| Title | Venue | Year | Impact | Source |
| 651 | Therapies to Prevent Progression of COVID-19, Including Hydroxychloroquine, Azithromycin, Zinc and Vitamin D3 With or Without Intravenous Vitamin C: An International, Multicenter, Randomized Trial Background COVID-19 is a global pandemic. Treatment with hydroxychloroquine (HCQ), zinc, and azithromycin (AZM), also known as the Zelenko protocol, and treatment with intravenous (IV) vitamin C (IVC) have shown encouraging results in a large number of trials worldwide. In addition, vitamin D levels are an important indicator of the severity of symptoms in patients with COVID-19. Objectives Our multicenter, randomized, open-label study aimed to assess the effectiveness of HCQ, AZM, and zinc with or without IVC in hospitalized patients with COVID-19 in reducing symptom severity and duration and preventing death. Methods Hospitalized patients with COVID-19 in seven participating hospitals in Turkey were screened for eligibility and randomly allocated to receive either HCQ, AZM, and zinc (group 1) or HCQ, AZM, zinc plus IV vitamin C treatment (group 2) for 14 days. The patients also received nontherapeutic levels of vitamin D3. The trial is registered on the Australian and New Zealand Clinical Trial Registry ACTRN12620000557932 and has been approved by the Australian Therapeutic Goods Administration (TGA). Results A total of 237 hospitalized patients with COVID-19 aged 22-99 years (mean: 63.3 ± 15.7 years) were enrolled in the study. Almost all patients were vitamin D deficient (97%), 55% were severely vitamin D deficient (<25 nmol/L) and 42% were vitamin D deficient (<50 nmol/L); 3% had insufficient vitamin D levels (<75 nmol/L), and none had optimal vitamin D levels. Of the patients, 73% had comorbidities, including diabetes (35%), heart disease (36%), and lung disease (34%). All but one patient (99.6%; n = 236/237) treated with HCQ, AZM, and zinc with or without high-dose IV vitamin C (IVC) fully recovered. Additional IVC therapy contributed significantly to a quicker recovery (15 days versus 45 days until discharge; p = 0.0069). Side effects such as diarrhea, nausea, and vomiting, reported by 15%-27% of the patients, were mild to moderate and transient. No cardiac side effects were observed. Low vitamin D levels were significantly correlated with a higher probability of admission to the intensive care unit (ICU) and longer hospital stay. Sadly, one 70-year-old female patient with heart and lung disease died after 17 days in ICU and 22 days in the hospital. Her vitamin D level was 6 nmol/L on admission (i.e., severely deficient). Conclusions Our study suggests that the treatment protocol of HCQ, AZM, and zinc with or without vitamin C is safe and effective in the treatment of COVID-19, with high dose IV vitamin C leading to a significantly quicker recovery. Importantly, our study confirms vitamin D deficiency to be a high-risk factor of severe COVID-19 disease and hospitalization, with 97% of our study’s patient cohort being vitamin D deficient, 55% of these being severely vitamin D deficient, and none had optimal levels. Future trials are warranted to evaluate the treatment with a combination of high-dose vitamin D3 in addition to HCQ, AZM, and zinc and high-dose intravenous vitamin C. | Cureus | 2021 | | LitCov and CORD-19 |
| 652 | The impact of COVID-19 on idiopathic scoliosis referrals: cause for concern STUDY DESIGN: Retrospective comparative review. OBJECTIVE: The aim of this study was to determine the short-term impact of the COVID-19 pandemic on the demographic and clinical profile of new idiopathic scoliosis (IS) patients, with a particular focus on treatment and late referral. SUMMARY OF BACKGROUND DATA: The COVID-19 pandemic has limited health-care services and public access and, as a result, the diagnosis and management of non-COVID-19 health conditions have been compromised. Delayed diagnosis of IS may limit conservative treatment options and subsequently, increase a patient’s risk of requiring surgical intervention. METHODS: The volume of spine referrals received and new IS clinic visits were compared between March 15–October 15, 2019 and the same period in 2020. A chart and radiographic review detailed the patient profile at initial presentation. Descriptive statistics and comparative analyses examined the referral source, curve magnitude, skeletal maturity, and prescribed treatment. Late referrals were those with a curve magnitude ≥ 50°, or > 40° and Risser 2 or less. RESULTS: During the 2020 study period, the referral volume decreased 76% and clinic visits 55%. The 2019 cohort was similar in age (13.7 ± 2.1 years vs 13.3 ± 2.3 years, p = 0.08), Risser score distribution (p = 0.32), menarchal status (0.07), and curve magnitude (37.1° ± 3.8° vs 39.0° ± 16.0°, p = 0.22). During the pandemic, there was an increased proportion of referrals made by pediatricians (41 to 54%, p = 0.01). The proportion of brace prescriptions increased from 30 to 42% (p = 0.01). The proportion of surgical bookings and late referrals were increased but did not reach significance. CONCLUSION: Despite no significant increase in the magnitude of the curve at initial presentation or the proportion of late referrals, there was a marked decrease in referral volume, over the first 7 months of the COVID-19 pandemic. This suggests that the majority of expected new IS patients remain undiagnosed. A future increase in late referrals should be anticipated. LEVEL OF EVIDENCE: III. | Spine Deform | 2021 | | LitCov and CORD-19 |
| 653 | Melatonin for the Early Treatment of COVID-19: A Narrative Review of Current Evidence and Possible Efficacy OBJECTIVE: To date, there are no FDA approved medications for treatment of early COVID-19 infection. Recently, use of melatonin, a naturally occurring tryptophan-derivative synthesized in the pineal gland and immune cells, has been suggested as an early treatment option for COVID-19. Melatonin has known anti-inflammatory, immunomodulatory, and protective antioxidant mechanisms that may attenuate the severity of COVID-19 symptoms. The objective of the present narrative review is to discuss the use of melatonin as an early treatment option on the first day of diagnosis for COVID-19. METHODS: The MeSH terms “COVID-19” and “viral diseases” were manually searched on PubMed and relevant articles were included. RESULTS: Results showed that melatonin acts to reduce reactive-oxygen-species mediated damage, cytokine-induced inflammation, and lymphopenia in viral diseases similar to COVID-19. CONCLUSIONS: These conclusions provide evidence for potential benefits in melatonin use for COVID-19 treatment as early as the day of diagnosis. | Endocr Pract | 2021 | | LitCov and CORD-19 |
| 654 | Food donation management under supply and demand uncertainties in COVID-19: A robust optimization approach COVID-19 pandemic and the associated lockdown have globally impacted the food-insecure low-income population. A community-based initiative of an NPO - working on malnutrition issues among the below poverty line children in an urban Indian setting - towards adoption of the slum- and shelter-dwelling children, faced challenges during the pandemic in tackling the twofold uncertainties regarding supply capacity reduction and demand surge. This paper extends earlier research on this NPO's pre-COVID-time food assistance program by introducing a robust optimization-based mathematical programming model to determine the donors to engage, donor-to-beneficiary allocations, and the associated optimal donation flows while addressing these uncertainties. The issue of over-conservatism in robust optimization is addressed by parameterizing the decision-maker's uncertainty budget. We present a detailed numerical study on a test problem along with interesting observations elicited by our sensitivity analyses. | Socioecon Plann Sci | 2021 | | LitCov and CORD-19 |
| 655 | Change in covid-19 risk over time following vaccination with CoronaVac: test negative case-control study N/A | BMJ | 2022 | | LitCov |
| 656 | Effectiveness and mechanism of a 4-week online self-help mindfulness intervention among individuals with emotional distress during COVID-19 in China N/A | BMC Psychol | 2022 | | LitCov |
| 657 | Mental health of Covid-19 risk groups during the first Covid-19 lockdown in Germany: a cross-sectional study N/A | BMC Public Health | 2022 | | LitCov |
