\ 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
4601Unbiased Screens Show CD8+ T Cells of COVID-19 Patients Recognize Shared Epitopes in SARS-CoV-2 that Largely Reside outside the Spike Protein  

Developing effective strategies to prevent or treat COVID-19 requires understanding the natural immune response to SARS-CoV-2. We used an unbiased, genome-wide screening technology to determine the precise peptide sequences in SARS-CoV-2 that are recognized by the memory CD8+ T cells of COVID-19 patients. In total, we identified 3–8 epitopes for each of the six most prevalent human leukocyte antigen (HLA) types. These epitopes were broadly shared across patients and located in regions of the virus that are not subject to mutational variation. Notably, only 3 of the 29 shared epitopes were located in the spike protein, whereas most epitopes were located in ORF1ab or the nucleocapsid protein. We also found that CD8+ T cells generally do not cross-react with epitopes in the four seasonal coronaviruses that cause the common cold. Overall, these findings can inform development of next-generation vaccines that better recapitulate natural CD8+ T cell immunity to SARS-CoV-2.

Immunity2020       LitCov and CORD-19
4602Assessment of Seroprevalence of SARS-CoV-2 and Risk Factors Associated With COVID-19 Infection Among Outpatients in Virginia  

IMPORTANCE: Data from seroepidemiologic surveys measuring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure in diverse communities and ascertaining risk factors associated with infection are important to guide future prevention strategies. OBJECTIVE: To assess the prevalence of previous SARS-CoV-2 infection across Virginia and the risk factors associated with infection after the first wave of coronavirus disease 2019 (COVID-19) infections in the US. DESIGN, SETTING, AND PARTICIPANTS: In this statewide cross-sectional surveillance study, 4675 adult outpatients presenting for health care not associated with COVID-19 in Virginia between June 1 and August 14, 2020, were recruited to participate in a questionnaire and receive venipuncture to assess SARS-CoV-2 serology. Eligibility was stratified to meet age, race, and ethnicity quotas that matched regional demographic profiles. MAIN OUTCOMES AND MEASURES: The main outcome was SARS-CoV-2 seropositivity, as measured by the Abbott SARS-CoV-2 immunoglobulin G assay. RESULTS: Among 4675 adult outpatients (mean [SD] age, 48.8 [16.9] years; 3119 women [66.7%]; 3098 White [66.3%] and 4279 non-Hispanic [91.5%] individuals) presenting for non–COVID-19–associated health care across Virginia, the weighted seroprevalence was 2.4% (95% CI, 1.8%-3.1%) and ranged from 0% to 20% by zip code. Seroprevalence was notably higher among participants who were Hispanic (10.2%; 95% CI, 6.1%-14.3%), residing in the northern region (4.4%; 95% CI, 2.8%-6.1%), aged 40 to 49 years (4.4%; 95% CI, 1.8%-7.1%), and uninsured (5.9%; 95% CI, 1.5%-10.3%). Higher seroprevalence was associated with Hispanic ethnicity (adjusted odds ratio [aOR], 3.56; 95% CI, 1.76-7.21), residence in a multifamily unit (aOR, 2.55; 95% CI, 1.25-5.22), and contact with an individual with confirmed COVID-19 infection (aOR, 4.33; 95% CI, 1.77-10.58). The sensitivity of serology results was 94% (95% CI, 70%-100%) among those who reported receiving a previous polymerase chain reaction test for COVID-19 infection. Among 101 participants with seropositive results, 67 individuals (66.3%) were estimated to have asymptomatic infection. These data suggested a total estimated COVID-19 burden that was 2.8-fold higher than that ascertained by PCR-positive case counts. CONCLUSIONS AND RELEVANCE: This large statewide serologic study estimated that 2.4% of adults in Virginia had exposure to SARS-CoV-2, which was 2.8-fold higher than confirmed case counts. Hispanic ethnicity, residence in a multifamily unit, and contact with an individual with confirmed COVID-19 infection were significant risk factors associated with exposure. Most infections were asymptomatic. As of August 2020, the population in Virginia remained largely immunologically naive to the virus.

JAMA Netw Open2021       LitCov and CORD-19
4603Immune Response of Neonates Born to Mothers Infected With SARS-CoV-2  

IMPORTANCE: Although several studies have provided information on short-term clinical outcomes in children with perinatal exposure to SARS-CoV-2, data on the immune response in the first months of life among newborns exposed to the virus in utero are lacking. OBJECTIVE: To characterize systemic and mucosal antibody production during the first 2 months of life among infants who were born to mothers infected with SARS-CoV-2. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study enrolled 28 pregnant women who tested positive for SARS-CoV-2 infection and who gave birth at Policlinico Umberto I in Rome, Italy, from November 2020 to May 2021, and their newborns. Maternal and neonatal systemic immune responses were investigated by detecting spike-specific antibodies in serum, and the mucosal immune response was assessed by measuring specific antibodies in maternal breastmilk and infant saliva 48 hours after delivery and 2 months later. EXPOSURES: Maternal infection with SARS-CoV-2 in late pregnancy. MAIN OUTCOMES AND MEASURES: The systemic immune response was evaluated by the detection of SARS-CoV-2 IgG and IgA antibodies and receptor binding domain–specific IgM antibodies in maternal and neonatal serum. The mucosal immune response was assessed by measuring spike-specific antibodies in breastmilk and in infant saliva, and the presence of antigen-antibody spike IgA immune complexes was investigated in breastmilk samples. All antibodies were detected using an enzyme-linked immunosorbent assay. RESULTS: In total, 28 mother-infant dyads (mean [SD] maternal age, 31.8 [6.4] years; mean [SD] gestational age, 38.1 [2.3] weeks; 18 [60%] male infants) were enrolled at delivery, and 21 dyads completed the study at 2 months’ follow-up. Because maternal infection was recent in all cases, transplacental transfer of virus spike-specific IgG antibodies occurred in only 1 infant. One case of potential vertical transmission and 1 case of horizontal infection were observed. Virus spike protein–specific salivary IgA antibodies were significantly increased (P = .01) in infants fed breastmilk (0.99 arbitrary units [AU]; IQR, 0.39-1.68 AU) vs infants fed an exclusive formula diet (0.16 AU; IQR, 0.02-0.83 AU). Maternal milk contained IgA spike immune complexes at 48 hours (0.53 AU; IQR, 0.25-0.39 AU) and at 2 months (0.09 AU; IQR, 0.03-0.17 AU) and may have functioned as specific stimuli for the infant mucosal immune response. CONCLUSIONS AND RELEVANCE: In this cohort study, SARS-CoV-2 spike–specific IgA antibodies were detected in infant saliva, which may partly explain why newborns are resistant to SARS-CoV-2 infection. Mothers infected in the peripartum period appear to not only passively protect the newborn via breastmilk secretory IgA but also actively stimulate and train the neonatal immune system via breastmilk immune complexes.

JAMA Netw Open2021       LitCov and CORD-19
4604Cognitive and mental health changes and their vulnerability factors related to COVID-19 lockdown in Italy  

The COVID-19 pandemic and government imposed social restrictions like lockdown exposed most individuals to an unprecedented stress, increasing mental health disorders worldwide. We explored subjective cognitive functioning and mental health changes and their possible interplay related to COVID-19-lockdown. We also investigated potential risk factors to identify more vulnerable groups. Across Italy, 1215 respondents completed our Qualtrics-based online-survey during the end of a seven to 10-week imposed lockdown and home confinement (from April 29 to May 17, 2020). We found subjective cognitive functioning and mental health severely changed in association with the lockdown. Under government regulations, cognitive complaints were mostly perceived in routine tasks involving attention, temporal orientation and executive functions—with no changes in language abilities. A paradoxical effect was observed for memory, with reduced forgetfulness compared to pre-lockdown. We found higher severity and prevalence of depression, anxiety disorders, abnormal sleep, appetite changes, reduced libido and health anxiety: with mild-to-severe depression and anxiety prevalence climbing to 32 and 36 percent, respectively, under restrictions. Being female, under 45 years, working from home or being underemployed were all identified as relevant risk factors for worsening cognition and mental health. Frequent consumers of COVID-19 mass media information or residents in highly infected communities reported higher depression and anxiety symptoms, particularly hypochondria in the latter. If similar restrictions are reimposed, governments must carefully consider these more vulnerable groups in their decisions, whilst developing effective global and long-term responses to the cognitive and mental health challenges of this type of pandemic; as well as implementing appropriate psychological interventions with specific guidelines: particularly regarding exposure to COVID-19 mass-media reports.

