\ 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
1051SARS-CoV-2 vaccination and myocarditis or myopericarditis: Population-Based cohort study  

OBJECTIVE: To investigate the association between SARS-CoV-2 vaccination and myocarditis or myopericarditis. DESIGN: Population based cohort study. SETTING: Denmark. PARTICIPANTS: 4 931 775 individuals aged 12 years or older, followed from 1 October 2020 to 5 October 2021. MAIN OUTCOME MEASURES: The primary outcome, myocarditis or myopericarditis, was defined as a combination of a hospital diagnosis of myocarditis or pericarditis, increased troponin levels, and a hospital stay lasting more than 24 hours. Follow-up time before vaccination was compared with follow-up time 0-28 days from the day of vaccination for both first and second doses, using Cox proportional hazards regression with age as an underlying timescale to estimate hazard ratios adjusted for sex, comorbidities, and other potential confounders. RESULTS: During follow-up, 269 participants developed myocarditis or myopericarditis, of whom 108 (40%) were 12-39 years old and 196 (73%) were male. Of 3 482 295 individuals vaccinated with BNT162b2 (Pfizer-BioNTech), 48 developed myocarditis or myopericarditis within 28 days from the vaccination date compared with unvaccinated individuals (adjusted hazard ratio 1.34 (95% confidence interval 0.90 to 2.00); absolute rate 1.4 per 100 000 vaccinated individuals within 28 days of vaccination (95% confidence interval 1.0 to 1.8)). Adjusted hazard ratios among female participants only and male participants only were 3.73 (1.82 to 7.65) and 0.82 (0.50 to 1.34), respectively, with corresponding absolute rates of 1.3 (0.8 to 1.9) and 1.5 (1.0 to 2.2) per 100 000 vaccinated individuals within 28 days of vaccination, respectively. The adjusted hazard ratio among 12-39 year olds was 1.48 (0.74 to 2.98) and the absolute rate was 1.6 (1.0 to 2.6) per 100 000 vaccinated individuals within 28 days of vaccination. Among 498 814 individuals vaccinated with mRNA-1273 (Moderna), 21 developed myocarditis or myopericarditis within 28 days from vaccination date (adjusted hazard ratio 3.92 (2.30 to 6.68); absolute rate 4.2 per 100 000 vaccinated individuals within 28 days of vaccination (2.6 to 6.4)). Adjusted hazard ratios among women only and men only were 6.33 (2.11 to 18.96) and 3.22 (1.75 to 5.93), respectively, with corresponding absolute rates of 2.0 (0.7 to 4.8) and 6.3 (3.6 to 10.2) per 100 000 vaccinated individuals within 28 days of vaccination, respectively. The adjusted hazard ratio among 12-39 year olds was 5.24 (2.47 to 11.12) and the absolute rate was 5.7 (3.3 to 9.3) per 100 000 vaccinated individuals within 28 days of vaccination. CONCLUSIONS: Vaccination with mRNA-1273 was associated with a significantly increased risk of myocarditis or myopericarditis in the Danish population, primarily driven by an increased risk among individuals aged 12-39 years, while BNT162b2 vaccination was only associated with a significantly increased risk among women. However, the absolute rate of myocarditis or myopericarditis after SARS-CoV-2 mRNA vaccination was low, even in younger age groups. The benefits of SARS-CoV-2 mRNA vaccination should be taken into account when interpreting these findings. Larger multinational studies are needed to further investigate the risks of myocarditis or myopericarditis after vaccination within smaller subgroups.

BMJ2021       LitCov and CORD-19
1052REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19  

BACKGROUND: Recent data suggest that complications and death from coronavirus disease 2019 (Covid-19) may be related to high viral loads. METHODS: In this ongoing, double-blind, phase 1–3 trial involving nonhospitalized patients with Covid-19, we investigated two fully human, neutralizing monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, used in a combined cocktail (REGN-COV2) to reduce the risk of the emergence of treatment-resistant mutant virus. Patients were randomly assigned (1:1:1) to receive placebo, 2.4 g of REGN-COV2, or 8.0 g of REGN-COV2 and were prospectively characterized at baseline for endogenous immune response against SARS-CoV-2 (serum antibody–positive or serum antibody–negative). Key end points included the time-weighted average change in viral load from baseline (day 1) through day 7 and the percentage of patients with at least one Covid-19–related medically attended visit through day 29. Safety was assessed in all patients. RESULTS: Data from 275 patients are reported. The least-squares mean difference (combined REGN-COV2 dose groups vs. placebo group) in the time-weighted average change in viral load from day 1 through day 7 was −0.56 log(10) copies per milliliter (95% confidence interval [CI], −1.02 to −0.11) among patients who were serum antibody–negative at baseline and −0.41 log(10) copies per milliliter (95% CI, −0.71 to −0.10) in the overall trial population. In the overall trial population, 6% of the patients in the placebo group and 3% of the patients in the combined REGN-COV2 dose groups reported at least one medically attended visit; among patients who were serum antibody–negative at baseline, the corresponding percentages were 15% and 6% (difference, −9 percentage points; 95% CI, −29 to 11). The percentages of patients with hypersensitivity reactions, infusion-related reactions, and other adverse events were similar in the combined REGN-COV2 dose groups and the placebo group. CONCLUSIONS: In this interim analysis, the REGN-COV2 antibody cocktail reduced viral load, with a greater effect in patients whose immune response had not yet been initiated or who had a high viral load at baseline. Safety outcomes were similar in the combined REGN-COV2 dose groups and the placebo group. (Funded by Regeneron Pharmaceuticals and the Biomedical and Advanced Research and Development Authority of the Department of Health and Human Services; ClinicalTrials.gov number, NCT04425629.)

N Engl J Med2020       LitCov and CORD-19
1053Effectiveness of mRNA-1273 against delta, mu and other emerging variants of SARS-CoV-2: test negative case-control study  

OBJECTIVES: To evaluate the effectiveness of the mRNA-1273 vaccine against SARS-CoV-2 variants and assess its effectiveness against the delta variant by time since vaccination. DESIGN: Test negative case-control study. SETTING: Kaiser Permanente Southern California (KPSC), an integrated healthcare system. PARTICIPANTS: Adult KPSC members with a SARS-CoV-2 positive test sent for whole genome sequencing or a negative test from 1 March 2021 to 27 July 2021. INTERVENTIONS: Two dose or one dose vaccination with mRNA-1273 (Moderna covid-19 vaccine) ≥14 days before specimen collection versus no covid-19 vaccination. MAIN OUTCOME MEASURES: Outcomes included infection with SARS-CoV-2 and hospital admission with covid-19. In pre-specified analyses for each variant type, test positive cases were matched 1:5 to test negative controls on age, sex, race/ethnicity, and specimen collection date. Conditional logistic regression was used to compare odds of vaccination among cases versus controls, with adjustment for confounders. Vaccine effectiveness was calculated as (1–odds ratio)×100%. RESULTS: The study included 8153 cases and their matched controls. Two dose vaccine effectiveness was 86.7% (95% confidence interval 84.3% to 88.7%) against infection with the delta variant, 98.4% (96.9% to 99.1%) against alpha, 90.4% (73.9% to 96.5%) against mu, 96-98% against other identified variants, and 79.9% (76.9% to 82.5%) against unidentified variants (that is, specimens that failed sequencing). Vaccine effectiveness against hospital admission with the delta variant was 97.5% (92.7% to 99.2%). Vaccine effectiveness against infection with the delta variant declined from 94.1% (90.5% to 96.3%) 14-60 days after vaccination to 80.0% (70.2% to 86.6%) 151-180 days after vaccination. Waning was less pronounced for non-delta variants. Vaccine effectiveness against delta infection was lower among people aged ≥65 years (75.2%, 59.6% to 84.8%) than those aged 18-64 years (87.9%, 85.5% to 89.9%). One dose vaccine effectiveness was 77.0% (60.7% to 86.5%) against infection with delta. CONCLUSIONS: Two doses of mRNA-1273 were highly effective against all SARS-CoV-2 variants, especially against hospital admission with covid-19. However, vaccine effectiveness against infection with the delta variant moderately declined with increasing time since vaccination.

BMJ2021       LitCov and CORD-19
1054Metagenomic Next-Generation Sequencing of Nasopharyngeal Specimens Collected from Confirmed and Suspect COVID-19 Patients  

Metagenomic next-generation sequencing (mNGS) offers an agnostic approach for emerging pathogen detection directly from clinical specimens. In contrast to targeted methods, mNGS also provides valuable information on the composition of the microbiome and might uncover coinfections that may associate with disease progression and impact prognosis. To evaluate the use of mNGS for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and/or other infecting pathogens, we applied direct Oxford Nanopore long-read third-generation metatranscriptomic and metagenomic sequencing. Nasopharyngeal (NP) swab specimens from 50 patients under investigation for CoV disease 2019 (COVID-19) were sequenced, and the data were analyzed by the CosmosID bioinformatics platform. Further, we characterized coinfections and the microbiome associated with a four-point severity index. SARS-CoV-2 was identified in 77.5% (31/40) of samples positive by RT-PCR, correlating with lower cycle threshold (Ct) values and fewer days from symptom onset. At the time of sampling, possible bacterial or viral coinfections were detected in 12.5% of SARS-CoV-2-positive specimens. A decrease in microbial diversity was observed among COVID-19-confirmed patients (Shannon diversity index, P = 0.0082; Chao richness estimate, P = 0.0097; Simpson diversity index, P = 0.018), and differences in microbial communities were linked to disease severity (P = 0.022). Furthermore, statistically significant shifts in the microbiome were identified among SARS-CoV-2-positive and -negative patients, in the latter of whom a higher abundance of Propionibacteriaceae (P = 0.028) and a reduction in the abundance of Corynebacterium accolens (P = 0.025) were observed. Our study corroborates the growing evidence that increased SARS-CoV-2 RNA detection from NP swabs is associated with the early stages rather than the severity of COVID-19. Further, we demonstrate that SARS-CoV-2 causes a significant change in the respiratory microbiome. This work illustrates the utility of mNGS for the detection of SARS-CoV-2, for diagnosing coinfections without viral target enrichment or amplification, and for the analysis of the respiratory microbiome.

mBio2020       LitCov and CORD-19
1055COVID-19 Vaccination Reactogenicity in Persons With Multiple Sclerosis  