| 658 | Navigating migraine care through the COVID-19 pandemic: an update The worldwide treatment gap for migraine before COVID-19 inevitably widens as attention focuses on an international emergency. Migraine hits people particularly in their early and middle years, potentially reduces quality of life and productivity, and remains a common emergency presentation. This article examines the impact of COVID-19 on migraine, and changing aspects of migraine care during and after the pandemic. Many risk factors for severe COVID-19—older age, male gender, cardiac and respiratory diseases, diabetes, obesity, and immunosuppression—are less frequent in migraineurs. Telemedicine is effective for migraine follow-up, and needs ongoing evaluation. Most migraine treatments can start or continue in acute COVID-19, with care to avoid drug interactions. Close contact procedures (botulinum toxin, acupuncture and steroid injections) are avoided in lockdown or in the vulnerable. Secondary effects of COVID-19, including long COVID and its economic impact, are probably equal or greater in people with migraine. Migraine and other long-term conditions need adequate resourcing to prevent personal, social and economic suffering. Treating migraine, a sequel of COVID, potentially reduces the impact of long COVID. | J Neurol | 2021 | | LitCov and CORD-19 |
| 659 | Effectiveness of personal protective health behaviour against COVID-19 BACKGROUND: Novel coronavirus disease 2019 (COVID-19) has become a pandemic, and over 80 million cases and over 1.8 million deaths were reported in 2020. This highly contagious virus is spread primarily via respiratory droplets from face-to-face contact and contaminated surfaces as well as potential aerosol spread. Over half of transmissions occur from presymptomatic and asymptomatic carriers. Although several vaccines are currently available for emergency use, there are uncertainties regarding the duration of protection and the efficacy of preventing asymptomatic spread. Thus, personal protective health behaviour and measures against COVID-19 are still widely recommended after immunization. This study aimed to clarify the efficacy of these measures, and the results may provide valuable guidance to policymakers to educate the general public about how to reduce the individual-level risk of COVID-19 infection. METHODS: This case-control study enrolled 24 laboratory-confirmed COVID-19 patients from Centro Hospitalar Conde de São Januário (C.H.C.S.J.), which was the only hospital designated to manage COVID-19 patients in Macao SAR, China, and 1113 control participants who completed a 14-day mandatory quarantine in 12 designated hotels due to returning from high-risk countries between 17 March and 15 April 2020. A questionnaire was developed to extract demographic information, contact history, and personal health behaviour. RESULTS: Participants primarily came from the United Kingdom (33.2%), followed by the United States (10.5%) and Portugal (10.2%). Independent factors for COVID-19 infection were having physical contact with confirmed/suspected COVID-19 patients (adjusted OR, 12.108 [95% CI, 3.380–43.376], P < 0.005), participating in high-risk gathering activities (adjusted OR, 1.129 [95% CI, 1.048–1.216], P < 0.005), handwashing after outdoor activity (adjusted OR, 0.021 [95% CI, 0.003–0.134], P < 0.005), handwashing before touching the mouth and nose area (adjusted OR, 0.303 [95% CI, 0.114–0.808], P < 0.05), and wearing a mask whenever outdoors (adjusted OR, 0.307 [95% CI, 0.109–0.867], P < 0.05). The daily count of handwashing remained similar between groups. Only 31.6% of participants had a sufficient 20-s handwashing duration. CONCLUSIONS: Participating in high-risk gatherings, wearing a mask whenever outdoors, and practising hand hygiene at key times should be advocated to the public to mitigate COVID-19 infection. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-021-10680-5. | BMC Public Health | 2021 | | LitCov and CORD-19 |
| 660 | Neuropathology of COVID-19 (neuro-COVID): clinicopathological update N/A | Free Neuropathol | 2021 | | LitCov and CORD-19 |
| 661 | SARS-CoV-2 in semen: Potential for sexual transmission in COVID-19 | Int J Surg | 2020 | | LitCov and CORD-19 |
| 662 | Severe disease exacerbation after mRNA COVID-19 vaccination unmasks suspected multiple sclerosis as neuromyelitis optica spectrum disorder: a case report BACKGROUND: Since the beginning of the COVID-19 pandemic and development of new vaccines, the issue of post-vaccination exacerbation or manifestation of demyelinating central nervous system (CNS) disorders has gained increasing attention. CASE PRESENTATION: We present a case of a 68-year-old woman previously diagnosed with multiple sclerosis (MS) since the 1980s who suffered a rapidly progressive severe sensorimotor paraparesis with loss of bladder and bowel control due to an acute longitudinal extensive transverse myelitis (LETM) after immunization with the mRNA Pfizer–BioNTech COVID-19 vaccine. Detection of Aquaporin-4-antibodies (AQP4) in both serum and CSF led to diagnosis of AQP4-antibody positive neuromyelitis optica spectrum disorder (NMOSD). Treatment with intravenous corticosteroids and plasmapheresis led to a slight improvement of the patient’s symptoms. CONCLUSIONS: Pathogenic mechanisms of post-vaccination occurrence of NMOSD are still unknown. However, cases like this should make aware of rare neurological disorders manifesting after vaccination and potentially contribute to improvement of management of vaccinating patients with inflammatory CNS disorders in the future. So far two cases of AQP4-antibody positive NMOSD have been reported in association with viral vector COVID-19 vaccines. To our knowledge, we report the first case of AQP4-antibody positive NMOSD after immunization with an mRNA COVID-19-vaccine. | BMC Neurol | 2022 | | LitCov and CORD-19 |
| 663 | COVID-19 epidemiology and changes in health service utilization in Azraq and Zaatari refugee camps in Jordan: A retrospective cohort study BACKGROUND: The effects of the Coronavirus Disease 2019 (COVID-19) pandemic in humanitarian contexts are not well understood. Specific vulnerabilities in such settings raised concerns about the ability to respond and maintain essential health services. This study describes the epidemiology of COVID-19 in Azraq and Zaatari refugee camps in Jordan (population: 37,932 and 79,034, respectively) and evaluates changes in routine health services during the COVID-19 pandemic. METHODS AND FINDINGS: We calculate the descriptive statistics of COVID-19 cases in the United Nations High Commissioner for Refugees (UNHCR)’s linelist and adjusted odds ratios (aORs) for selected outcomes. We evaluate the changes in health services using monthly routine data from UNHCR’s health information system (HIS; January 2018 to March 2021) and apply interrupted time series analysis with a generalized additive model and negative binomial (NB) distribution, accounting for long-term trends and seasonality, reporting results as incidence rate ratios (IRRs). COVID-19 cases were first reported on September 8 and September 13, 2020 in Azraq and Zaatari camps, respectively, 6 months after the first case in Jordan. Incidence rates (IRs) were lower in camps than neighboring governorates (by 37.6% in Azraq (IRR: 0.624, 95% confidence interval [CI]: [0.584 to 0.666], p-value: <0.001) and 40.2% in Zaatari (IRR: 0.598, 95% CI: [0.570, 0.629], p-value: <0.001)) and lower than Jordan (by 59.7% in Azraq (IRR: 0.403, 95% CI: [0.378 to 0.430], p-value: <0.001) and by 63.3% in Zaatari (IRR: 0.367, 95% CI: [0.350 to 0.385], p-value: <0.001)). Characteristics of cases and risk factors for negative disease outcomes were consistent with increasing COVID-19 evidence. The following health services reported an immediate decline during the first year of COVID-19: healthcare utilization (by 32% in Azraq (IRR: 0.680, 95% CI [0.549 to 0.843], p-value < 0.001) and by 24.2% in Zaatari (IRR: 0.758, 95% CI [0.577 to 0.995], p-value = 0.046)); consultations for respiratory tract infections (RTIs; by 25.1% in Azraq (IRR: 0.749, 95% CI: [0.596 to 0.940], p-value = 0.013 and by 37.5% in Zaatari (IRR: 0.625, 95% CI: [0.461 to 0.849], p-value = 0.003)); and family planning (new and repeat family planning consultations decreased by 47.4% in Azraq (IRR: 0.526, 95% CI: [0.376 to 0.736], p-value = <0.001) and 47.6% in Zaatari (IRR: 0.524, 95% CI: [0.312 to 0.878], p-value = 0.014)). Maternal and child health services as well as noncommunicable diseases did not show major changes compared to pre–COVID-19 period. Conducting interrupted time series analyses in volatile settings such refugee camps can be challenging as it may be difficult to meet some analytical assumptions and to mitigate threats to validity. The main limitation of this study relates therefore to possible unmeasured confounding. CONCLUSIONS: COVID-19 transmission was lower in camps than outside of camps. Refugees may have been affected from external transmission, rather than driving it. Various types of health services were affected differently, but disruptions appear to have been limited in the 2 camps compared to other noncamp settings. These insights into Jordan’s refugee camps during the first year of the COVID-19 pandemic set the stage for follow-up research to investigate how infection susceptibility evolved over time, as well as which mitigation strategies were more successful and accepted. | PLoS Med | 2022 | | LitCov and CORD-19 |
