\ 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
2801Serological Assays for Assessing Postvaccination SARS-CoV-2 Antibody Response  

Serological assays for measuring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies have crucial applications in the control and surveillance of the current COVID-19 pandemic. A large number of such assays have been developed and are now commercially available. However, there are limited studies evaluating the performance of these tests. We evaluated the performances of the following six commercially available serological assays for detecting SARS-CoV-2 antibodies: (i) Genscript cPass surrogate virus neutralization test (Genscript cPass), (ii) Diasorin-SARS-CoV-2 S1/S2 IgG detection (Diasorin-S1/S2 IgG), (iii) Alinity SARS-CoV-2 IgG II (Alinity IgG II), (iv) Diasorin-SARS-CoV-2 TrimericS IgG (Diasorin-TrimericS IgG), (v) Roche Elecsys anti-SARS-CoV-2-cobas (Roche Elecsys), and (vi) AESKU enzyme linked immunosorbent assay (AESKULISA). The results of these tests were compared against the gold standard plaque reduction neutralization test (PRNT). Roche Elecsys had the highest sensitivity, and the Genscript cPass had the highest specificity. Diasorin-TrimericS IgG had the best overall performance with the highest agreement with the PRNT results. Parallel testing of Genscript cPass with Diasorin-TrimericS IgG and Diasorin-S1/S2 IgG had the optimum performance. Based on the receiver operating characteristic (ROC) curve, lowering the cutoff from 30% to 20% in the Genscript cPass significantly increased the sensitivity and the overall agreement with the PRNT results. Commercially available serological assays are good alternatives to the standard PRNT. However, further studies on larger sample numbers are required for optimization of the assay cutoff values and for evaluation of cost effectiveness. IMPORTANCE Commercial serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now widely available. This study adds new knowledge regarding the optimization of these assays for evaluating postvaccination antibodies status. It highlights the positive and negative aspects of each assay in terms of sensitivity, specificity, and positive and negative predictive values, compared to the gold standard neutralization test. When using serological assays to assess postvaccine immune status, a balance of all parameters needs to be considered and not simply the high specificity. This balance is particularly relevant in the current situation where countries are aiming to mass vaccinate their populations and bring this pandemic under control. Assays with good sensitivity will have a lower percentage of false negatives and thus provide confidence for vaccination. Understanding the strengths and limitations of commercially available serological assays is important, not only for better application of these tests but also to understand the immune response and the duration of protection postvaccination.

Microbiol Spectr2021       LitCov and CORD-19
2802Clinical characteristics and risk factors for severity of COVID-19 outside Wuhan: a double-center retrospective cohort study of 213 cases in Hunan, China  

AIM: To investigate clinical characteristics and identify risk factors for severity of coronavirus disease 2019 (COVID-19) pneumonia outside of Wuhan, China. MATERIALS AND METHODS: We included 213 patients with confirmed COVID-19 who had been discharged or died by 15 March 2020. We retrospectively collected epidemiological, clinical, laboratory, computed tomography imaging and outcome data. Clinical characteristics were described and relative risk factors were compared. RESULTS: Most clinical characteristics of this study were similar to those from studies in Wuhan, but there were lower mortality rate and milder severity. The median time from onset of symptoms to confirmation and hospitalization was 4 and 5 days, respectively. The median virus clearance and shedding times were 10 and 15 days, respectively. When the severe/critical group was compared with the mild/moderate group, significant risk factors included: older age; dyspnea; hypertension; poor appetite; fatigue; higher white cell count, neutrophil count, prothrombin time, creatine kinase, creatine kinase-MB, D-dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and C-reactive protein; and lower lymphocyte count and albumin (p < 0.05). In the intensive care unit (ICU) group compared with the non-ICU group, risk factors included: older age; chronic obstructive pulmonary disease (COPD); dyspnea; poor appetite; higher white cell count, D-dimer, ALT, AST and LDH; and lower lymphocyte count and albumin (p < 0.05). Independent risk factors associated with the severe/critical group were dyspnea [odds ratio (OR) = 19.48], ALT (OR = 6.02) and albumin (OR = 3.36). Independent risk factors associated with the ICU group were dyspnea (OR = 8.88), COPD (OR = 31.80), D-dimer (OR = 8.37), ALT (OR = 28.76) and LDH (OR = 9.95) (p < 0.05). CONCLUSION: The severity of COVID-19 outside Wuhan, China was milder than that within Wuhan. The clinical infective period was long, and the longest virus shedding time was 35 days. The most important risk factors were dyspnea, COPD, D-dimer, ALT, LDH and albumin. The reviews of this paper are available via the supplemental material section.

Ther Adv Respir Dis2020       LitCov and CORD-19
2803Factors Associated with the Implementation of Non-Pharmaceutical Interventions for Reducing COVID-19: A Systematic Review  

There has been much discussion recently about the importance of implementing non-pharmaceutical interventions (NPIs) to protect the public from coronavirus disease 2019 (COVID-19) infection. Different governments across the world have adopted NPIs (e.g., social distancing, quarantine, isolation, lockdowns, curfews, travel restrictions, closures of schools and colleges). Two fundamental strategies, namely a strict containment strategy—also called suppression strategy—and a mitigation strategy have been adopted in different countries, mainly to reduce the reproduction number (R(0)) to below one and hence to reduce case numbers to low levels or eliminate human-to-human transmission, as well as to use NPIs to interrupt transmission completely and to reduce the health impact of epidemics, respectively. However, the adoption of these NPI strategies is varied and the factors impacting NPI are inconsistent and unclear. This study, therefore, aimed to review the factors associated with the implementation of NPIs (social distancing, social isolation and quarantine) for reducing COVID-19. Following PRISMA guidelines, we searched for published and unpublished studies, undertaking a systematic search of: MEDLINE, EMBASE, Allied and Complementary Medicine, COVID-19 Research, WHO database on COVID-19, and Google Scholar. Thirty-three studies were included in the study. Seven descriptive themes emerged on enablers and barriers to NPIs: the positive impact of NPIs, effective public health interventions, positive change in people’s behaviour and concerns about COVID-19, the role of mass media, physical and psychological impacts, and ethnicity/age associated with COVID-19. This study has highlighted that the effectiveness of NPIs in isolation is likely to be limited, therefore, a combination of multiple measures e.g., SD, isolation and quarantine, and workplace distancing appeared more effective in reducing COVID-19. Studies suggest that targeted approaches alongside social distancing might be the way forward, and more acceptable. Further research to promote country- and context-specific adoption of NPIs to deliver public health measures is needed. Studies comparing the effectiveness of interventions and strategies will help provide more evidence for future pandemics.

Int J Environ Res Public Healt2021       LitCov and CORD-19
2804Association of Receipt of the Fourth BNT162b2 Dose With Omicron Infection and COVID-19 Hospitalizations Among Residents of Long-term Care Facilities  

N/A

JAMA Intern Med2022       LitCov
2805Development and External Validation of a Machine Learning Tool to Rule Out COVID-19 Among Adults in the Emergency Department Using Routine Blood Tests: A Large, Multicenter, Real-World Study  

BACKGROUND: Conventional diagnosis of COVID-19 with reverse transcription polymerase chain reaction (RT-PCR) testing (hereafter, PCR) is associated with prolonged time to diagnosis and significant costs to run the test. The SARS-CoV-2 virus might lead to characteristic patterns in the results of widely available, routine blood tests that could be identified with machine learning methodologies. Machine learning modalities integrating findings from these common laboratory test results might accelerate ruling out COVID-19 in emergency department patients. OBJECTIVE: We sought to develop (ie, train and internally validate with cross-validation techniques) and externally validate a machine learning model to rule out COVID 19 using only routine blood tests among adults in emergency departments. METHODS: Using clinical data from emergency departments (EDs) from 66 US hospitals before the pandemic (before the end of December 2019) or during the pandemic (March-July 2020), we included patients aged ≥20 years in the study time frame. We excluded those with missing laboratory results. Model training used 2183 PCR-confirmed cases from 43 hospitals during the pandemic; negative controls were 10,000 prepandemic patients from the same hospitals. External validation used 23 hospitals with 1020 PCR-confirmed cases and 171,734 prepandemic negative controls. The main outcome was COVID 19 status predicted using same-day routine laboratory results. Model performance was assessed with area under the receiver operating characteristic (AUROC) curve as well as sensitivity, specificity, and negative predictive value (NPV). RESULTS: Of 192,779 patients included in the training, external validation, and sensitivity data sets (median age decile 50 [IQR 30-60] years, 40.5% male [78,249/192,779]), AUROC for training and external validation was 0.91 (95% CI 0.90-0.92). Using a risk score cutoff of 1.0 (out of 100) in the external validation data set, the model achieved sensitivity of 95.9% and specificity of 41.7%; with a cutoff of 2.0, sensitivity was 92.6% and specificity was 59.9%. At the cutoff of 2.0, the NPVs at a prevalence of 1%, 10%, and 20% were 99.9%, 98.6%, and 97%, respectively. CONCLUSIONS: A machine learning model developed with multicenter clinical data integrating commonly collected ED laboratory data demonstrated high rule-out accuracy for COVID-19 status, and might inform selective use of PCR-based testing.

J Med Internet Res2020       LitCov and CORD-19
2806CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells  

In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2, no specific and effective drugs for treating this disease have been reported until today. Angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2, mediates the virus infection by binding to spike protein. Although ACE2 is expressed in the lung, kidney, and intestine, its expressing levels are rather low, especially in the lung. Considering the great infectivity of COVID-19, we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection. Here, we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein. The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody, Meplazumab, inhibits SARS-CoV-2 amplification. Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells, which can be neutralized by CD147 extracellular fragment. Viral loads are detectable in the lungs of human CD147 (hCD147) mice infected with SARS-CoV-2, but not in those of virus-infected wild type mice. Interestingly, virions are observed in lymphocytes of lung tissue from a COVID-19 patient. Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dose-dependent manner, which is specifically inhibited by Meplazumab. Furthermore, CD147 mediates virus entering host cells by endocytosis. Together, our study reveals a novel virus entry route, CD147-spike protein, which provides an important target for developing specific and effective drug against COVID-19.