BACKGROUND AND OBJECTIVES: There are limited data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine reactogenicity in persons with multiple sclerosis (PwMS) and how reactogenicity is affected by disease-modifying therapies (DMTs). The objective of this retrospective cross-sectional study was to generate real-world multiple sclerosis–specific vaccine safety information, particularly in the context of specific DMTs, and provide information to mitigate specific concerns in vaccine hesitant PwMS. METHODS: Between 3/2021 and 6/2021, participants in iConquerMS, an online people-powered research network, reported SARS-CoV-2 vaccines, experiences of local (itch, pain, redness, swelling, or warmth at injection site) and systemic (fever, chills, fatigue, headache, joint pain, malaise, muscle ache, nausea, allergic, and other) reactions within 24 hours (none, mild, moderate, and severe), DMT use, and other attributes. Multivariable models characterized associations between clinical factors and reactogenicity. RESULTS: In 719 PwMS, 64% reported experiencing a reaction after their first vaccination shot, and 17% reported a severe reaction. The most common reactions were pain at injection site (54%), fatigue (34%), headache (28%), and malaise (21%). Younger age, being female, prior SARS-CoV-2 infection, and receiving the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vs BNT162b2 (Pfizer-BioNTech) vaccine were associated with experiencing a reaction after the first vaccine dose. Similar relationships were observed for a severe reaction, including higher odds of reactions among PwMS with more physical impairment and lower odds of reactions for PwMS on an alpha4-integrin blocker or sphingosine-1-phosphate receptor modulator. In 442 PwMS who received their second vaccination shot, 74% reported experiencing a reaction, whereas 22% reported a severe reaction. Reaction profiles after the second shot were similar to those reported after the first shot. Younger PwMS and those who received the mRNA-1273 (Moderna) vs BNT162b2 vaccine reported higher reactogenicity after the second shot, whereas those on a sphingosine-1-phosphate receptor modulator or fumarate were significantly less likely to report a reaction. DISCUSSION: SARS-CoV-2 vaccine reactogenicity profiles and the associated factors in this convenience sample of PwMS appear similar to those reported in the general population. PwMS on specific DMTs were less likely to report vaccine reactions. Overall, the short-term vaccine reactions experienced in the study population were mostly self-limiting, including pain at the injection site, fatigue, headache, and fever.

Neurol Neuroimmunol Neuroinfla2021       LitCov and CORD-19
1056The Coronavirus Pandemic: What Does the Evidence Show?  

N/A

J Nepal Health Res Counc2020       LitCov and CORD-19
1057The presence of headache at onset in SARS-CoV-2 infection is associated with long-term post-COVID headache and fatigue: A case-control study  

OBJECTIVE: To investigate the association of headache during the acute phase of SARS-CoV-2 infection with long-term post-COVID headache and other post-COVID symptoms in hospitalised survivors. METHODS: A case-control study including patients hospitalised during the first wave of the pandemic in Spain was conducted. Patients reporting headache as a symptom during the acute phase and age- and sex-matched patients without headache during the acute phase participated. Hospitalisation and clinical data were collected from medical records. Patients were scheduled for a telephone interview 7 months after hospital discharge. Participants were asked about a list of post-COVID symptoms and were also invited to report any additional symptom they might have. Anxiety/depressive symptoms and sleep quality were assessed with the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index. RESULTS: Overall, 205 patients reporting headache and 410 patients without headache at hospitalisation were assessed 7.3 months (Standard Deviation 0.6) after hospital discharge. Patients with headache at onset presented a higher number of post-COVID symptoms (Incident Rate Ratio: 1.16, 95% CI: 1.03–1.30). Headache at onset was associated with a previous history of migraine (Odd Ratio: 2.90, 95% Confidence Interval: 1.41–5.98) and with the development of persistent tension-type like headache as a new post-COVID symptom (Odd Ratio: 2.65, 95% CI: 1.66–4.24). Fatigue as a long-term symptom was also more prevalent in patients with headache at onset (Odd Ratio: 1.55, 95% CI: 1.07–2.24). No between-group differences in the prevalence of anxiety/depressive symptoms or sleep quality were seen. CONCLUSION: Headache in the acute phase of SARS-CoV-2 infection was associated with higher prevalence of headache and fatigue as long-term post-COVID symptoms. Monitoring headache during the acute phase could help to identify patients at risk of developing long-term post-COVID symptoms, including post-COVID headache.

Cephalalgia2021       LitCov and CORD-19
1058Omicron (B.1.1.529)-variant of concern-molecular profile and epidemiology: a mini review  

N/A

Eur Rev Med Pharmacol Sci2021       LitCov and CORD-19
1059Home Treatment of Older People with Symptomatic SARS-CoV-2 Infection: A structured Summary of a Study Protocol for a Multi-Arm Multi-Stage (MAMS) Randomized Trial to Evaluate the Efficacy and Tolerability of Several Experimental Treatments to Reduce the Risk of Hospitalisation or Death in outpatient  

OBJECTIVES: To assess the efficacy of several repurposed drugs to prevent hospitalisation or death in patients aged 65 or more with recent symptomatic SARS-CoV-2 infection (COVID-19) and no criteria for hospitalisation. TRIAL DESIGN: Phase III, multi-arm (5) and multi-stage (MAMS), randomized, open-label controlled superiority trial. Arm 1: Control arm. Arms 2 to 5: Experimental treatment arms. Planned interim analyses will be conducted at regular intervals. Their results will be reviewed by an Independent Data and Safety Monitoring Board. Experimental arms may be terminated for futility, efficacy or toxicity before the end of the trial. New experimental arms may be added if new evidence suggests that other treatments should be tested. A feasibility and acceptability substudy as well as an immunological substudy will be conducted alongside the trial. PARTICIPANTS: Inclusion criteria are: 65-year-old or more; Positive test for SARS-CoV-2 on a nasopharyngeal swab; Symptoms onset within 3 days before diagnosis; No hospitalisation criteria; Signed informed consent; Health insurance. Exclusion criteria are: Inability to make an informed decision to participate (e.g.: dementia, guardianship); Rockwood Clinical Frailty Scale ≥7; Long QT syndrome; QTc interval > 500 ms; Heart rate <50/min; Kalaemia >5.5 mmol/L or <3.5 mmol/L; Ongoing treatment with piperaquine, halofantrine, dasatinib, nilotinib, hydroxyzine, domperidone, citalopram, escitalopram, potent inhibitors or inducers of cytochrome P450 CYP3A4 isoenzyme, repaglinide, azathioprine, 6-mercaptopurine, theophylline, pyrazinamide, warfarin; Known hypersensitivity to any of the trial drugs or to chloroquine and other 4-aminoquinolines, amodiaquine, mefloquine, glafenine, floctafenine, antrafenine, ARB; Hepatic porphyria; Liver failure (Child-Pugh stage ≥B); Stage 4 or 5 chronic kidney disease (GFR <30 mL/min/1.73 m²); Dialysis; Hypersentivity to lactose; Lactase deficiency; Abnormalities in galactose metabolism; Malabsorption syndrome; Glucose-6-phosphate dehydrogenase deficiency; Symptomatic hyperuricemia; Ileus; Colitis; Enterocolitis; Chronic hepatitis B virus disease. The trial is being conducted in France in the Bordeaux, Corse, Dijon, Nancy, Paris and Toulouse areas as well as in the Grand Duchy of Luxembourg. Participants are recruited either at home, nursing homes, general practices, primary care centres or hospital outpatient consultations. INTERVENTION AND COMPARATOR: The four experimental treatments planned in protocol version 1.2 (April 8(th), 2020) are: (1) Hydroxychloroquine 200 mg, 2 tablets BID on day 0, 2 tablets QD from day 1 to 9; (2) Imatinib 400 mg, 1 tablet QD from day 0 to 9; (3) Favipiravir 200 mg, 12 tablets BID on day 0, 6 tablets BID from day 1 to 9; (4) Telmisartan 20 mg, 1 tablet QD from day 0 to 9. The comparator is a complex of vitamins and trace elements (AZINC Forme et Vitalité®), 1 capsule BID for 10 days, for which there is no reason to believe that they are active on the virus. In protocol version 1.2 (April 8th, 2020): People in the control arm will receive a combination of vitamins and trace elements; people in the experimental arms will receive hydroxychloroquine, or favipiravir, or imatinib, or telmisartan. MAIN OUTCOME: The primary outcome is the proportion of participants with an incidence of hospitalisation and/or death between inclusion and day 14 in each arm. RANDOMISATION: Participants are randomized in a 1:1:1:1:1 ratio to each arm using a web-based randomisation tool. Participants not treated with an ARB or ACEI prior to enrolment are randomized to receive the comparator or one of the four experimental drugs. Participants already treated with an ARB or ACEI are randomized to receive the comparator or one of the experimental drugs except telmisartan (i.e.: hydroxychloroquine, imatinib, or favipiravir). Randomisation is stratified on ACEI or ARBs treatment at inclusion and on the type of residence (personal home vs. nursing home). BLINDING (MASKING): This is an open-label trial. Participants, caregivers, investigators and statisticians are not blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 1057 participants will be enrolled if all arms are maintained until the final analysis and no additional arm is added. Three successive futility interim analyses are planned, when the number of participants reaches 30, 60 and 102 in the control arm. Two efficacy analyses (interim n°3 and final) will be performed successively. TRIAL STATUS: This describes the Version 1.2 (April 8(th), 2020) of the COVERAGE protocol that was approved by the French regulatory authority and ethics committee. The trial was opened for enrolment on April 15(th), 2020 in the Nouvelle Aquitaine region (South-West France). Given the current decline of the COVID-19 pandemic in France and its unforeseeable dynamic in the coming months, new trial sites in 5 other French regions and in Luxembourg are currently being opened. A revised version of the protocol was submitted to the regulatory authority and ethics committee on June 15(th), 2020. It contains the following amendments: (i) Inclusion criteria: age ≥65 replaced by age ≥60; time since first symptoms <3 days replaced by time since first symptoms <5 days; (ii) Withdrawal of the hydroxychloroquine arm (due to external data); (iii) increase in the number of trial sites. TRIAL REGISTRATION: The trial was registered on Clinical Trials.gov on April 22(nd), 2020 (Identifier: NCT04356495): and on EudraCT on April 10(th), 2020 (Identifier: 2020-001435-27). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Trials2020       LitCov and CORD-19
1060Coronavirus biology and replication: implications for SARS-CoV-2  

The SARS-CoV-2 pandemic and its unprecedented global societal and economic disruptive impact has marked the third zoonotic introduction of a highly pathogenic coronavirus into the human population. Although the previous coronavirus SARS-CoV and MERS-CoV epidemics raised awareness of the need for clinically available therapeutic or preventive interventions, to date, no treatments with proven efficacy are available. The development of effective intervention strategies relies on the knowledge of molecular and cellular mechanisms of coronavirus infections, which highlights the significance of studying virus–host interactions at the molecular level to identify targets for antiviral intervention and to elucidate critical viral and host determinants that are decisive for the development of severe disease. In this Review, we summarize the first discoveries that shape our current understanding of SARS-CoV-2 infection throughout the intracellular viral life cycle and relate that to our knowledge of coronavirus biology. The elucidation of similarities and differences between SARS-CoV-2 and other coronaviruses will support future preparedness and strategies to combat coronavirus infections.