| 664 | Strongyloidiasis in the COVID era: a warning for an implementation of the screening protocol | Infection | 2021 | | LitCov and CORD-19 |
| 665 | A broadly neutralizing antibody protects Syrian hamsters against SARS-CoV-2 Omicron challenge N/A | Nat Commun | 2022 | | LitCov |
| 666 | Awareness and preparedness of healthcare workers against the first wave of the COVID-19 pandemic: A cross-sectional survey across 57 countries BACKGROUND: Since the COVID-19 pandemic began, there have been concerns related to the preparedness of healthcare workers (HCWs). This study aimed to describe the level of awareness and preparedness of hospital HCWs at the time of the first wave. METHODS: This multinational, multicenter, cross-sectional survey was conducted among hospital HCWs from February to May 2020. We used a hierarchical logistic regression multivariate analysis to adjust the influence of variables based on awareness and preparedness. We then used association rule mining to identify relationships between HCW confidence in handling suspected COVID-19 patients and prior COVID-19 case-management training. RESULTS: We surveyed 24,653 HCWs from 371 hospitals across 57 countries and received 17,302 responses from 70.2% HCWs overall. The median COVID-19 preparedness score was 11.0 (interquartile range [IQR] = 6.0–14.0) and the median awareness score was 29.6 (IQR = 26.6–32.6). HCWs at COVID-19 designated facilities with previous outbreak experience, or HCWs who were trained for dealing with the SARS-CoV-2 outbreak, had significantly higher levels of preparedness and awareness (p<0.001). Association rule mining suggests that nurses and doctors who had a ’great-extent-of-confidence’ in handling suspected COVID-19 patients had participated in COVID-19 training courses. Male participants (mean difference = 0.34; 95% CI = 0.22, 0.46; p<0.001) and nurses (mean difference = 0.67; 95% CI = 0.53, 0.81; p<0.001) had higher preparedness scores compared to women participants and doctors. INTERPRETATION: There was an unsurprising high level of awareness and preparedness among HCWs who participated in COVID-19 training courses. However, disparity existed along the lines of gender and type of HCW. It is unknown whether the difference in COVID-19 preparedness that we detected early in the pandemic may have translated into disproportionate SARS-CoV-2 burden of disease by gender or HCW type. | PLoS One | 2021 | | LitCov and CORD-19 |
| 667 | Recreational Screen Time Behaviors during the COVID-19 Pandemic in the U.S.: A Mixed-Methods Study among a Diverse Population-Based Sample of Emerging Adults Understanding how screen time behaviors changed during the COVID-19 pandemic is important to inform the design of health promotion interventions. The purpose of this study was to quantify and describe changes in recreational screen time from 2018 to 2020 among a diverse sample of emerging adults. Participants (n = 716) reported their average weekly recreational screen time in 2018 and again during the pandemic in 2020. Additionally, participants qualitatively reported how events related to COVID-19 had influenced their screen time. Weekly recreational screen time increased from 25.9 ± 11.9 h in 2018 to 28.5 ± 11.6 h during COVID-19 (p < 0.001). The form of screen time most commonly reported to increase was TV shows and streaming services (n = 233). Commonly reported reasons for changes in screen time were boredom (n = 112) and a desire to connect with others (n = 52). Some participants reported trying to reduce screen time because of its negative impact on their mental health (n = 32). Findings suggest that screen time and mental health may be intertwined during the pandemic as it may lead to poorer mental health for some, while promoting connectedness for others. Health professionals and public health messaging could promote specific forms for screen time to encourage social connection during the COVID-19 pandemic and beyond. | Int J Environ Res Public Healt | 2021 | | LitCov and CORD-19 |
| 668 | Cysteamine exerts in vitro antiviral activity against the SARS-CoV-2 Delta and Omicron variants N/A | Cell Death Discov | 2022 | | LitCov |
| 669 | A sprayable Acid-Oxidizing solution containing hypochlorous acid (AOS2020) efficiently and safely inactivates SARS-Cov-2: a new potential solution for upper respiratory tract hygiene INTRODUCTION: To eliminate the COVID-19 pandemic, the transmission of the virus SARS-CoV-2 among the population needs to be blocked and/or at least reduced. Upper respiratory tract viral loads are highest in the early stages of the disease, and high loads are associated with higher mortality rates. This study aims to evaluate the virucidal efficacy of AOS2020, a novel sprayable Acid-Oxidizing solution containing pure and stable hypochlorous acid (HClO), on human coronavirus SARS-Cov-2 in vitro, and the tolerability profile on nasal and oral mucosa suggesting to be a potential solution for upper respiratory hygiene. METHOD: Virucidal assays and intranasal and oral irritation tests were undertaken in accordance with relevant national and international guidance and methods. RESULTS: In pre-clinical tests, the AOS2020, showed > 99.8% virucidal efficacy in < 1 min against SARS-Cov-2. The safety profile testing on both the nasal and oral mucosa indicates that AOS2020 is non-irritant. CONCLUSION: These initial results indicate that this product has the potential treatment to reduce viral load in the upper respiratory tract. | Eur Arch Otorhinolaryngol | 2021 | | LitCov and CORD-19 |
| 670 | A scoping review of strategies to support public health recovery in the transition to a "new normal" in the age of COVID-19 N/A | BMC Public Health | 2022 | | LitCov |
| 671 | Reemergence of Human Monkeypox and Declining Population Immunity in the Context of Urbanization, Nigeria, 2017-2020 A monkeypox outbreak in Nigeria during 2017–2020 provides an illustrative case study for emerging zoonoses. We built a statistical model to simulate declining immunity from monkeypox at 2 levels: At the individual level, we used a constant rate of decline in immunity of 1.29% per year as smallpox vaccination rates fell. At the population level, the cohort of vaccinated residents decreased over time because of deaths and births. By 2016, only 10.1% of the total population in Nigeria was vaccinated against smallpox; the serologic immunity level was 25.7% among vaccinated persons and 2.6% in the overall population. The substantial resurgence of monkeypox in Nigeria in 2017 appears to have been driven by a combination of population growth, accumulation of unvaccinated cohorts, and decline in smallpox vaccine immunity. The expanding unvaccinated population means that entire households, not just children, are now more susceptible to monkeypox, increasing risk of human-to-human transmission. | Emerg Infect Dis | 2021 | | CORD-19 |
| 672 | Intensive Treatment With Ivermectin and Iota-Carrageenan as Pre-exposure Prophylaxis for COVID-19 in Healthcare Workers From Tucuman, Argentina | Am J Ther | 2021 | | LitCov and CORD-19 |
| 673 | Cyclin dependent kinase inhibitors as a new potential therapeutic option in management of COVID-19 | Med Hypotheses | 2020 | | LitCov and CORD-19 |
| 674 | Studying severe long COVID to understand post-infectious disorders beyond COVID-19 N/A | Nat Med | 2022 | | LitCov and CORD-19 |
