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)
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| Title | Venue | Year | Impact | Source | |
|---|---|---|---|---|---|
| 1551 | Safety and Immunogenicity Analysis of a Newcastle Disease Virus (NDV-HXP-S) Expressing the Spike Protein of SARS-CoV-2 in Sprague Dawley Rats Despite global vaccination efforts, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve and spread globally. Relatively high vaccination rates have been achieved in most regions of the United States and several countries worldwide. However, access to vaccines in low- and mid-income countries (LMICs) is still suboptimal. Second generation vaccines that are universally affordable and induce systemic and mucosal immunity are needed. Here we performed an extended safety and immunogenicity analysis of a second-generation SARS-CoV-2 vaccine consisting of a live Newcastle disease virus vector expressing a pre-fusion stabilized version of the spike protein (NDV-HXP-S) administered intranasally (IN), intramuscularly (IM), or IN followed by IM in Sprague Dawley rats. Local reactogenicity, systemic toxicity, and post-mortem histopathology were assessed after the vaccine administration, with no indication of severe local or systemic reactions. Immunogenicity studies showed that the three vaccination regimens tested elicited high antibody titers against the wild type SARS-CoV-2 spike protein and the NDV vector. Moreover, high antibody titers were induced against the spike of B.1.1.7 (alpha), B.1.351 (beta) and B.1.617.2 (delta) variants of concern (VOCs). Importantly, robust levels of serum antibodies with neutralizing activity against the authentic SARS-CoV-2 USA‐WA1/2020 isolate were detected after the boost. Overall, our study expands the pre-clinical safety and immunogenicity characterization of NDV-HXP-S and reinforces previous findings in other animal models about its high immunogenicity. Clinical testing of this vaccination approach is ongoing in different countries including Thailand, Vietnam, Brazil and Mexico. | Front Immunol | 2021 | LitCov and CORD-19 | |
| 1552 | Cyclosporine A Inhibits Viral Infection and Release as Well as Cytokine Production in Lung Cells by Three SARS-CoV-2 Variants In December 2019, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started spreading worldwide causing the coronavirus disease 2019 (COVID-19) pandemic. The hyperactivation of the immune system has been proposed to account for disease severity and death in COVID-19 patients. Despite several approaches having been tested, no therapeutic protocol has been approved. Given that Cyclosporine A (CsA) is well-known to exert a strong antiviral activity on several viral strains and an anti-inflammatory role in different organs with relevant benefits in diverse pathological contexts, we tested its effects on SARS-CoV-2 infection of lung cells. We found that treatment with CsA either before or after infection of CaLu3 cells by three SARS-CoV-2 variants: (i) reduces the expression of both viral RNA and proteins in infected cells; (ii) decreases the number of progeny virions released by infected cells; (iii) dampens the virus-triggered synthesis of cytokines (including IL-6, IL-8, IL1α and TNF-α) that are involved in cytokine storm in patients. Altogether, these data provide a rationale for CsA repositioning for the treatment of severe COVID-19 patients. IMPORTANCE SARS-CoV-2 is the most recently identified member of the betacoronavirus genus responsible for the COVID-19 pandemic. Repurposing of available drugs has been a “quick and dirty” approach to try to reduce mortality and severe symptoms in affected patients initially, and can still represent an undeniable and valuable approach to face COVID-19 as the continuous appearance and rapid diffusion of more “aggressive”/transmissible variants, capable of eluding antibody neutralization, challenges the effectiveness of some anti-SARS-CoV-2 vaccines. Here, we tested a known antiviral and anti-inflammatory drug, Cyclosporine A (CsA), and found that it dampens viral infection and cytokine release from lung cells upon exposure to three different SARS-CoV-2 variants. Knock down of the main intracellular target of CsA, Cyclophilin A, does not phenocopy the drug inhibition of viral infection. Altogether, these findings shed new light on the cellular mechanisms of SARS-CoV-2 infection and provide the rationale for CsA repositioning to treat severe COVID-19 patients. | Microbiol Spectr | 2022 | LitCov and CORD-19 | |