PLoS One2021       LitCov and CORD-19
4605SARS-CoV-2: a storm is raging  

N/A

J Clin Invest2020       LitCov and CORD-19
4606Quantifying Absolute Neutralization Titers against SARS-CoV-2 by a Standardized Virus Neutralization Assay Allows for Cross-Cohort Comparisons of COVID-19 Sera  

The global coronavirus disease 2019 (COVID-19) pandemic has mobilized efforts to develop vaccines and antibody-based therapeutics, including convalescent-phase plasma therapy, that inhibit viral entry by inducing or transferring neutralizing antibodies (nAbs) against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (CoV2-S). However, rigorous efficacy testing requires extensive screening with live virus under onerous biosafety level 3 (BSL3) conditions, which limits high-throughput screening of patient and vaccine sera. Myriad BSL2-compatible surrogate virus neutralization assays (VNAs) have been developed to overcome this barrier. Yet, there is marked variability between VNAs and how their results are presented, making intergroup comparisons difficult. To address these limitations, we developed a standardized VNA using CoV2-S pseudotyped particles (CoV2pp) based on vesicular stomatitis virus bearing the Renilla luciferase gene in place of its G glycoprotein (VSVΔG); this assay can be robustly produced at scale and generate accurate neutralizing titers within 18 h postinfection. Our standardized CoV2pp VNA showed a strong positive correlation with CoV2-S enzyme-linked immunosorbent assay (ELISA) results and live-virus neutralizations in confirmed convalescent-patient sera. Three independent groups subsequently validated our standardized CoV2pp VNA (n > 120). Our data (i) show that absolute 50% inhibitory concentration (absIC(50)), absIC(80), and absIC(90) values can be legitimately compared across diverse cohorts, (ii) highlight the substantial but consistent variability in neutralization potency across these cohorts, and (iii) support the use of the absIC(80) as a more meaningful metric for assessing the neutralization potency of a vaccine or convalescent-phase sera. Lastly, we used our CoV2pp in a screen to identify ultrapermissive 293T clones that stably express ACE2 or ACE2 plus TMPRSS2. When these are used in combination with our CoV2pp, we can produce CoV2pp sufficient for 150,000 standardized VNAs/week.

mBio2021       LitCov and CORD-19
4607Development of a Parallel Reaction Monitoring Mass Spectrometry Assay for the Detection of SARS-CoV-2 Spike Glycoprotein and Nucleoprotein  

[Image: see text] There is an urgent need for robust and high-throughput methods for SARS-CoV-2 detection in suspected patient samples to facilitate disease management, surveillance, and control. Although nucleic acid detection methods such as reverse transcription polymerase chain reaction (RT-PCR) are the gold standard, during the current pandemic, the deployment of RT-PCR tests has been extremely slow, and key reagents such as PCR primers and RNA extraction kits are at critical shortages. Rapid point-of-care viral antigen detection methods have been previously employed for the diagnosis of respiratory viruses such as influenza and respiratory syncytial viruses. Therefore, the direct detection of SARS-CoV-2 viral antigens in patient samples could also be used for diagnosis of active infection, and alternative methodologies for specific and sensitive viral protein detection should be explored. Targeted mass spectrometry techniques have enabled the identification and quantitation of a defined subset of proteins/peptides at single amino acid resolution with attomole level sensitivity and high reproducibility. Herein, we report a targeted mass spectrometry assay for the detection of SARS-CoV-2 spike protein and nucleoprotein in a relevant biological matrix. Recombinant full-length spike protein and nucleoprotein were digested and proteotypic peptides were selected for parallel reaction monitoring (PRM) quantitation using a high-resolution Orbitrap instrument. A spectral library, which contained seven proteotypic peptides (four from spike protein and three from nucleoprotein) and the top three to four transitions, was generated and evaluated. From the original spectral library, we selected two best performing peptides for the final PRM assay. The assay was evaluated using mock test samples containing inactivated SARS-CoV-2 virions, added to in vitro derived mucus. The PRM assay provided a limit of detection of ∼200 attomoles and a limit of quantitation of ∼ 390 attomoles. Extrapolating from the test samples, the projected titer of virus particles necessary for the detection of SARS-CoV-2 spike and nucleoprotein detection was approximately 2 × 10(5) viral particles/mL, making it an attractive alternative to RT-PCR assays. Potentially, mass spectrometry-based methods for viral antigen detection may deliver higher throughput and could serve as a complementary diagnostic tool to RT-PCR. Furthermore, this assay could be used to evaluate the presence of SARS-CoV-2 in archived or recently collected biological fluids, in vitro-derived research materials, and wastewater samples.

Anal Chem2020       LitCov and CORD-19
4608Underage Youth and Young Adult e-Cigarette Use and Access Before and During the COVID-19 Pandemic  

IMPORTANCE: Understanding patterns of e-cigarette use and access during the coronavirus disease 2019 (COVID-19) pandemic is important because e-cigarettes may put users at risk for more severe respiratory effects and other health problems. OBJECTIVE: To examine whether underage youth and young adults who ever used e-cigarettes self-reported changes in access and use of e-cigarettes since the COVID-19 pandemic began. DESIGN, SETTING, AND PARTICIPANTS: A national, cross-sectional online survey study was conducted from May 6 to May 14, 2020. This sample of 4351 participants aged 13 to 24 years across the US included 2167 e-cigarette ever-users. Quota sampling was used to balance for age, sex, race/ethnicity, and 50% having ever used e-cigarettes. MAIN OUTCOMES AND MEASURES: Change in e-cigarette use (increase, decrease, quit, no change, and switch to another product) and access to e-cigarettes (easier or harder, and change in point-of-purchase) before and after the COVID-19 pandemic began, reasons for change, number of times e-cigarettes were used, nicotine dependence, and sociodemographic data. RESULTS: This study focused on 2167 e-cigarette ever-users among 4351 participants who completed the survey. Among 2167 e-cigarette users, a total of 1442 were younger than 21 years and 725 were aged 21 years or older; 1397 were female (64.5%) and 438 identified as lesbian, gay, bisexual, transgender, queer (20.2%). The survey completion rate was 40%. Since the COVID-19 pandemic began, 1198 of 2125 e-cigarette users (56.4%) changed their use: 388 individuals (32.4%) quit, 422 individuals (35.3%) reduced the amount of nicotine, 211 individuals (17.6%) increased nicotine use, 94 individuals (7.8%) increased cannabis use, and 82 individuals (6.9%) switched to other products. Participants reported that not being able to go to vape shops and product unavailability were the reasons accessing e-cigarettes was difficult after the pandemic began. Since the COVID-19 pandemic began, individuals reported purchasing from alternative retail stores (disposables, 150 of 632 [23.7%]; pod-based, 144 of 797 [18.1%]; and other e-cigarette, 125 of 560 [22.3%], ie, between 18.1% and 23.7%), purchasing online instead of retail (disposables, 115 of 632 [18.2%]; pod-based, 156 of 797 [19.6%]; and other e-cigarette, 111 of 560 [19.8%], ie, between 18.2% to 19.8%), and shifted to retail instead of online (disposables, 11 of 632 [1.7%]; pod-based, 17 of 797 [2.0%]; and other e-cigarette, 13 of 560 [2.3%], ie, between 1.7%-2.3%). Other individuals reported no change: from retail stores (disposables 262 of 632 [41.5%]; pod-based 344 of 797 [43.2%]; and other e-cigarette, 223 of 560 [39.8%], ie, between 39.8% and 43.2%) and online (disposables 94 of 632 [14.9%]; pod-based 136 of 797 [17.1%]; and other e-cigarette, 88 of 560 [15.8%], ie, between 14.9% and 17.1%). Underage youth reported e-cigarette deliveries from vape shops and/or dealers or friends who received such deliveries, and 63 of 229 (27.5%) self-reported accessing e-cigarettes without age verification. e-Cigarette users were 52% less likely to quit or reduce their use if they previously used e-cigarettes between 11 and 99 times (adjusted odds ratio, 0.48; 95% CI, 0.30-0.78), 68% less likely to quit if they previously used e-cigarettes more than 100 times (adjusted odds ratio, 0.32; 95% CI, 0.20-0.51), and 51% were less likely to quit if they were nicotine dependent (adjusted odds ratio, 0.49; 95% CI, 0.35-0.70). CONCLUSIONS AND RELEVANCE: During the COVID-19 pandemic, youth e-cigarette users reported changes in e-cigarette use, point-of-purchase, and ability to purchase e-cigarettes without age verification. The US Food and Drug Administration and local policy makers may find these data useful to inform policies to prevent e-cigarette sales to underage youth.

JAMA Netw Open2020       LitCov and CORD-19
4609Targeting SARS-CoV-2 main protease: structure based virtual screening, in silico ADMET studies and molecular dynamics simulation for identification of potential inhibitors  

COVID-19 pandemic has created a healthcare crisis across the world and has put human life under life-threatening circumstances. The recent discovery of the crystallized structure of the main protease (M(pro)) from SARS-CoV-2 has provided an opportunity for utilizing computational tools as an effective method for drug discovery. Targeting viral replication has remained an effective strategy for drug development. M(pro) of SARS-COV-2 is the key protein in viral replication as it is involved in the processing of polyproteins to various structural and nonstructural proteins. Thus, M(pro) represents a key target for the inhibition of viral replication specifically for SARS-CoV-2. We have used a virtual screening strategy by targeting M(pro) against a library of commercially available compounds to identify potential inhibitors. After initial identification of hits by molecular docking-based virtual screening further MM/GBSA, predictive ADME analysis, and molecular dynamics simulation were performed. The virtual screening resulted in the identification of twenty-five top scoring structurally diverse hits that have free energy of binding (ΔG) values in the range of −26-06 (for compound AO-854/10413043) to −59.81 Kcal/mol (for compound 329/06315047). Moreover, the top-scoring hits have favorable AMDE properties as calculated using in silico algorithms. Additionally, the molecular dynamics simulation revealed the stable nature of protein-ligand interaction and provided information about the amino acid residues involved in binding. Overall, this study led to the identification of potential SARS-CoV-2 M(pro) hit compounds with favorable pharmacokinetic properties. We believe that the outcome of this study can help to develop novel M(pro) inhibitors to tackle this pandemic. Communicated by Ramaswamy H. Sarma

J Biomol Struct Dyn2020       LitCov and CORD-19
4610Comparative epidemiology between the 2009 H1N1 influenza and COVID-19 pandemics  

In a short time, humanity has experienced two pandemics: the influenza A virus pandemic (pH1N1) in 2009 and the coronavirus disease 2019 (COVID-19) pandemic in 2020. Therefore, it is likely that the general population will erroneously seek to compare the two pandemics and adopt similar attitudes in facing them. However, the two pandemics have their intrinsic characteristics that distinguish them considerably; for example, the virulence of the infectious agents and the availability of treatment and vaccine. Consequently, given this knowledge gap between the pH1N1 and COVID-19 pandemics, we conducted this review to clarify and summarize, above all, the epidemiological historical aspects of these two viruses of great importance to global public health.