Signal Transduct Target Ther2020       LitCov and CORD-19
2807Importance of Neutralizing Monoclonal Antibodies Targeting Multiple Antigenic Sites on the Middle East Respiratory Syndrome Coronavirus Spike Glycoprotein To Avoid Neutralization Escape  

N/A

J Virol2018       CORD-19
2808A single dose of recombinant VSV-∆G-spike vaccine provides protection against SARS-CoV-2 challenge  

The COVID-19 pandemic caused by SARS-CoV-2 imposes an urgent need for rapid development of an efficient and cost-effective vaccine, suitable for mass immunization. Here, we show the development of a replication competent recombinant VSV-∆G-spike vaccine, in which the glycoprotein of VSV is replaced by the spike protein of SARS-CoV-2. In-vitro characterization of this vaccine indicates the expression and presentation of the spike protein on the viral membrane with antigenic similarity to SARS-CoV-2. A golden Syrian hamster in-vivo model for COVID-19 is implemented. We show that a single-dose vaccination results in a rapid and potent induction of SARS-CoV-2 neutralizing antibodies. Importantly, vaccination protects hamsters against SARS-CoV-2 challenge, as demonstrated by the abrogation of body weight loss, and alleviation of the extensive tissue damage and viral loads in lungs and nasal turbinates. Taken together, we suggest the recombinant VSV-∆G-spike as a safe, efficacious and protective vaccine against SARS-CoV-2.

Nat Commun2020       LitCov and CORD-19
2809Understanding and Addressing Sources of Anxiety Among Healthcare Professionals During the COVID-19 Pandemic  

N/A

JAMA2020       LitCov and CORD-19
2810Treatment of COVID-19 with convalescent plasma: lessons from past coronavirus outbreaks  

BACKGROUND: There is currently no treatment known to alter the course of COVID-19. Convalescent plasma has been used to treat a number of infections during pandemics, including SARS-CoV, MERS-CoV, and now COVID-19. OBJECTIVES: To summarize the existing literature and registered clinical trials on the efficacy and safety of convalescent plasma for treating coronaviruses, and discuss issues of feasibility, and donor and patient selection. SOURCES: A review of articles published in PubMed was performed on July 13, 2020, to summarize the currently available evidence in human studies for convalescent plasma as a treatment for coronaviruses. The World Health Organization International Clinical Trials Registry and clinicaltrials.gov were searched to summarize the currently registered randomized clinical trials for convalescent plasma in COVID-19. CONTENT: There were sixteen COVID-19, four MERS-CoV, and five SARS-CoV reports describing convalescent plasma use in humans. There were two randomized control trials, both of which were for COVID-19 and were terminated early. Most COVID-19 reports described a potential benefit of convalescent plasma on clinical outcomes in severe or critically ill patients with few immediate adverse events. However, there were a number of limitations, including the concurrent use of antivirals, steroids, and other treatments, small sample sizes, lack of randomization or control groups, and short follow-up time. Data from SARS-CoV and COVID-19 suggest that earlier administration likely yields better outcomes. The ideal candidates for recipients and donors are not known. Still, experience with prior coronaviruses tells us that antibodies in convalescent patients are probably short-lived. Patients who had more severe disease and who are earlier in their course of recovery may be more likely to have adequate titres. Finally, a number of practical challenges were identified. IMPLICATIONS: There is currently no effective treatment for COVID-19, and preliminary trials for convalescent plasma suggest there may be some benefits. However, research to date is at high risk of bias, and randomized control trials are desperately needed to determine the efficacy and safety of this therapeutic option.

Clin Microbiol Infect2020       LitCov and CORD-19
2811SARS-CoV-2 seroprevalence worldwide: a systematic review and meta-analysis  

BACKGROUND: COVID-19 is arguably the most important public health concern in 2020 worldwide, and efforts are now escalating to suppress or eliminate its spread. OBJECTIVE: In this study, we undertook a meta-analysis to estimate the global and regional SARS-CoV-2 seroprevalence rates in humans, and to assess whether seroprevalence associates with geographical, climatic and socio-demographic factors. DATA SOURCES: We systematically reviewed PubMed, Scopus, Embase, medRxiv and bioRxiv databases for preprints or peer-reviewed articles (up to 14 August 2020). STUDY ELIGIBILITY CRITERIA: Population-based studies describing the prevalence of anti-SARS-CoV-2 (IgG and/or IgM) serum antibodies. PARTICIPANTS: People of different socio-economic and ethnic backgrounds – from the general population – whose prior COVID-19 status was unknown were tested for the presence of anti-SARS-CoV-2 serum antibodies. INTERVENTIONS: There were no interventions. METHODS: We used a random-effects model to estimate pooled seroprevalence, and then extrapolated the findings to the global population (for 2020). Subgroup and meta-regression analyses explored potential sources of heterogeneity in the data, and relationships between seroprevalence and socio-demographic, geographical and/or climatic factors. RESULTS: In total, 47 studies involving 399,265 people from 23 countries met the inclusion criteria. Heterogeneity (I(2) = 99.4%, P < 0.001) was seen among studies; the SARS-CoV-2 seroprevalence in the general population varied from 0.37% to 22.1%, with a pooled estimate of 3.38% (95% CI, 3.05%–3.72%; 15,879/399,265). On a regional level, seroprevalence varied from 1.45% (0.95–1.94%; South America) to 5.27% (3.97–6.57%; Northern Europe, although some variation appeared to relate to the serological assay used. The findings suggested an association of seroprevalence with income levels, human development indices, geographical latitudes and/or climate. Extrapolating to the 2020 world population, we estimated that 263.5 million individuals had been exposed or infected at the time of this study. CONCLUSION: This study showed that SARS-CoV-2 seroprevalence varied markedly among geographic regions, as might be expected early in a pandemic. Longitudinal surveys to continually monitor seroprevalence around the globe will be critical to support prevention and control efforts, and might indicate levels of endemic stability or instability in particular countries and regions. A. Rostami, Clin Microbiol Infect 2020.

Clin Microbiol Infect2020       LitCov and CORD-19
2812In Silico Investigation of the New UK (B.1.1.7) and South African (501Y.V2) SARS-CoV-2 Variants with a Focus at the ACE2-Spike RBD Interface  

SARS-CoV-2 exploits angiotensin-converting enzyme 2 (ACE2) as a receptor to invade cells. It has been reported that the UK and South African strains may have higher transmission capabilities, eventually in part due to amino acid substitutions on the SARS-CoV-2 Spike protein. The pathogenicity seems modified but is still under investigation. Here we used the experimental structure of the Spike RBD domain co-crystallized with part of the ACE2 receptor, several in silico methods and numerous experimental data reported recently to analyze the possible impacts of three amino acid replacements (Spike K417N, E484K, N501Y) with regard to ACE2 binding. We found that the N501Y replacement in this region of the interface (present in both the UK and South African strains) should be favorable for the interaction with ACE2, while the K417N and E484K substitutions (South African strain) would seem neutral or even unfavorable. It is unclear if the N501Y substitution in the South African strain could counterbalance the K417N and E484K Spike replacements with regard to ACE2 binding. Our finding suggests that the UK strain should have higher affinity toward ACE2 and therefore likely increased transmissibility and possibly pathogenicity. If indeed the South African strain has a high transmission level, this could be due to the N501Y replacement and/or to substitutions in regions located outside the direct Spike–ACE2 interface but not so much to the K417N and E484K replacements. Yet, it should be noted that amino acid changes at Spike position 484 can lead to viral escape from neutralizing antibodies. Further, these amino acid substitutions do not seem to induce major structural changes in this region of the Spike protein. This structure–function study allows us to rationalize some observations made for the UK strain but raises questions for the South African strain.

Int J Mol Sci2021       LitCov and CORD-19
2813SARS-CoV-2 evolution during treatment of chronic infection  

SARS-CoV-2 Spike protein is critical for virus infection via engagement of ACE2(1), and is a major antibody target. Here we report chronic SARS-CoV-2 with reduced sensitivity to neutralising antibodies in an immune suppressed individual treated with convalescent plasma, generating whole genome ultradeep sequences over 23 time points spanning 101 days. Little change was observed in the overall viral population structure following two courses of remdesivir over the first 57 days. However, following convalescent plasma therapy we observed large, dynamic virus population shifts, with the emergence of a dominant viral strain bearing D796H in S2 and ΔH69/ΔV70 in the S1 N-terminal domain NTD of the Spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype diminished in frequency, before returning during a final, unsuccessful course of convalescent plasma. In vitro, the Spike escape double mutant bearing ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, whilst maintaining infectivity similar to wild type. D796H appeared to be the main contributor to decreased susceptibility but incurred an infectivity defect. The ΔH69/ΔV70 single mutant had two-fold higher infectivity compared to wild type, possibly compensating for the reduced infectivity of D796H. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy associated with emergence of viral variants with evidence of reduced susceptibility to neutralising antibodies.