| 1553 | Outbreak of pneumonia of unknown etiology in Wuhan, China: The mystery and the miracle Since December 2019, a total of 41 cases of pneumonia of unknown etiology have been confirmed in Wuhan city, Hubei Province, China. Wuhan city is a major transportation hub with a population of more than 11 million people. Most of the patients visited a local fish and wild animal market last month. At a national press conference held today, Dr. Jianguo Xu, an academician of the Chinese Academy of Engineering, who led a scientific team announced that a new-type coronavirus, tentatively named by World Health Organization as the 2019-new coronavirus (2019-nCoV), had caused this outbreak (1). | J Med Virol | 2020 | LitCov and CORD-19 | |
| 1554 | Associations of BNT162b2 vaccination with SARS-CoV-2 infection and hospital admission and death with covid-19 in nursing homes and healthcare workers in Catalonia: prospective cohort study OBJECTIVE: To determine associations of BNT162b2 vaccination with SARS-CoV-2 infection and hospital admission and death with covid-19 among nursing home residents, nursing home staff, and healthcare workers. DESIGN: Prospective cohort study. SETTING: Nursing homes and linked electronic medical record, test, and mortality data in Catalonia on 27 December 2020. PARTICIPANTS: 28 456 nursing home residents, 26 170 nursing home staff, and 61 791 healthcare workers. MAIN OUTCOME MEASURES: Participants were followed until the earliest outcome (confirmed SARS-CoV-2 infection, hospital admission or death with covid-19) or 26 May 2021. Vaccination status was introduced as a time varying exposure, with a 14 day run-in after the first dose. Mixed effects Cox models were fitted to estimate hazard ratios with index month as a fixed effect and adjusted for confounders including sociodemographics, comorbidity, and previous medicine use. RESULTS: Among the nursing home residents, SARS-CoV-2 infection was found in 2482, 411 were admitted to hospital with covid-19, and 450 died with covid-19 during the study period. In parallel, 1828 nursing home staff and 2968 healthcare workers were found to have SARS-CoV-2 infection, but fewer than five were admitted or died with covid-19. The adjusted hazard ratio for SARS-CoV-2 infection after two doses of vaccine was 0.09 (95% confidence interval 0.08 to 0.11) for nursing home residents, 0.20 (0.17 to 0.24) for nursing home staff, and 0.13 (0.11 to 0.16) for healthcare workers. Adjusted hazard ratios for hospital admission and mortality after two doses of vaccine were 0.05 (0.04 to 0.07) and 0.03 (0.02 to 0.04), respectively, for nursing home residents. Nursing home staff and healthcare workers recorded insufficient events for mortality analysis. CONCLUSIONS: Vaccination was associated with 80-91% reduction in SARS-CoV-2 infection in all three cohorts and greater reductions in hospital admissions and mortality among nursing home residents for up to five months. More data are needed on longer term effects of covid-19 vaccines. | BMJ | 2021 | LitCov and CORD-19 | |
| 1555 | The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health-The latest 2019 novel coronavirus outbreak in Wuhan, China | Int J Infect Dis | 2020 | LitCov and CORD-19 | |
| 1556 | Update on SARS-CoV-2 infection in children N/A | Paediatr Int Child Health | 2021 | LitCov and CORD-19 | |
| 1557 | Neutralizing antibodies against the SARS-CoV-2 Omicron variant BA.1 following homologous and heterologous CoronaVac or BNT162b2 vaccination N/A | Nat Med | 2022 | LitCov and CORD-19 | |
| 1558 | Anxiety, depression and health anxiety in undergraduate students living in initial US outbreak "hotspot" during COVID-19 pandemic N/A | Cogn Behav Ther | 2021 | LitCov and CORD-19 | |