J Infect Public Health2020       LitCov and CORD-19
4611Characteristics of personal protective equipment training programs in Australia and New Zealand hospitals: A survey  

BACKGROUND: Using personal protective equipment (PPE) is one of several fundamental measures to prevent the transmission of infection and infectious diseases and is particularly pertinent in the current COVID-19 pandemic. Appropriate use of PPE by healthcare workers is, however, often suboptimal. Training and monitoring of PPE competency are essential components of an infection prevention and control program but there is a paucity of research and data on the content of such training programs across Australasia. This paper reports the results of a survey that characterised the nature of PPE training in Australian and New Zealand hospitals. METHODS: A population-based online survey was distributed to members of three major Australasian colleges representing infection prevention and control. RESULTS: Results indicate that, although training is frequently provided at orientation, many healthcare workers do not receive regular updates. Training programmes combine online and classroom sessions, but over a third do not include a practical component. The frequency of monitoring PPE competency is variable with one third of respondents indicating that no auditing occurs. PPE items used for high-level training are variable, with use of powered air purifying respirators (PAPRs) uncommon. CONCLUSION: The results of this study suggest that HCWs’ confidence, competence and familiarity with PPE are a concern, which in the context of the current global COVID-19 pandemic is problematic. More research is needed into how PPE training programs could be better designed, to prepare HCWs for practice using PPE safely and confidently.

Infect Dis Health2020       LitCov and CORD-19
4612Immediate impact of the COVID-19 pandemic on the work and personal lives of Australian hospital clinical staff  

N/A

Aust Health Rev2021       LitCov and CORD-19
4613Anxiety and Post-Traumatic Stress Disorder Symptoms in Pregnant Women during the COVID-19 Pandemic's Delay Phase  

N/A

Psychiatr Danub2020       LitCov and CORD-19
4614SARS-CoV-2 BA.1 variant is neutralized by vaccine booster-elicited serum but evades most convalescent serum and therapeutic antibodies  

The rapid spread of the highly contagious Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) along with its high number of mutations in the spike gene has raised alarms about the effectiveness of current medical countermeasures. To address this concern, we measured neutralization of the Omicron BA.1 variant pseudovirus by post-vaccination serum samples after two and three immunizations with the Pfizer/BioNTech162b2 SARS-CoV-2 mRNA (Pfizer/BNT162b2) vaccine, convalescent serum samples from unvaccinated individuals infected by different variants, and clinical-stage therapeutic antibodies. We found that titers against the Omicron variant were low or undetectable after two immunizations and in many convalescent serum samples, regardless of the infecting variant. A booster vaccination increased titers more than 30-fold against Omicron to values comparable to those seen against the D614G variant after two immunizations. Neither age nor sex were associated with differences in post-vaccination antibody responses. We also evaluated eighteen clinical-stage therapeutic antibody products and an antibody mimetic protein product obtained directly from the manufacturers. Five monoclonal antibodies, the antibody mimetic protein, three antibody cocktails, and two polyclonal antibody preparations retained measurable neutralization activity against Omicron with a varying degree of potency. Of these, only three retained potencies comparable to the D614G variant. Two therapeutic antibody cocktails in the tested panel that are authorized for emergency use in the United States did not neutralize Omicron. These findings underscore the potential benefit of mRNA vaccine boosters for protection against Omicron and the need for rapid development of antibody therapeutics that maintain potency against emerging variants.

Sci Transl Med2022       LitCov and CORD-19
4615Extraction-free SARS-CoV-2 detection by rapid RT-qPCR universal for all primary respiratory materials  

BACKGROUND: Fast and reliable detection of SARS-CoV-2 is crucial for efficient control of the COVID-19 pandemic. Due to the high demand for SARS-CoV-2 testing there is a worldwide shortage of RNA extraction reagents. Therefore, extraction-free RT-qPCR protocols are urgently needed. OBJECTIVES: To establish a rapid RT-qPCR protocol for the detection of SARS-CoV-2 without the need of RNA extraction suitable for all respiratory materials. MATERIAL AND METHODS: Different SARS-CoV-2 positive respiratory materials from our routine laboratory were used as crude material after heat inactivation in direct RT-qPCR with the PrimeDirect™ Probe RT-qPCR Mix (TaKaRa). SARS-CoV-2 was detected using novel primers targeted to the E-gene. RESULTS: The protocol for the detection of SARS-CoV-2 in crude material used a prepared frozen-PCR mix with optimized primers and 5 µl of fresh, undiluted and pre-analytically heat inactivated respiratory material. For validation, 91 respiratory samples were analyzed in direct comparison to classical RNA-based RT-qPCR. Overall 81.3% of the samples were detected in both assays with a strong correlation between both Ct values (r = 0.8492, p < 0.0001). The SARS-CoV-2 detection rate by direct RT-qPCR was 95.8% for Ct values <35. All negative samples were characterized by low viral loads (Ct >35) and/or long storage times before sample processing. CONCLUSION: Direct RT-qPCR is a suitable alternative to classical RNA RT-qPCR, provided that only fresh samples (storage <1 week) are used. RNA extraction should be considered if samples have longer storage times or if PCR inhibition is observed. In summary, this protocol is fast, inexpensive and suitable for all respiratory materials.

J Clin Virol2020       LitCov and CORD-19
4616Physical Activity Change during COVID-19 Confinement  

Background: The lockdown and social distancing caused by COVID-19 may influence common health behavior. The unprecedent worldwide confinement, in which Spain has been one of the most affected—with severe rules governing confinement—may have changed physical activity (PA) and sedentary habits due to prolonged stays at home. Purpose: The aim of this study is to evaluate how self-reported PA and sedentary time (ST) have changed during confinement in the Spanish population. Methods: 3800 healthy adults (age 18–64 years) residing in Spain answered the international physical activity questionnaire short (IPAQ-S) twice between 23 March and 1 April (confinement). Data analysis was carried out taking into consideration meeting general PA recommendations before confinement, age and gender. Results: Self-reported PA decreased significantly during confinement in our sample. Vigorous physical activities (VPA) and walking time decreased by 16.8% (p < 0.001) and 58.2% (p < 0.001), respectively, whereas ST increased by 23.8% (p < 0.001). The percent of people fulfilling the 75 min/week of VPA recommendation decreased by 10.7% (p < 0.001) while the percent of people who reached 150 min/week of moderate activity barely changed (1.4%). The group that performed the most VPA before confinement showed the greatest decrease (30.5%, p < 0.001). Men reduced time in VPA more than women (21% vs 9%, respectively) who even increased time in moderate PA by 11% (p < 0.05) and reported less increase in ST than men (35% vs 25.3%, respectively). Conclusion: The Spanish adult population, especially young people, students and very active men, decreased daily self-reported PA and increased ST during COVID-19 confinement.

Int J Environ Res Public Healt2020       LitCov and CORD-19
4617Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans  

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly across the USA, causing extensive morbidity and mortality, particularly in the African American community. Autopsy can considerably contribute to our understanding of many disease processes and could provide crucial information to guide management of patients with coronavirus disease 2019 (COVID-19). We report on the relevant cardiopulmonary findings in, to our knowledge, the first autopsy series of ten African American decedents, with the cause of death attributed to COVID-19. METHODS: Autopsies were performed on ten African American decedents aged 44–78 years with cause of death attributed to COVID-19, reflective of the dominant demographic of deaths following COVID-19 diagnosis in New Orleans. Autopsies were done with consent of the decedents' next of kin. Pulmonary and cardiac features were examined, with relevant immunostains to characterise the inflammatory response, and RNA labelling and electron microscopy on representative sections. FINDINGS: Important findings include the presence of thrombosis and microangiopathy in the small vessels and capillaries of the lungs, with associated haemorrhage, that significantly contributed to death. Features of diffuse alveolar damage, including hyaline membranes, were present, even in patients who had not been ventilated. Cardiac findings included individual cell necrosis without lymphocytic myocarditis. There was no evidence of secondary pulmonary infection by microorganisms. INTERPRETATION: We identify key pathological states, including thrombotic and microangiopathic pathology in the lungs, that contributed to death in patients with severe COVID-19 and decompensation in this demographic. Management of these patients should include treatment to target these pathological mechanisms. FUNDING: None.

Lancet Respir Med2020       LitCov and CORD-19
4618RIG-I-Like Receptor-Mediated Recognition of Viral Genomic RNA of SARS-CoV-2 and Viral Escape From the Host Innate Immune Responses  

RIG-I-like receptors (RLR), RIG-I and MDA5, are cytoplasmic viral RNA sensors that recognize viral double-stranded RNAs and trigger signals to induce antiviral responses, including type I interferon production. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused the coronavirus disease 2019 pandemic. However, the RLR role in innate immune response to SARS-CoV-2 has not been fully elucidated. Here, we studied the roles of RLR in cytokine expression responding to SARS-CoV-2 and found that not only MDA5 but also RIG-I are involved in innate immune responses in some types of human cells. Transfection of total RNAs extracted from SARS-CoV-2-infected cells into epithelial cells induced IFN-β, IP-10, and Ccl5 mRNA expression. The cytokine expression was reduced by knockout of either RIG-I or MDA5, suggesting that both proteins are required for appropriate innate immune response to SARS-CoV-2. Two viral genomic RNA regions strongly induced type I IFN expression, and a 200-base fragment of viral RNA preferentially induced type I IFN in a RIG-I-dependent manner. In contrast, SARS-CoV-2 infectious particles hardly induced cytokine expression, suggesting viral escape from the host response. Viral 9b protein inhibited RIG-I and MAVS interaction, and viral 7a protein destabilized the TBK1 protein, leading to attenuated IRF-3 phosphorylation required for type I IFN expression. Our data elucidated the mechanism underlying RLR-mediated response to SARS-CoV-2 infection and viral escape from the host innate immune response.