Nat Rev Microbiol2020       LitCov and CORD-19
1061Timely mental Healthcare for the 2019 novel coronavirus outbreak is urgently needed  

Lancet Psychiatry2020       LitCov and CORD-19
1062Association of Public Health Interventions With the Epidemiology of the COVID-19 Outbreak in Wuhan, China  

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JAMA2020       LitCov and CORD-19
1063Effects of COVID-19 Home Confinement on Eating Behaviour and Physical Activity: Results of the ECLB-COVID-19 International Online Survey  

Background: Public health recommendations and governmental measures during the COVID-19 pandemic have resulted in numerous restrictions on daily living including social distancing, isolation and home confinement. While these measures are imperative to abate the spreading of COVID-19, the impact of these restrictions on health behaviours and lifestyles at home is undefined. Therefore, an international online survey was launched in April 2020, in seven languages, to elucidate the behavioural and lifestyle consequences of COVID-19 restrictions. This report presents the results from the first thousand responders on physical activity (PA) and nutrition behaviours. Methods: Following a structured review of the literature, the “Effects of home Confinement on multiple Lifestyle Behaviours during the COVID-19 outbreak (ECLB-COVID19)” Electronic survey was designed by a steering group of multidisciplinary scientists and academics. The survey was uploaded and shared on the Google online survey platform. Thirty-five research organisations from Europe, North-Africa, Western Asia and the Americas promoted the survey in English, German, French, Arabic, Spanish, Portuguese and Slovenian languages. Questions were presented in a differential format, with questions related to responses “before” and “during” confinement conditions. Results: 1047 replies (54% women) from Asia (36%), Africa (40%), Europe (21%) and other (3%) were included in the analysis. The COVID-19 home confinement had a negative effect on all PA intensity levels (vigorous, moderate, walking and overall). Additionally, daily sitting time increased from 5 to 8 h per day. Food consumption and meal patterns (the type of food, eating out of control, snacks between meals, number of main meals) were more unhealthy during confinement, with only alcohol binge drinking decreasing significantly. Conclusion: While isolation is a necessary measure to protect public health, results indicate that it alters physical activity and eating behaviours in a health compromising direction. A more detailed analysis of survey data will allow for a segregation of these responses in different age groups, countries and other subgroups, which will help develop interventions to mitigate the negative lifestyle behaviours that have manifested during the COVID-19 confinement.

Nutrients2020       LitCov and CORD-19
1064An investigation into the beneficial effects of high-dose interferon beta 1-a, compared to low-dose interferon beta 1-a (the base therapeutic regimen) in moderate to severe COVID-19: A structured summary of a study protocol for a randomized controlled l trial  

OBJECTIVES: We will investigate the effectiveness of high dose Interferon Beta 1a, compared to low dose Interferon Beta 1a (the base therapeutic regimen) in COVID-19 Confirmed Cases (Either RT-PCR or CT Scan Confirmed) with moderate to severe disease TRIAL DESIGN: This is a single center, open label, randomized, controlled, 2-arm parallel group (1:1 ratio), clinical trial. PARTICIPANTS: The eligibility criteria in this study is: age ≥ 18 years, oxygen saturation (SPO2) ≤ 93% or respiratory rate ≥ 24, at least one of the following manifestation: radiation contactless body temperature ≥37.8, Cough, shortness of breath, nasal congestion/ discharge, myalgia/arthralgia, diarrhea/vomiting, headache or fatigue on admission. The onset of the symptoms should be acute (≤ 14 days). The exclusion criteria include refusal to participate, using drugs with potential interaction with lopinavir/ritonavir or interferon-β 1a, blood ALT/AST levels > 5 times the upper limit of normal on laboratory results, pregnant or lactating women, history of alcohol or drug addiction in the past 5 years, the patients who be intubated less than one hours after admission to hospital. This study will be undertaken at the Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences. INTERVENTION AND COMPARATOR: COVID- 19 confirmed patients (using the RT-PCR test or CT scan) will be randomly assigned to one of two groups. The intervention group (Arms1) will be treated with lopinavir / ritonavir (Kaletra) + high dose Interferon-β 1a (Recigen) and the control group will be treated with lopinavir / ritonavir (Kaletra) + low dose Interferon-β 1a (Recigen) (the base therapeutic regimen). Both groups will receive standard care consisting of the necessary oxygen support, non-invasive, or invasive mechanical ventilation. MAIN OUTCOMES: Primary outcome: Time to clinical improvement is our primary outcome measure. This is an improvement of two points on a seven-category ordinal scale (recommended by the World Health Organization: Coronavirus disease (COVID-2019) R&D. Geneva: World Health Organization) or discharge from the hospital, whichever comes first. Secondary outcomes: mortality from the date of randomization until the last day of the study which will be the day all of the patients have had at least one of the following outcomes: 1) Improvement of two points on a seven-category ordinal scale. 2) Discharge from the hospital 3) Death. Improvement of SPO2 during the hospitalization, duration of hospitalization from date of randomization until the date of hospital discharge or death, whichever comes first. The incidence of new mechanical ventilation uses from the date of randomization until the last day of the study and the duration of it will be extracted. Please note that we are trying to add further secondary outcomes and this section of the protocol is still evolving. RANDOMIZATION: Eligible patients with confirmed SARS-Cov-2 infections will be randomly assigned in a 1:1 ratio to two therapeutic arms using permuted, block-randomization to balance the number of patients allocated to each group. The permuted block (three or six patients per block) randomization sequence will be generated, using Package ‘randomizeR’ in R software version 3.6.1. and placed in individual sealed and opaque envelopes by the statistician. The investigator will enroll the patients and only then open envelopes to assign patients to the different treatment groups. This method of allocation concealment will result in minimum selection and confounding biases. BLINDING (MASKING): The present research is open-label (no masking) of patients and health care professionals who are undertaking outcome assessment of the primary outcome - time to clinical improvement. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Of the 100 patients randomised, 50 patients will be assigned to receive high dose Interferon beta-1a plus lopinavir/ritonavir (Kaletra), 50 patients will be assigned to receive low dose Interferon beta 1a plus lopinavir/ritonavir (Kaletra). TRIAL STATUS: Protocol version 1.2.1. Recruitment is finished, the start date of recruitment was on August 20(th) 2020, and the end date was on September 4(th) 2020. Last point of data collection will be the last day on which all of the 100 participants have had an outcome of clinical improvement or death, up to 14th days after hospitalization. TRIAL REGISTRATION: This study was registered with National Institutes of Health Clinical trials (www.clinicaltrials.gov; identification number NCT04521400, https://clinicaltrials.gov/ct2/show/NCT04521400, registered August 18, 2020 and first available online August 20, 2020). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. SUPPLEMENTARY INFORMATION: Supplementary information accompanies this paper at 10.1186/s13063-020-04812-2.

Trials2020       LitCov and CORD-19
1065Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women  

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JAMA2021       LitCov and CORD-19
1066The impact of the COVID-19 pandemic on the perinatal mental health of women  

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J Perinat Med2020       LitCov and CORD-19
1067How far has the digitization of medical teaching progressed in times of COVID-19? A multinational survey among medical students and lecturers in German-speaking central Europe  

BACKGROUND: To ensure successful medical education despite the COVID-19 pandemic, the demand for online instruction has substantially increased. Fast and efficient teaching in a digital format poses a great challenge for medical students and lecturers as well as the universities. OBJECTIVE: The aim of this study is to capture the readiness of medical students and faculty members to participate in rapidly- evolving online education. METHODS: This cross-sectional study is based on two questionnaires distributed among medical students and associate deans for education in Germany, Austria and Switzerland. Questions included decision- making questions, categorical questions, and open-ended questions, all addressing the frequency and format of the digital education offered, the perceived quality of digital education, and medical student satisfaction with digital education. Questions about missing content and areas for improvement from the perspectives of medical students were included. The associate deans were asked for their opinions about the impact of the pandemic on teaching, the organizational setup and implementation of digital education by universities, and plans for future initiatives. RESULTS: Three thousand and thirty medical students (m = 752 and f = 2245) from 53 universities participated in the study. The study showed that 92% of students were affected by the pandemic, and 19% of the students viewed the changes as entirely negative. 97% of the medical students were able to participate in digital courses, but only 4% were able to learn exclusively online. For 77% of the medical students, digital offerings accounted for over 80% of the education offered. In terms of content, medical students complained about a lack of practical teaching, such as contact with patients, lecturers, fellow medical students, and a poor perceived quality of teaching due to dubbing, frequent changeover of seminars, problem-oriented learning groups and in-person teaching, a lack of interaction possibilities and a lack of technical equipment, such as lecturers’ knowledge and server capacities, at the universities. Overall, almost half of the medical students (42%) rated the implementation of digital teaching at their universities as good or very good. Forty-one of the 53 associate deans responded to the questionnaire, and 35 felt medical education was influenced by the pandemic. The associate deans (80%; 33/41) felt that the digitalization of medical education was negatively influenced by the pandemic. Only 44% (18/41) felt that their universities were well or very well positioned for digital teaching. All the associate deans believe that digital teaching in medicine will continue after the pandemic. CONCLUSIONS: In the German-speaking world, the rapid conversion of medical teaching to a digital format has been well implemented in many cases. The perceived quality of the implementation of digital education still lacks practical relevance and the use of new digital media, such as learning games, VR, and online question time. The digital format of medical education will likely continue beyond the COVID-19 pandemic.