| 675 | First case of postmortem study in a patient vaccinated against SARS-CoV-2 A previously symptomless 86-year-old man received single mRNA vaccine BNT162b2. Four weeks later, he succumbed to death due to acute renal and respiratory failure. Although he did not present with any symptoms specific for Coronavirus disease 19 (COVID19), he obtained positive testing for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), before he died. S1 antigen-binding notably showed significant levels for IgG, while nucleocapsid IgG/IgM was not elicited . By means of autopsy, acute bronchopneumonia and acute tubular failure were assigned as cause death of death. However, we did not observe any characteristic morphological features of COVID19. Postmortem molecular mapping by real time-polymerase chain reaction (RT-PCR) additionally revealed relevant SARS-CoV-2 Ct values in all organs examined (oropharynx, olfactory mucosa, trachea, lungs, heart, kidney, and cerebrum) except for liver and olfactory bulb. These results might contribute to the view that first vaccination induces immunogenicity, but not sterile immunity. | Int J Infect Dis | 2021 | | LitCov and CORD-19 |
| 676 | Haemophagocytic lymphohistiocytosis following COVID-19 mRNA vaccination The development of vaccinations has been instrumental in the ongoing effort to combat the COVID-19 pandemic. Although the benefits of vaccination are unquestionable, there have been reports of potentially rare life-threatening complications following vaccination including thrombocytopaenia, haemolytic anaemia, vasculitis and myocarditis. Haemophagocytic lymphohistiocytosis (HLH), a rare but life-threatening inflammatory condition, has also been described postadenoviral vector COVID-19 vaccination but it has never been reported post-messenger RNA (mRNA) COVID-19 vaccination. We report two cases of HLH admitted to our hospital after administration of COVID-19 mRNA vaccines. We also searched the vaccine adverse event reporting system and found 50 reports of suspected HLH following COVID-19 vaccination. Presently, we cannot define a causality between COVID-19 mRNA vaccination and HLH development. However, we hope the reporting of our two cases (and additional cases seen in the adverse event reporting database) will help us determine whether there is a potential relationship. Prompt recognition of this condition is of utmost importance to initiate life-saving therapy. | BMJ Case Rep | 2022 | | LitCov and CORD-19 |
| 677 | No evidence that vitamin D is able to prevent or affect the severity of COVID-19 in individuals with European ancestry: a Mendelian randomisation study of open data BACKGROUND: Upper respiratory tract infections are reportedly more frequent and more severe in individuals with lower vitamin D levels. Based on these findings, it has been suggested that vitamin D can prevent or reduce the severity of COVID-19. METHODS: We used two-sample Mendelian randomisation (MR) to assess the causal effect of vitamin D levels on SARS-CoV-2 infection risk and COVID-19 severity using publicly available data. We also carried out a genome-wide association analysis (GWA) of vitamin D deficiency in the UK Biobank (UKB) and used these results and two-sample MR to assess the causal effect of vitamin D deficiency on SARS-CoV-2 infection risk and COVID-19 severity. RESULTS: We found no evidence that vitamin D levels causally affect the risk of SARS-CoV-2 infection (ln(OR)=0.17 (95% CI −0.22 to 0.57, p=0.39)) nor did we find evidence that vitamin D levels causally affect COVID-19 severity (ln(OR)=0.36 (95% CI −0.89 to 1.61, p=0.57)). Based on our GWA analysis, we found that 17 independent variants are associated with vitamin D deficiency in the UKB. Using these variants as instruments for our two-sample MR analyses, we found no evidence that vitamin D deficiency causally affects the risk of SARS-CoV-2 infection (ln(OR)=−0.04 (95% CI −0.1 to 0.03, p=0.25)) nor did we find evidence that vitamin D deficiency causally affects COVID-19 severity (ln(OR)=−0.24 (95% CI −0.55 to 0.08, p=0.14)). CONCLUSIONS: In conclusion, we found no evidence that vitamin D is protective against SARS-CoV-2 infection or COVID-19 severity. Our data support the recent statement by the National Institute for Health and Care Excellence that the use of vitamin D supplementation to mitigate COVID-19 is not supported by the available data. | BMJ Nutr Prev Health | 2021 | | LitCov and CORD-19 |
| 678 | SARS-CoV-2 vaccination can elicit a CD8 T-cell dominant hepatitis BACKGROUND & AIMS: Autoimmune hepatitis episodes have been described following SARS-CoV-2 infection and vaccination but their pathophysiology remains unclear. Here, we report the case of a 52-year-old male, presenting with bimodal episodes of acute hepatitis, each occurring 2-3 weeks after BNT162b2 mRNA vaccination and sought to identify the underlying immune correlates. The patient received first oral budesonide, relapsed, but achieved remission under systemic steroids. METHODS: Imaging mass cytometry for spatial immune profiling was performed on liver biopsy tissue. Flow cytometry was performed to dissect CD8 T cell phenotypes and identify SARS-CoV-2-specific and EBV-specific T cells longitudinally. Vaccine-induced antibodies were determined by ELISA. Data was correlated with clinical labs. RESULTS: Analysis of the hepatic tissue revealed an immune infiltrate quantitatively dominated by activated cytotoxic CD8 T cells with panlobular distribution. An enrichment of CD4 T cells, B cells, plasma cells and myeloid cells was also observed compared to controls. The intrahepatic infiltrate showed enrichment for CD8 T cells with SARS-CoV-2-specificity compared to the peripheral blood. Notably, hepatitis severity correlated longitudinally with an activated cytotoxic phenotype of peripheral SARS-CoV-2-specific, but not EBV-specific CD8+ T cells or vaccine-induced immunoglobulins. CONCLUSIONS: COVID19 vaccination can elicit a distinct T cell-dominant immune-mediated hepatitis with a unique pathomechanism associated with vaccination induced antigen-specific tissue-resident immunity requiring systemic immunosuppression. LAY SUMMARY: Liver inflammation is observed during SARS-CoV-2 infection but can also occur in some individuals after vaccination and shares some typical features with autoimmune liver disease. In this report, we show that highly activated T cells accumulate and are evenly distributed in the different areas of the liver in a patient with liver inflammation following SARS-CoV-2 vaccination. Moreover, within these liver infiltrating T cells, we observed an enrichment of T cells that are reactive to SARS-CoV-2, suggesting that these vaccine-induced cells can contribute to the liver inflammation in this context. | J Hepatol | 2022 | | LitCov and CORD-19 |
| 679 | A systematic review of effectiveness of BNT162b2 mRNA and ChAdOx1 adenoviral vector COVID-19 vaccines in the general population BACKGROUND: High effectiveness of COVID-19 vaccines is essential for the pandemic control. This study systematically reviewed available evidence on effectiveness of ChAdOx1 and BNT162b2 vaccines in the general population, for improved vaccine policies and strategies. MAIN BODY OF THE ABSTRACT: Using several keywords, a search of Scopus, PubMed, Google scholar and Hinari databases was conducted from December 1, 2020 to June 9, 2021. Eligible studies comprising original studies reporting effectiveness of the vaccines, were included following PRISMA guidelines. Individual studies were assessed for quality using National Heart, Lung and Blood Institute quality assessment tool. A total of 1766 titles were retrieved and 11 were included, out of which only 5 were peer-reviewed. Although data availability was limited, studies suggest equivalent effectiveness of BNT162b2 and ChAdOx1 COVID-19 vaccine against SARS-CoV-2 infection and COVID-19 related morbidity and mortality. Vaccine effectiveness increased steadily to about 35 days, with an enhanced effectiveness following the second dose. SHORT CONCLUSION: BNT162 and ChAdOx1 vaccines were associated with equivalent and high effectiveness which increased with time and a second dose in the general population. This encourages continued practice of other preventive measures, particularly during the first week of vaccination, and reinforces the need for a second dose. | Bull Natl Res Cent | 2021 | | LitCov and CORD-19 |