Nature2021       LitCov and CORD-19
2814A Barcoded Flow Cytometric Assay to Explore the Antibody Responses Against SARS-CoV-2 Spike and Its Variants  

The SARS-CoV-2 pandemic has spread to all parts of the world and can cause life-threatening pneumonia and other severe disease manifestations known as COVID-19. This health crisis has resulted in a significant effort to stop the spread of this new coronavirus. However, while propagating itself in the human population, the virus accumulates mutations and generates new variants with increased fitness and the ability to escape the human immune response. Here we describe a color-based barcoded spike flow cytometric assay (BSFA) that is particularly useful to evaluate and directly compare the humoral immune response directed against either wild type (WT) or mutant spike (S) proteins or the receptor-binding domains (RBD) of SARS-CoV-2. This assay employs the human B lymphoma cell line Ramos, transfected for stable expression of WT or mutant S proteins or a chimeric RBD-CD8 fusion protein. We find that the alpha and beta mutants are more stably expressed than the WT S protein on the Ramos B cell surface and/or bind with higher affinity to the viral entry receptor ACE2. However, we find a reduce expression of the chimeric RBD-CD8 carrying the point mutation N501Y and E484K characteristic for the alpha and beta variant, respectively. The comparison of the humoral immune response of 12 vaccinated probands with 12 COVID-19 patients shows that after the boost, the S-specific IgG class immune response in the vaccinated group is similar to that of the patient group. However, in comparison to WT the specific IgG serum antibodies bind less well to the alpha variant and only poorly to the beta variant S protein. This is in line with the notion that the beta variant is an immune escape variant of SARS-CoV-2. The IgA class immune response was more variable than the IgG response and higher in the COVID-19 patients than in the vaccinated group. In summary, we think that our BSFA represents a useful tool to evaluate the humoral immunity against emerging variants of SARS-CoV-2 and to analyze new vaccination protocols against these variants.

Front Immunol2021       LitCov and CORD-19
2815A trial platform to assess approved SARS-CoV-2 vaccines in immunocompromised patients: first sub-protocol for a pilot trial comparing the mRNA vaccines Comirnaty and COVID-19 mRNA Vaccine Moderna  

BACKGROUND: Late 2019, a new highly contagious coronavirus SARS-CoV-2 has emerged in Wuhan, China, causing within 2 months a pandemic with the highest disease burden in elderly and people with pre-existing medical conditions. The pandemic has highlighted that new and more flexible clinical trial approaches, such as trial platforms, are needed to assess the efficacy and safety of interventions in a timely manner. The two existing Swiss cohorts of immunocompromised patients (i.e., Swiss HIV Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS)) are an ideal foundation to set-up a trial platform in Switzerland leveraging routinely collected data. Within a newly founded trial platform, we plan to assess the efficacy of the first two mRNA SARS-CoV-2 vaccines that reached market authorization in Switzerland in the frame of a pilot randomized controlled trial (RCT) while at the same time assessing the functionality of the trial platform. METHODS: We will conduct a multicenter randomized controlled, open-label, 2-arm sub-study pilot trial of a platform trial nested into two Swiss cohorts. Patients included in the SHCS or the STCS will be eligible for randomization to either receiving the mRNA vaccine Comirnaty® (Pfizer/BioNTech) or the COVID-19 mRNA Vaccine Moderna®. The primary clinical outcome will be change in pan-lg antibody response (pan-Ig anti-S1-RBD; baseline vs. 3 months after first vaccination; binary outcome, considering ≥ 0.8 units/ml as a positive antibody response). The pilot study will also enable us to assess endpoints related to trial conduct feasibility (i.e., duration of RCT set-up; time of patient recruitment; patient consent rate; proportion of missing data). Assuming vaccine reactivity of 90% in both vaccine groups, we power our trial, using a non-inferiority margin such that a 95% two-sided confidence interval excludes a difference in favor of the reference group of more than 10%. A sample size of 380 (190 in each treatment arm) is required for a statistical power of 90% and a type I error of 0.025. The study is funded by the Swiss National Science Foundation (National Research Program NRP 78, “COVID-19”). DISCUSSION: This study will provide crucial information about the efficacy and safety of the mRNA SARS-CoV-2 vaccines in HIV patients and organ transplant recipients. Furthermore, this project has the potential to pave the way for further platform trials in Switzerland. TRIAL REGISTRATION: ClinicalTrials.govNCT04805125. Registered on March 18, 2021

Trials2021       LitCov and CORD-19
2816Timing of SARS-CoV-2 vaccination during the third trimester of pregnancy and transplacental antibody transfer: a prospective cohort study  

OBJECTIVE: We aimed to assess the impact of early versus late third-trimester maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination on transplacental transfer and neonatal levels of SARS-CoV-2 antibodies. METHODS: Maternal and cord blood sera were collected following term delivery after antenatal SARS-CoV-2 BNT162b2 mRNA vaccination, with the first vaccine dose administered between 27 and 36 weeks of gestation. SARS-CoV-2 spike protein (S) and receptor-binding domain (RBD) -specific, IgG levels and neutralizing potency were evaluated in maternal and cord blood samples. RESULTS: The study cohort consisted of 171 parturients—median age 31 years (interquartile range (IQR) 27–35 years); median gestational age 39(+5) weeks (IQR 38(+5)–40(+4) weeks)–83 (48.5%) were immunized in early thrird-trimester (first dose at 27–31 weeks) and 88 (51.5%) were immunized in late third trimester (first dose at 32–36 weeks). All mother–infant paired sera were positive for anti S- and anti-RBD-specific IgG. Anti-RBD-specific IgG concentrations in neonatal sera were higher following early versus late third-trimester vaccination (median 9620 AU/mL (IQR 5131–15332 AU/mL) versus 6697 AU/mL (IQR 3157–14731 AU/mL), p 0.02), and were positively correlated with increasing time since vaccination (r = 0.26; p 0.001). Median antibody placental transfer ratios were increased following early versus late third-trimester immunization (anti-S ratio: 1.3 (IQR 1.1–1.6) versus 0.9 (IQR 0.6–1.1); anti-RBD-specific ratio: 2.3 (IQR 1.7–3.0) versus 0.7 (IQR 0.5–1.2), p <0.001). Neutralizing antibodies placental transfer ratio was greater following early versus late third-trimester immunization (median 1.9 (IQR 1.7–2.5) versus 0.8 (IQR 0.5–1.1), p <0.001), and was positively associated with longer duration from vaccination (r = 0.77; p <0.001). CONCLUSIONS: Early compared with late third-trimester maternal SARS-CoV-2 immunization enhanced transplacental antibody transfer and increased neonatal neutralizing antibody levels. Our findings highlight that vaccination of pregnant women early in the third trimester may enhance neonatal seroprotection.

Clin Microbiol Infect2021       LitCov and CORD-19
2817Notifiable diseases after implementation of COVID-19 public health prevention measures in Central Queensland, Australia  

N/A

Commun Dis Intell (2018)2021       LitCov and CORD-19
2818Predicting infectious SARS-CoV-2 from diagnostic samples  

BACKGROUND: RT-PCR has become the primary method to diagnose viral diseases, including SARS-CoV-2. RT-PCR detects RNA, not infectious virus, thus its ability to determine duration of infectivity of patients is limited. Infectivity is a critical determinant in informing public health guidelines/interventions. Our goal was to determine the relationship between E gene SARS-CoV-2 RT-PCR cycle threshold (Ct) values from respiratory samples, symptom onset to test (STT) and infectivity in cell culture. METHODS: In this retrospective cross-sectional study, we took SARS-CoV-2 RT-PCR confirmed positive samples and determined their ability to infect Vero cell lines. RESULTS: Ninety RT-PCR SARS-CoV-2 positive samples were incubated on Vero cells. Twenty-six samples (28.9%) demonstrated viral growth. Median TCID50/ml was 1780 (282-8511). There was no growth in samples with a Ct > 24 or STT > 8 days. Multivariate logistic regression using positive viral culture as a binary predictor variable, STT and Ct demonstrated an odds ratio for positive viral culture of 0.64 (95% CI 0.49-0.84, p<0.001) for every one unit increase in Ct. Area under the receiver operating characteristic curve for Ct vs. positive culture was OR 0.91 (95% CI 0.85-0.97, p<0.001), with 97% specificity obtained at a Ct of >24. CONCLUSIONS: SARS-CoV-2 Vero cell infectivity was only observed for RT-PCR Ct < 24 and STT < 8 days. Infectivity of patients with Ct >24 and duration of symptoms >8 days may be low. This information can inform public health policy and guide clinical, infection control and occupational health decisions. Further studies of larger size are needed.