| 1559 | Alveolar macrophage dysfunction and cytokine storm in the pathogenesis of two severe COVID-19 patients BACKGROUND: The novel coronavirus pneumonia COVID-19 caused by SARS-CoV-2 infection could lead to a serious of clinical symptoms and severe illness, including acute respiratory distress syndrome (ARDS) and fatal organ failure. We report the fundamental pathological investigation in the lungs and other organs of fatal cases for the mechanistic understanding of severe COVID-19 and the development of specific therapy in these cases. METHODS: The autopsy and pathological investigations of specimens were performed on bodies of two deceased cases with COVID-19. Gross anatomy and histological investigation by Hematoxylin and eosin (HE) stained were reviewed on each patient. Alcian blue/periodic acid-Schiff (AB-PAS) staining and Masson staining were performed for the examinations of mucus, fibrin and collagen fiber in lung tissues. Immunohistochemical staining were performed on the slides of lung tissues from two patients. Real-time PCR was performed to detect the infection of SARS-CoV-2. Flow cytometry analyses were performed to detect the direct binding of S protein and the expression of ACE2 on the cell surface of macrophages. FINDINGS: The main pathological features in lungs included extensive impairment of type I alveolar epithelial cells and atypical hyperplasia of type II alveolar cells, with formation of hyaline membrane, focal hemorrhage, exudation and pulmonary edema, and pulmonary consolidation. The mucous plug with fibrinous exudate in the alveoli and the dysfunction of alveolar macrophages were characteristic abnormalities. The type II alveolar epithelial cells and macrophages in alveoli and pulmonary hilum lymphoid tissue were infected by SARS-CoV-2. S protein of SARS-CoV-2 directly bound to the macrophage via the S-protein-ACE2 interaction. INTERPRETATION: Infection of Alveolar macrophage by SARS-CoV-2 might be drivers of the “cytokine storm”, which might result in damages in pulmonary tissues, heart and lung, and leading to the failure of multiple organs . FUNDING: Shanghai Guangci Translational Medical Research Development Foundation, Shanghai, China | EBioMedicine | 2020 | LitCov and CORD-19 | |
| 1560 | An outbreak of severe Kawasaki-like disease at the Italian epicenter of the SARS-CoV-2 epidemic: an observational cohort study BACKGROUND: The Bergamo province, which is extensively affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic, is a natural observatory of virus manifestations in the general population. In the past month we recorded an outbreak of Kawasaki disease; we aimed to evaluate incidence and features of patients with Kawasaki-like disease diagnosed during the SARS-CoV-2 epidemic. METHODS: All patients diagnosed with a Kawasaki-like disease at our centre in the past 5 years were divided according to symptomatic presentation before (group 1) or after (group 2) the beginning of the SARS-CoV-2 epidemic. Kawasaki- like presentations were managed as Kawasaki disease according to the American Heart Association indications. Kawasaki disease shock syndrome (KDSS) was defined by presence of circulatory dysfunction, and macrophage activation syndrome (MAS) by the Paediatric Rheumatology International Trials Organisation criteria. Current or previous infection was sought by reverse-transcriptase quantitative PCR in nasopharyngeal and oropharyngeal swabs, and by serological qualitative test detecting SARS-CoV-2 IgM and IgG, respectively. FINDINGS: Group 1 comprised 19 patients (seven boys, 12 girls; aged 3·0 years [SD 2·5]) diagnosed between Jan 1, 2015, and Feb 17, 2020. Group 2 included ten patients (seven boys, three girls; aged 7·5 years [SD 3·5]) diagnosed between Feb 18 and April 20, 2020; eight of ten were positive for IgG or IgM, or both. The two groups differed in disease incidence (group 1 vs group 2, 0·3 vs ten per month), mean age (3·0 vs 7·5 years), cardiac involvement (two of 19 vs six of ten), KDSS (zero of 19 vs five of ten), MAS (zero of 19 vs five of ten), and need for adjunctive steroid treatment (three of 19 vs eight of ten; all p<0·01). INTERPRETATION: In the past month we found a 30-fold increased incidence of Kawasaki-like disease. Children diagnosed after the SARS-CoV-2 epidemic began showed evidence of immune response to the virus, were older, had a higher rate of cardiac involvement, and features of MAS. The SARS-CoV-2 epidemic was associated with high incidence of a severe form of Kawasaki disease. A similar outbreak of Kawasaki-like disease is expected in countries involved in the SARS-CoV-2 epidemic. FUNDING: None. | Lancet | 2020 | LitCov and CORD-19 | |