| 680 | Food Insecurity and Health-Related Concerns Among Elementary Schoolteachers During the COVID-19 Pandemic N/A | Prev Chronic Dis | 2022 | | LitCov and CORD-19 |
| 681 | Body temperature screening to identify SARS-CoV-2 infected young adult travellers is ineffective | Travel Med Infect Dis | 2020 | | LitCov and CORD-19 |
| 682 | Transcriptomics-based drug repositioning pipeline identifies therapeutic candidates for COVID-19 The novel SARS-CoV-2 virus emerged in December 2019 and has few effective treatments. We applied a computational drug repositioning pipeline to SARS-CoV-2 differential gene expression signatures derived from publicly available data. We utilized three independent published studies to acquire or generate lists of differentially expressed genes between control and SARS-CoV-2-infected samples. Using a rank-based pattern matching strategy based on the Kolmogorov–Smirnov Statistic, the signatures were queried against drug profiles from Connectivity Map (CMap). We validated 16 of our top predicted hits in live SARS-CoV-2 antiviral assays in either Calu-3 or 293T-ACE2 cells. Validation experiments in human cell lines showed that 11 of the 16 compounds tested to date (including clofazimine, haloperidol and others) had measurable antiviral activity against SARS-CoV-2. These initial results are encouraging as we continue to work towards a further analysis of these predicted drugs as potential therapeutics for the treatment of COVID-19. | Sci Rep | 2021 | | LitCov and CORD-19 |
| 683 | Causal relationship between physical activity, leisure sedentary behaviors and COVID-19 risk: a Mendelian randomization study BACKGROUND: The 2019 coronavirus disease pandemic (COVID-19) poses an enormous threat to public health worldwide, and the ensuing management of social isolation has greatly decreased opportunities for physical activity (PA) and increased opportunities for leisure sedentary behaviors (LSB). Given that both PA and LSB have been established as major influencing factors for obesity, diabetes and cardiometabolic syndrome, whether PA/LSB in turn affects the susceptibility to COVID-19 by disrupting metabolic homeostasis remains to be explored. In this study, we aimed to systematically evaluate the causal relationship between PA/LSB and COVID-19 susceptibility, hospitalization and severity using a Mendelian randomization study. METHODS: Data were obtained from a large-scale PA dataset (N = 377,000), LSB dataset (N = 422,218) and COVID-19 Host Genetics Initiative (N = 2,586,691). The causal effects were estimated with inverse variance weighted, MR-Egger, weighted median and MR-PRESSO. Sensitivity analyses were implemented with Cochran’s Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis and the funnel plot. Risk factor analyses were further conducted to investigate the potential mediators. RESULTS: Genetically predicted accelerometer-assessed PA decreased the risk for COVID-19 hospitalization (OR = 0.93, 95% CI 0.88–0.97; P = 0.002), while leisure television watching significantly increased the risk of COVID-19 hospitalization (OR = 1.55, 95% CI 1.29–1.88; P = 4.68 × 10(–6)) and disease severity (OR = 1.85, 95% CI 1.33–2.56; P = 0.0002) after Bonferroni correction. No causal effects of self-reported moderate to vigorous physical activity (MVPA), accelerometer fraction of accelerations > 425 milligravities, computer use or driving on COVID-19 progression were observed. Risk factor analyses indicated that the above causal associations might be mediated by several metabolic risk factors, including smoking, high body mass index, elevated serum triglyceride levels, insulin resistance and the occurrence of type 2 diabetes. CONCLUSION: Our findings supported a causal effect of accelerometer-assessed PA on the reduced risk of COVID-19 hospitalization as well as television watching on the increased risk of COVID-19 hospitalization and severity, which was potentially mediated by smoking, obesity and type 2 diabetes-related phenotypes. Particular attention should be given to reducing leisure sedentary behaviors and encouraging proper exercise during isolation and quarantine for COVID-19. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-022-03407-6. | J Transl Med | 2022 | | LitCov and CORD-19 |
| 684 | The Prevalence of Post-traumatic Stress Disorder Among Healthcare Workers During the COVID-19 Pandemic: An Umbrella Review and Meta-Analysis Introduction: Frontline health care workers (HCWs) have had an increased risk of developing health problems during the COVID-19 pandemic. In addition to physical illness, they have experienced mental health challenges, including post-traumatic stress disorder (PTSD). The aim of this study is to investigate the prevalence of PTSD among HCWs during the COVID-19 pandemic via an umbrella review and meta-analysis. Methods: This study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline to perform a systematic literature search using various medical databases (Web of science, PubMed, Scopus, Cochrane, ProQuest, Science Direct, Embase, and Google scholar). The search included all articles published through the first of January 2020 the end of March 2021. The systematic review and meta-analysis studies that reported the prevalence of PTSD among health care workers were included in the study, and studies that reported the prevalence of PTSD in normal people or other epidemics were excluded. The random effects model was used to perform a meta-analysis, and the I(2) index was used to evaluate heterogeneity among studies. Publication bias was assessed using the Egger test. Data was analyzed using STATA (version 14) software. Results: The initial literature search yielded 145 studies. After excluding duplicates and assessing the quality of the studies, 7 studies were selected for meta-analysis. The results showed that the overall prevalence of PTSD among HCWs during the COVID-19 pandemic was 13.52% (95% CI: 9.06–17.98, I(2) = 65.5%, p = 0.008). Conclusion: There is a high prevalence of PTSD among frontline HCWs during the COVID-19 pandemic. It is important to invest in efforts to screen HCWs for mental health disorders such as PTSD and provide them with mental health support. | Front Psychiatry | 2021 | | LitCov and CORD-19 |
| 685 | Symptoms After COVID-19 Vaccination in Patients with Post-Acute Sequelae of SARS-CoV-2 | J Gen Intern Med | 2022 | | LitCov and CORD-19 |
| 686 | Reduced antibody cross-reactivity following infection with B.1.1.7 than with parental SARS-CoV-2 strains BACKGROUND: The degree of heterotypic immunity induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains is a major determinant of the spread of emerging variants and the success of vaccination campaigns, but remains incompletely understood. METHODS: We examined the immunogenicity of SARS-CoV-2 variant B.1.1.7 (Alpha) that arose in the United Kingdom and spread globally. We determined titres of spike glycoprotein-binding antibodies and authentic virus neutralising antibodies induced by B.1.1.7 infection to infer homotypic and heterotypic immunity. RESULTS: Antibodies elicited by B.1.1.7 infection exhibited significantly reduced recognition and neutralisation of parental strains or of the South Africa variant B.1.351 (Beta) than of the infecting variant. The drop in cross-reactivity was significantly more pronounced following B.1.1.7 than parental strain infection. CONCLUSIONS: The results indicate that heterotypic immunity induced by SARS-CoV-2 variants is asymmetric. FUNDING: This work was supported by the Francis Crick Institute and the Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg. | Elife | 2021 | | LitCov and CORD-19 |