Clin Infect Dis2020       LitCov and CORD-19
2819Analysis of Hip Fractures in France During the First COVID-19 Lockdown in Spring 2020  

IMPORTANCE: The COVID-19 pandemic has posed a number of unprecedented challenges to the health care system in France, where hip fractures in the elderly population are a major public health concern. OBJECTIVE: To explore the association of the first nationwide COVID-19 lockdown in France with the absolute number of hip fractures among patients 50 years or older. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from the French national hospitals database to identify patients 50 years or older who were hospitalized for hip fracture in France from January to July 2019 and January to July 2020. EXPOSURES: The first nationwide COVID-19 lockdown in France from March 16 to May 10, 2020. MAIN OUTCOMES AND MEASURES: The main outcome was the number of hospitalizations for hip fracture from January to July 2020 (study period) compared with the number of hospitalizations for hip fracture during the same period in 2019 (control period). Hospitalization rate ratios (HRRs) comparing the study period with the control period were calculated for 3 intervals (before lockdown [January 1 to March 15], during lockdown [March 16 to May 10], and after lockdown [May 11 to July 31]) and were stratified by gender, age and hospital type. RESULTS: The study included 46 393 patients hospitalized for hip fracture during January to July 2019 (34 589 [74.4%] women; mean [SD] age, 82.8 [10.5] years) and 44 767 patients hospitalized for hip fracture from January to July 2020 (33 160 [74.1%] women; mean [SD] age, 82.9 [10.5] years). During the lockdown in 2020, 10 429 patients (23.30%) were hospitalized for hip fracture compared with 11 782 patients (25.40%) during the same period in 2019 (HRR, 0.89; 95% CI, 0.86-0.91; P < .001). The lockdown period was associated with a decrease in the number of hip fractures of 11% among women (from 8756 in 2019 to 7788 in 2020) and 13% among men (from 3026 in 2019 to 2641 in 2020). When the absolute number of hip fractures was stratified by age group, the lockdown period was associated with a decrease in the number of hip fractures in all age groups except in patients older than 89 years (HRR, 0.97; 95% CI, 0.92-1.01; P = .17). In the group of patients aged 80 to 89 years, the number of hip fractures decreased from 4925 to 4370 (HRR, 0.89; 95% CI, 0.85-0.92; P < .001). During the lockdown, hospitalizations decreased by 33% (HRR, 0.67; 95% CI, 0.63-0.71; P < .001) in public university hospitals and by 24% (HRR, 0.76; 95% CI, 0.73-0.79; P < .001) in public general hospitals but increased by 46% (HRR, 1.46; 95% CI,1.38-1.54; P < .001) in private for-profit hospitals. CONCLUSIONS AND RELEVANCE: In this cohort study, hospitalizations for hip fractures in France decreased by 11% during the first nationwide COVID-19 lockdown. Further studies are needed to investigate the long-lasting consequences of the COVID-19 pandemic on the incidence of osteoporotic fractures.

JAMA Netw Open2021       LitCov and CORD-19
2820Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies  

Coronavirus disease 2019 (COVID-19), caused by the novel human coronavirus SARS-CoV-2, is currently a major threat to public health worldwide. The viral spike protein binds the host receptor angiotensin-converting enzyme 2 (ACE2) via the receptor-binding domain (RBD), and thus is believed to be a major target to block viral entry. Both SARS-CoV-2 and SARS-CoV share this mechanism. Here we functionally analyzed the key amino acid residues located within receptor binding motif of RBD that may interact with human ACE2 and available neutralizing antibodies. The in vivo experiments showed that immunization with either the SARS-CoV RBD or SARS-CoV-2 RBD was able to induce strong clade-specific neutralizing antibodies in mice; however, the cross-neutralizing activity was much weaker, indicating that there are distinct antigenic features in the RBDs of the two viruses. This finding was confirmed with the available neutralizing monoclonal antibodies against SARS-CoV or SARS-CoV-2. It is worth noting that a newly developed SARS-CoV-2 human antibody, HA001, was able to neutralize SARS-CoV-2, but failed to recognize SARS-CoV. Moreover, the potential epitope residues of HA001 were identified as A475 and F486 in the SARS-CoV-2 RBD, representing new binding sites for neutralizing antibodies. Overall, our study has revealed the presence of different key epitopes between SARS-CoV and SARS-CoV-2, which indicates the necessity to develop new prophylactic vaccine and antibody drugs for specific control of the COVID-19 pandemic although the available agents obtained from the SARS-CoV study are unneglectable.

Cell Mol Immunol2020       LitCov and CORD-19
2821Comparative evaluation of nasopharyngeal swab and saliva specimens for the molecular detection of SARS-CoV-2 RNA in Japanese patients with COVID-19  

Considering the issues of shortage of medical resources and the invasiveness and infection risk involved in the collection of nasopharyngeal swab specimens, there is a need for an effective alternative test specimen for SARS-CoV-2 RNA detection. Here, we investigated suitability of saliva as a non-invasively obtained specimen for molecular detection of SARS-CoV-2 RNA in Japanese patients with COVID-19. In total, 28 paired clinical specimens of saliva and nasopharyngeal swabs were collected from 12 patients at various time points after symptom onset. Each specimen was assayed using reverse transcription real-time polymerase chain reaction (rRT-PCR) on the BD MAX open system using primers and probes targeting the N-gene. The saliva and nasopharyngeal swab specimens showed 19 and 15 positive results, respectively. No invalid (PCR inhibition) result was observed for any specimen. The qualitative results of each specimen obtained in the period immediately after symptom onset were similar. Three convalescent patients presented saliva-positive results, whereas their nasopharyngeal swabs were negative at four different time points, suggesting that saliva may be superior to nasopharyngeal swabs in terms of obtaining stable assay result of SARS-CoV-2. In conclusion, our results suggest that saliva can potentially serve as an alternative to nasopharyngeal swabs as a specimen for SARS-CoV-2 rRT-PCR. As saliva can be collected by patients themselves, it may be an effective way to overcome the shortage of personal protective equipment and specimen sampling tools.

J Infect Chemother2020       LitCov and CORD-19
2822Impact of the COVID-19 Epidemic on Lifestyle Behaviors and Their Association With Subjective Well-Being Among the General Population in Mainland China: Cross-Sectional Study  

BACKGROUND: The world is experiencing an unprecedented challenge due to the coronavirus disease (COVID-19) pandemic. However, it is unclear whether people’s lifestyles will change as a result. OBJECTIVE: The aim of this study is to explore perceived lifestyle changes after the outbreak of COVID-19 and their association with subjective well-being (SWB) among the general population in Mainland China. METHODS: An online survey was conducted in May 2020. Lifestyle behaviors including leisure-time physical exercise, leisure-time screen time, and dietary intake were self-reported. SWB was measured using the General Wellbeing Schedule (GWS). Other covariates including sociodemographic factors, self-rated physical health, perceived social support, and loneliness were also assessed by a structured questionnaire. A multivariate ordinal regression method was used to analyze the association between SWB and lifestyle behaviors as well as perceived lifestyle changes. RESULTS: A total of 1033 participants aged between 18 and 60 years were included in this study. The mean GWS score was 71.7 points. About 70% of the respondents reported spending more time looking at screens, whereas about 30% reported an increased frequency of vegetable and fruit intake after the outbreak of COVID-19. Inactive physical exercise (odds ratio [OR] 1.16, 95% CI 1.02-1.48), infrequent vegetable intake (OR 1.45, 95% CI 1.10-1.90), infrequent fruit intake (OR 1.31, 95% CI 1.01-1.70), and often skipping breakfast (OR 1.43, 95% CI 1.08-1.91) were associated with lower SWB after adjusting for sociodemographic factors, self-rated physical health, perceived social support, and loneliness. Moreover, participants who perceived a decrease in the frequency of vegetable, fruit, and breakfast intake were more likely to report lower SWB. CONCLUSIONS: The COVID-19 pandemic may have positive and negative impacts on different aspects of lifestyle behaviors. Both unhealthy lifestyle behaviors and negative lifestyle changes were associated with lower SWB. These findings provide scientific evidence that can inform lifestyle guidelines and public mental health interventions during the COVID-19 outbreak.

J Med Internet Res2020       LitCov and CORD-19
2823Comparison of immune activation of the COVID vaccines: ChAdOx1, BNT162b2, mRNA-1273, BBIBP-CorV and Gam-COVID-Vac from serological human samples in Hungary showed higher protection after mRNA-based immunization  

N/A

Eur Rev Med Pharmacol Sci2022       LitCov
2824Characteristics of Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status-United States, January 22-June 7, 2020  

As of June 16, 2020, the coronavirus disease 2019 (COVID-19) pandemic has resulted in 2,104,346 cases and 116,140 deaths in the United States.* During pregnancy, women experience immunologic and physiologic changes that could increase their risk for more severe illness from respiratory infections (1,2). To date, data to assess the prevalence and severity of COVID-19 among pregnant U.S. women and determine whether signs and symptoms differ among pregnant and nonpregnant women are limited. During January 22-June 7, as part of COVID-19 surveillance, CDC received reports of 326,335 women of reproductive age (15-44 years) who had positive test results for SARS-CoV-2, the virus that causes COVID-19. Data on pregnancy status were available for 91,412 (28.0%) women with laboratory-confirmed infections; among these, 8,207 (9.0%) were pregnant. Symptomatic pregnant and nonpregnant women with COVID-19 reported similar frequencies of cough (>50%) and shortness of breath (30%), but pregnant women less frequently reported headache, muscle aches, fever, chills, and diarrhea. Chronic lung disease, diabetes mellitus, and cardiovascular disease were more commonly reported among pregnant women than among nonpregnant women. Among women with COVID-19, approximately one third (31.5%) of pregnant women were reported to have been hospitalized compared with 5.8% of nonpregnant women. After adjusting for age, presence of underlying medical conditions, and race/ethnicity, pregnant women were significantly more likely to be admitted to the intensive care unit (ICU) (aRR = 1.5, 95% confidence interval [CI] = 1.2-1.8) and receive mechanical ventilation (aRR = 1.7, 95% CI = 1.2-2.4). Sixteen (0.2%) COVID-19-related deaths were reported among pregnant women aged 15-44 years, and 208 (0.2%) such deaths were reported among nonpregnant women (aRR = 0.9, 95% CI = 0.5-1.5). These findings suggest that among women of reproductive age with COVID-19, pregnant women are more likely to be hospitalized and at increased risk for ICU admission and receipt of mechanical ventilation compared with nonpregnant women, but their risk for death is similar. To reduce occurrence of severe illness from COVID-19, pregnant women should be counseled about the potential risk for severe illness from COVID-19, and measures to prevent infection with SARS-CoV-2 should be emphasized for pregnant women and their families.