| 1561 | pediatric hospitalisations due to COVID-19 during the first SARS-CoV-2 omicron (B.1.1.529) variant wave in South Africa: a multicenter observational study BACKGROUND: South Africa reported a notable increase in COVID-19 cases from mid-November, 2021, onwards, starting in Tshwane District, which coincided with the rapid community spread of the SARS-CoV-2 omicron (B.1.1.529) variant. This increased infection rate coincided with a rapid increase in paediatric COVID-19-associated admissions to hospital (hereafter referred to as hospitalisations). METHODS: The Tshwane Maternal-Child COVID-19 study is a multicentre observational study in which we investigated the clinical manifestations and outcomes of paediatric patients (aged ≤19 years) who had tested positive for SARS-CoV-2 and were admitted to hospital for any reason in Tshwane District during a 6-week period at the beginning of the fourth wave of the COVID-19 epidemic in South Africa. We used five data sources, which were: (1) COVID-19 line lists; (2) collated SARS-CoV-2 testing data; (3) SARS-CoV-2 genomic sequencing data; (4) COVID-19 hospitalisation surveillance; and (5) clinical data of public sector COVID-19-associated hospitalisations among children aged 13 years and younger. FINDINGS: Between Oct 31 and Dec 11, 2021, 6287 children and adolescents in Tshwane District were recorded as having COVID-19. During this period, 2550 people with COVID-19 were hospitalised, of whom 462 (18%) were aged 19 years or younger. The number of paediatric cases was higher than in the three previous SARS-CoV-2 waves, uncharacteristically increasing ahead of adult hospitalisations. 75 viral samples from adults and children in the district were sequenced, of which 74 (99%) were of the omicron variant. Detailed clinical notes were available for 138 (75%) of 183 children aged ≤13 years with COVID-19 who were hospitalised. 87 (63%) of 138 children were aged 0–4 years. In 61 (44%) of 138 cases COVID-19 was the primary diagnosis, among whom symptoms included fever (37 [61%] of 61), cough (35 [57%]), shortness of breath (19 [31%]), seizures (19 [31%]), vomiting (16 [26%]), and diarrhoea (15 [25%]). Median length of hospital stay was 2 days [IQR 1–3]). 122 (88%) of 138 children with available data needed standard ward care and 27 (20%) needed oxygen therapy. Seven (5%) of 138 children were ventilated and four (3%) died during the study period, all related to complex underlying copathologies. All children and 77 (92%) of 84 parents or guardians with available data were unvaccinated to COVID-19. INTERPRETATION: Rapid increases in paediatric COVID-19 cases and hospitalisations mirror high community transmission of the SARS-CoV-2 omicron variant in Tshwane District, South Africa. Continued monitoring is needed to understand the long-term effect of the omicron variant on children and adolescents. FUNDING: South African Medical Research Council, South African Department of Science & Innovation, G7 Global Health Fund. | Lancet Child Adolesc Health | 2022 | LitCov and CORD-19 | |
| 1562 | Modeling SARS-CoV-2 spike/ACE2 protein-protein interactions for predicting the binding affinity of new spike variants for ACE2 and novel ACE2 structurally related human protein targets, for COVID-19 handling in the 3PM context AIMS: The rapid spread of new SARS-CoV-2 variants has highlighted the crucial role played in the infection by mutations occurring at the SARS-CoV-2 spike receptor binding domain (RBD) in the interactions with the human ACE2 receptor. In this context, it urgently needs to develop new rapid tools for quickly predicting the affinity of ACE2 for the SARS-CoV-2 spike RBD protein variants to be used with the ongoing SARS-CoV-2 genomic sequencing activities in the clinics, aiming to gain clues about the transmissibility and virulence of new variants, to prevent new outbreaks and to quickly estimate the severity of the disease in the context of the 3PM. METHODS: In our study, we used a computational pipeline for calculating the interaction energies at the SARS-CoV-2 spike RBD/ACE2 protein–protein interface for a selected group