| 687 | Gut microbiota dynamics in a prospective cohort of patients with post-acute COVID-19 syndrome BACKGROUND: Long-term complications after COVID-19 are common, but the potential cause for persistent symptoms after viral clearance remains unclear. OBJECTIVE: To investigate whether gut microbiome composition is linked to post-acute COVID-19 syndrome (PACS), defined as at least one persistent symptom 4 weeks after clearance of the SARS-CoV-2 virus. METHODS: We conducted a prospective study of 106 patients with a spectrum of COVID-19 severity followed up from admission to 6 months and 68 non-COVID-19 controls. We analysed serial faecal microbiome of 258 samples using shotgun metagenomic sequencing, and correlated the results with persistent symptoms at 6 months. RESULTS: At 6 months, 76% of patients had PACS and the most common symptoms were fatigue, poor memory and hair loss. Gut microbiota composition at admission was associated with occurrence of PACS. Patients without PACS showed recovered gut microbiome profile at 6 months comparable to that of non-COVID-19 controls. Gut microbiome of patients with PACS were characterised by higher levels of Ruminococcus gnavus, Bacteroides vulgatus and lower levels of Faecalibacterium prausnitzii. Persistent respiratory symptoms were correlated with opportunistic gut pathogens, and neuropsychiatric symptoms and fatigue were correlated with nosocomial gut pathogens, including Clostridium innocuum and Actinomyces naeslundii (all p<0.05). Butyrate-producing bacteria, including Bifidobacterium pseudocatenulatum and Faecalibacterium prausnitzii showed the largest inverse correlations with PACS at 6 months. CONCLUSION: These findings provided observational evidence of compositional alterations of gut microbiome in patients with long-term complications of COVID-19. Further studies should investigate whether microbiota modulation can facilitate timely recovery from post-acute COVID-19 syndrome. | Gut | 2022 | | LitCov and CORD-19 |
| 688 | Randomized placebo-controlled pilot clinical trial on the efficacy of ayurvedic treatment regime on COVID-19 positive patients BACKGROUND: Specific treatment for COVID-19 is still an unmet need. Outcomes of clinical trials on repurposed drugs have not been yielding success. Therefore, it is necessary to include complementary approaches of medicine against COVID-19. PURPOSE: This study was designed to evaluate the impact of traditional Indian Ayurvedic treatment regime on asymptomatic patients with COVID-19 infection. STUDY DESIGN: It is a placebo controlled randomized double-blind pilot clinical trial. METHODS: The study was registered with Clinical Trial Registry-India (vide Registration No. CTRI/2020/05/025273) and conducted at the Department of Medicine in National Institute of Medical Sciences and Research, Jaipur, India. 1 g of Giloy Ghanvati (Tinospora cordifolia) and 2 g of Swasari Ras (traditional herbo-mineral formulation) and 0.5 g each of Ashwagandha (Withania somnifera) and Tulsi Ghanvati (Ocimum sanctum) were given orally to the patients in treatment group twice per day for 7 days. Medicines were given in the form of tablets and each tablet weighed 500 mg. While, Swasari Ras was administered in powdered form, 30 min before breakfasts and dinners, rest were scheduled for 30 min post-meals. Patients in the treatment group also received 4 drops of Anu taila (traditional nasal drop) in each nostril every day 1 h before breakfast. Patients in the placebo group received identical-looking tablets and drops, post randomization and double blinded assortments. RT-qPCR test was used for the detection of viral load in the nasopharyngeal and oropharyngeal swab samples of study participants during the study. Chemiluminescent immunometric assay was used to quantify serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and high sensitivity C-reactive protein (hs-CRP) on day 1 and day 7 of the study. RESULTS: By day 3, 71.1 % and 50.0 % patients recovered in the treatment and placebo groups, respectively. Treatment group witnessed 100% recovery by day 7, while it was 60.0 % in the placebo group. Average fold changes in serum levels of hs-CRP, IL-6 and TNF-α in treatment group were respectively, 12.4, 2.5 and 20 times lesser than those in the placebo group at day 7. There was 40% absolute reduction in the risk of delayed recovery from infection in the treatment group. CONCLUSIONS: Ayurvedic treatment can expedite virological clearance, help in faster recovery and concomitantly reduce the risk of viral dissemination. Reduced inflammation markers suggested less severity of SARS-CoV-2 infection in the treatment group. Moreover, there was no adverse effect observed to be associated with this treatment. | Phytomedicine | 2021 | | LitCov and CORD-19 |
| 689 | SARS-CoV-2 spike-specific memory B cells express higher levels of T-bet and FcRL5 after nonsevere COVID-19 as compared to severe disease SARS-CoV-2 infection elicits a robust B cell response, resulting in the generation of long-lived plasma cells and memory B cells. Here, we aimed to determine the effect of COVID-19 severity on the memory B cell response and characterize changes in the memory B cell compartment between recovery and five months post-symptom onset. Using high-parameter spectral flow cytometry, we analyzed the phenotype of memory B cells with reactivity against the SARS-CoV-2 spike protein or the spike receptor binding domain (RBD) in recovered individuals who had been hospitalized with non-severe (n = 8) or severe (n = 5) COVID-19. One month after symptom onset, a substantial proportion of spike-specific IgG(+) B cells showed an activated phenotype. In individuals who experienced non-severe disease, spike-specific IgG(+) B cells showed increased expression of markers associated with durable B cell memory, including T-bet and FcRL5, as compared to individuals who experienced severe disease. While the frequency of T-bet(+) spike-specific IgG(+) B cells differed between the two groups, these cells predominantly showed an activated switched memory B cell phenotype in both groups. Five months post-symptom onset, the majority of spike-specific memory B cells had a resting phenotype and the percentage of spike-specific T-bet(+) IgG(+) memory B cells decreased to baseline levels. Collectively, our results highlight subtle differences in the B cells response after non-severe and severe COVID-19 and suggest that the memory B cell response elicited during non-severe COVID-19 may be of higher quality than the response after severe disease. | PLoS One | 2021 | | LitCov and CORD-19 |
| 690 | Time of day influences immune response to an inactivated vaccine against SARS-CoV-2 | Cell Res | 2021 | | LitCov and CORD-19 |
| 691 | The impact of the COVID-19 pandemic on the research activity and working experience of clinical academics, with a focus on gender and ethnicity: a qualitative study in the UK N/A | BMJ Open | 2022 | | LitCov |
| 692 | Low vitamin D levels do not aggravate COVID-19 risk or death and vitamin D supplementation does not improve outcomes in hospitalized patients with COVID-19: a meta-analysis and GRADE assessment of cohort studies and RCTs BACKGROUND: The associations between vitamin D and coronavirus disease 2019 (COVID-19) infection and clinical outcomes are controversial. The efficacy of vitamin D supplementation in COVID-19 is also not clear. METHODS: We identified relevant cohort studies that assessed the relationship between vitamin D, COVID-19 infection and associated death and randomized controlled trials (RCTs) that reported vitamin D supplementation on the outcomes in patients with COVID-19 by searching the PubMed, EMBASE, and medRxiv databases up to June 5th, 2021. Evidence quality levels and recommendations were assessed using the GRADE system. RESULTS: Eleven cohort studies with 536,105 patients and two RCTs were identified. Vitamin D deficiency (< 20 ng/ml) or insufficiency (< 30 ng/ml) was not associated with an significant increased risk of COVID-19 infection (OR for < 20 ng/ml: 1.61, 95% CI: 0.92–2.80, I2 = 92%) or in-hospital death (OR for < 20 ng/ml: 2.18, 95% CI: 0.91–5.26, I2 = 72%; OR for < 30 ng/ml: 3.07, 95% CI: 0.64–14.78, I2 = 66%). Each 10 ng/ml increase in serum vitamin D was not associated with a significant decreased risk of COVID-19 infection (OR: 0.92, 95% CI: 0.79–1.08, I2 = 98%) or death (OR: 0.65, 95% CI: 0.40–1.06, I2 = 79%). The overall quality of evidence (GRADE) for COVID-19 infection and associated death was very low. Vitamin D supplements did not significantly decrease death (OR: 0.57, I2 = 64%) or ICU admission (OR: 0.14, I2 = 90%) in patients with COVID-19. The level of evidence as qualified using GRADE was low. CONCLUSIONS: Current evidence suggested that vitamin D deficiency or insufficiency was not significantly linked to susceptibility to COVID-19 infection or its associated death. Vitamin D supplements did not significantly improve clinical outcomes in patients with COVID-19. The overall GRADE evidence quality was low, we suggest that vitamin D supplementation was not recommended for patients with COVID-19. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12937-021-00744-y. | Nutr J | 2021 | | LitCov and CORD-19 |