MMWR Morb Mortal Wkly Rep2020       LitCov and CORD-19
2825SARS-CoV-2 productively infects human gut enterocytes  

The virus severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) can cause coronavirus disease 2019 (COVID-19), an influenza-like disease that is primarily thought to infect the lungs with transmission via the respiratory route. However, clinical evidence suggests that the intestine may present another viral target organ. Indeed, the SARS-CoV-2 receptor angiotensin converting enzyme 2 (ACE2) is highly expressed on differentiated enterocytes. In human small intestinal organoids (hSIOs), enterocytes were readily infected by SARS-CoV and SARS-CoV-2 as demonstrated by confocal- and electron-microscopy. Consequently, significant titers of infectious viral particles were detected. mRNA expression analysis revealed strong induction of a generic viral response program. Hence, intestinal epithelium supports SARS-CoV-2 replication, and hSIOs serve as an experimental model for coronavirus infection and biology

Science2020       LitCov and CORD-19
2826Identify potent SARS-CoV-2 main protease inhibitors via accelerated free energy perturbation-based virtual screening of existing drugs  

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global crisis. There is no therapeutic treatment specific for COVID-19. It is highly desirable to identify potential antiviral agents against SARS-CoV-2 from existing drugs available for other diseases and thus repurpose them for treatment of COVID-19. In general, a drug repurposing effort for treatment of a new disease, such as COVID-19, usually starts from a virtual screening of existing drugs, followed by experimental validation, but the actual hit rate is generally rather low with traditional computational methods. Here we report a virtual screening approach with accelerated free energy perturbation-based absolute binding free energy (FEP-ABFE) predictions and its use in identifying drugs targeting SARS-CoV-2 main protease (M(pro)). The accurate FEP-ABFE predictions were based on the use of a restraint energy distribution (RED) function, making the practical FEP-ABFE−based virtual screening of the existing drug library possible. As a result, out of 25 drugs predicted, 15 were confirmed as potent inhibitors of SARS-CoV-2 M(pro). The most potent one is dipyridamole (inhibitory constant K(i) = 0.04 µM) which has shown promising therapeutic effects in subsequently conducted clinical studies for treatment of patients with COVID-19. Additionally, hydroxychloroquine (K(i) = 0.36 µM) and chloroquine (K(i) = 0.56 µM) were also found to potently inhibit SARS-CoV-2 M(pro). We anticipate that the FEP-ABFE prediction-based virtual screening approach will be useful in many other drug repurposing or discovery efforts.

Proc Natl Acad Sci U S A2020       LitCov and CORD-19
2827Effectiveness of BNT162b2 Vaccine against Omicron Variant in South Africa  

N Engl J Med2021       LitCov and CORD-19
2828coinfections in people with COVID-19: a systematic review and meta-analysis  

Abstract Objectives : In previous influenza pandemics, bacterial co-infections have been a major cause of mortality. We aimed to evaluate the burden of co-infections in patients with COVID-19. Methods : We systematically searched Embase, Medline, Cochrane Library, LILACS and CINAHL for eligible studies published from 1 January 2020 to 17 April 2020. We included patients of all ages, in all settings. The main outcome was the proportion of patients with a bacterial, fungal or viral co-infection. . Results : Thirty studies including 3834 patients were included. Overall, 7% of hospitalised COVID-19 patients had a bacterial co-infection (95% CI 3-12%, n=2183, I2=92∙2%). A higher proportion of ICU patients had bacterial co-infections than patients in mixed ward/ICU settings (14%, 95% CI 5-26, I2=74∙7% versus 4%, 95% CI 1-9, I2= 91∙7%). The commonest bacteria were Mycoplasma pneumonia, Pseudomonas aeruginosa and Haemophilus influenzae. The pooled proportion with a viral co-infection was 3% (95% CI 1-6, n=1014, I2=62∙3%), with Respiratory Syncytial Virus and influenza A the commonest. Three studies reported fungal co-infections. Conclusions : A low proportion of COVID-19 patients have a bacterial co-infection; less than in previous influenza pandemics. These findings do not support the routine use of antibiotics in the management of confirmed COVID-19 infection.

J Infect2020       LitCov and CORD-19
2829Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting: a meta-analysis  

BACKGROUND: Several SARS-CoV-2 variants of concern have been identified that partly escape serum neutralisation elicited by current vaccines. Studies have also shown that vaccines demonstrate reduced protection against symptomatic infection with SARS-CoV-2 variants. We explored whether in-vitro neutralisation titres remain predictive of vaccine protection from infection with SARS-CoV-2 variants. METHODS: In this meta-analysis, we analysed published data from 24 identified studies on in-vitro neutralisation and clinical protection to understand the loss of neutralisation to existing SARS-CoV-2 variants of concern. We integrated the results of this analysis into our existing statistical model relating in-vitro neutralisation to protection (parameterised on data from ancestral virus infection) to estimate vaccine efficacy against SARS-CoV-2 variants. We also analysed data on boosting of vaccine responses and use the model to predict the impact of booster vaccination on protection against SARS-CoV-2 variants. FINDINGS: The neutralising activity against the ancestral SARS-CoV-2 was highly predictive of neutralisation of variants of concern. Decreases in neutralisation titre to the alpha (1·6-fold), beta (8·8-fold), gamma (3·5-fold), and delta (3·9-fold) variants (compared to the ancestral virus) were not significantly different between different vaccines. Neutralisation remained strongly correlated with protection from symptomatic infection with SARS-CoV-2 variants of concern (r(S)=0·81, p=0·0005) and the existing model remained predictive of vaccine efficacy against variants of concern once decreases in neutralisation to the variants of concern were incorporated. Modelling of predicted vaccine efficacy against variants over time suggested that protection against symptomatic infection might decrease below 50% within the first year after vaccination for some vaccines. Boosting of previously infected individuals with existing vaccines (which target ancestral virus) is predicted to provide a higher degree of protection from infection with variants of concern than primary vaccination schedules alone. INTERPRETATION: In-vitro neutralisation titres remain a correlate of protection from SARS-CoV-2 variants and modelling of the effects of waning immunity predicts a loss of protection to the variants after vaccination. However, booster vaccination with current vaccines should enable higher neutralisation to SARS-CoV-2 variants than is achieved with primary vaccination, which is predicted to provide robust protection from severe infection outcomes with the current SARS-CoV-2 variants of concern, at least in the medium term. FUNDING: The National Health and Medical Research Council (Australia), the Medical Research Future Fund (Australia), and the Victorian Government.

Lancet Microbe2021       LitCov and CORD-19
2830The effect of spike mutations on SARS-CoV-2 neutralization  

Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines show protective efficacy, which is most likely mediated by neutralizing antibodies recognizing the viral entry protein, spike. Because new SARS-CoV-2 variants are emerging rapidly, as exemplified by the B.1.1.7, B.1.351, and P.1 lineages, it is critical to understand whether antibody responses induced by infection with the original SARS-CoV-2 virus or current vaccines remain effective. In this study, we evaluate neutralization of a series of mutated spike pseudotypes based on divergence from SARS-CoV and then compare neutralization of the B.1.1.7 spike pseudotype and individual mutations. Spike-specific monoclonal antibody neutralization is reduced dramatically; in contrast, polyclonal antibodies from individuals infected in early 2020 remain active against most mutated spike pseudotypes, but potency is reduced in a minority of samples. This work highlights that changes in SARS-CoV-2 spike can alter neutralization sensitivity and underlines the need for effective real-time monitoring of emerging mutations and their effect on vaccine efficacy.

Cell Rep2021       LitCov and CORD-19
2831Atypical symptoms, SARS-CoV-2 test results and immunization rates in 456 residents from eight nursing homes facing a COVID-19 outbreak  

BACKGROUND: Frail older persons may have an atypical presentation of COVID-19. The value of rRT-PCR testing for identifying SARS-CoV-2 nursing homes (NH) residents is not known. OBJECTIVE: To determine whether (i) atypical symptoms may predict rRT-PCR results and (ii) rRT-PCR results may predict immunization against SARS-CoV-2 in NH residents. DESIGN: A retrospective longitudinal study. SETTING: eight NHs with at least ten rRT-PCR-positive residents. SUBJECTS: 456 residents. METHODS: Typical and atypical symptoms recorded in residents’ files during the 14 days before and after rRT-PCR testing were analyzed. Residents underwent blood testing for IgG-SARS-CoV-2 nucleocapsid protein 6 to 8 weeks after testing. Univariate and multivariate analyses compared symptoms and immunization rates in rRT-PCR-positive and negative residents. RESULTS: 161 residents had a positive rRT-PCR (35.3%), 17.4% of whom were asymptomatic before testing. Temperature > 37.8°C, oxygen saturation < 90%, unexplained anorexia, behavioural change, exhaustion, malaise, and falls before testing were independent predictors of a further positive rRT-PCR. Among the rRT-PCR-positive residents, 95.2% developed SARS-CoV-2 antibodies vs 7.6% in the rRT-PCR-negative residents. Among the residents with a negative rRT-PCR, those who developed SARS-CoV-2 antibodies more often had typical or atypical symptoms (p = 0.02 and < 0.01, respectively). CONCLUSION: This study supports a strategy based on (i) testing residents with typical or unexplained atypical symptoms for an early identification of the first SARS-CoV-2 cases, (ii) rT-PCR testing for identifying COVID-19 residents, (iii) repeated wide-facility testing (including asymptomatic cases) as soon as a resident is tested positive for SARS-CoV-2, and (iv) implementing SARS-CoV-2 infection control measures in rRT-PCR-negative residents when they have unexplained typical or atypical symptoms.