BMC Med Educ2022       LitCov and CORD-19
1068Autoantibodies against type I IFNs in patients with life-threatening COVID-19  

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), against the 13 types of IFN-α (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.

Science2020       LitCov and CORD-19
1069An Analysis of 38 Pregnant Women With COVID-19, Their Newborn Infants and Maternal-Fetal Transmission of SARS-CoV-2: Maternal Coronavirus Infections and Pregnancy Outcomes  

N/A

Arch Pathol Lab Med2020       LitCov and CORD-19
1070BNT162b2 booster after heterologous prime-boost vaccination induces potent neutralizing antibodies and T-cell reactivity against SARS-CoV-2 Omicron BA.1 in young adults  

N/A

Front Immunol2022       LitCov
1071Identification of HLA-A*24:02-Restricted CTL candidate epitopes derived from the non-structural polyprotein 1a of SARS-CoV-2 and Analysis of Their Conservation Using the Mutation Database of SARS-CoV-2 Variants  

COVID-19 vaccines are currently being administered worldwide and playing a critical role in controlling the pandemic. They have been designed to elicit neutralizing antibodies against Spike protein of the original SARS-CoV-2, and hence they are less effective against SARS-CoV-2 variants with mutated Spike than the original virus. It is possible that novel variants with abilities of enhanced transmissibility and/or immunoevasion will appear in the near future and perfectly escape from vaccine-elicited immunity. Therefore, the current vaccines may need to be improved to compensate for the viral evolution. For this purpose, it may be beneficial to take advantage of CD8(+) cytotoxic T lymphocytes (CTLs). Several lines of evidence suggest the contribution of CTLs on the viral control in COVID-19, and CTLs target a wide range of proteins involving comparatively conserved nonstructural proteins. Here, we identified 22 HLA-A*24:02-restricted CTL candidate epitopes derived from the nonstructural polyprotein 1a (pp1a) of SARS-CoV-2 using computational algorithms, HLA-A*24:02 transgenic mice and the peptide-encapsulated liposomes. We focused on pp1a and HLA-A*24:02 because pp1a is relatively conserved and HLA-A*24:02 is predominant in East Asians such as Japanese. The conservation analysis revealed that the amino acid sequences of 7 out of the 22 epitopes were hardly affected by a number of mutations in the Sequence Read Archive database of SARS-CoV-2 variants. The information of such conserved epitopes might be useful for designing the next-generation COVID-19 vaccine that is universally effective against any SARS-CoV-2 variants by the induction of both anti-Spike neutralizing antibodies and CTLs specific for conserved epitopes. IMPORTANCE COVID-19 vaccines have been designed to elicit neutralizing antibodies against the Spike protein of the original SARS-CoV-2, and hence they are less effective against variants. It is possible that novel variants will appear and escape from vaccine-elicited immunity. Therefore, the current vaccines may need to be improved to compensate for the viral evolution. For this purpose, it may be beneficial to take advantage of CD8(+) cytotoxic T lymphocytes (CTLs). Here, we identified 22 HLA-A*24:02-restricted CTL candidate epitopes derived from the nonstructural polyprotein 1a (pp1a) of SARS-CoV-2. We focused on pp1a and HLA-A*24:02 because pp1a is conserved and HLA-A*24:02 is predominant in East Asians. The conservation analysis revealed that the amino acid sequences of 7 out of the 22 epitopes were hardly affected by mutations in the database of SARS-CoV-2 variants. The information might be useful for designing the next-generation COVID-19 vaccine that is universally effective against any variants.

Microbiol Spectr2021       LitCov and CORD-19
1072Factors affecting the mental health of pregnant women using UK maternity services during the COVID-19 pandemic: a qualitative interview study  

BACKGROUND: People using maternity services in the United Kingdom (UK) have faced significant changes brought on by the COVID-19 pandemic and social distancing regulations. We focused on the experiences of pregnant women using UK maternity services during the pandemic and the impact of social distancing rules on their mental health and wellbeing. METHODS: We conducted 23 qualitative semi-structured interviews from June 2020 to August 2021, with women from across the UK who experienced a pregnancy during the pandemic. Nineteen participants in the study carried their pregnancy to term and four had experienced a miscarriage during the pandemic. Interviews took place remotely over video or telephone call, discussing topics such as mental health during pregnancy and use of UK maternity services. We used reflexive thematic analysis to analyse interview transcripts. RESULTS: We generated six higher order themes: [1] Some pregnancy discomforts alleviated by social distancing measures, [2] The importance of relationships that support coping and adjustment, [3] Missed pregnancy and parenthood experiences, [4] The mental health consequences of birth partner and visitor restrictions, [5] Maternity services under pressure, and [6] Lack of connection with staff. Many participants felt a sense of loss over a pregnancy experience that differed so remarkably to what they had expected because of the pandemic. Supportive relationships were important to help cope with pregnancy and pandemic-related changes; but feelings of isolation were compounded for some participants because opportunities to build social connections through face-to-face parent groups were unavailable. Participants also described feeling alone due to restrictions on their partners being present when accessing UK maternity services. CONCLUSIONS: Our findings highlight some of the changes that may have affected pregnant women’s mental health during the COVID-19 pandemic. Reduced social support and being unable to have a partner or support person present during maternity service use were the greatest concerns reported by participants in this study. Absence of birth partners removed a protective buffer in times of uncertainty and distress. This suggests that the availability of a birth partner or support person must be prioritised wherever possible in times of pandemics to protect the mental health of people experiencing pregnancy and miscarriage. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12884-022-04602-5.

BMC Pregnancy Childbirth2022       LitCov and CORD-19
1073Coping styles and mental health in response to societal changes during the COVID-19 pandemic  

N/A

Int J Soc Psychiatry2021       LitCov and CORD-19
1074Neutralizing Activity Against SARS-CoV-2 Delta and Omicron Variants Following a Third BNT162b2 Booster Dose According to Three Homologous or Heterologous COVID-19 Vaccination Schedules  

N/A

Front Cell Infect Microbiol2022       LitCov
1075Levels of Severity of Depressive Symptoms Among At-Risk Groups in the UK During the COVID-19 Pandemic  

IMPORTANCE: An immediate research priority is to investigate and monitor the psychological well-being among high-risk groups during the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE: To examine levels of severity of depressive symptoms over time among individuals with high risk in the UK during the COVID-19 pandemic. DESIGN, SETTING, AND PARTICIPANTS: This cohort study is part of an ongoing large panel study of adults aged 18 years and older residing in the UK, the COVID-19 Social Study, established on March 21, 2020. Data analysis was conducted in May 2020. EXPOSURES: Sociodemographic risk factors included belonging to the Black, Asian, and minority racial/ethnic communities, low socioeconomic position (SEP), and essential worker roles (eg, workers in health and social care, education, childcare, or key public services). Health-related and psychosocial risk factors included preexisting physical and mental health conditions, experience of psychological or physical abuse, and low social support. MAIN OUTCOMES AND MEASURES: Depressive symptoms were measured on 7 occasions from March 21 to April 2, 2020, using the 9-item Patient Health Questionnaire (PHQ-9). Group-based depressive symptom trajectories were derived using latent growth mixture modeling. RESULTS: The analytical sample comprised 51 417 adults aged 18 years and older (mean [SD] age, 48.8 [16.8] years; 26 276 [51.1%] women; 6145 members [12.0%] of Black, Asian, and minority racial/ethnic communities). Among these, 17 143 participants (33.3%) were in the lowest SEP quartile, and 11 342 participants (22.1%) were classified as essential workers. Three levels of severity of depressive symptoms were identified: low (30 850 participants [60.0%]), moderate (14 911 participants [29.0%]), and severe (5656 participants [11.0%]). After adjusting for covariates, experiences of physical or psychological abuse (odds ratio [OR], 13.16; 95% CI, 12.95-13.37; P < .001), preexisting mental health conditions (OR, 12.99; 95% CI, 12.87-13.11; P < .001), preexisting physical health conditions (OR, 3.41; 95% CI, 3.29-3.54; P < .001), low social support (OR, 12.72; 95% CI, 12.57-12.86; P < .001), and low SEP (OR, 5.22; 95% CI, 5.08-5.36; P < .001) were significantly associated with severe depressive symptoms. No significant association was found for race/ethnicity (OR, 1.07; 95% CI, 0.85-1.28; P = .56). Participants with essential worker roles were less likely to experience severe depressive symptoms (OR, 0.66; 95% CI, 0.53-0.80; P < .001). Similar patterns of associations were found for the group of participants with moderate depressive symptoms (abuse: OR, 5.34; 95% CI, 5.15-5.54; P < .001; mental health condition: OR, 4.24; 95% CI, 4.24-4.24; P < .001; physical health condition: OR, 1.89; 95% CI, 1.80-1.98; P < .001; low social support: OR, 4.71; 95% CI, 4.60-4.82; P < .001; low SEP: OR, 1.97; 95% CI, 1.87-2.08; P < .001). CONCLUSIONS AND RELEVANCE: In this cohort study of UK adults participating in the COVID-19 Social Study, people with psychosocial and health-related risk factors, as well as those with low SEP, were at the most risk of experiencing moderate or severe depressive symptoms during the COVID-19 pandemic.

