hesitancy to ensure more-vulnerable populations are adequately covered.

Am J Health Syst Pharm2021       LitCov and CORD-19
6344Coronavirus Occurrence in the Household Influenza Vaccine Evaluation (HIVE) Cohort of Michigan Households: Reinfection Frequency and Serologic Responses to Seasonal and Severe Acute Respiratory Syndrome Coronaviruses  

BACKGROUND: We investigated frequency of reinfection with seasonal coronaviruses (HCoV) and serum antibody response following infection over 8 years in the Household Influenza Vaccine Evaluation cohort. METHODS: Households were followed annually for identification of acute respiratory illness with RT-PCR confirmed HCoV infection. Serum collected before and at two time points post infection were tested using a multiplex binding assay to quantify antibody to seasonal, SARS-CoV-1, and SARS-CoV-2 spike proteins and SARS-CoV-2 spike sub-domains and N protein. RESULTS: Of 3418 participants, 40% were followed for ≥3years. A total of 1004 HCoV infections were documented; 303 (30%) were reinfections of any HCoV type. The number of HCoV infections ranged from 1 to 13 per individual. The mean time to reinfection with the same type was estimated at 983 days for 229E, 578 days for HKU1, 615 days for OC43, and 711 days for NL63. Binding antibody levels to seasonal HCoVs were high, with little increase post-infection, and were maintained over time. Homologous, pre-infection antibody levels did not significantly correlate with odds of infection, and there was little cross response to SARS-CoV-2 proteins. CONCLUSIONS: Reinfection with seasonal HCoVs is frequent. Binding anti-spike protein antibodies do not correlate with protection from seasonal HCoV infection.

J Infect Dis2021       LitCov and CORD-19
6345The Impact of Evolving SARS-CoV-2 Mutations and Variants on COVID-19 Vaccines  

The emergence of several new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in recent months has raised concerns around the potential impact on ongoing vaccination programs. Data from clinical trials and real-world evidence suggest that current vaccines remain highly effective against the alpha variant (B.1.1.7), while some vaccines have reduced efficacy and effectiveness against symptomatic disease caused by the beta variant (B.1.351) and the delta variant (B.1.617.2); however, effectiveness against severe disease and hospitalization caused by delta remains high. Although data on the effectiveness of the primary regimen against omicron (B.1.1.529) are limited, booster programs using mRNA vaccines have been shown to restore protection against infection and symptomatic disease (regardless of the vaccine used for the primary regimen) and maintain high effectiveness against hospitalization. However, effectiveness against infection and symptomatic disease wanes with time after the booster dose. Studies have demonstrated reductions of varying magnitude in neutralizing activity of vaccine-elicited antibodies against a range of SARS-CoV-2 variants, with the omicron variant in particular exhibiting partial immune escape. However, evidence suggests that T-cell responses are preserved across vaccine platforms, regardless of variant of concern. Nevertheless, various mitigation strategies are under investigation to address the potential for reduced efficacy or effectiveness against current and future SARS-CoV-2 variants, including modification of vaccines for certain variants (including omicron), multivalent vaccine formulations, and different delivery mechanisms.

mBio2022       LitCov and CORD-19
6346The first laboratory-confirmed imported infections of SARS-CoV-2 in Sudan  

BACKGROUND: The rapidly growing pandemic of coronavirus disease 2019 (COVID-19) has challenged health systems globally. Here we report the first identified infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; aetiology of COVID-19) among recent international arrivals to Sudan and their contacts. METHODS: Suspected cases were identified clinically and/or epidemiologically. Samples from suspected cases and their contacts were tested in the National Influenza Centre following World Health Organization protocols. Two real-time reverse transcription quantitative polymerase chain reaction assays were used to detect and confirm SARS-CoV-2 infection. RESULTS: Seven cases of COVID-19, including two deaths, were confirmed in Sudan between 27 February and 30 March 2020. Suspected cases were identified and tested. As of 30 March, no local transmission was yet reported in the country. Fifty-nine percent of the suspected cases were international travellers coming from areas with current COVID-19 epidemics. Cough and fever were the major symptoms, presented by 65% and 60% of the suspected cases, respectively. By early April, an additional seven cases were confirmed through limited contact tracing that identified the first locally acquired infections in recent contact with imported cases. CONCLUSIONS: The high mortality rate of COVID-19 cases in Sudan might be due to limitations in test and trace and case management services. Unfortunately, infections have spread further into other states and the country has no capacity for mass community screening to better estimate disease prevalence. Therefore external support is urgently needed to improve the healthcare and surveillance systems.