| 693 | Immediate effect of the COVID-19 pandemic on patient health, health-care use and behaviours: results from an international survey of people with rheumatic diseases BACKGROUND: The impact and consequences of the COVID-19 pandemic on people with rheumatic disease are unclear. We developed the COVID-19 Global Rheumatology Alliance Patient Experience Survey to assess the effects of the COVID-19 pandemic on people with rheumatic disease worldwide. METHODS: Survey questions were developed by key stakeholder groups and disseminated worldwide through social media, websites, and patient support organisations. Questions included demographics, rheumatic disease diagnosis, COVID-19 diagnosis, adoption of protective behaviours to mitigate COVID-19 exposure, medication access and changes, health-care access and communication with rheumatologists, and changes in employment or schooling. Adults age 18 years and older with inflammatory or autoimmune rheumatic diseases were eligible for inclusion. We included participants with and without a COVID-19 diagnosis. We excluded participants reporting only non-inflammatory rheumatic diseases such as fibromyalgia or osteoarthritis. FINDINGS: 12 117 responses to the survey were received between April 3 and May 8, 2020, and of these, 10 407 respondents had included appropriate age data. We included complete responses from 9300 adults with rheumatic disease (mean age 46·1 years; 8375 [90·1%] women, 893 [9·6%] men, and 32 [0·3%] participants who identified as non-binary). 6273 (67·5%) of respondents identified as White, 1565 (16·8%) as Latin American, 198 (2·1%) as Black, 190 (2·0%) as Asian, and 42 (0·5%) as Native American or Aboriginal or First Nation. The most common rheumatic disease diagnoses included rheumatoid arthritis (3636 [39·1%] of 9300), systemic lupus erythematosus (2882 [31·0%]), and Sjögren's syndrome (1290 [13·9%]). Most respondents (6921 [82·0%] of 8441) continued their antirheumatic medications as prescribed. Almost all (9266 [99·7%] of 9297) respondents adopted protective behaviours to limit SARS-CoV-2 exposure. A change in employment status occurred in 2524 (27·1%) of 9300) of respondents, with a 13·6% decrease in the number in full-time employment (from 4066 to 3514). INTERPRETATION: People with rheumatic disease maintained therapy and followed public health advice to mitigate the risks of COVID-19. Substantial employment status changes occurred, with potential implications for health-care access, medication affordability, mental health, and rheumatic disease activity. FUNDING: American College of Rheumatology. | Lancet Rheumatol | 2021 | | LitCov and CORD-19 |
| 694 | A single-cell and spatial atlas of autopsy tissues reveals pathology and cellular targets of SARS-CoV-2 The SARS-CoV-2 pandemic has caused over 1 million deaths globally, mostly due to acute lung injury and acute respiratory distress syndrome, or direct complications resulting in multiple-organ failures. Little is known about the host tissue immune and cellular responses associated with COVID-19 infection, symptoms, and lethality. To address this, we collected tissues from 11 organs during the clinical autopsy of 17 individuals who succumbed to COVID-19, resulting in a tissue bank of approximately 420 specimens. We generated comprehensive cellular maps capturing COVID-19 biology related to patients’ demise through single-cell and single-nucleus RNA-Seq of lung, kidney, liver and heart tissues, and further contextualized our findings through spatial RNA profiling of distinct lung regions. We developed a computational framework that incorporates removal of ambient RNA and automated cell type annotation to facilitate comparison with other healthy and diseased tissue atlases. In the lung, we uncovered significantly altered transcriptional programs within the epithelial, immune, and stromal compartments and cell intrinsic changes in multiple cell types relative to lung tissue from healthy controls. We observed evidence of: alveolar type 2 (AT2) differentiation replacing depleted alveolar type 1 (AT1) lung epithelial cells, as previously seen in fibrosis; a concomitant increase in myofibroblasts reflective of defective tissue repair; and, putative TP63(+) intrapulmonary basal-like progenitor (IPBLP) cells, similar to cells identified in H1N1 influenza, that may serve as an emergency cellular reserve for severely damaged alveoli. Together, these findings suggest the activation and failure of multiple avenues for regeneration of the epithelium in these terminal lungs. SARS-CoV-2 RNA reads were enriched in lung mononuclear phagocytic cells and endothelial cells, and these cells expressed distinct host response transcriptional programs. We corroborated the compositional and transcriptional changes in lung tissue through spatial analysis of RNA profiles in situ and distinguished unique tissue host responses between regions with and without viral RNA, and in COVID-19 donor tissues relative to healthy lung. Finally, we analyzed genetic regions implicated in COVID-19 GWAS with transcriptomic data to implicate specific cell types and genes associated with disease severity. Overall, our COVID-19 cell atlas is a foundational dataset to better understand the biological impact of SARS-CoV-2 infection across the human body and empowers the identification of new therapeutic interventions and prevention strategies. | bioRxiv | 2021 | | CORD-19 |
| 695 | National attitudes of medical students towards mandating the COVID-19 vaccine and its association with knowledge of the vaccine BACKGROUND: With the introduction of the novel COVID-19 vaccine, public hesitancy is being experienced with many turning to healthcare professionals for advice. As future physicians, medical students play a critical role in the public’s view of the vaccine. OBJECTIVES: To determine the attitude of U.S. medical students toward mandating the COVID-19 vaccine to healthcare workers and patients, as well as whether their knowledge of the vaccine plays a role in their view. METHODS: The authors emailed a survey link to all U.S. medical schools with request to distribute it to their medical students. The survey remained open from 02/09/2021 to 03/15/2021 and included questions to determine the attitude of the medical students toward recommending the COVID-19 vaccine, and general knowledge questions about the vaccine. Chi square, Fisher’s exact test, and linear regression were conducted to determine associations between willingness to recommend the COVID-19 vaccine and general knowledge of the vaccine. RESULTS: Among the 1,899 responses from medical students representing 151 U.S. medical schools, 57.82% approved of making the COVID-19 vaccine mandatory to healthcare workers, and 16.27% approved of making it mandatory to patients. Additionally, those who tested most knowledgeable of the vaccine were less likely to approve of making the vaccine mandatory for patients (66.67% vs. 72.70). Those that tested most knowledgeable were also more likely to personally receive the vaccine (72.35% vs 62.99%) as opposed to those that tested the least knowledgeable who were less willing to personally receive the vaccine (4.12% vs 14.17%). CONCLUSIONS: The data revealed that a slight majority of medical students support a vaccine mandate toward healthcare workers while a minority of medical students support a vaccine mandate toward healthcare workers. Additionally, medical students that had relatively high knowledge of the vaccine correlated with not approving of making the vaccine mandatory for patients. However increased knowledge of the vaccine correlated with increased willingness to personally receive the vaccine. | PLoS One | 2021 | | LitCov and CORD-19 |