JAMA Netw Open2020       LitCov and CORD-19
1076Clinical and Immune Features of Hospitalized Pediatric Patients With COVID-19 in Wuhan, China  

IMPORTANCE: The epidemiologic and clinical characteristics of pediatric patients with coronavirus disease 2019 (COVID-19) have been reported, but information on immune features associated with disease severity is scarce. OBJECTIVE: To delineate and compare the immunologic features of mild and moderate COVID-19 in pediatric patients. DESIGN, SETTING, AND PARTICIPANTS: This single-center case series included 157 pediatric patients admitted to Wuhan Children’s Hospital with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data were collected from January 25 to April 18, 2020. EXPOSURES: Documented SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES: Clinical and immunologic characteristics were collected and analyzed. Outcomes were observed until April 18, 2020. RESULTS: Of the 157 pediatric patients with COVID-19, 60 (38.2%) had mild clinical type with pneumonia, 88 (56.1%) had moderate cases, 6 (3.8%) had severe cases, and 3 (1.9%) were critically ill. The 148 children with mild or moderate disease had a median (interquartile range [IQR]) age of 84 (18-123) months, and 88 (59.5%) were girls. The most common laboratory abnormalities were increased levels of alanine aminotransferase (ALT) (median [IQR], 16.0 [12.0-26.0] U/L), aspartate aminotransferase (AST) (median [IQR], 30.0 [23.0-41.8] U/L), creatine kinase MB (CK-MB) activity (median [IQR], 24.0 [18.0-34.0] U/L), and lactate dehydrogenase (LDH) (median [IQR], 243.0 [203.0-297.0] U/L), which are associated with liver and myocardial injury. Compared with mild cases, levels of inflammatory cytokines including interleukin 6, tumor necrosis factor α, and interferon γ were unchanged, whereas the level of immune suppressive interleukin 10 was markedly increased in moderate cases compared with mild cases (median [IQR], 3.96 [3.34-5.29] pg/mL vs 3.58 [3.10-4.36] pg/mL; P = .048). There was no statistically significant difference in absolute number of lymphocytes (including T cells and B cells) between mild and moderate cases, but moderate cases were associated with a decrease in neutrophil levels compared with mild cases (median [IQR], 2310/μL [1680/μL-3510/μL] vs 3120/μL [2040/μL-4170/μL]; P = .01). Immunoglobin G and the neutrophil to lymphocyte ratio were negatively associated with biochemical indices related to liver and myocardial injury (immunoglobulin G, ALT: r, −0.3579; AST: r, −0.5280; CK-MB activity: r, −0.4786; LDH: r, −0.4984; and neutrophil to lymphocyte ratio, ALT: r, −0.1893; AST: r, −0.3912; CK-MB activity: r, −0.3428; LDH: r, −0.3234), while counts of lymphocytes, CD4(+) T cells, and interleukin 10 showed positive associations (lymphocytes, ALT: r, 0.2055; AST: r, 0.3615; CK-MB activity: r, 0.338; LDH: r, 0.3309; CD4(+) T cells, AST: r, 0.4701; CK-MB activity: r, 0.4151; LDH: r, 0.4418; interleukin 10, ALT: r, 0.2595; AST: r, 0.3386; CK-MB activity: r, 0.3948; LDH: r, 0.3794). CONCLUSIONS AND RELEVANCE: In this case series, systemic inflammation rarely occurred in pediatric patients with COVID-19, in contrast with the lymphopenia and aggravated inflammatory responses frequently observed in adults with COVID-19. Gaining a deeper understanding of the role of neutrophils, CD4(+) T cells, and B cells in the pathogenesis of SARS-CoV-2 infection could be important for the clinical management of COVID-19.

JAMA Netw Open2020       LitCov and CORD-19
1077Antibody Responses to the BNT162b2 mRNA Vaccine in Healthcare Workers in a General Hospital in Japan: A Comparison of Two Assays for Anti-spike Protein Immunoglobulin G  

OBJECTIVE: This study assessed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody responses to the BNT162b2 mRNA vaccine in Japanese healthcare workers. METHODS: In this prospective cohort study, participants received two doses of the BNT162b2 mRNA vaccine on days 0 and 21 and provided blood for anti-SARS-CoV-2 antibody testing before the first vaccine and on days 21 and 35 after vaccination. Anti-spike protein immunoglobulin G (S-IgG) was measured using Abbott and Fujirebio chemiluminescent immunoassays. PATIENTS: One hundred healthcare workers (median age: 39 years old, interquartile range: 30-48 years old), including 6 who had been previously infected with SARS-CoV-2 and 3 individuals taking immunosuppressive drugs, participated in the study. RESULTS: The S-IgG antibody titers (AU/mL) measured using both the Abbott and Fujirebio assays increased significantly (p<0.001) over time, both with a prevalence of 100% at 35 days after the first vaccination. The multivariate log-normal linear regression analysis indicated the effect of immunosuppressant medication using both the Abbott (p=0.013) and Fujirebio (p=0.039) assays on S-IgG levels after complete vaccination. Pearson's correlation coefficient between the Abbott and Fujirebio S-IgG results in all 300 samples collected before and after vaccination and 50 positive controls from patients with coronavirus disease 2019 were 0.963 [95% confidence interval (CI): 0.954-0.970, p<0.001] and 0.909 (95% CI: 0.845-0.948, p<0.001), respectively. CONCLUSION: The BNT162b2 mRNA vaccine was effective at increasing S-IgG levels in Japanese immunocompetent healthcare workers. The Fujirebio S-IgG assay showed high diagnostic accuracy, using the Abbott S-IgG assay as the reference test.

Intern Med2021       LitCov and CORD-19
1078Trends in the Incidence of New-Onset Anorexia Nervosa and Atypical Anorexia Nervosa Among Youth During the COVID-19 Pandemic in Canada  

IMPORTANCE: The COVID-19 pandemic has had considerable mental health consequences for children and adolescents, including the exacerbation of previously diagnosed eating disorders. Whether the pandemic is a factor associated with the concomitant increase in new-onset anorexia nervosa or atypical anorexia nervosa remains unknown. OBJECTIVE: To assess the incidence and severity of newly diagnosed anorexia nervosa or atypical anorexia nervosa in a national sample of youth before and during the first wave of the COVID-19 pandemic. DESIGN, SETTING, AND PARTICIPANTS: This repeated cross-sectional study analyzed new eating disorder assessments that were conducted at 6 pediatric tertiary-care hospitals in Canada between January 1, 2015, and November 30, 2020. Patients aged 9 to 18 years with a new anorexia nervosa or atypical anorexia nervosa diagnosis at the index assessment were included. EXPOSURES: COVID-19–associated public health confinement measures during the first wave of the pandemic (March 1 to November 30, 2020). MAIN OUTCOMES AND MEASURES: Primary outcomes were the incidence and hospitalization rates within 7 days of de novo anorexia nervosa or atypical anorexia nervosa diagnosis. Event rate trends during the first wave were compared with trends in the 5-year prepandemic period (January 1, 2015, to February 28, 2020) using an interrupted time series with linear regression models. Demographic and clinical variables were compared using a χ(2) test for categorical data and t tests for continuous data. RESULTS: Overall, 1883 children and adolescents with newly diagnosed anorexia nervosa or atypical anorexia nervosa (median [IQR] age, 15.9 [13.8-16.9] years; 1713 female patients [91.0%]) were included. Prepandemic anorexia nervosa or atypical anorexia nervosa diagnoses were stable over time (mean [SD], 24.5 [1.6] cases per month; β coefficient, 0.043; P = .33). New diagnoses increased during the first wave of the pandemic to a mean (SD) of 40.6 (20.1) cases per month with a steep upward trend (β coefficient, 5.97; P < .001). Similarly, hospitalizations for newly diagnosed patients increased from a mean (SD) of 7.5 (2.8) to 20.0 (9.8) cases per month, with a significant increase in linear trend (β coefficient, −0.008 vs 3.23; P < .001). These trends were more pronounced in Canadian provinces with higher rates of COVID-19 infections. Markers of disease severity were worse among patients who were diagnosed during the first wave rather than before the pandemic, including more rapid progression (mean [SD], 7.0 [4.2] months vs 9.8 [7.4] months; P < .001), greater mean (SD) weight loss (19.2% [9.4%] vs 17.5% [9.6%]; P = .01), and more profound bradycardia (mean [SD] heart rate, 57 [15.8] beats per minute vs 63 [15.9] beats per minute; P < .001). CONCLUSIONS AND RELEVANCE: This cross-sectional study found a higher number of new diagnoses of and hospitalizations for anorexia nervosa or atypical anorexia nervosa in children and adolescents during the first wave of the COVID-19 pandemic in Canada. Research is needed to better understand the drivers and prognosis for these patients and to prepare for their mental health needs in the event of future pandemics or prolonged social isolation.

JAMA Netw Open2021       LitCov and CORD-19
1079Detection of Hate Speech in COVID-19-Related Tweets in the Arab Region: Deep Learning and Topic Modeling Approach  

BACKGROUND: The massive scale of social media platforms requires an automatic solution for detecting hate speech. These automatic solutions will help reduce the need for manual analysis of content. Most previous literature has cast the hate speech detection problem as a supervised text classification task using classical machine learning methods or, more recently, deep learning methods. However, work investigating this problem in Arabic cyberspace is still limited compared to the published work on English text. OBJECTIVE: This study aims to identify hate speech related to the COVID-19 pandemic posted by Twitter users in the Arab region and to discover the main issues discussed in tweets containing hate speech. METHODS: We used the ArCOV-19 dataset, an ongoing collection of Arabic tweets related to COVID-19, starting from January 27, 2020. Tweets were analyzed for hate speech using a pretrained convolutional neural network (CNN) model; each tweet was given a score between 0 and 1, with 1 being the most hateful text. We also used nonnegative matrix factorization to discover the main issues and topics discussed in hate tweets. RESULTS: The analysis of hate speech in Twitter data in the Arab region identified that the number of non–hate tweets greatly exceeded the number of hate tweets, where the percentage of hate tweets among COVID-19 related tweets was 3.2% (11,743/547,554). The analysis also revealed that the majority of hate tweets (8385/11,743, 71.4%) contained a low level of hate based on the score provided by the CNN. This study identified Saudi Arabia as the Arab country from which the most COVID-19 hate tweets originated during the pandemic. Furthermore, we showed that the largest number of hate tweets appeared during the time period of March 1-30, 2020, representing 51.9% of all hate tweets (6095/11,743). Contrary to what was anticipated, in the Arab region, it was found that the spread of COVID-19–related hate speech on Twitter was weakly related with the dissemination of the pandemic based on the Pearson correlation coefficient (r=0.1982, P=.50). The study also identified the commonly discussed topics in hate tweets during the pandemic. Analysis of the 7 extracted topics showed that 6 of the 7 identified topics were related to hate speech against China and Iran. Arab users also discussed topics related to political conflicts in the Arab region during the COVID-19 pandemic. CONCLUSIONS: The COVID-19 pandemic poses serious public health challenges to nations worldwide. During the COVID-19 pandemic, frequent use of social media can contribute to the spread of hate speech. Hate speech on the web can have a negative impact on society, and hate speech may have a direct correlation with real hate crimes, which increases the threat associated with being targeted by hate speech and abusive language. This study is the first to analyze hate speech in the context of Arabic COVID-19–related tweets in the Arab region.