Front Immunol2021       LitCov and CORD-19
4619Experiences of cancer care during COVID-19: Phase 1 results of a longitudinal qualitative study  

BACKGROUND: Healthcare services have responded to the challenges of service delivery during COVID-19 with telehealth and hybrid models of care. However, there is limited understanding of the experiences of care among people affected by cancer and how their experiences may change and evolve against the shifting landscape of COVID-19 incidence, mortality, vaccination and refinements in service delivery. OBJECTIVES: This study explores the experiences of cancer care among people affected by cancer in Ireland during the COVID-19 pandemic. This paper presents the results of the initial cross-sectional semi-structured interviews and the longitudinal qualitative research design which will be employed in this study. DESIGN: A longitudinal descriptive qualitative study. SETTING: Ireland PARTICIPANTS: People living with and after cancer or caring for someone with cancer during the COVID-19 pandemic. METHODS: Participants were recruited to the study via social media advertisements and consented to participate in up to three semi-structured interviews between January and July 2021. Initial semi-structured interviews were conducted with 16 participants in January 2021. Participants completed measures of resilience (2-item Connor‐Davidson Resilience Scale) and distress (The National Comprehensive Cancer Network Distress Thermometer). Interviews were recorded, transcribed and analyzed thematically. RESULTS: Participants reported low levels of distress and moderate to high levels of resilience on average. Three themes were generated from analysis of the first phase of cross-sectional interviews. Participants described a counterbalance of being cautious of infection and keeping safe through prevention and shielding strategies. Although hospitals felt safe and were working efficiently, some participants felt COVID-19 had compromised person-centredness and empathy in care. While participants valued the restrictions being taken to minimize infection risk, substitution of face-to-face appointments with telehealth services and attending essential face-to-face appointments alone restricted participants' access to professional and social support. Despite this, many participants felt public health measures to reduce transmission of COVID-19 had created a sense of not missing out, feeling safe and reduced difficult social interactions requiring explanation of their diagnosis. CONCLUSIONS: There is an opportunity to learn from the experiences of healthcare delivery from the perspectives of people affected by cancer during the COVID-19 pandemic. The results highlight the complexities and dualities of living with, after or caring for someone with cancer during the COVID-19 pandemic. Opportunities for longitudinal qualitative research to explore the evolving experiences, concerns and persistent and emerging unmet information and clinical needs within the rapidly changing socio-political, socio-cultural and healthcare contexts of the COVID-19 pandemic are highlighted.

Int J Nurs Stud Adv2021       LitCov and CORD-19
4620Anisotine and amarogentin as promising inhibitory candidates against SARS-CoV-2 proteins: a computational investigation  

The coronavirus disease 2019 (COVID-19) pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents an unprecedented challenge to global public health with researchers striving to find a possible therapeutic candidate that could limit the spread of the virus. In this context, the present study employed an in silico molecular interaction-based approach to estimate the inhibitory potential of the phytochemicals from ethnomedicinally relevant Indian plants including Justicia adhatoda, Ocimum sanctum and Swertia chirata, with reported antiviral activities against crucial SARS-CoV-2 proteins. SARS-CoV-2 proteins associated with host attachment and viral replication namely, spike protein, main protease enzyme M(pro) and RNA-dependent RNA polymerase (RdRp) are promising druggable targets for COVID-19 therapeutic research. Extensive molecular docking of the phytocompounds at the binding pockets of the viral proteins revealed their promising inhibitory potential. Subsequent assessment of physicochemical features and potential toxicity of the compounds followed by robust molecular dynamics simulations and analysis of MM-PBSA energy scoring function revealed anisotine against SARS-CoV-2 spike and M(pro) proteins and amarogentin against SARS-CoV-2 RdRp as potential inhibitors. It was interesting to note that these compounds displayed significantly higher binding energy scores against the respective SARS-CoV-2 proteins compared to the relevant drugs that are currently being targeted against them. Present research findings confer scopes to explore further the potential of these compounds in vitro and in vivo towards deployment as efficient SARS-CoV-2 inhibitors and development of novel effective therapeutics. Communicated by Ramaswamy H. Sarma

J Biomol Struct Dyn2020       LitCov and CORD-19
4621Immunogenicity of a Single Dose of SARS-CoV-2 Messenger RNA Vaccine in Solid Organ Transplant Recipients  

N/A

JAMA2021       LitCov and CORD-19
4622Prevalence of COVID-19 Pandemic, Self-Esteem and Its Effect on Depression Among University Students in Saudi Arabia  

BACKGROUND AND AIMS: University students are commonly identified as susceptible, suffering from higher anxiety, stress, and depression than the overall population. During the Corona Virus Disease pandemic (COVID), education was shifted to the virtual learning environment. Students' ambiguity regarding academic accomplishment, imminent careers, changes in social life, and other concerns all these factors played a role in amplifying their stress levels, anxiety, and depression worldwide. This study investigates university students' self-esteem and depressions after they have been online learning for over 1 year due to the COVID-19 pandemic in Saudi Arabia. METHODS: For this research, an adapted questionnaire of Rosenberg (Self-Esteem Scale) and Zung (Self-Rating Depression Scale) was used to get the responses of the participants of public and private universities in Saudi Arabia during March-April 2021. We received a total of 151 valid responses from respondents. For data analysis, we used descriptive statistics, ANOVA, multiple regression and binary logistic regression. FINDINGS: The results showed that 75% of the students experienced different levels of depressions, with half (37.5%) having moderate to extreme levels of depression. A total of 41% of students experienced low self-esteem (38% females and 45% males). The regression results indicated depressive symptoms for low self-esteem. Furthermore, results of logistic regression showed that high self-esteem reduces the chances of getting depressive symptoms by 17%. The depressive symptoms were higher in female students than their male counterparts; furthermore, males experienced depressive symptoms less than females by 38%. CONCLUSIONS: Based on the current research results, it is concluded that the presence of the COVID-19 pandemic has dramatically increased the depressive symptoms in students, especially in female students. The findings suggested instant consideration and support for students. It is also suggested to the quest for potential managing policies that have been known and effective during the pandemic. Moreover, training should be provided for students to shift their educational experience mindset to an adaptive mindset, which can help them adapt to the new ways of learning and education.

Front Public Health2022       LitCov and CORD-19
4623Conversion and optimization of telehealth in obstetric care during the COVID-19 pandemic  

When New York City became the international epicenter of the COVID-19 pandemic, telehealth at Columbia University Irving Medical Center was expanded in the inpatient and outpatient settings. The goals of telehealth during the pandemic were to maintain patient access to care while reducing the risk for COVID-19 exposure for patients and staff. Recommendations are made on how telehealth can be implemented and utilized to accomplish these goals. In the outpatient setting, virtual prenatal care visits and consultations can replace most in-person visits. When visitor restrictions are in effect telehealth can be used to engage support persons in the delivery room. Telehealth innovations can be leveraged to greatly improve care for COVID-19 mothers and their infants during the COVID-19 pandemic and beyond.

Semin Perinatol2020       LitCov and CORD-19
4624Association of Remdesivir Treatment With Survival and Length of Hospital Stay Among US Veterans Hospitalized With COVID-19  

IMPORTANCE: Randomized clinical trials have yielded conflicting results about the effects of remdesivir therapy on survival and length of hospital stay among people with COVID-19. OBJECTIVE: To examine associations between remdesivir treatment and survival and length of hospital stay among people hospitalized with COVID-19 in routine care settings. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from the Veterans Health Administration (VHA) to identify adult patients in 123 VHA hospitals who had a first hospitalization with laboratory-confirmed COVID-19 from May 1 to October 8, 2020. Propensity score matching of patients initiating remdesivir treatment to control patients who had not initiated remdesivir treatment by the same hospital day was used to create the analytic cohort. EXPOSURES: Remdesivir treatment. MAIN OUTCOMES AND MEASURES: Time to death within 30 days of remdesivir treatment initiation (or corresponding hospital day for matched control individuals) and time to hospital discharge with time to death as a competing event. Associations between remdesivir treatment and these outcomes were assessed using Cox proportional hazards regression in the matched cohort. RESULTS: The initial cohort included 5898 patients admitted to 123 hospitals, 2374 (40.3%) of whom received remdesivir treatment (2238 men [94.3%]; mean [SD] age, 67.8 [12.8] years) and 3524 (59.7%) of whom never received remdesivir treatment (3302 men [93.7%]; mean [SD] age, 67.0 [14.4] years). After propensity score matching, the analysis included 1172 remdesivir recipients and 1172 controls, for a final matched cohort of 2344 individuals. Remdesivir recipients and matched controls were similar with regard to age (mean [SD], 66.6 [14.2] years vs 67.5 [14.1] years), sex (1101 men [93.9%] vs 1101 men [93.9%]), dexamethasone use (559 [47.7%] vs 559 [47.7%]), admission to the intensive care unit (242 [20.7%] vs 234 [19.1%]), and mechanical ventilation use (69 [5.9%] vs 45 [3.8%]). Standardized differences were less than 10% for all measures. Remdesivir treatment was not associated with 30-day mortality (143 remdesivir recipients [12.2%] vs 124 controls [10.6%]; log rank P = .26; adjusted hazard ratio [HR], 1.06; 95% CI, 0.83-1.36). Results were similar for people receiving vs not receiving dexamethasone at remdesivir initiation (dexamethasone recipients: adjusted HR, 0.93; 95% CI, 0.64-1.35; nonrecipients: adjusted HR, 1.19; 95% CI, 0.84-1.69). Remdesivir recipients had a longer median time to hospital discharge compared with matched controls (6 days [interquartile range, 4-12 days] vs 3 days [interquartile range, 1-7 days]; P < .001). CONCLUSIONS AND RELEVANCE: In this cohort study of US veterans hospitalized with COVID-19, remdesivir treatment was not associated with improved survival but was associated with longer hospital stays. Routine use of remdesivir may be associated with increased use of hospital beds while not being associated with improvements in survival.