of characterized infectious variants of concern/interest (VoC/VoI). By using our pipeline, we built 3D comparative models of the SARS-CoV-2 spike RBD/ACE2 protein complexes for the VoC B.1.1.7-United Kingdom (carrying the mutations of concern/interest N501Y, S494P, E484K at the RBD), P.1-Japan/Brazil (RBD mutations: K417T, E484K, N501Y), B.1.351-South Africa (RBD mutations: K417N, E484K, N501Y), B.1.427/B.1.429-California (RBD mutations: L452R), the B.1.141 (RBD mutations: N439K), and the recent B.1.617.1-India (RBD mutations: L452R; E484Q) and the B.1.620 (RBD mutations: S477N; E484K). Then, we used the obtained 3D comparative models of the SARS-CoV-2 spike RBD/ACE2 protein complexes for predicting the interaction energies at the protein–protein interface. RESULTS: Along SARS-CoV-2 mutation database screening and mutation localization analysis, it was ascertained that the most dangerous mutations at VoC/VoI spike proteins are located mainly at three regions of the SARS-CoV-2 spike “boat-shaped” receptor binding motif, on the RBD domain. Notably, the P.1 Japan/Brazil variant present three mutations, K417T, E484K, N501Y, located along the entire receptor binding motif, which apparently determines the highest interaction energy at the SARS-CoV-2 spike RBD/ACE2 protein–protein interface, among those calculated. Conversely, it was also observed that the replacement of a single acidic/hydrophilic residue with a basic residue (E484K or N439K) at the “stern” or “bow” regions, of the boat-shaped receptor binding motif on the RBD, appears to determine an interaction energy with ACE2 receptor higher than that observed with single mutations occurring at the “hull” region or with other multiple mutants. In addition, our pipeline allowed searching for ACE2 structurally related proteins, i.e., THOP1 and NLN, which deserve to be investigated for their possible involvement in interactions with the SARS-CoV-2 spike protein, in those tissues showing a low expression of ACE2, or as a novel receptor for future spike variants. A freely available web-tool for the in silico calculation of the interaction energy at the SARS-CoV-2 spike RBD/ACE2 protein–protein interface, starting from the sequences of the investigated spike and/or ACE2 variants, was made available for the scientific community at: https://www.mitoairm.it/covid19affinities. CONCLUSION: In the context of the PPPM/3PM, the employment of the described pipeline through the provided webservice, together with the ongoing SARS-CoV-2 genomic sequencing, would help to predict the transmissibility of new variants sequenced from future patients, depending on SARS-CoV-2 genomic sequencing activities and on the specific amino acid replacement and/or on its location on the SARS-CoV-2 spike RBD, to put in play all the possible counteractions for preventing the most deleterious scenarios of new outbreaks, taking into consideration that a greater transmissibility has not to be necessarily related to a more severe manifestation of the disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-021-00267-w. | EPMA J | 2022 | LitCov and CORD-19 | |
| 1563 | Interplay of Antibody and Cytokine Production Reveals CXCL13 as a Potential Novel Biomarker of Lethal SARS-CoV-2 Infection The SARS-CoV-2 pandemic is impacting the global population. This study was designed to assess the interplay of antibodies with the cytokine response in SARS-CoV-2 patients. We demonstrate that significant levels of anti-SARS-CoV-2 antibody to receptor binding domain (RBD), nucleocapsid, and spike S1 subunit of SARS-CoV-2 develop over the first 10 to 20 days of infection. The majority of patients produced antibodies against all three antigens (219/255 SARS-CoV-2(+) patient specimens, 86%), suggesting a broad response to viral proteins. Antibody levels to SARS-CoV-2 antigens were different based on patient mortality, sex, blood type, and age. Analyses of these findings may help explain variation in immunity between these populations. To better understand the systemic immune response, we analyzed the levels of 20 cytokines by SARS-CoV-2 patients throughout infection. Cytokine analysis of SARS-CoV-2(+) patients exhibited increases in proinflammatory markers (interleukin 6 [IL-6], IL-8, IL-18, and gamma interferon [IFN-γ]) and chemotactic markers (IP-10 and eotaxin) relative to healthy individuals. Patients who succumbed to infection produced decreased IL-2, IL-4, IL-12, RANTES, tumor necrosis factor alpha (TNF-α), GRO-α, and MIP-1α relative to patients who survived infection. We also observed that the chemokine CXCL13 was particularly elevated in patients who succumbed to infection. CXCL13 is involved in B cell activation, germinal center development, and antibody maturation, and we observed that CXCL13 levels in blood trended with anti-SARS-CoV-2 antibody levels. Furthermore, patients who succumbed to infection produced high CXCL13 and had a higher ratio of nucleocapsid to RBD antibodies. This study provides insights into SARS-CoV-2 immunity implicating the magnitude and specificity of response in relation to patient outcomes. IMPORTANCE The SARS-CoV-2 pandemic is continuing to impact the global population, and knowledge of the immune response to COVID-19 is still developing. This study assesses the interplay of different parts of the immune system during COVID-19 disease. We demonstrate that COVID-19 patients produce antibodies to three proteins of the COVID-19 virus (SARS-CoV-2) and identify many other immunological proteins that are involved during infection. The data suggest that one of these proteins (CXCL13) may be a novel biomarker for severe COVID-19 that can be readily measured in blood. This information combined with our broad-scale analysis of immune activity during COVID-19 provides new information on the immunological response throughout the course of disease and identifies a novel potential marker for assessing disease severity. | mSphere | 2021 | LitCov and CORD-19 | |
| 1564 | A rapid review of evidence on the determinants of and strategies for COVID-19 vaccine acceptance in low- and middle-income countries BACKGROUND: Vaccine acceptance and hesitancy among the general population and health care workers play an important role in successfully controlling the Coronavirus Disease (COVID)-19 pandemic. While there is evidence for vaccine hesitancy across the globe, wide variation in factors influencing vaccine acceptance has been reported, mainly from High-Income Countries (HIC). However, the evidence from Low- and Middle-Income Countries (LMICs) remains unclear. The objective of this review was to describe the determinants of vaccine acceptance and strategies to address those in an LMIC context. METHODS: The World Health Organization’s (WHO) Measuring Behavioral and Social Drivers of Vaccination (BeSD) Increasing Vaccination Model was employed to identify factors that influenced vaccine acceptance. All evidence related to supply-side and demand-side determinants and social and health system processes were examined. A comprehensive search for published literature was conducted in three databases and grey literature in relevant websites of government, multinational agencies, and COVID-19 resource aggregators, followed by a narrative synthesis. RESULTS: Overall, the results showed that the vaccine acceptance rates differed across LMICs, with a wide variety of reasons cited for vaccine hesitancy. Vaccine acceptance was reportedly greater among males, those with higher education, elevated socio-economic status, the unmarried, those employed as health care workers. Evidence suggested that exposure to misinformation about COVID-19 vaccines and public concerns over the safety of vaccines may contribute to lower acceptance rates. Strategies to increase vaccine acceptance rates included direct engagement with communities through influencers, including community leaders and health experts; clear and transparent communication about COVID-19 vaccines, financial and non-financial incentives; and strong endorsement from health care workers. Trust in government was identified as a significant enabler of vaccine acceptance. CONCLUSIONS: There is a need for measures to address public acceptability, trust and concern over the safety and benefit of approved vaccines. Local context is essential to consider while developing programs to promote vaccine uptake. The governments worldwide also need to strategize to develop plans to address the anxiety and vaccine related concerns of community regarding vaccine hesitancy. There is a need for further research to evaluate strategies to address vaccine hesitancy in LMIC. | J Glob Health | 2021 | LitCov and CORD-19 | |