Age Ageing2021       LitCov and CORD-19
2832RECOVERY- Respiratory Support: Respiratory Strategies for patients with suspected or proven COVID-19 respiratory failure; Continuous Positive Airway Pressure, High-flow Nasal Oxygen and standard care: A structured summary of a study protocol for a randomised controlled trial  

OBJECTIVE: The trial objective is to determine if Continuous Positive Airway Pressure (CPAP) or High-Flow Nasal Oxygen (HFNO) is clinically effective compared to standard oxygen therapy in patients with confirmed or suspected COVID-19. TRIAL DESIGN: Adaptive (group-sequential), parallel group, pragmatic, superiority randomised controlled, open-label, multi-centre, effectiveness trial. PARTICIPANTS: The trial is being conducted across approximately 60 hospitals across England, Wales, Scotland, and Northern Ireland. Inpatients at participating hospitals are eligible to participate if they have respiratory failure with suspected or proven COVID-19, and meet all of the inclusion criteria and none of the exclusion criteria. Inclusion criteria: 1) Adults ≥ 18 years; 2) Admitted to hospital with suspected or proven COVID-19; 3) Receiving oxygen with fraction of inspired oxygen (FiO(2)) ≥0.4 and peripheral oxygen saturation (SpO(2)) ≤94%; and 4) Plan for escalation to tracheal intubation if needed. Exclusion criteria: 1) Planned tracheal intubation and mechanical ventilation imminent within 1 hour; 2) Known or clinically apparent pregnancy; 3) Any absolute contraindication to CPAP or HFNO; 4) Decision not to intubate due to ceiling of treatment or withdrawal of treatment anticipated; and 5) Equipment for both CPAP and HFNO not available. INTERVENTION AND COMPARATOR: Intervention one: Continuous positive airway pressure delivered by any device. Set-up and therapy titration is not protocolised and is delivered in accordance with clinical discretion. Intervention two: High-flow nasal oxygen delivered by any device. Set-up and therapy titration is not protocolised and is delivered in accordance with clinical discretion. Comparator group: Standard care- oxygen delivered by face mask or nasal cannula (excluding the use of continuous positive airway pressure or high-flow nasal oxygen). Set-up and therapy titration is not protocolised and is delivered in accordance with clinical discretion. Intervention delivery continues up to the point of death, tracheal intubation, or clinical determination that there is no ongoing need (palliation or improvement). MAIN OUTCOMES: The primary outcome is a composite outcome comprising tracheal intubation or mortality within 30 days following randomisation. Secondary outcomes include tracheal intubation rate, time to tracheal intubation, duration of invasive ventilation, mortality rate, time to mortality, length of hospital stay, and length of critical care stay. RANDOMISATION: Participants are randomised in a 1:1:1 ratio to receive either continuous positive airway pressure, high-flow nasal oxygen or standard care. Due to the challenging environment of study delivery, a specific intervention may not always be available at the hospital site. The study uses two integrated randomisation systems to allow, where required, the site to randomise between all three interventions, between CPAP and standard care, and between HFNO and standard care. System integration ensures maintenance of balance between interventions. Randomisation is performed using a telephone-based interactive voice response system to maintain allocation concealment. The randomisation sequence was computer-generated using the minimisation method. Participant randomisation is stratified by site, gender (M/F), and age (<50, >=50 years). BLINDING (MASKING): The nature of the trial interventions precludes blinding of the researcher, patient and clinical team. Primary and secondary outcomes are all objective outcomes, thereby minimising the risk of detection bias. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 4002 participants (1334 to be randomized to each of the three study arms) TRIAL STATUS: Current protocol: Version 4.0, 29(th) May 2020. Recruitment began on April 6, 2020 and is anticipated to be complete by April 5, 2021. The trial has been awarded Urgent Public Health status by the National Institute of Health Research on 13(th) April 2020. TRIAL REGISTRATION: ISRCTN, ISRCTN16912075. Registered 6(th) April 2020, http://www.isrctn.com/ISRCTN16912075 FULL PROTOCOL: The full protocol (version 4.0, 29(th) May 2020) 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
2833A hundred days into the coronavirus disease pandemic  

Euro Surveill2020       LitCov and CORD-19
2834Kinetics of viral load and antibody response in relation to COVID-19 severity  

N/A

J Clin Invest2020       LitCov and CORD-19
2835Psychological distress in Nepalese residents during COVID-19 pandemic: a community level survey  

BACKGROUND: COVID-19 pandemic has created unprecedented health and economic impact. Psychological stress, anxiety and depression are affecting not only COVID-19 patients but also health professionals, and general population. Fear of contracting COVID-19, forced restrictive social measures, and economic hardship are causing mental trauma. Nepal is a developing country from South Asia where the COVID-19 pandemic is still evolving. This online survey has been carried out to understand impact of COVID- 19 on mental health of Nepalese community dwellers. METHODS: The COVID-19 Peritraumatic Distress Index (CPDI) questionnaire adapted from the Shanghai Mental Health Centre was used for online data collection from 11 April-17 May 2020. Collected data were extracted to Microsoft excel-13 and imported and analyzed using SPSS (Statistical Package for Social Sciences) version-22. An initial univariate analysis was conducted for all variables to assess the distribution. Logistic regression analyses were done to estimate the odds ratios of relevant predicting variables. RESULTS: A total of 410 participants completed the self-rated questionnaires. Mean age of study participants was 34.8 ± 11.7 years with male preponderance. 88.5% of the respondents were not in distress (score less than 28) while, 11% had mild to moderate distress and 0.5% had severe distress. The prevalence of distress is higher among age group > 45 years, female gender, and post-secondary education group. Health professional were more likely to get distressed. Respondents with post-secondary education had higher odds (OR = 3.32; p = 0.020) of developing distress as compared to respondents with secondary education or lower. CONCLUSION: There is lower rate of psychological distress in city dwellers and people with low education. Adequate intervention and evaluation into mental health awareness, and psychosocial support focused primarily on health care workers, female and elderly individuals is necessary.

BMC Psychiatry2020       LitCov and CORD-19
2836Food insecurity during COVID-19 pandemic: A genuine concern for people from disadvantaged community and low-income families in Province 2 of Nepal  

BACKGROUND: Food insecurity is a serious social and public health problem which is exacerbated by the COVID-19 pandemic especially in resource-poor countries such as Nepal. However, there is a paucity of evidence at local levels. This study aims to explore food insecurity among people from the disadvantaged community and low-income families during the COVID-19 pandemic in Province-2 of Nepal. METHODS: The semi-structured qualitative interviews were conducted virtually among purposively selected participants (n = 41) from both urban and rural areas in eight districts of Province 2 in Nepal. All the interviews were conducted in the local language between July and August 2020. The data analysis was performed using thematic network analysis in Nvivo 12 Pro software. RESULTS: The results of this study are grouped into four global themes: i) Impact of COVID-19 on food security; ii) Food insecurity and coping strategies during the COVID-19 pandemic, iii) Food relief and emergency support during the COVID-19 pandemic, and iv) Impact of COVID-19 and food insecurity on health and wellbeing. Most participants in the study expressed that families from low socioeconomic backgrounds and disadvantaged communities such as those working on daily wages and who rely on remittance had experienced increased food insecurity during the COVID-19 pandemic. Participants used different forms of coping strategies to meet their food requirements during the pandemic. Community members experienced favouritism, nepotism, and partiality from local politicians and authorities during the distribution of food relief. The food insecurity among low-income and disadvantaged families has affected their health and wellbeing making them increasingly vulnerable to the COVID-19 infection. CONCLUSION: Food insecurity among low-income and disadvantaged families was found to be a serious problem during the COVID-19 pandemic. The study suggests that the relief support plan and policies should be focused on the implementation of immediate sustainable food security strategies to prevent hunger, malnutrition, and mental health problems among the most vulnerable groups in the community.

PLoS One2021       LitCov and CORD-19
2837Depression, Anxiety and Stress on Caregivers of Persons with Dementia (CGPWD) in Hong Kong amid COVID-19 Pandemic  

Background: Coronavirus disease 2019 (COVID-19) contributed to increasing prevalence of depressive symptoms and other psychological repercussions, particularly in the disease population in Hong Kong. Nonetheless, the caregiver burden of caregivers of persons with dementia (CGPWD), has been under-investigated. Aims: This study examined the psychological impact and its correlates on the CGPWD in Hong Kong amid the COVID-19 outbreak. Methods: CGPWD referred from rehabilitation clinics and online seminar were used to recruit participants to complete an online questionnaire by the end of the second-wave of the COVID-19 outbreak (June 2021). To be eligible, either full-time or part-time CGPWD, aged 18 or above, can understand Cantonese, currently reside in Hong Kong and offering care to PWD for at least one year, were recruited. Those CGPWD diagnosed with any type of psychiatric disorder were excluded from this study. The Chinese Center for Epidemiologic Studies Depression Scale (CES-D), Perceived Stress Scale (PSS-10), Generalized Anxiety Disorder (GAD-7), Zarit Burden Interview (ZBI-22), and Nonattachment Scale (NAS-7) were used to measure participants’ depression, perceived stress, anxiety symptoms, caregiver burden and wisdom in subjective feelings of internal stress. The modified Medical Outcomes Study Social Support Survey (mMOS-SS) and the SARS Appraisal Inventory (SAI) were also administered to measure participants’ perceived support and coping efficacy. Follow-up responses were gathered by the end of third-wave outbreak (October 2021). Results: A total of 51 CGPWD participated, of which, 33 (64.7%) suffered from probable depression (CES-D score ≥ 16). Participants also showed a significant increase in depression symptom scores at the three-month follow-up period (t = 2.25, p = 0.03). CGPWD with probable depression had less non-attachment awareness and higher scores in anxiety, stress, caregiving burden, and coronavirus impact (all p < 0.05) than those without. Conclusions: High prevalence of depressive symptoms was noted among our CGPWD sample and these symptoms seemed to worsen substantially. Contingent online mental health support should be prioritized to those CGPWD to reduce psychiatric morbidity and the global disease burden.