JAMA Netw Open2021       LitCov and CORD-19
4625Evolution of Early SARS-CoV-2 and Cross-Coronavirus Immunity  

The novel coronavirus, SARS-coronavirus (CoV)-2 (SARS-CoV-2), has caused over 17 million infections in just a few months, with disease manifestations ranging from largely asymptomatic infection to critically severe disease. The remarkable spread and unpredictable disease outcomes continue to challenge management of this infection. Among the hypotheses to explain the heterogeneity of symptoms is the possibility that exposure to other coronaviruses (CoVs), or overall higher capability to develop immunity against respiratory pathogens, may influence the evolution of immunity to SARS-CoV-2. Thus, we profiled the immune response across multiple coronavirus receptor binding domains (RBDs), respiratory viruses, and SARS-CoV-2, to determine whether heterologous immunity to other CoV-RBDs or other infections influenced the evolution of the SARS-CoV-2 humoral immune response. Overall changes in subclass, isotype, and Fc-receptor binding were profiled broadly across a cohort of 43 individuals against different coronaviruses—RBDs of SARS-CoV-2 and the more common HKU1 and NL63 viruses. We found rapid functional evolution of responses to SARS-CoV-2 over time, along with broad but relatively more time-invariant responses to the more common CoVs. Moreover, there was little evidence of correlation between SARS-CoV-2 responses and HKU1, NL63, and respiratory infection (influenza and respiratory syncytial virus) responses. These findings suggest that common viral infections including common CoV immunity, targeting the receptor binding domain involved in viral infection, do not appear to influence the rapid functional evolution of SARS-CoV-2 immunity, and thus should not impact diagnostics or shape vaccine-induced immunity. IMPORTANCE A critical step to ending the spread of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the ability to detect, diagnose, and understand why some individuals develop mild and others develop severe disease. For example, defining the early evolutionary patterns of humoral immunity to SARS-CoV-2, and whether prevalent coronaviruses or other common infections influence the evolution of immunity, remains poorly understood but could inform diagnostic and vaccine development. Here, we deeply profiled the evolution of SARS-CoV-2 immunity, and how it is influenced by other coinfections. Our data suggest an early and rapid rise in functional humoral immunity in the first 2 weeks of infection across antigen-specific targets, which is negligibly influenced by cross-reactivity to additional common coronaviruses or common respiratory infections. These data suggest that preexisting receptor binding domain-specific immunity does not influence or bias the evolution of immunity to SARS-CoV-2 and should have negligible influence on shaping diagnostic or vaccine-induced immunity.

mSphere2020       LitCov and CORD-19
4626Telemedicine Use and Health-Related Concerns of Patients With Chronic Conditions During COVID-19: Survey of Members of Online Health Communities  

BACKGROUND: It has been widely communicated that individuals with underlying health conditions are at higher risk of severe disease due to COVID-19 than healthy peers. As social distancing measures continue during the COVID-19 pandemic, experts encourage individuals with underlying conditions to engage in telehealth appointments to maintain continuity of care while minimizing risk exposure. To date, however, little information has been provided regarding telehealth uptake among this high-risk population. OBJECTIVE: The aim of this study is to describe the telehealth use, resource needs, and information sources of individuals with chronic conditions during the COVID-19 pandemic. Secondary objectives include exploring differences in telehealth use by sociodemographic characteristics. METHODS: Data for this study were collected through an electronic survey distributed between May 12-14, 2020, to members of 26 online health communities for individuals with chronic disease. Descriptive statistics were run to explore telehealth use, support needs, and information sources, and z tests were run to assess differences in sociodemographic factors and information and support needs among those who did and did not use telehealth services. RESULTS: Among the 2210 respondents, 1073 (49%) reported engaging in telehealth in the past 4 months. Higher proportions of women engaged in telehealth than men (890/1781, 50% vs 181/424, 43%; P=.007), and a higher proportion of those earning household incomes of more than US $100,000 engaged in telehealth than those earning less than US $30,000 (195/370, 53% vs 241/530 45%; P=.003). Although 59% (133/244) of those younger than 40 years and 54% (263/486) of those aged 40-55 years used telehealth, aging populations were less likely to do so, with only 45% (677/1500) of individuals 56 years or older reporting telehealth use (P<.001 and P=.001, respectively). Patients with cystic fibrosis, lupus, and ankylosing spondylitis recorded the highest proportions of individuals using telehealth when compared to those with other diagnoses. Of the 2210 participants, 1333 (60%) participants either looked up information about the virus online or planned to in the future, and when asked what information or support would be most helpful right now, over half (1151/2210, 52%) responded “understanding how COVID-19 affects people with my health condition.” CONCLUSIONS: Nearly half of the study sample reported participating in telehealth in the past 4 months. Future efforts to engage individuals with underlying medical conditions in telehealth should focus on outreach to men, members of lower-income households, and aging populations. These results may help inform and refine future health communications to further engage this at-risk population in telehealth as the pandemic continues.

J Med Internet Res2021       LitCov and CORD-19
4627Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Patients  

On 4(th) November 2021, the first oral antiviral drug for COVID-19, molnupiravir (Lagevrio(®)), received full regulatory approval from the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK. Molnupiravir is an orally bioavailable antiviral drug for use at home when a SARS-CoV-2 test is positive. On 22(nd) December 2022, the FDA granted emergency use authorization (EUA) for the oral antiviral drug, nirmatrelvir/ritonavir (Paxlovid(®)) for adults and children with mild and moderate COVID-19 at increased risk of progression to severe COVID-19. These regulatory drug approvals come at a crucial time when new variants of concern of the SARS-CoV-2 virus are spreading rapidly. Although the FDA approved remdesivir (Veklury(®)) on 22(nd) October 2020 for use in adults and children for the treatment of COVID-19 requiring hospitalization, its use has been limited by the requirement for intravenous administration in a healthcare facility. The four FDA-approved therapeutic neutralizing monoclonal antibodies, imdevimab, bamlanivimab, etesevimab, and casirivimab are costly and also require medically-supervised intravenous administration. The availability of effective, low-cost oral antiviral drugs available in a community setting that can be used at an early stage of SARS-CoV-2 infection is now a priority in controlling COVID-19. An increasing number of repurposed antiviral drugs are currently under investigation or in the early stages of regulatory approval. This Editorial aims to present an update on the current status of orally bioavailable antiviral drug treatments for SARS-CoV-2 infection.

Med Sci Monit2022       LitCov and CORD-19
4628Resistance of SARS-CoV-2 variants to neutralization by antibodies induced in convalescent patients with COVID-19  

Administration of plasma from convalescent patients or neutralizing monoclonal antibodies (mAbs) is potent therapeutic option for COVID-19 caused by SARS-CoV-2 infection. However, SARS-CoV-2 variants with mutations in the spike protein have emerged in many countries. To evaluate the efficacy of neutralizing antibodies induced in convalescent patients against emerging variants, we isolate anti-Spike mAbs from two convalescent patients with COVID-19 infected with prototypic SARS-CoV-2 by single cell sorting of IgG+ memory B cells. Anti-Spike antibody induction is robust in these patients and five mAbs have potent neutralizing activities. The efficacy of most neutralizing mAbs and convalescent plasma samples is maintained against B.1.1.7 and mink cluster 5 variants but is significantly decreased against variants B.1.351 from South Africa and P.1 from Brazil. However, mAbs with a high affinity to the receptor-binding domain remain effective against these neutralization-resistant variants. Rapid spread of these variants significantly impacts antibody-based therapies and vaccine strategies against SARS-CoV-2.