| 696 | A Mechanistic Link Between Selenium and COVID-19 PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) is a rapidly emerging disease caused by a highly contagious virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and this disease has affected millions of people across the world and led to hundreds of thousands of deaths worldwide. Nutrition is a key factor related to this disease, and nutritional status may determine the risk and outcomes of SARS-CoV-2 infection. Selenium is one of the major trace elements required for redox functions and has significant roles in viral infections. The purpose of this review was to examine the current evidence on the role of selenium in COVID-19. We reviewed studies on selenium and COVID-19, and other relevant studies to understand how selenium status can modify the risk of SARS-CoV-2 infection, and how selenium status might affect a person post-infection. RECENT FINDINGS: We found that oxidative stress is a characteristic feature of COVID-19 disease, which is linked with the immunopathological disorder observed in individuals with severe COVID-19. Selenium plays a key role in strengthening immunity, reducing oxidative stress, preventing viral infections and supporting critical illness. Moreover, selenium deficiency is related to oxidative stress and hyperinflammation seen in critical illness, and selenium deficiency is found to be associated with the severity of COVID-19 disease. SUMMARY: Selenium supplementation at an appropriate dose may act as supportive therapy in COVID-19. Future studies in large cohorts of COVID-19 are warranted to verify the benefits of selenium supplementation for reducing risk and severity of COVID-19. | Curr Nutr Rep | 2021 | | LitCov and CORD-19 |
| 697 | Serum ferritin as a predictive biomarker in COVID-19. A systematic review, meta-analysis and meta-regression analysis Ferritin is a known inflammatory biomarker in COVID-19. However, many factors and co-morbidities can confound the level of serum ferritin. This current metaanalysis evaluates serum ferritin level in different severity levels in COVID-19. Studies evaluating serum ferritin level in different clinical contexts (COVID-19 vs. control, mild to moderate vs. severe to critical, non-survivor vs. survivor, organ involvement, ICU and mechanical ventilation requirement) were included (total 9 literature databases searched). Metaanalysis and metaregression was carried out using metaphor “R” package. Compared to control (COVID-19 negative), higher ferritin levels were found among the COVID-19 patients [SMD −0.889 (95% C.I. −1.201, −0.577), I(2) = 85%]. Severe to critical COVID-19 patients showed higher ferritin levels compared to mild to moderate COVID-19 patients [SMD 0.882 (0.738, 1.026), I(2) = 85%]. In meta-regression, high heterogeneity was observed could be attributed to difference in “mean age”, and “percentage of population with concomitant co-morbidities”. Non-survivors had higher serum ferritin level compared to survivors [SMD 0.992 (0.672, 1.172), I(2) = 92.33%]. In meta-regression, high heterogeneity observed could be attributed to difference in “mean age” and “percentage of male sex”. Patients requiring ICU [SMD 0.674 (0.515 to 0.833), I(2) = 80%] and mechanical ventilation [SMD 0.430 (0.258, 0.602), I(2) = 32%] had higher serum ferritin levels compared to those who didn't. To conclude, serum ferritin level may serve as an important biomarker which can aid in COVID-19 management. However, presence of other co-morbid conditions/confounders warrants cautious interpretation. | J Crit Care | 2021 | | LitCov and CORD-19 |
| 698 | Transmission of SARS-CoV-2 in domestic cats imposes a narrow bottleneck The evolutionary mechanisms by which SARS-CoV-2 viruses adapt to mammalian hosts and, potentially, undergo antigenic evolution depend on the ways genetic variation is generated and selected within and between individual hosts. Using domestic cats as a model, we show that SARS-CoV-2 consensus sequences remain largely unchanged over time within hosts, while dynamic sub-consensus diversity reveals processes of genetic drift and weak purifying selection. We further identify a notable variant at amino acid position 655 in Spike (H655Y), which was previously shown to confer escape from human monoclonal antibodies. This variant arises rapidly and persists at intermediate frequencies in index cats. It also becomes fixed following transmission in two of three pairs. These dynamics suggest this site may be under positive selection in this system and illustrate how a variant can quickly arise and become fixed in parallel across multiple transmission pairs. Transmission of SARS-CoV-2 in cats involved a narrow bottleneck, with new infections founded by fewer than ten viruses. In RNA virus evolution, stochastic processes like narrow transmission bottlenecks and genetic drift typically act to constrain the overall pace of adaptive evolution. Our data suggest that here, positive selection in index cats followed by a narrow transmission bottleneck may have instead accelerated the fixation of S H655Y, a potentially beneficial SARS-CoV-2 variant. Overall, our study suggests species- and context-specific adaptations are likely to continue to emerge. This underscores the importance of continued genomic surveillance for new SARS-CoV-2 variants as well as heightened scrutiny for signatures of SARS-CoV-2 positive selection in humans and mammalian model systems. | PLoS Pathog | 2021 | | LitCov and CORD-19 |
| 699 | Estimating aerosol transmission risk of SARS-CoV-2 in New York City public schools during reopening The objective of this study was to estimate the risk of SARS-CoV-2 transmission among students and teachers in New York City public schools, the largest school system in the US. Classroom measurements conducted from December 2017 to September 2018 were used to estimate risk of SARS-CoV-2 transmission using a modified Wells-Riley equation under a steady-state conditions and varying exposure scenarios (infectious student versus teacher, susceptible student versus teacher, with and without masks). We then used multivariable linear regression with GEE to identify school and classroom factors that impact transmission risk. Overall, 101 classrooms in 19 schools were assessed, 86 during the heating season, 69 during cooling season, and 54 during both. The mean probability of transmission was generally low but varied by scenario (range: 0.0015-0.81). Transmission rates were higher during the heating season (beta=0.108, p=0.010), in schools in higher income neighborhoods (>80K versus 20K-40K beta=0.196, p<0.001) and newer buildings (<50 years beta=0.237, p=<0.001; 50-99 years beta=0.230, p=0.013 versus 100+ years) and lower in schools with mechanical ventilation (beta=0.141, p=0.057). Surprisingly, schools located in older buildings and lower-income neighborhoods had lower transmission probabilities, likely due to the greater outdoor airflow associated with an older, non-renovated buildings that allow air to leak in (i.e. drafty buildings). Despite the generally low risk of school-based transmission found in this study, with SARS-CoV-2 prevalence rising in New York City this risk will increase and additional mitigation steps should be implemented in schools now. | Environ Res | 2021 | | LitCov and CORD-19 |
| 700 | 'It is a disease which comes and kills directly': What refugees know about COVID-19 and key influences of compliance with preventive measures BACKGROUND: Refugees are at increased risk for COVID-19 infection in part due to their living conditions, which make it harder to adopt and adhere to widely accepted preventive measures. Little empirical evidence exists about what refugees know about COVID-19 and what they do to prevent infection. This study explored what refugee women and their health care workers understand about COVID-19 prevention, the extent of their compliance to public health recommendations, and what influences the adoption of these measures. METHODS: In October 2020, we conducted 25 in-depth interviews with facility and community health care staff (n = 10) and refugee women attending antenatal and postnatal care services (n = 15) in Eastleigh, Nairobi. FINDINGS: While researchers found a high level of awareness about COVID-19 and related prevention and control measures among refugee women, various barriers affected compliance with such measures, due in part to poverty and in part to rampant misconceptions informed by religious beliefs and political narratives about the virus. CONCLUSIONS: These findings indicated that Kenya’s Ministry of Health needs to institute a concerted and continuous education program to bring refugee communities up to speed about COVID-19 and its prevention. In addition to disseminating information about the need to wear masks and repeatedly wash hands, supplies—masks, soap and access to water—need to be made available to poor refugee communities. Future research could explore which measures for disseminating factual information work best in refugee populations with different cultural norms and how best to target interventions to these groups. | PLoS One | 2021 | | LitCov and CORD-19 |