J Med Internet Res2020       LitCov and CORD-19
1080Structural Basis for Human Receptor Recognition by SARS-CoV-2 Omicron Variant BA.1  

The highly contagious and fast-spreading omicron variant of SARS-CoV-2 infects the respiratory tracts efficiently. The receptor-binding domain (RBD) of the omicron spike protein recognizes human angiotensin-converting enzyme 2 (ACE2) as its receptor and plays a critical role in the tissue tropism of SARS-CoV-2. Here, we showed that the omicron RBD (strain BA.1) binds to ACE2 more strongly than does the prototypic RBD from the original Wuhan strain. We also measured how individual omicron mutations affect ACE2 binding. We further determined the crystal structure of the omicron RBD (engineered to facilitate crystallization) complexed with ACE2 at 2.6 Å. The structure shows that omicron mutations caused significant structural rearrangements of two mutational hot spots at the RBD/ACE2 interface, elucidating how each omicron mutation affects ACE2 binding. The enhanced ACE2 binding by the omicron RBD may facilitate the omicron variant’s infection of the respiratory tracts where ACE2 expression level is low. Our study provides insights into the receptor recognition and tissue tropism of the omicron variant. IMPORTANCE Despite the scarcity of the SARS-CoV-2 receptor—human angiotensin-converting enzyme 2 (ACE2)—in the respiratory tract, the omicron variant efficiently infects the respiratory tract, causing rapid and widespread infections of COVID-19. The omicron variant contains extensive mutations in the receptor-binding domain (RBD) of its spike protein that recognizes human ACE2. Here, using a combination of biochemical and X-ray crystallographic approaches, we showed that the omicron RBD binds to ACE2 with enhanced affinity and also elucidated the role of each of the omicron mutations in ACE2 binding. The enhanced ACE2 binding by the omicron RBD may contribute to the omicron variant’s new viral tropism in the respiratory tract despite the low level of ACE2 expression in the tissue. These findings help us to understand tissue tropism of the omicron variant and shed light on the molecular evolution of SARS-CoV-2.

J Virol2022       LitCov and CORD-19
1081Convergent antibody responses to SARS-CoV-2 in convalescent individuals  

During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-2(1–5). Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal pseudovirus neutralizing titers: less than 1:50 in 33% and below 1:1000 in 79%, while only 1% showed titers >1:5000. Antibody sequencing revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titers, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC(50)s) as low as single digit ng/mL. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.

Nature2020       LitCov and CORD-19
1082An inflammatory cytokine signature predicts COVID-19 severity and survival  

N/A

Nat Med2020       LitCov and CORD-19
1083The impact of the COVID-19 pandemic on stress, mental health and coping behavior in German University students-a longitudinal study before and after the onset of the pandemic  

BACKGROUND: The COVID-19 pandemic has led to massive restrictions in public and private lives, including a shut-down of face-to-face teaching at universities in Germany. We aimed to examine the impact of these changes on perceived stress, mental health and (study-)related health behavior of students in a longitudinal study. METHODS: For two timepoints – the year before the COVID-19 pandemic (2019, n = 1377) and the year during the COVID-19 pandemic (2020, n = 1867) – we surveyed students of all faculties at one German university for perceptions and preventive behavior regarding the COVID-19 pandemic using standard instruments for stress, anxiety, depression, and behavior and experience patterns. RESULTS: About 90% of students (n = 1633) in 2020 did not have a known contact infected with SARS-CoV-2, while 180 (9.8%) did have one. Only 10 respondents (0.5%) reported an infection with SARS-CoV-2. Wearing masks and washing hands more often were practiced by ≥80% of students. Taking more care about cleanliness (51.8%) and using disinfectants (39.2%) were practiced much less. A higher percentage of female compared with male students and medical/health science students compared with science, technology, engineering, and mathematics students engaged more frequently in specific or nonspecific preventive measures. More than three quarters (77.1%) of all students rated their general health as (very) good. There were no significant differences in general health, stress, and depression between 2019 and 2020 in the students who responded at both timepoints. The distribution of behavior and experience patterns for this group showed a slight but significant difference from 2019 to 2020, namely decreasing proportions of students with a healthy pattern and a risk pattern for overexertion. Students with different behavior and experience patterns showed marked differences in perceptions and reaction to the COVID-19 pandemic as well as psychosocial stress and symptoms, with higher scores for mental health symptoms and lower scores in preventive behavior regarding risk patterns. CONCLUSION: Despite massive alterations to students’ lives in 2020, there were only moderate consequences for mental health compared with 2019 in the total student group of this German university. However, identifying students at risk would offer opportunities to foster mental health in relevant subgroups. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-021-11295-6.

BMC Public Health2021       LitCov and CORD-19
1084Longitudinal changes in COVID-19 vaccination intent among South African adults: evidence from the NIDS-CRAM panel survey, February to May 2021  

BACKGROUND: COVID-19 vaccine hesitancy has threatened the ability of many countries worldwide to contain the pandemic. Given the severe impact of the pandemic in South Africa and disruptions to the roll-out of the vaccine in early 2021, slower-than-expected uptake is a pressing public health challenge in the country. We examined longitudinal changes in COVID-19 vaccination intent among South African adults, as well as determinants of intent to receive a vaccine. METHODS: We used longitudinal data from Wave 4 (February/March 2021) and Wave 5 (April/May 2021) of the National Income Dynamics Study: Coronavirus Rapid Mobile Survey (NIDS-CRAM), a national and broadly representative panel survey of adults in South Africa. We conducted cross-sectional analyses on aggregate and between-group variation in vaccination intent, examined individual-level changes between waves, and modeled demographic predictors of intent. RESULTS: We analysed data for 5629 (Wave 4; 48% male, mean age 41.5 years) and 5862 (Wave 5; 48% male, mean age 41.6 years) respondents. Willingness to get a COVID-19 vaccine significantly increased from 70.8% (95% CI: 68.5–73.1) in Wave 4 to 76.1% (95% CI: 74.2–77.8) in Wave 5. Individual-level analyses indicated that only 6.6% of respondents remained strongly hesitant between survey waves. Although respondents aged 18–24 years were 8.5 percentage points more likely to report hesitancy, hesitant respondents in this group were 5.6 percentage points more likely to change their minds by Wave 5. Concerns about rushed testing and safety of the vaccines were frequent and strongly-held reasons for hesitancy. CONCLUSIONS: Willingness to receive a COVID-19 vaccine has increased among adults in South Africa, and those who were entrenched in their reluctance make up a small proportion of the country’s population. Younger adults, those in formal housing, and those who trusted COVID-19 information on social media were more likely to be hesitant. Given that stated vaccination intent may not translate into behaviour, our finding that three-quarters of the population were willing to accept the vaccine may reflect an upper bound. Vaccination promotion campaigns should continue to frame vaccine acceptance as the norm and tailor strategies to different demographic groups. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-022-12826-5.

BMC Public Health2022       LitCov and CORD-19
1085Safety of Inactivated and mRNA COVID-19 Vaccination Among Patients Treated for Hypothyroidism: A Population-Based Cohort Study  

N/A

Thyroid2022       LitCov and CORD-19
1086Prevalence and Influencing Factors on Fatigue of First-line Nurses Combating with COVID-19 in China: A Descriptive Cross-Sectional Study  

Nurses’ work-related fatigue has been recognized as a threat to nurse health and patient safety. The aim of this study was to assess the prevalence of fatigue among first-line nurses combating with COVID-19 in Wuhan, China, and to analyze its influencing factors on fatigue. A multi-center, descriptive, cross-sectional design with a convenience sample was used. The statistical population consisted of the first-line nurses in 7 tertiary general hospitals from March 3, 2020 to March 10, 2020 in Wuhan of China. A total of 2667 samples from 2768 contacted participants completed the investgation, with a response rate of 96.35%. Social-demographic questionnaire, work-related questionnaire, Fatigue Scale-14, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Chinese Perceived Stress Scale were used to conduct online survey. The descriptive statistic of nurses’ social-demographic characteristics was conducted, and the related variables of work, anxiety, depression, perceived stress and fatigue were analyzed by t-tests, nonparametric test and Pearson’s correlation analysis. The significant factors which resulted in nurses’ fatigue were further analyzed by multiple linear regression analysis. The median score for the first-line nurses’ fatigue in Wuhan was 4 (2, 8). The median score of physical and mental fatigue of them was 3 (1, 6) and 1 (0, 3) respectively. According to the scoring criteria, 35.06% nurses (n=935) of all participants were in the fatigue status, their median score of fatigue was 10 (8, 11), and the median score of physical and mental fatigue of them was 7 (5, 8) and 3 (2, 4) respectively. Multiple linear regression analysis revealed the participants in the risk groups of anxiety, depression and perceived stress had higher scores on physical and mental fatigue and the statistically significant positive correlation was observed between the variables and nurses’ fatigue, the frequency of exercise and nurses’ fatigue had a statistically significant negative correlation, and average daily working hours had a significantly positive correlation with nurses’ fatigue, and the frequency of weekly night shift had a low positive correlation with nurses’ fatigue (P<0.01). There was a moderate level of fatigue among the first-line nurses fighting against COVID-19 pandemic in Wuhan, China. Government and health authorities need to formulate and take effective intervention strategies according to the relevant risk factors, and undertake preventive measures aimed at reducing health hazards due to increased work-related fatigue among first-line nurses, and to enhance their health status and provide a safe occupational environment worldwide. Promoting both medical and nursing safety while combating with the pandemic currently is warranted.