Cell Rep2021       LitCov and CORD-19
4629Immunogenicity and safety of a third dose of CoronaVac and immune persistence of a two-dose schedule, in healthy adults: interim results from two single center, double-blind, randomised, placebo-controlled phase 2 clinical trials  

BACKGROUND: Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. METHODS: In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18–59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574. FINDINGS: 540 (90%) of 600 participants aged 18–59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1–5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2–8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9–190·4) for cohort 1b-14d-8m and 143·1 (110·8–184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3–27·6) on day 28 after the second dose to 45·8 (35·7–58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4–51·1) to 49·7 (39·9–61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1–12·0) in cohort 1a-14d-2m and 10·0 (7·3–13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0–59·4) on day 28 after the second dose to 158·5 (96·6–259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. INTERPRETATION: A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. FUNDING: National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Lancet Infect Dis2021       LitCov and CORD-19
4630Rapid decline in vaccine-boosted neutralizing antibodies against SARS-CoV-2 Omicron variant  

N/A

Cell Rep Med2022       LitCov
4631Convalescent plasma transfusion therapy in severe COVID-19 patients- a safety, efficacy and dose response study: A structured summary of a study protocol of a phase II randomized controlled trial  

OBJECTIVES: General: To assess the safety, efficacy and dose response of convalescent plasma (CP) transfusion in severe COVID-19 patients Specific: a. To identify the appropriate effective dose of CP therapy in severe patients b. To identify the efficacy of the therapy with their end point based on clinical improvement within seven days of treatment or until discharge whichever is later and in-hospital mortality c. To assess the clinical improvement after CP transfusion in severe COVID-19 patients d. To assess the laboratory improvement after CP transfusion in severe COVID-19 patients TRIAL DESIGN: This is a multicentre, multi-arm phase II Randomised Controlled Trial. PARTICIPANTS: Age and sex matched COVID-19 positive (by RT-PCR) severe cases will be enrolled in this trial. Severe case is defined by the World Health Organization (W.H.O) clinical case definition. The inclusion criteria are 1. Respiratory rate > 30 breaths/min; PLUS 2. Severe respiratory distress; or SpO2 ≤ 88% on room air or PaO2/FiO2≤ 300 mm of Hg, PLUS 3. Radiological (X-ray or CT scan) evidence of bilateral lung infiltrate, AND OR 4. Systolic BP < 90 mm of Hg or diastolic BP <60 mm of Hg. AND/OR 5. Criteria 1 to 4 AND or patient in ventilator support Patients’ below18 years, pregnant and lactating women, previous history of allergic reaction to plasma, patients who have already received plasma from a different source will be excluded. Patients will be enrolled at Bangabandhu Sheikh Mujib Medical University (BSMMU) hospital, Dhaka medical college hospital (DMCH) and Mugda medical college hospital (MuMCH). Apheretic plasma will be collected at the transfusion medicine department of SHNIBPS hospital, ELISA antibody titre will be done at BSMMU and CMBT and neutralizing antibody titre will be checked in collaboration with the University of Oxford. Patients who have recovered from COVID-19 will be recruited as donors of CP. The recovery criteria are normality of body temperature for more than 3 days, resolution of respiratory symptoms, two consecutively negative results of sputum SARS-CoV-2 by RT-PCR assay (at least 24 hours apart) 22 to 35 days of post onset period, and neutralizing antibody titre ≥ 1:160. INTERVENTION AND COMPARATOR: This RCT consists of three arms, a. standard care, b. standard care and 200 ml CP and c. standard care and 400 ml CP. Patients will receive plasma as a single transfusion. Intervention arms will be compared to the standard care arm. MAIN OUTCOMES: The primary outcome will be time to clinical improvement within seven days of treatment or until discharge whichever is later and in-hospital mortality. The secondary outcome would be improvement of laboratory parameters after therapy (neutrophil, lymphocyte ratio, CRP, serum ferritin, SGPT, SGOT, serum creatinine and radiology), length of hospital stay, length of ICU stay, reduction in proportion of deaths, requirement of ventilator and duration of oxygen and ventilator support. RANDOMISATION: Randomization will be done by someone not associated with the care or assessment of the patients by means of a computer generated random number table using an allocation ratio of 1:1:1. BLINDING (MASKING): This is an open level study; neither the physician nor the patients will be blinded. However, the primary and secondary outcome (oxygen saturations, PaO2/FiO2, BP, day specific laboratory tests) will be recorded using an objective automated method; the study staff will not be able to influence the recording of these data. NUMBER TO BE RANDOMISED (SAMPLE SIZE): No similar study has been performed previously. Therefore no data are available that could be used to generate a sample size calculation. This phase II study is required to provide some initial data on efficacy and safety that will allow design of a larger study. The trial will recruit 60 participants (20 in each arm). TRIAL STATUS: Protocol version 1.4 dated May 5, 2020 and amended version 1.5, dated June 16, 2020. First case was recruited on May 27, 2020. By August 10, 2020, the trial had recruited one-third (21 out of 60) of the participants. The recruitment is expected to finish by October 31, 2020. TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT04403477. Registered 26 May, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trial’s 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.

Trials2020       LitCov and CORD-19
4632Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody  

The newly identified 2019 novel coronavirus (2019-nCoV) has caused more than 11,900 laboratory-confirmed human infections, including 259 deaths, posing a serious threat to human health. Currently, however, there is no specific antiviral treatment or vaccine. Considering the relatively high identity of receptor-binding domain (RBD) in 2019-nCoV and SARS-CoV, it is urgent to assess the cross-reactivity of anti-SARS CoV antibodies with 2019-nCoV spike protein, which could have important implications for rapid development of vaccines and therapeutic antibodies against 2019-nCoV. Here, we report for the first time that a SARS-CoV-specific human monoclonal antibody, CR3022, could bind potently with 2019-nCoV RBD (KD of 6.3 nM). The epitope of CR3022 does not overlap with the ACE2 binding site within 2019-nCoV RBD. These results suggest that CR3022 may have the potential to be developed as candidate therapeutics, alone or in combination with other neutralizing antibodies, for the prevention and treatment of 2019-nCoV infections. Interestingly, some of the most potent SARS-CoV-specific neutralizing antibodies (e.g. m396, CR3014) that target the ACE2 binding site of SARS-CoV failed to bind 2019-nCoV spike protein, implying that the difference in the RBD of SARS-CoV and 2019-nCoV has a critical impact for the cross-reactivity of neutralizing antibodies, and that it is still necessary to develop novel monoclonal antibodies that could bind specifically to 2019-nCoV RBD.

Emerg Microbes Infect2020       LitCov and CORD-19
4633Risk Factors for Intensive Care Unit Admission and In-hospital Mortality among Hospitalized Adults Identified through the US COVID-19 Associated Hospitalization Surveillance Network (COVID-NET)  

BACKGROUND: Currently, the United States has the largest number of reported coronavirus disease 2019 (COVID-19) cases and deaths globally. Using a geographically diverse surveillance network, we describe risk factors for severe outcomes among adults hospitalized with COVID-19. METHODS: We analyzed data from 2,491 adults hospitalized with laboratory-confirmed COVID-19 during March 1–May 2, 2020 identified through the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network comprising 154 acute care hospitals in 74 counties in 13 states. We used multivariable analyses to assess associations between age, sex, race and ethnicity, and underlying conditions with intensive care unit (ICU) admission and in-hospital mortality. RESULTS: Ninety-two percent of patients had ≥1 underlying condition; 32% required ICU admission; 19% invasive mechanical ventilation; and 17% died. Independent factors associated with ICU admission included ages 50-64, 65-74, 75-84 and ≥85 years versus 18-39 years (adjusted risk ratio (aRR) 1.53, 1.65, 1.84 and 1.43, respectively); male sex (aRR 1.34); obesity (aRR 1.31); immunosuppression (aRR 1.29); and diabetes (aRR 1.13). Independent factors associated with in-hospital mortality included ages 50-64, 65-74, 75-84 and ≥85 years versus 18-39 years (aRR 3.11, 5.77, 7.67 and 10.98, respectively); male sex (aRR 1.30); immunosuppression (aRR 1.39); renal disease (aRR 1.33); chronic lung disease (aRR 1.31); cardiovascular disease (aRR 1.28); neurologic disorders (aRR 1.25); and diabetes (aRR 1.19). CONCLUSION: In-hospital mortality increased markedly with increasing age. Aggressive implementation of prevention strategies, including social distancing and rigorous hand hygiene, may benefit the population as a whole, as well as those at highest risk for COVID-19-related complications.

Clin Infect Dis2020       LitCov and CORD-19
4634Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review  

N/A

Cochrane Database Syst Rev2020       LitCov and CORD-19
4635Mother-Infant Dyads with COVID-19 at an Urban, Safety-Net Hospital: Clinical Manifestations and Birth Outcomes  

N/A

Am J Perinatol2021       LitCov and CORD-19
4636Study on the extracorporeal membrane oxygenation inter-hospital transport during COVID-19 epidemic: based on the transport experience of 6 cases of severe H1N1 influenza virus pneumonia on extracorporeal membrane oxygenation  

N/A

Zhonghua Wei Zhong Bing Ji Jiu2020       LitCov and CORD-19
4637Clinical Course and Outcomes of Patients with SARS-CoV-2 Infection: a Preliminary Report of the First 28 Patients from the Korean Cohort Study on COVID-19  

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pneumonia emerged in Wuhan, China in December 2019. In this retrospective multicenter study, we investigated the clinical course and outcomes of novel coronavirus disease 2019 (COVID-19) from early cases in Republic of Korea. METHODS: All of the cases confirmed by real time polymerase chain reaction were enrolled from the 1st to the 28th patient nationwide. Clinical data were collected and analyzed for changes in clinical severity including laboratory, radiological, and virologic dynamics during the progression of illness. RESULTS: The median age was 40 years (range, 20–73 years) and 15 (53.6%) patients were male. The most common symptoms were cough (28.6%) and sore throat (28.6%), followed by fever (25.0%). Diarrhea was not common (10.7%). Two patients had no symptoms. Initial chest X-ray (CXR) showed infiltration in 46.4% of the patients, but computed tomography scan confirmed pneumonia in 88.9% (16/18) of the patients. Six patients (21.4%) required supplemental oxygen therapy, but no one needed mechanical ventilation. Lymphopenia was more common in severe cases. Higher level of C-reactive protein and worsening of chest radiographic score was observed during the 5–7 day period after symptom onset. Viral shedding was high from day 1 of illness, especially from the upper respiratory tract (URT). CONCLUSION: The prodromal symptoms of COVID-19 were mild and most patients did not have limitations of daily activity. Viral shedding from URT was high from the prodromal phase. Radiological pneumonia was common from the early days of illness, but it was frequently not evident in simple CXR. These findings could be plausible explanations for the easy and rapid spread of SARS-CoV-2 in the community.