| 1565 | How will country-based mitigation measures influence the course of the COVID-19 epidemic? | Lancet | 2020 | LitCov and CORD-19 | |
| 1566 | Safety and immunogenicity of a recombinant tandem-repeat dimeric RBD-based protein subunit vaccine (ZF2001) against COVID-19 in adults: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials BACKGROUND: Although several COVID-19 vaccines have been developed so far, they will not be sufficient to meet the global demand. Development of a wider range of vaccines, with different mechanisms of action, could help control the spread of SARS-CoV-2 globally. We developed a protein subunit vaccine against COVID-19 using a dimeric form of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein as the antigen. We aimed to assess the safety and immunogenicity of this vaccine, ZF2001, and determine the appropriate dose and schedule for an efficacy study. METHODS: We did two randomised, double-blind, placebo-controlled, phase 1 and phase 2 trials. Phase 1 was done at two university hospitals in Chongqing and Beijing, China, and phase 2 was done at the Hunan Provincial Center for Disease Control and Prevention in Xiangtan, China. Healthy adults aged 18–59 years, without a history of SARS-CoV or SARS-CoV-2 infection, an RT-PCR-positive test result for SARS-CoV-2, a history of contact with confirmed or suspected COVID-19 cases, and severe allergies to any component of the vaccine were eligible for enrolment. In phase 1, participants were randomly assigned (2:2:1) to receive three doses of the vaccine (25 μg or 50 μg) or placebo intramuscularly, 30 days apart. In phase 2, participants were randomly assigned (1:1:1:1:1:1) to receive the vaccine (25 μg or 50 μg) or placebo intramuscularly, 30 days apart, in either a two-dose schedule or a three-dose schedule. Investigators, participants, and the laboratory team were masked to group allocation. For phase 1, the primary outcome was safety, measured by the occurrence of adverse events and serious adverse events. For phase 2, the primary outcome was safety and immunogenicity (the seroconversion rate and the magnitude, in geometric mean titres [GMTs], of SARS-CoV-2-neutralising antibodies). Analyses were done on an intention-to-treat and per-protocol basis. These trials are registered with ClinicalTrials.gov (NCT04445194 and NCT04466085) and participant follow-up is ongoing. FINDINGS: Between June 22 and July 3, 2020, 50 participants were enrolled into the phase 1 trial and randomly assigned to receive three doses of placebo (n=10), the 25 μg vaccine (n=20), or the 50 μg vaccine (n=20). The mean age of participants was 32·6 (SD 9·4) years. Between July 12 and July 17, 2020, 900 participants were enrolled into the phase 2 trial and randomly assigned to receive two doses of placebo (n=150), 25 μg vaccine (n=150), or 50 μg vaccine (n=150), or three doses of placebo (n=150), 25 μg vaccine (n=150), or 50 μg vaccine (n=150). The mean age of participants was 43·5 (SD 9·2) years. In both phase 1 and phase 2, adverse events reported within 30 days after vaccination were mild or moderate (grade 1 or 2) in most cases (phase 1: six [60%] of ten participants in the placebo group, 14 [70%] of 20 in the 25 μg group, and 18 [90%] of 20 in the 50 μg group; phase 2: 37 [25%] of 150 in the two-dose placebo group, 43 [29%] of 150 in the two-dose 25 μg group, 50 [33%] of 150 in the two-dose 50 μg group, 47 [31%] of 150 in the three-dose placebo group, 72 [48%] of 150 in the three-dose 25 μg group, and 65 [43%] of 150 in the three-dose 50 μg group). In phase 1, two (10%) grade 3 or worse adverse events were reported in the 50 μg group. In phase 2, grade 3 or worse adverse events were reported by 18 participants (four [3%] in the two-dose 25 μg vaccine group, two [1%] in the two-dose 50 μg vaccine group, two [1%] in the three-dose placebo group, four [3%] in the three-dose 25 μg vaccine group, and six [4%] in the three-dose 50 μg vaccine group), and 11 were considered vaccine related (two [1%] in the two-dose 25 μg vaccine group, one [1%] in the two-dose 50 μg vaccine group, one [1%] in the three-dose