Curr Med Sci2020       LitCov and CORD-19
1087Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts  

BACKGROUND: Isolation of cases and contact tracing is used to control outbreaks of infectious diseases, and has been used for coronavirus disease 2019 (COVID-19). Whether this strategy will achieve control depends on characteristics of both the pathogen and the response. Here we use a mathematical model to assess if isolation and contact tracing are able to control onwards transmission from imported cases of COVID-19. METHODS: We developed a stochastic transmission model, parameterised to the COVID-19 outbreak. We used the model to quantify the potential effectiveness of contact tracing and isolation of cases at controlling a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-like pathogen. We considered scenarios that varied in the number of initial cases, the basic reproduction number (R(0)), the delay from symptom onset to isolation, the probability that contacts were traced, the proportion of transmission that occurred before symptom onset, and the proportion of subclinical infections. We assumed isolation prevented all further transmission in the model. Outbreaks were deemed controlled if transmission ended within 12 weeks or before 5000 cases in total. We measured the success of controlling outbreaks using isolation and contact tracing, and quantified the weekly maximum number of cases traced to measure feasibility of public health effort. FINDINGS: Simulated outbreaks starting with five initial cases, an R(0) of 1·5, and 0% transmission before symptom onset could be controlled even with low contact tracing probability; however, the probability of controlling an outbreak decreased with the number of initial cases, when R(0) was 2·5 or 3·5 and with more transmission before symptom onset. Across different initial numbers of cases, the majority of scenarios with an R(0) of 1·5 were controllable with less than 50% of contacts successfully traced. To control the majority of outbreaks, for R(0) of 2·5 more than 70% of contacts had to be traced, and for an R(0) of 3·5 more than 90% of contacts had to be traced. The delay between symptom onset and isolation had the largest role in determining whether an outbreak was controllable when R(0) was 1·5. For R(0) values of 2·5 or 3·5, if there were 40 initial cases, contact tracing and isolation were only potentially feasible when less than 1% of transmission occurred before symptom onset. INTERPRETATION: In most scenarios, highly effective contact tracing and case isolation is enough to control a new outbreak of COVID-19 within 3 months. The probability of control decreases with long delays from symptom onset to isolation, fewer cases ascertained by contact tracing, and increasing transmission before symptoms. This model can be modified to reflect updated transmission characteristics and more specific definitions of outbreak control to assess the potential success of local response efforts. FUNDING: Wellcome Trust, Global Challenges Research Fund, and Health Data Research UK.

Lancet Glob Health2020       LitCov and CORD-19
1088Caregiver willingness to vaccinate their children against COVID-19: Cross sectional survey  

Background More than 100 COVID-19 vaccine candidates are in development since the SARS-CoV-2 genetic sequence was published in January 2020. The uptake of a COVID-19 vaccine among children will be instrumental in limiting the spread of the disease as herd immunity may require vaccine coverage of up to 80% of the population. Prior history of pandemic vaccine coverage was as low as 40% among children in the United States during the 2009 H1N1 influenza pandemic. Purpose To investigate predictors associated with global caregivers’ intent to vaccinate their children against COVID-19, when the vaccine becomes available. Method An international cross sectional survey of 1541 caregivers arriving with their children to 16 pediatric Emergency Departments (ED) across six countries from March 26 to May 31, 2020. Results 65% (n = 1005) of caregivers reported that they intend to vaccinate their child against COVID-19, once a vaccine is available. A univariate and subsequent multivariate analysis found that increased intended uptake was associated with children that were older, children with no chronic illness, when fathers completed the survey, children up-to-date on their vaccination schedule, recent history of vaccination against influenza, and caregivers concerned their child had COVID-19 at the time of survey completion in the ED. The most common reason reported by caregivers intending to vaccinate was to protect their child (62%), and the most common reason reported by caregivers refusing vaccination was the vaccine’s novelty (52%). Conclusions The majority of caregivers intend to vaccinate their children against COVID-19, though uptake will likely be associated with specific factors such as child and caregiver demographics and vaccination history. Public health strategies need to address barriers to uptake by providing evidence about an upcoming COVID-19 vaccine’s safety and efficacy, highlighting the risks and consequences of infection in children, and educating caregivers on the role of vaccination.

Vaccine2020       LitCov and CORD-19
1089Association between living with children and outcomes from covid-19: OpenSAFELY cohort study of 12 million adults in England  

OBJECTIVE: To investigate whether risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and outcomes of coronavirus disease 2019 (covid-19) differed between adults living with and without children during the first two waves of the UK pandemic. DESIGN: Population based cohort study, on behalf of NHS England. SETTING: Primary care data and pseudonymously linked hospital and intensive care admissions and death records from England, during wave 1 (1 February to 31 August 2020) and wave 2 (1 September to 18 December 2020). PARTICIPANTS: Two cohorts of adults (18 years and over) registered at a general practice on 1 February 2020 and 1 September 2020. MAIN OUTCOME MEASURES: Adjusted hazard ratios for SARS-CoV-2 infection, covid-19 related admission to hospital or intensive care, or death from covid-19, by presence of children in the household. RESULTS: Among 9 334 392adults aged 65 years and under, during wave 1, living with children was not associated with materially increased risks of recorded SARS-CoV-2 infection, covid-19 related hospital or intensive care admission, or death from covid-19. In wave 2, among adults aged 65 years and under, living with children of any age was associated with an increased risk of recorded SARS-CoV-2 infection (hazard ratio 1.06 (95% confidence interval 1.05 to 1.08) for living with children aged 0-11 years; 1.22 (1.20 to 1.24) for living with children aged 12-18 years) and covid-19 related hospital admission (1.18 (1.06 to 1.31) for living with children aged 0-11; 1.26 (1.12 to 1.40) for living with children aged 12-18). Living with children aged 0-11 was associated with reduced risk of death from both covid-19 and non-covid-19 causes in both waves; living with children of any age was also associated with lower risk of dying from non-covid-19 causes. For adults 65 years and under during wave 2, living with children aged 0-11 years was associated with an increased absolute risk of having SARS-CoV-2 infection recorded of 40-60 per 10 000 people, from 810 to between 850 and 870, and an increase in the number of hospital admissions of 1-5 per 10 000 people, from 160 to between 161 and 165. Living with children aged 12-18 years was associated with an increase of 160-190 per 10 000 in the number of SARS-CoV-2 infections and an increase of 2-6 per 10 000 in the number of hospital admissions. CONCLUSIONS: In contrast to wave 1, evidence existed of increased risk of reported SARS-CoV-2 infection and covid-19 outcomes among adults living with children during wave 2. However, this did not translate into a materially increased risk of covid-19 mortality, and absolute increases in risk were small.

BMJ2021       LitCov and CORD-19
1090Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19  

N/A

JAMA2021       LitCov and CORD-19
1091GISAID: Global initiative on sharing all influenza data-from vision to reality  

Euro Surveill2017       CORD-19
1092Six-month humoral response to mRNA SARS-CoV-2 vaccination in patients with multiple sclerosis treated with ocrelizumab and fingolimod  

INTRODUCTION: Real-world clinical data suggest an attenuated short-term humoral response to SARS-CoV-2 vaccines in patients with multiple sclerosis (pwMS) receiving high efficacy (HE) disease modifying therapies (DMTs) such as Ocrelizumab (OCR) and Fingolimod (FNG). Long-term humoral response in pwMS treated with these HE-DMTs has been poorly investigated. The aim of our study was to explore: i) the humoral response up to six months after a full cycle of the BNT162b2 mRNA Covid-19 vaccine in pwMS treated with OCR and FNG and to compare it to age- and sex-matched healthy controls (HCs); ii) the relationship between humoral response and clinical and immunological characteristics of the studied population. METHODS: Serum samples were collected from HCs and pwMS treated with OCR or FNG at the following time points: before BNT162b2 mRNA Covid-19 vaccine (T0), and 4 (T1), 8 (T2), 16 (T3) and 24 (T4) weeks after the first dose. Sera were stored at −20 °C and tested for the quantitative detection of IgG antibodies to SARS-CoV-2 trimeric spike protein (Anti-TSP IgG) expressed in binding antibody units (BAU). At T1 neutralizing antibodies (NAbs) titres were assessed. The relationship between Anti-TSP IgG at each time-point and clinical and laboratoristic analyses were analysed by the Spearman correlation coefficient. RESULTS: 47 HCs and 50 pwMS (28 on OCR and 22 on FNG) were included in the study. All HCs mounted a positive humoral response at T1 and preserved it up to six months. At T1 only 57.1% pwMS on OCR (p < 0.001 compared with HCs) and 40.9% on FNG (p < 0.001) had a positive humoral response at T1, with only 39.3% and 27.3% maintaining a positive response at sixth months (T4), respectively. A strong positive correlation was observed between Nabs titres and Anti-TSP IgG at T1 (rho 0.87, p < 0.0001) with NAbs titres significantly higher in HCs compared with pwMS on OCR and FNG (p<0.0001). We also found a strong positive correlation between time-window since last OCR infusion and anti-TSP IgG titres at all time-points (T1 rho=0.58, p = 0.001; T2 rho=0.59, p = 0.001; T3 rho=0.53, p = 0.004; T4 rho=0.47, p = 0.01). In the FNG group we observed a significant correlation between the humoral response measured from T1 to T4 and: i) treatment duration (T1: rho -0.65, p = 0.001; T2: rho -0.8 p< 0.001; T3: rho -0.72, p=<0.001; T4: rho -0.67, p<0.001), ii) disease duration (T1: rho -0.5, p = 0.017; T2: rho -0.6, p = 0.003; T3: rho -0.58, p = 0.005; T4: rho -0.57, p = 0.006), and iii) baseline total lymphocyte count (T1: rho 0.37, p = 0.08; T2: rho 0.45, p = 0.03; T3: rho 0.43, p = 0.04; T4: rho 0.45, p = 0.03). CONCLUSIONS: Our long-term data show a weakened and short-lasting humoral response to SARS-CoV-2 mRNA vaccine in pwMS treated with OCR and FNG when compared with HCs. MS neurologists should take into account the time elapsed since the last infusion for pwMS on OCR, and the lymphocyte count as well as the disease and treatment duration for those on FNG when called to counsel such pwMS regarding the vaccination with the SARS-CoV-2 mRNA vaccine.

Mult Scler Relat Disord2022       LitCov and CORD-19
1093Humoral Immune Response in Inactivated SARS-CoV-2 Vaccine: When Should a Booster Dose be Administered?  