J Korean Med Sci2020       LitCov and CORD-19
4638Effectiveness of public health measures in reducing the incidence of covid-19, SARS-CoV-2 transmission and covid-19 mortality: systematic review and meta-analysis  

N/A

BMJ2021       LitCov and CORD-19
4639Association of COVID-19 Vaccination During Pregnancy With Incidence of SARS-CoV-2 Infection in Infants  

N/A

JAMA Intern Med2022       LitCov
4640Communicative Blame in Online Communication of the COVID-19 Pandemic: Computational Approach of Stigmatizing Cues and Negative Sentiment Gauged With Automated Analytic Techniques  

BACKGROUND: Information about a new coronavirus emerged in 2019 and rapidly spread around the world, gaining significant public attention and attracting negative bias. The use of stigmatizing language for the purpose of blaming sparked a debate. OBJECTIVE: This study aims to identify social stigma and negative sentiment toward the blameworthy agents in social communities. METHODS: We enabled a tailored text-mining platform to identify data in their natural settings by retrieving and filtering online sources, and constructed vocabularies and learning word representations from natural language processing for deductive analysis along with the research theme. The data sources comprised of ten news websites, eleven discussion forums, one social network, and two principal media sharing networks in Taiwan. A synthesis of news and social networking analytics was present from December 30, 2019, to March 31, 2020. RESULTS: We collated over 1.07 million Chinese texts. Almost two-thirds of the texts on COVID-19 came from news services (n=683,887, 63.68%), followed by Facebook (n=297,823, 27.73%), discussion forums (n=62,119, 5.78%), and Instagram and YouTube (n=30,154, 2.81%). Our data showed that online news served as a hotbed for negativity and for driving emotional social posts. Online information regarding COVID-19 associated it with China—and a specific city within China through references to the “Wuhan pneumonia”—potentially encouraging xenophobia. The adoption of this problematic moniker had a high frequency, despite the World Health Organization guideline to avoid biased perceptions and ethnic discrimination. Social stigma is disclosed through negatively valenced responses, which are associated with the most blamed targets. CONCLUSIONS: Our sample is sufficiently representative of a community because it contains a broad range of mainstream online media. Stigmatizing language linked to the COVID-19 pandemic shows a lack of civic responsibility that encourages bias, hostility, and discrimination. Frequently used stigmatizing terms were deemed offensive, and they might have contributed to recent backlashes against China by directing blame and encouraging xenophobia. The implications ranging from health risk communication to stigma mitigation and xenophobia concerns amid the COVID-19 outbreak are emphasized. Understanding the nomenclature and biased terms employed in relation to the COVID-19 outbreak is paramount. We propose solidarity with communication professionals in combating the COVID-19 outbreak and the infodemic. Finding solutions to curb the spread of virus bias, stigma, and discrimination is imperative.

J Med Internet Res2020       LitCov and CORD-19
4641Cross-Platform Comparative Study of Public Concern on Social Media during the COVID-19 Pandemic: An Empirical Study Based on Twitter and Weibo  

The COVID-19 pandemic has created a global health crisis that has affected economies and societies worldwide. During these times of uncertainty and crisis, people have turned to social media platforms as communication tools and primary information sources. Online discourse is conducted under the influence of many different factors, such as background, culture, politics, etc. However, parallel comparative research studies conducted in different countries to identify similarities and differences in online discourse are still scarce. In this study, we combine the crisis lifecycle and opinion leader concepts and use data mining and a set of predefined search terms (coronavirus and COVID-19) to investigate discourse on Twitter (101,271 tweets) and Sina Weibo (92,037 posts). Then, we use a topic modeling technique, Latent Dirichlet Allocation (LDA), to identify the most common issues posted by users and temporal analysis to research the issue’s trend. Social Network Analysis (SNA) allows us to discover the opinion leader on the two different platforms. Finally, we find that online discourse reflects the crisis lifecycle according to the stage of COVID-19 in China and the US. Regarding the status of the COVID-19 pandemic, users of Twitter tend to pay more attention to the economic situation while users of Weibo pay more attention to public health. The issues focused on in online discourse have a strong relationship with the development of the crisis in different countries. Additionally, on the Twitter platform many political actors act as opinion leaders, while on the Weibo platform official media and government accounts control the release of information.

Int J Environ Res Public Healt2021       LitCov and CORD-19
4642COVID-19 detection in CT and CXR images using deep learning models  

Infectious diseases pose a threat to human life and could affect the whole world in a very short time. Corona-2019 virus disease (COVID-19) is an example of such harmful diseases. COVID-19 is a pandemic of an emerging infectious disease, called coronavirus disease 2019 or COVID-19, caused by the coronavirus SARS-CoV-2, which first appeared in December 2019 in Wuhan, China, before spreading around the world on a very large scale. The continued rise in the number of positive COVID-19 cases has disrupted the health care system in many countries, creating a lot of stress for governing bodies around the world, hence the need for a rapid way to identify cases of this disease. Medical imaging is a widely accepted technique for early detection and diagnosis of the disease which includes different techniques such as Chest X-ray (CXR), Computed Tomography (CT) scan, etc. In this paper, we propose a methodology to investigate the potential of deep transfer learning in building a classifier to detect COVID-19 positive patients using CT scan and CXR images. Data augmentation technique is used to increase the size of the training dataset in order to solve overfitting and enhance generalization ability of the model. Our contribution consists of a comprehensive evaluation of a series of pre-trained deep neural networks: ResNet50, InceptionV3, VGGNet-19, and Xception, using data augmentation technique. The findings proved that deep learning is effective at detecting COVID-19 cases. From the results of the experiments it was found that by considering each modality separately, the VGGNet-19 model outperforms the other three models proposed by using the CT image dataset where it achieved 88.5% precision, 86% recall, 86.5% F1-score, and 87% accuracy while the refined Xception version gave the highest precision, recall, F1-score, and accuracy values which equal 98% using CXR images dataset. On the other hand, and by applying the average of the two modalities X-ray and CT, VGG-19 presents the best score which is 90.5% for the accuracy and the F1-score, 90.3% for the recall while the precision is 91.5%. These results enables to automatize the process of analyzing chest CT scans and X-ray images with high accuracy and can be used in cases where RT-PCR testing and materials are limited.

Biogerontology2022       LitCov and CORD-19
4643Using Reports of Symptoms and Diagnoses on Social Media to Predict COVID-19 Case Counts in Mainland China: Observational Infoveillance Study  

BACKGROUND: Coronavirus disease (COVID-19) has affected more than 200 countries and territories worldwide. This disease poses an extraordinary challenge for public health systems because screening and surveillance capacity is often severely limited, especially during the beginning of the outbreak; this can fuel the outbreak, as many patients can unknowingly infect other people. OBJECTIVE: The aim of this study was to collect and analyze posts related to COVID-19 on Weibo, a popular Twitter-like social media site in China. To our knowledge, this infoveillance study employs the largest, most comprehensive, and most fine-grained social media data to date to predict COVID-19 case counts in mainland China. METHODS: We built a Weibo user pool of 250 million people, approximately half the entire monthly active Weibo user population. Using a comprehensive list of 167 keywords, we retrieved and analyzed around 15 million COVID-19–related posts from our user pool from November 1, 2019 to March 31, 2020. We developed a machine learning classifier to identify “sick posts,” in which users report their own or other people’s symptoms and diagnoses related to COVID-19. Using officially reported case counts as the outcome, we then estimated the Granger causality of sick posts and other COVID-19 posts on daily case counts. For a subset of geotagged posts (3.10% of all retrieved posts), we also ran separate predictive models for Hubei province, the epicenter of the initial outbreak, and the rest of mainland China. RESULTS: We found that reports of symptoms and diagnosis of COVID-19 significantly predicted daily case counts up to 14 days ahead of official statistics, whereas other COVID-19 posts did not have similar predictive power. For the subset of geotagged posts, we found that the predictive pattern held true for both Hubei province and the rest of mainland China regardless of the unequal distribution of health care resources and the outbreak timeline. CONCLUSIONS: Public social media data can be usefully harnessed to predict infection cases and inform timely responses. Researchers and disease control agencies should pay close attention to the social media infosphere regarding COVID-19. In addition to monitoring overall search and posting activities, leveraging machine learning approaches and theoretical understanding of information sharing behaviors is a promising approach to identify true disease signals and improve the effectiveness of infoveillance.

J Med Internet Res2020       LitCov and CORD-19
4644Antibody response to the inactivated SARS-CoV-2 vaccine among healthcare workers, Indonesia  

Background As healthcare workers (HCWs) are at high risk for SARS-CoV-2 infection, they have prioritized the COVID-19 vaccine. Inactivated SARS-CoV-2 vaccine has been mainly used in Indonesia to induce HCWs antibody response against SARS-CoV-2 infection. However, information regarding the kinetics of antibody-induced by this vaccine remains scarce. Objective To investigate the magnitude and durability of antibodies against spike (S) protein (anti-S) after complete dose of vaccination among HCWs by using the electrochemiluminescence immunoassay. Results Seroconversion of anti-S antibodies was observed among 159 (99.4%) of 160 HCWs after 14 days of full-dose vaccination. The levels of anti-S antibodies significantly decreased after day 42 compared to day 14 post-vaccination, but it persisted up to 98 days following vaccination. In contrast, the vaccinated HCWs with prior SARS-CoV-2 infection had significantly higher and stably elevated anti-S antibodies concentrations than vaccinated HCWs without SARS-CoV-2 infection history. Conclusion The remarkable decline and lower anti-S antibodies concentration among infection-naïve HCWs potentially indicate the additional booster dose of SARS-CoV-2 vaccination may be required to ascertain COVID-19 protection among HCWs by this vaccine. This early study of antibody response induced by inactivated SARS-CoV-2 vaccine among HCWs potentially contributes to the future policy decision regarding vaccination.