Trans R Soc Trop Med Hyg2020       LitCov and CORD-19
6347Screening and Testing Pregnant Patients for SARS-CoV-2: First-Wave Experience of a Designated COVID-19 Hospitalization Centre in Montréal  

OBJECTIVE: Coronavirus Disease 2019 (COVID-19) may present asymptomatically in a large proportion of cases in endemic areas. Accordingly, universal testing has been suggested as a potential strategy for reducing transmission in the obstetrical setting. We describe the clinical characteristics of patients who tested positive for Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) during pregnancy at a designated COVID-19 hospitalization centre in Montreal, Quebec. METHODS: A single-centre retrospective cohort was constructed to include all pregnant patients who tested positive for SARS-CoV-2 between March 22 and July 31, 2020, and received care at the Jewish General Hospital. Initially, testing was restricted to at-risk patients, identified through the use of a screening questionnaire. Beginning on May 15, 2020, universal testing was implemented, and all pregnant patients admitted to hospital were tested. Data were collected through chart review. RESULTS: Of 803 patients tested for SARS-CoV-2 during the study period, 41 (5%) tested positive. Among those patients who were symptomatic, the most commonly reported symptoms were cough (53%), fever (37%), dyspnea (30%), and anosmia and/or ageusia (20%). Prior to the implementation of universal testing, 13% (3/24) of patients with SARS-CoV-2 were asymptomatic. Following the implementation of universal testing, 80% (8/10) of patients with SARS-CoV-2 were asymptomatic. CONCLUSION: Our findings suggest that most pregnant patients with SARS-CoV-2 are asymptomatic or have mild symptoms of COVID-19. Particularly in endemic areas, universal testing of pregnant patients presenting to hospital should be strongly considered as an important measure to prevent in-hospital and community transmission of COVID-19.

J Obstet Gynaecol Can2020       LitCov and CORD-19
6348Myocarditis following COVID-19 mRNA vaccination  

BACKGROUND: Clinical trials of the BNT162b2 vaccine, revealed efficacy and safety. We report six cases of myocarditis, which occurred shortly after BNT162b2 vaccination. METHODS: Patients were identified upon presentation to the emergency department with symptoms of chest pain/discomfort. In all study patients, we excluded past and current COVID-19. Routine clinical and laboratory investigations for common etiologies of myocarditis were performed. Laboratory tests also included troponin and C-reactive protein levels. The diagnosis of myocarditis was established after cardiac MRI. FINDINGS: Five patients presented after the second and one after the first dose of the vaccine. All patients were males with a median age of 23 years. Myocarditis was diagnosed in all patients, there was no evidence of COVID-19 infection. Laboratory assays excluded concomitant infection; autoimmune disorder was considered unlikely. All patients responded to the BNT162b2 vaccine. The clinical course was mild in all six patients. INTERPRETATION: Our report of myocarditis after BNT162b2 vaccination may be possibly considered as an adverse reaction following immunization. We believe our information should be interpreted with caution and further surveillance is warranted.

Vaccine2021       LitCov and CORD-19
6349Nasal prevention of SARS-CoV-2 infection by intranasal influenza-based boost vaccination in mouse models  

BACKGROUND: Vaccines in emergency use are efficacious against COVID-19, yet vaccine-induced prevention against nasal SARS-CoV-2 infection remains suboptimal. METHODS: Since mucosal immunity is critical for nasal prevention, we investigated the efficacy of an intramuscular PD1-based receptor-binding domain (RBD) DNA vaccine (PD1-RBD-DNA) and intranasal live attenuated influenza-based vaccines (LAIV-CA4-RBD and LAIV-HK68-RBD) against SARS-CoV-2. FINDINGS: Substantially higher systemic and mucosal immune responses, including bronchoalveolar lavage IgA/IgG and lung polyfunctional memory CD8 T cells, were induced by the heterologous PD1-RBD-DNA/LAIV-HK68-RBD as compared with other regimens. When vaccinated animals were challenged at the memory phase, prevention of robust SARS-CoV-2 infection in nasal turbinate was achieved primarily by the heterologous regimen besides consistent protection in lungs. The regimen-induced antibodies cross-neutralized variants of concerns. Furthermore, LAIV-CA4-RBD could boost the BioNTech vaccine for improved mucosal immunity. INTERPRETATION: Our results demonstrated that intranasal influenza-based boost vaccination induces mucosal and systemic immunity for effective SARS-CoV-2 prevention in both upper and lower respiratory systems. FUNDING: This study was supported by the Research Grants Council Collaborative Research Fund, General Research Fund and Health and Medical Research Fund in Hong Kong; Outbreak Response to Novel Coronavirus (COVID-19) by the Coalition for Epidemic Preparedness Innovations; Shenzhen Science and Technology Program and matching fund from Shenzhen Immuno Cure BioTech Limited; the Health@InnoHK, Innovation and Technology Commission of Hong Kong; National Program on Key Research Project of China; donations from the Friends of Hope Education Fund; the Theme-Based Research Scheme.

EBioMedicine2021       LitCov and CORD-19
6350Neutralizing Antibodies against SARS-CoV-2 and Other Human Coronaviruses  

Coronavirus (CoV) disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS)-CoV-2 (also known as 2019-nCoV) is threatening global public health, social stability, and economic development. To meet this challenge, this article discusses advances in the research and development of neutralizing antibodies (nAbs) for the prevention and treatment of infection by SARS-CoV-2 and other human CoVs.

Trends Immunol2020       LitCov and CORD-19

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