Int J Environ Res Public Healt2021       LitCov and CORD-19
2838A Cell-Based ELISA to Improve the Serological Analysis of Anti-SARS-CoV-2 IgG  

Knowledge of the antibody-mediated immune response to SARS-CoV-2 is crucial to understand virus immunogenicity, establish seroprevalence, and determine whether subjects or recovered patients are at risk for infection/reinfection and would therefore benefit from vaccination. Here, we describe a novel and simple cell-ELISA specifically designed to measure viral spike S1-specific IgG produced in vitro by B cells in peripheral blood mononuclear cell (PBMC) cultures from a cohort of 45 asymptomatic (n = 24) and symptomatic (n = 21) individuals, with age ranging from 8 to 99 years. All subjects underwent ELISA serological screening twice, at the same time as the cell-ELISA (T2) as well as 35–60 days earlier (T1). Cryopreserved PBMCs of healthy donors obtained years before the COVID-19 pandemic were also included in the analysis. The preliminary results presented here show that out of 45 tested subjects, 16 individuals (35.5%) were positive to the cell-ELISA, 11 (24.5%) were concomitantly positive in the serological screening (T1 and/or T2), and only one person was exclusively positive in ELISA (T1) and negative in cell-ELISA, though values were close to the cutoff. Of note, five individuals (11.2%) tested negative in ELISA but positive in cell-ELISA and thus, they appear to have circulating B cells that produce antibodies against SARS-CoV-2, likely at levels that are undetectable in the serum, which challenges the negative results of the serological screening. The relative level of in vitro secreted IgG was measurable in positive subjects, ranging from 7 to 50 ng/well. Accordingly, all anti-SARS-CoV-2 antibody-positive subjects previously reported moderate to severe symptoms attributable to COVID-19, even though the RT-PCR data were rarely available to confirm viral infection. Overall, the described cell-ELISA might be an effective method for detecting subjects who encountered the virus in the past, and thus helpful to improve serological ELISA tests in the case of undetectable/equivocal circulating IgG levels, and a suitable and improved tool to better evaluate SARS-CoV-2-specific humoral immunity in the COVID-19 pandemic.

Viruses2020       LitCov and CORD-19
2839Potential Maternal and Infant Outcomes from Coronavirus 2019-nCoV Infecting Pregnant Women: Lessons from SARS, MERS and Other Human Coronavirus Infections  

In early December 2019 a cluster of cases of pneumonia of unknown cause was identified in Wuhan, a city of 11 million persons in the People’s Republic of China. Further investigation revealed these cases to result from infection with a newly identified coronavirus, initially termed 2019-nCoV and subsequently SARS-CoV-2. The infection moved rapidly through China, spread to Thailand and Japan, extended into adjacent countries through infected persons travelling by air, eventually reaching multiple countries and continents. Similar to such other coronaviruses as those causing the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS), the new coronavirus was reported to spread via natural aerosols from human-to-human. In the early stages of this epidemic the case fatality rate is estimated to be approximately 2%, with the majority of deaths occurring in special populations. Unfortunately, there is limited experience with coronavirus infections during pregnancy, and it now appears certain that pregnant women have become infected during the present 2019-nCoV epidemic. In order to assess the potential of the Wuhan 2019-nCoV to cause maternal, fetal and neonatal morbidity and other poor obstetrical outcomes, this communication reviews the published data addressing the epidemiological and clinical effects of SARS, MERS, and other coronavirus infections on pregnant women and their infants. Recommendations are also made for the consideration of pregnant women in the design, clinical trials, and implementation of future 2019-nCoV vaccines.

Viruses2020       LitCov and CORD-19
2840Factors associated with COVID-19 vaccine hesitancy amongst refugees in Australia  

BACKGROUND: Refugees may be especially vulnerable to the adverse effects of COVID-19. Therefore it is critical that refugee communities are supported to access COVID-19 vaccines and for public health responses to address vaccine hesitancy. OBJECTIVE: To investigate the key demographic factors, barriers and attitudes associated with vaccine hesitancy in a community sample of refugees. METHOD: Participants in the Refugee Adjustment Study, a cohort of refugees living in Australia, were invited to complete a survey about their COVID-19 vaccine intentions, barriers to access and attitudes relating to the vaccine. RESULTS: Of the 516 participants, 88% were unvaccinated and 28.1% were classed as vaccine hesitant. Key predictors of vaccine hesitancy were younger age, information and trust barriers, lower logistical barriers, and attitudes relating to low control and risk posed by COVID-19. CONCLUSIONS: Findings suggest that public health strategies need to address trust, control and risk perception attitudes to increase COVID-19 vaccine uptake in resettled refugee communities.

Eur J Psychotraumatol2021       LitCov and CORD-19
2841Health literacy and disparities in COVID-19-related knowledge, attitudes, beliefs and behaviours in Australia  

N/A

Public Health Res Pract2020       LitCov and CORD-19
2842Mortality predictors of hospitalized patients with COVID-19: Retrospective cohort study from Nur-Sultan, Kazakhstan  

BACKGROUND: First reported case of Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in Kazakhstan was identified in March 2020. Many specialized tertiary hospitals in Kazakhstan including National Research Cardiac Surgery Center (NRCSC) were re-organized to accept coronavirus disease 2019 (COVID-19) infected patients during summer months of 2020. Although many studies from worldwide reported their experience in treating patients with COVID-19, there are limited data available from the Central Asia countries. The aim of this study is to identify predictors of mortality associated with COVID-19 in NRCSC tertiary hospital in Nur-Sultan, Kazakhstan. METHODS: This is a retrospective cohort study of patients admitted to the NRCSC between June 1(st)–August 31(st) 2020 with COVID-19. Demographic, clinical and laboratory data were collected from electronic records. In-hospital mortality was assessed as an outcome. Patients were followed-up until in-hospital death or discharge from the hospital. Descriptive statistics and factors associated with mortality were assessed using univariate and multivariate logistic regression models. RESULTS: Two hundred thirty—nine admissions were recorded during the follow-up period. Mean age was 57 years and 61% were males. Median duration of stay at the hospital was 8 days and 34 (14%) patients died during the hospitalization. Non-survivors were more likely to be admitted later from the disease onset, with higher fever, lower oxygen saturation and increased respiratory rate compared to survivors. Leukocytosis, lymphopenia, anemia, elevated liver and kidney function tests, hypoproteinemia, elevated inflammatory markers (C-reactive protein (CRP), ferritin, and lactate dehydrogenase (LDH)) and coagulation tests (fibrinogen, D-dimer, international normalized ratio (INR), and activated partial thromboplastin time (aPTT)) at admission were associated with mortality. Age (OR 1.2, CI:1.01–1.43), respiratory rate (OR 1.38, CI: 1.07–1.77), and CRP (OR 1.39, CI: 1.04–1.87) were determined to be independent predictors of mortality. CONCLUSION: This study describes 14% mortality rate from COVID-19 in the tertiary hospital. Many abnormal clinical and laboratory variables at admission were associated with poor outcome. Age, respiratory rate and CRP were found to be independent predictors of mortality. Our finding would help healthcare providers to predict the risk factors associated with high risk of mortality. Further investigations involving large cohorts should be provided to support our findings.

PLoS One2021       LitCov and CORD-19
2843Myocardial injury and COVID-19: Possible mechanisms  

Abstract Coronavirus Disease 2019 (COVID-19) has quickly progressed to a global health emergency. Respiratory illness is the major cause of morbidity and mortality in these patients with the disease spectrum ranging from asymptomatic subclinical infection, to severe pneumonia progressing to acute respiratory distress syndrome. There is growing evidence describing pathophysiological resemblance of SARS-CoV-2 infection with other coronavirus infections such as Severe Acute Respiratory Syndrome coronavirus and Middle East Respiratory Syndrome coronavirus (MERS-CoV). Angiotensin Converting Enzyme-2 receptors play a pivotal role in the pathogenesis of the virus. Disruption of this receptor leads to cardiomyopathy, cardiac dysfunction, and heart failure. Patients with cardiovascular disease are more likely to be infected with SARS-CoV-2 and they are more likely to develop severe symptoms. Hypertension, arrhythmia, cardiomyopathy and coronary heart disease are amongst major cardiovascular disease comorbidities seen in severe cases of COVID-19. There is growing literature exploring cardiac involvement in SARS-CoV-2. Myocardial injury is one of the important pathogenic features of COVID-19. As a surrogate for myocardial injury, multiple studies have shown increased cardiac biomarkers mainly cardiac troponins I and T in the infected patients especially those with severe disease. Myocarditis is depicted as another cause of morbidity amongst COVID-19 patients. The exact mechanisms of how SARS-CoV-2 can cause myocardial injury are not clearly understood. The proposed mechanisms of myocardial injury are direct damage to the cardiomyocytes, systemic inflammation, myocardial interstitial fibrosis, interferon mediated immune response, exaggerated cytokine response by Type 1 and 2 helper T cells, in addition to coronary plaque destabilization, and hypoxia.