Int J Infect Dis2021       LitCov and CORD-19
4645Ongoing Mycophenolate Treatment Impairs Anti-SARS-CoV-2 Vaccination Response in Patients Affected by Chronic Inflammatory Autoimmune Diseases or Liver Transplantation Recipients: Results of the RIVALSA Prospective Cohort  

N/A

Viruses2022       LitCov
4646Perceived infection transmission routes, infection control practices, psychosocial changes and management of COVID-19 infected healthcare workers in a tertiary acute care hospital in Wuhan: a cross-sectional survey  

BACKGROUND: Many healthcare workers were infected by coronavirus disease 2019 (COVID-19) early in the epidemic posing a big challenge for epidemic control. Hence, this study aims to explore perceived infection routes, influencing factors, psychosocial changes, and management procedures for COVID-19 infected healthcare workers. METHODS: This is a cross-sectional, single hospital-based study. We recruited all 105 confirmed COVID-19 healthcare workers in the Zhongnan Hospital of Wuhan University from February 15 to 29, 2020. All participants completed a validated questionnaire. Electronic consent was obtained from all participants. Perceived causes of infection, infection prevention, control knowledge and behaviour, psychological changes, symptoms and treatment were measured. RESULTS: Finally, 103 professional staff with COVID-19 finished the questionnaire and was included (response rate: 98.1%). Of them, 87 cases (84.5%) thought they were infected in working environment in hospital, one (1.0%) thought their infection was due to the laboratory environment, and 5 (4.9%) thought they were infected in daily life or community environment. Swab of throat collection and physical examination were the procedures perceived as most likely causing their infection by nurses and doctors respectively. Forty-three (41.8%) thought their infection was related to protective equipment, utilization of common equipment (masks and gloves). The top three first symptoms displayed before diagnosis were fever (41.8%), lethargy (33.0%) and muscle aches (30.1%). After diagnosis, 88.3% staff experienced psychological stress or emotional changes during their isolation period, only 11.7% had almost no emotional changes. Arbidol (Umifenovir; an anti-influza drug; 69.2%) was the drug most commonly used to target infection in mild and moderate symptoms. CONCLUSION: The main perceived mode of transmission was not maintaining protection when working at a close distance and having intimate contact with infected cases. Positive psychological intervention is necessary.

Mil Med Res2020       LitCov and CORD-19
4647Genetic grouping of SARS-CoV-2 coronavirus sequences using informative subtype markers for pandemic spread visualization  

We propose an efficient framework for genetic subtyping of SARS-CoV-2, the novel coronavirus that causes the COVID-19 pandemic. Efficient viral subtyping enables visualization and modeling of the geographic distribution and temporal dynamics of disease spread. Subtyping thereby advances the development of effective containment strategies and, potentially, therapeutic and vaccine strategies. However, identifying viral subtypes in real-time is challenging: SARS-CoV-2 is a novel virus, and the pandemic is rapidly expanding. Viral subtypes may be difficult to detect due to rapid evolution; founder effects are more significant than selection pressure; and the clustering threshold for subtyping is not standardized. We propose to identify mutational signatures of available SARS-CoV-2 sequences using a population-based approach: an entropy measure followed by frequency analysis. These signatures, Informative Subtype Markers (ISMs), define a compact set of nucleotide sites that characterize the most variable (and thus most informative) positions in the viral genomes sequenced from different individuals. Through ISM compression, we find that certain distant nucleotide variants covary, including non-coding and ORF1ab sites covarying with the D614G spike protein mutation which has become increasingly prevalent as the pandemic has spread. ISMs are also useful for downstream analyses, such as spatiotemporal visualization of viral dynamics. By analyzing sequence data available in the GISAID database, we validate the utility of ISM-based subtyping by comparing spatiotemporal analyses using ISMs to epidemiological studies of viral transmission in Asia, Europe, and the United States. In addition, we show the relationship of ISMs to phylogenetic reconstructions of SARS-CoV-2 evolution, and therefore, ISMs can play an important complementary role to phylogenetic tree-based analysis, such as is done in the Nextstrain project. The developed pipeline dynamically generates ISMs for newly added SARS-CoV-2 sequences and updates the visualization of pandemic spatiotemporal dynamics, and is available on Github at https://github.com/EESI/ISM (Jupyter notebook), https://github.com/EESI/ncov_ism (command line tool) and via an interactive website at https://covid19-ism.coe.drexel.edu/.

PLoS Comput Biol2020       LitCov and CORD-19
4648Preventive behaviours and family inequalities during the COVID-19 pandemic: a cross-sectional study in China  

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is an international public health threat, and people's participation in disease-related preventive behaviours is the key to controlling infectious diseases. This study aimed to assess the differences in adopting preventive behaviours among populations to explore potential individual and household factors and inequalities within families. METHODS: This online survey was conducted in April 2020. The directional stratified convenient sampling method was used to select 4704 participants from eight provinces in eastern, central, and western China. The questionnaire included demographic information, household variables, and five target prevention behaviours. The chi-squared test, binary multilevel model, and Mantel–Haenszel hierarchical analysis were used for data analysis in the study. RESULTS: Approximately 71.2% of the participants had appropriate outdoor prevention, and 32.9% of the participants had indoor protection in place. Sharing behaviours (P < 0.001) and education level (P < 0.001) were positively associated with adopting preventive measures. The inhibiting effect of household crowding and stimulating effect of high household income on preventive behaviours were determined in this study. Household size was negatively associated with living area (β = -0.057, P < 0.05) and living style (β = -0.077, P < 0.05). Household income was positively associated with age (β = 0.023, P < 0.05), and relationship with friends (β = 0.053, P < 0.05). Vulnerable groups, such as older adults or women, are more likely to have inadequate preventive behaviours. Older adults (OR = 1.53, 95% CI 1.09–2.15), women (OR = 1.37, 95% CI 1.15–1.64), and those with more than 2 suspected symptoms (OR = 1.85, 95% CI 1.07–3.19) were more likely to be affected by the inhibiting effect of household crowding, while the stimulating effect of high household income was limited in these groups. CONCLUSIONS: Inequalities in COVID-19 prevention behaviours exist between families and inadequate adoption of prevention by vulnerable groups are noteworthy. This study expands the research perspective by emphasizing the role of household factors in preventive behaviours and by focusing on family inequalities. The government should use traditional media as a platform to enhance residents’ public health knowledge. Targeted additional wage subsidies, investments in affordable housing, financial support for multigenerational households, and temporary relocation policies may deserve more attention. Communities could play a critical role in COVID-19 prevention. GRAPHICAL ABSTRACT: [Image: see text]

Infect Dis Poverty2021       LitCov and CORD-19
4649The impact of the COVID-19 pandemic on emergency department visits and patient safety in the United States  

BACKGROUND: COVID-19 pandemic effects are still being elucidated. Stay-at-home orders and social distancing compounded with COVID-19 concerns have caused significant disruptions in daily life. One notable effect of these variables may be a change in the number of emergency department (ED) visits. This study aims to investigate the effects of COVID-19 on ED visits, and possible reasons for changes. METHODS: Retrospective analysis using CDC data for ED visits and percentage of visits for COVID-19-Like Illness (CLI) and Influenza-Like Illness (ILI). Google Trends was used to assess COVID-19 public awareness. Motor vehicle collision (MVC) data was collected from cities, which reported current data. A descriptive statistical analysis and two-sample t-test was performed on ED visit data to assess for significance and a descriptive analysis was conducted to assess COVID-19's impact on MVCs. RESULTS: The mean number of ED visits per week for the last four weeks of available data during the pandemic was significantly less than the four weeks prior to COVID-19 pandemic (p = 0.008). The ED visit decrease per week varied by region, with Region 1 having the greatest decrease (45%). MVCs decreased substantially across all cities studied, with New York City and Baton Rouge experiencing the greatest decrease (66%) during the pandemic. CONCLUSION: A number of factors have likely contributed to the substantial decrease in ED visits observed in this study. In light of these findings, it is important to raise patient awareness regarding acute conditions that are deadlier than COVID-19 and require immediate medical intervention to ensure recovery.

Am J Emerg Med2020       LitCov and CORD-19
4650Personal Safety during the COVID-19 Pandemic: Realities and Perspectives of Healthcare Workers in Latin America  

Healthcare workers exposed to coronavirus (COVID-19) may not have adequate access to personal protective equipment (PPE), safety procedures, and diagnostic protocols. Our objective was to evaluate the reality and perceptions about personal safety among healthcare workers in Latin America. This is a cross-sectional, online survey-based study administered to 936 healthcare professionals in Latin America from 31 March 2020 to 4 April 2020. A 12-item structured questionnaire was developed. A total of 936 healthcare workers completed the online survey. Of them, 899 (95.1%) were physicians, 28 (2.9%) were nurses, and 18 (1.9%) were allied health professionals. Access to protective equipment was as follows: gel hand sanitizer (n = 889; 95%), disposable gloves (n = 853; 91.1%), disposable gowns (n = 630; 67.3%), disposable surgical masks (785; 83.9%), N95 masks (n = 516; 56.1%), and facial protective shields (n = 305; 32.6%). The vast majority (n = 707; 75.5%) had access to personal safety policies and procedures, and 699 (74.7%) participants had access to diagnostic algorithms. On a 1-to-10 Likert scale, the participants expressed limited human resources support (4.92 ± 0.2; mean ± SD), physical integrity protection in the workplace (5.5 ± 0.1; mean ± SD), and support from public health authorities (5.01 ± 0.12; mean ± SD). Healthcare workers in Latin America had limited access to essential PPE and support from healthcare authorities during the COVID-19 pandemic.

Int J Environ Res Public Healt2020       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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