N/A

Mikrobiyol Bul2022       LitCov
1094Anxiety Severity Levels and Coping Strategies during the COVID-19 Pandemic among People Aged 15 Years and Above in Gonabad, Iran  

N/A

Arch Iran Med2020       LitCov and CORD-19
1095Extrapulmonary manifestations of COVID-19  

N/A

Nat Med2020       LitCov and CORD-19
1096A Multiplex Noninvasive Salivary Antibody Assay for SARS-CoV-2 Infection and Its Application in a Population-Based Survey by Mail  

Noninvasive salivary antibody immunoassays can enable low-cost epidemiological surveillance of infections. This study involved developing and validating a multiplex suspension immunoassay on the Luminex platform to measure immunoglobulin G (IgG) responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid and spike (S) proteins, and the spike protein’s S1 and S2 subunits and receptor binding domain. Multiple versions of these recombinant proteins acquired from commercial and noncommercial sources were evaluated. Assay development and validation utilized saliva and serum samples from coronavirus disease 2019 (COVID-19) cases procured from commercial sources and negative controls from a prepandemic survey. Saliva was also collected in a demonstration survey by mail involving adult individuals in the United States who were diagnosed with SARS-CoV-2 infection 15 to 80 days prior to sample collection. The survey had an 83% valid sample return rate (192 samples from 38 states). Most COVID-19 cases (93%) reported mildly symptomatic or asymptomatic infections. The final salivary assay based on the best-performing spike and nucleocapsid proteins had a sensitivity of 87.1% (95% bootstrap confidence interval, 82.1 to 91.7%) and specificity of 98.5% (95.0 to 100%) using 227 and 285 saliva samples, respectively. The same assay had 95.9% (92.8 to 98.9%) sensitivity and 100% (98.4 to 100%) specificity in serum (174 and 285 serum samples, respectively). Salivary and serum antibody responses to spike and nucleocapsid proteins were strongly correlated in 22 paired samples (r = 0.88 and r = 0.80, respectively). Antibody responses peaked at approximately 50 days postonset; greater illness severity was associated with stronger responses. This study demonstrated that a salivary antibody assay can be used in large-scale population surveys by mail to better characterize public health impacts of COVID-19. IMPORTANCE Given the enormous impacts of the COVID-19 pandemic, developing tools for population surveillance of infection is of paramount importance. This article describes the development of a multiplex immunoassay on a Luminex platform to measure salivary immunoglobulin G responses to the spike protein, its two subunits and receptor binding domain, and the nucleocapsid protein of SARS-CoV-2. The assay validation utilized serum and saliva samples from prepandemic controls and recent COVID-19 cases. A survey by mail targeting recent COVID-19 cases across the United States also demonstrated the utility of safe, at-home self-collection of saliva. By incorporating multiple SARS-CoV-2 proteins, this assay may differentiate responses to natural SARS-CoV-2 infections from responses to most vaccines. Application of this noninvasive immunoassay in COVID-19 surveillance can help provide estimates of cumulative incidence rates of symptomatic and asymptomatic infections in various communities and subpopulations, temporal patterns of antibody responses, and risk factors for infection.

Microbiol Spectr2021       LitCov and CORD-19
1097Mental Health in Frontline Medical Workers during the 2019 Novel Coronavirus Disease Epidemic in China: A Comparison with the General Population  

Background: Since December 2019, China has been affected by a severe outbreak of coronavirus disease 2019 (COVID-19). Frontline medical workers experienced difficulty due to the high risk of being infected and long and distressing work shifts. The current study aims to evaluate psychological symptoms in frontline medical workers during the COVID-19 epidemic in China and to perform a comparison with the general population. Methods: An online survey was conducted from 14 February 2020 to 29 March 2020. A total of 899 frontline medical workers and 1104 respondents in the general population participated. Depression, anxiety, insomnia, and resilience were assessed via the Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7), Insomnia Severity Index (ISI), and abbreviated Connor–Davidson Resilience Scale (CD-RISC-10), respectively. Results: Overall, 30.43%, 20.29%, and 14.49% of frontline medical workers in Hubei Province and 23.13%, 13.14%, and 10.64% of frontline medical workers in other regions reported symptoms of depression, anxiety, and insomnia, respectively. In addition, 23.33%, 16.67%, and 6.67% of the general population in Hubei Province and 18.25%, 9.22%, and 7.17% of the general population in other regions reported symptoms of depression, anxiety, and insomnia, respectively. The resilience of frontline medical staff outside Hubei Province was higher than that of the general population outside Hubei Province. Conclusion: A large proportion of frontline medical workers and the general public experienced psychological symptoms during the COVID-19 outbreak. Psychological services for frontline medical workers and the general public are needed.

Int J Environ Res Public Healt2020       LitCov and CORD-19
1098COVID-19 Incidence and Death Rates Among Unvaccinated and Fully Vaccinated Adults with and Without Booster Doses During Periods of Delta and Omicron Variant Emergence-25 US Jurisdictions, April 4-December 25, 2021  

N/A

MMWR Morb Mortal Wkly Rep2022       LitCov and CORD-19
1099COVID-19 on the Nile: Review on the Management and Outcomes of the COVID-19 Pandemic in the Arab Republic of Egypt from February to August 2020  

As the world fights the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the World Health Organization (WHO) reports that over 17 million people globally were infected with SARS-CoV-2 as of 1 August 2020. Although infections are asymptomatic in 80% of cases, severe respiratory illness occurs in 20% of cases, requiring hospitalization and highly specialized intensive care. The WHO, under the International Health Regulations, declared this pandemic a public health emergency of international concern; it has affected nearly all health systems worldwide. The health system in Egypt, similar to many others, was severely challenged when confronted with the need for urgent and major expansion required to manage such a significant pandemic. This review uses publicly available data to provide an epidemiological summary of the COVID-19 pandemic behavior during the first wave of the outbreak in Egypt. The article covers mathematical modeling predictions, Egypt’s healthcare system, economic and social impacts of COVID-19, as well as national responses that were crucial to the initial containment of the pandemic. We observed how the government managed the outbreak by enhancing testing capacity, contact tracing, announcing public health and social measures (PHSMs), as well as allocating extra funds and human resources to contain SARS-COV-2. Prospectively, economic losses from major sources of revenues—tourism, travel, and trade—may be reflected in future timelines, as Egypt continues to control cases and loss of life from COVID-19. Overall, trends indicate that the spread of COVID-19 in Egypt was initially contained. Revalidation of prediction models and follow-up studies may reveal the aftermath of the pandemic and how well it was managed in Egypt.

Int J Environ Res Public Healt2021       LitCov and CORD-19
1100Testing an early online intervention for the treatment of disturbed sleep during the COVID-19 pandemic (Sleep COVID-19): structured summary of a study protocol for a randomised controlled trial  

OBJECTIVES: The primary aim of the present study is to examine the efficacy of an online intervention for poor sleep in the context of an ongoing stressful major life event, by assessing if this intervention can reduce insomnia severity at short-term (one week post-intervention) and long-term (one and three months post-intervention) follow-up time points. It is hypothesised that the intervention will: 1) reduce insomnia severity in poor sleepers, compared to wait-list control poor sleepers, and good sleepers; 2) reduce subjective symptoms of anxiety and depression in all groups, and 3) prevent the transition to acute insomnia in good sleepers. TRIAL DESIGN: This study is a cluster randomised controlled trial. PARTICIPANTS: Both healthy good sleepers, who do not report having any current sleep problems, and individuals who report having sleep problems, will be recruited for the present study. This is a single-site study (Northumbria University). This study will be delivered using the internet and there are no geographic restrictions. Individuals who self-report as poor sleepers will meet DSM-5 criteria for acute insomnia, which is where individuals: 1) have difficulties in falling asleep, staying asleep, or awakening too early for at least three nights per week, for a time period of between two weeks and three months; and 2) report experiencing distress or impairment caused by sleep loss. Both 1) and 2) must have occurred despite the individual having had an adequate opportunity for sleep during this time period. Good sleepers will be individuals who do not have current sleep problems. All participants must have a sufficient level of English comprehension to understand and complete study measures. Individuals cannot participate if they report having chronic sleep problems (where they have existed for more than three months immediately prior to providing consent), nor will individuals who are actively seeking treatment for their sleep problems irrespective of how long they have had the sleep problem. Individuals also cannot participate if they have a self-reported history of head injuries, or if they have a self-reported diagnosis of schizophrenia, epilepsy or personality disorder, as the distraction techniques involved in the insomnia intervention may increase rumination in individuals with these conditions, and influence the effectiveness of the intervention. INTERVENTION AND COMPARATOR: Participants who receive the intervention will be provided with an online version of a self-help leaflet. A printed version of this leaflet has been successfully used in previous treatment studies, which have been conducted by our research group. Participants will be encouraged to download, save or print out this leaflet, which will be provided in PDF format. There will be no restrictions on use and participants will be encouraged to refer to this leaflet as often as they wish to. Briefly, this self-help leaflet aims to improve sleep by identifying and addressing sleep-related dysfunctional thinking by providing education about sleep, providing techniques to distract from intrusive worrisome thoughts at night, and providing guidelines for sleep-related stimulus control. The comparator is a wait-list control (i.e. where they will receive the intervention after a one month delay) group. MAIN OUTCOMES: The primary outcome measure will be insomnia severity, as measured using the Insomnia Severity Index (Bastien, Vallières, & Morin, 2001), assessed immediately prior to the intervention and at one week, one month and three months post-intervention, compared to baseline. Secondary outcome measures will include subjective mood, measured using the 7-item Generalised Anxiety Disorder Questionnaire (GAD-7; Spitzer, Kroenke, Williams, & Lowe, 2006)) and 9-item Patient Health Questionnaire (PHQ-9; Kroenke, Spitzer, & Williams, 2001), assessed immediately prior to the intervention, and one week, one month and three months post-intervention, compared to baseline. Additionally, subjective sleep continuity, derived from sleep diaries (Carney et al., 2012), will be compared pre and post-intervention. RANDOMISATION: This study will operate as a cluster randomised controlled trial. Good sleepers will be randomised into an intervention or a no-intervention group, with a 1:1 allocation. Poor sleepers will be randomised into an intervention or wait-list control group, with a 1:1 allocation. Randomisation will be conducted automatically using Qualtrics study software, where block sizes will be equal and randomisation will be computer-generated. BLINDING (MASKING): Participants will not be blinded to group assignment. The outcomes will be assessed by a blinded investigator. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The minimum sample size is 60. A total of 30 poor sleepers will be randomised to the intervention or wait-list control group. A total of 30 good sleepers will be randomised to the intervention or no intervention group. TRIAL STATUS: Recruitment for this study has yet to start. It is anticipated that recruitment will begin in August 2020 and end in April 2022. The current study protocol is version 1.0 (20 July 2020) TRIAL REGISTRATION: This study was prospectively registered in the ISRCTN registry (registration number ISRCTN43900695, date of registration: 8 April 2020). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Trials2020       LitCov and CORD-19

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

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