Life Sci2020       LitCov and CORD-19
2844Best Practice Guidance for Digital Contact Tracing Apps: A Cross-disciplinary Review of the Literature  

BACKGROUND: Digital contact tracing apps have the potential to augment contact tracing systems and disrupt COVID-19 transmission by rapidly identifying secondary cases prior to the onset of infectiousness and linking them into a system of quarantine, testing, and health care worker case management. The international experience of digital contact tracing apps during the COVID-19 pandemic demonstrates how challenging their design and deployment are. OBJECTIVE: This study aims to derive and summarize best practice guidance for the design of the ideal digital contact tracing app. METHODS: A collaborative cross-disciplinary approach was used to derive best practice guidance for designing the ideal digital contact tracing app. A search of the indexed and gray literature was conducted to identify articles describing or evaluating digital contact tracing apps. MEDLINE was searched using a combination of free-text terms and Medical Subject Headings search terms. Gray literature sources searched were the World Health Organization Institutional Repository for Information Sharing, the European Centre for Disease Prevention and Control publications library, and Google, including the websites of many health protection authorities. Articles that were acceptable for inclusion in this evidence synthesis were peer-reviewed publications, cohort studies, randomized trials, modeling studies, technical reports, white papers, and media reports related to digital contact tracing. RESULTS: Ethical, user experience, privacy and data protection, technical, clinical and societal, and evaluation considerations were identified from the literature. The ideal digital contact tracing app should be voluntary and should be equitably available and accessible. User engagement could be enhanced by small financial incentives, enabling users to tailor aspects of the app to their particular needs and integrating digital contact tracing apps into the wider public health information campaign. Adherence to the principles of good data protection and privacy by design is important to convince target populations to download and use digital contact tracing apps. Bluetooth Low Energy is recommended for a digital contact tracing app's contact event detection, but combining it with ultrasound technology may improve a digital contact tracing app's accuracy. A decentralized privacy-preserving protocol should be followed to enable digital contact tracing app users to exchange and record temporary contact numbers during contact events. The ideal digital contact tracing app should define and risk-stratify contact events according to proximity, duration of contact, and the infectiousness of the case at the time of contact. Evaluating digital contact tracing apps requires data to quantify app downloads, use among COVID-19 cases, successful contact alert generation, contact alert receivers, contact alert receivers that adhere to quarantine and testing recommendations, and the number of contact alert receivers who subsequently are tested positive for COVID-19. The outcomes of digital contact tracing apps' evaluations should be openly reported to allow for the wider public to review the evaluation of the app. CONCLUSIONS: In conclusion, key considerations and best practice guidance for the design of the ideal digital contact tracing app were derived from the literature.

JMIR Mhealth Uhealth2021       LitCov and CORD-19
2845Effect of Helmet Noninvasive Ventilation vs High-Flow Nasal Oxygen on Days Free of Respiratory Support in Patients With COVID-19 and Moderate to Severe Hypoxemic Respiratory Failure: The HENIVOT Randomized Clinical Trial  

N/A

JAMA2021       LitCov and CORD-19
2846Seroprevalence of anti-SARS-CoV-2 antibodies in Iquitos, Peru in July and August, 2020: a population-based study  

BACKGROUND: Detection of anti-SARS-CoV-2 antibodies among people at risk of infection is crucial for understanding both the past transmission of COVID-19 and vulnerability of the population to continuing transmission and, when done serially, the intensity of ongoing transmission over an interval in a community. We aimed to estimate the seroprevalence of COVID-19 in a representative population-based cohort in Iquitos, one of the regions with the highest mortality rates from COVID-19 in Peru, where a devastating number of cases occurred in March, 2020. METHODS: We did a population-based study of SARS-CoV-2 transmission in Iquitos at two timepoints: July 13–18, 2020 (baseline), and Aug 13–18, 2020 (1-month follow-up). We obtained a geographically stratified representative sample of the city population using the 2017 census data, which was updated on Jan 20, 2020. We included people who were inhabitants of Iquitos since COVID-19 was identified in Peru (March 6, 2020) or earlier. We excluded people living in institutions, people receiving any pharmacological treatment for COVID-19, people with any contraindication for phlebotomy, and health workers or individuals living with an active health worker. We tested each participant for IgG and IgM anti-SARS-CoV-2 antibodies using the COVID-19 IgG/IgM Rapid Test (Zhejiang Orient Gene Biotech, China). We used survey analysis methods to estimate seroprevalence accounting for the sampling design effect and test performance characteristics. FINDINGS: We identified 726 eligible individuals and enrolled a total of 716 participants (99%), distributed across 40 strata (four districts, two sexes, and five age groups). We excluded ten individuals who: did not have consent from a parent or legal representative (n=3), had moved to Iquitos after March 6, 2020 (n=3), were in transit (n=2), or had respiratory symptoms (n=1). After adjusting for the study sampling effects and sensitivity and specificity of the test, we estimated a seroprevalence of 70% (95% CI 67–73) at baseline and 66% (95% CI 62–70) at 1 month of follow-up, with a test-retest positivity of 65% (95% CI 61–68), and an incidence of new exposures of 2% (95% CI 1–3). We observed significant differences in the seroprevalence between age groups, with participants aged 18–29 years having lower seroprevalence than those aged younger than 12 years (prevalence ratio 0·85 [95% CI 0·73–0·98]; p=0·029). INTERPRETATION: After the first epidemic peak, Iquitos had one of the highest rates of seroprevalence of anti-SARS-CoV-2 antibodies worldwide. Nevertheless, the city experienced a second wave starting in January, 2021, probably due to the emergence of the SARS-CoV-2 P1 variant, which has shown higher transmissibility and reinfection rates. FUNDING: Dirección Regional de Salud de Loreto (DIRESA), Loreto, Peru. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Lancet Glob Health2021       LitCov and CORD-19
2847Early dynamics of transmission and control of COVID-19: a mathematical modelling study  

BACKGROUND: An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to 95 333 confirmed cases as of March 5, 2020. Understanding the early transmission dynamics of the infection and evaluating the effectiveness of control measures is crucial for assessing the potential for sustained transmission to occur in new areas. Combining a mathematical model of severe SARS-CoV-2 transmission with four datasets from within and outside Wuhan, we estimated how transmission in Wuhan varied between December, 2019, and February, 2020. We used these estimates to assess the potential for sustained human-to-human transmission to occur in locations outside Wuhan if cases were introduced. METHODS: We combined a stochastic transmission model with data on cases of coronavirus disease 2019 (COVID-19) in Wuhan and international cases that originated in Wuhan to estimate how transmission had varied over time during January, 2020, and February, 2020. Based on these estimates, we then calculated the probability that newly introduced cases might generate outbreaks in other areas. To estimate the early dynamics of transmission in Wuhan, we fitted a stochastic transmission dynamic model to multiple publicly available datasets on cases in Wuhan and internationally exported cases from Wuhan. The four datasets we fitted to were: daily number of new internationally exported cases (or lack thereof), by date of onset, as of Jan 26, 2020; daily number of new cases in Wuhan with no market exposure, by date of onset, between Dec 1, 2019, and Jan 1, 2020; daily number of new cases in China, by date of onset, between Dec 29, 2019, and Jan 23, 2020; and proportion of infected passengers on evacuation flights between Jan 29, 2020, and Feb 4, 2020. We used an additional two datasets for comparison with model outputs: daily number of new exported cases from Wuhan (or lack thereof) in countries with high connectivity to Wuhan (ie, top 20 most at-risk countries), by date of confirmation, as of Feb 10, 2020; and data on new confirmed cases reported in Wuhan between Jan 16, 2020, and Feb 11, 2020. FINDINGS: We estimated that the median daily reproduction number (R(t)) in Wuhan declined from 2·35 (95% CI 1·15–4·77) 1 week before travel restrictions were introduced on Jan 23, 2020, to 1·05 (0·41–2·39) 1 week after. Based on our estimates of R(t), assuming SARS-like variation, we calculated that in locations with similar transmission potential to Wuhan in early January, once there are at least four independently introduced cases, there is a more than 50% chance the infection will establish within that population. INTERPRETATION: Our results show that COVID-19 transmission probably declined in Wuhan during late January, 2020, coinciding with the introduction of travel control measures. As more cases arrive in international locations with similar transmission potential to Wuhan before these control measures, it is likely many chains of transmission will fail to establish initially, but might lead to new outbreaks eventually. FUNDING: Wellcome Trust, Health Data Research UK, Bill & Melinda Gates Foundation, and National Institute for Health Research.

Lancet Infect Dis2020       LitCov and CORD-19
2848COVID-19: Coagulopathy, Risk of Thrombosis and the Rationale for Anticoagulation  

The novel coronavirus infection (COVID-19) is caused by the new coronavirus SARS-CoV-2 and is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as adult respiratory syndrome, sepsis, coagulopathy, and death in a proportion of patients. Among other factors and direct viral effects, the increase in the vasoconstrictor angiotensin II, the decrease in the vasodilator angiotensin, and the sepsis-induced release of cytokines can trigger a coagulopathy in COVID-19. A coagulopathy has been reported in up to 50% of patients with severe COVID-19 manifestations. An increase in d-dimer is the most significant change in coagulation parameters in severe COVID-19 patients, and progressively increasing values can be used as a prognostic parameter indicating a worse outcome. Limited data suggest a high incidence of deep vein thrombosis and pulmonary embolism in up to 40% of patients, despite the use of a standard dose of low-molecular-weight heparin (LMWH) in most cases. In addition, pulmonary microvascular thrombosis has been reported and may play a role in progressive lung failure. Prophylactic LMWH has been recommended by the International Society on Thrombosis and Haemostasis (ISTH) and the American Society of Hematology (ASH), but the best effective dosage is uncertain. Adapted to the individual risk of thrombosis and the d-dimer value, higher doses can be considered, especially since bleeding events in COVID-19 are rare. Besides the anticoagulant effect of LMWH, nonanticoagulant properties such as the reduction in interleukin 6 release have been shown to improve the complex picture of coagulopathy in patients with COVID-19.

Clin Appl Thromb Hemost2020       LitCov and CORD-19
2849Likelihood of infecting or getting infected with COVID-19 as a function of vaccination status, as investigated with a stochastic model for Aotearoa New Zealand for Delta and Omicron variants  

N/A

N Z Med J2022       LitCov
2850Safety and immunogenicity of intradermal administration of fractional dose CoronaVac(), ChAdOx1 nCoV-19 and BNT162b2 as primary series vaccination  

N/A

Front Immunol2022       LitCov

(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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