placebo group, two [1%] in the three-dose 25 μg vaccine group, and five [3%] in the three-dose 50 μg vaccine group); seven participants reported serious adverse events (one [1%] in the two-dose 25 μg vaccine group, one [1%] in the two-dose 50 μg vaccine group, two [1%] in the three-dose placebo group, one [1%] in the three-dose 25 μg vaccine group, and two [1%] in the three-dose 50 μg vaccine group), but none was considered vaccine related. In phase 2, on the two-dose schedule, seroconversion rates of neutralising antibodies 14 days after the second dose were 76% (114 of 150 participants) in the 25 μg group and 72% (108 of 150) in the 50 μg group; on the three-dose schedule, seroconversion rates of neutralising antibodies 14 days after the third dose were 97% (143 of 148 participants) in the 25 μg group and 93% (138 of 148) in the 50 μg group. In the two-dose groups in phase 2, the SARS-CoV-2-neutralising GMTs 14 days after the second dose were 17·7 (95% CI 13·6–23·1) in the 25 μg group and 14·1 (10·8–18·3) in the 50 μg group. In the three-dose groups in phase 2, the SARS-CoV-2-neutralising GMTs 14 days after the third dose were 102·5 (95% CI 81·8–128·5) in the 25 μg group and 69·1 (53·0–90·0) in the 50 μg group. INTERPRETATION: The protein subunit vaccine ZF2001 appears to be well tolerated and immunogenic. The safety and immunogenicity data from the phase 1 and 2 trials support the use of the 25 μg dose in a three-dose schedule in an ongoing phase 3 trial for large-scale evaluation of ZF2001's safety and efficacy. FUNDING: National Program on Key Research Project of China, National Science and Technology Major Projects of Drug Discovery, Strategic Priority Research Program of the Chinese Academy of Sciences, and Anhui Zhifei Longcom Biopharmaceutical. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section. | Lancet Infect Dis | 2021 | LitCov and CORD-19 | |
| 1567 | Reduction and Functional Exhaustion of T Cells in Patients With COVID-19 Background: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed great threat to human health. T cells play a critical role in antiviral immunity but their numbers and functional state in COVID-19 patients remain largely unclear. Methods: We retrospectively reviewed the counts of T cells and serum cytokine concentration from data of 522 patients with laboratory-confirmed COVID-19 and 40 healthy controls. In addition, the expression of T cell exhaustion markers were measured in 14 COVID-19 cases. Results: The number of total T cells, CD4(+) and CD8(+) T cells were dramatically reduced in COVID-19 patients, especially in patients requiring Intensive Care Unit (ICU) care. Counts of total T cells, CD8(+) T cells or CD4(+) T cells lower than 800, 300, or 400/μL, respectively, were negatively correlated with patient survival. T cell numbers were negatively correlated to serum IL-6, IL-10, and TNF-α concentration, with patients in the disease resolution period showing reduced IL-6, IL-10, and TNF-α concentrations and restored T cell counts. T cells from COVID-19 patients had significantly higher levels of the exhausted marker PD-1. Increasing PD-1 and Tim-3 expression on T cells was seen as patients progressed from prodromal to overtly symptomatic stages. Conclusions: T cell counts are reduced significantly in COVID-19 patients, and the surviving T cells appear functionally exhausted. Non-ICU patients with total T cells counts lower than 800/μL may still require urgent intervention, even in the immediate absence of more severe symptoms due to a high risk for further deterioration in condition. | Front Immunol | 2020 | LitCov and CORD-19 | |
| 1568 | Antibody responses to SARS-CoV-2 in patients of novel COVID-19 BACKGROUND: The novel coronavirus SARS-CoV-2 is a newly emerging virus. The antibody response in infected patient remains largely unknown, and the clinical values of antibody testing have not been fully demonstrated. METHODS: A total of 173 patients with SARS-CoV-2 infection were enrolled. Their serial plasma samples (n=535) collected during the hospitalization were tested for total antibodies (Ab), IgM and IgG against SARS-CoV-2. The dynamics of antibodies with the disease progress was analyzed. RESULTS: Among 173 patients, the seroconversion rate for Ab, IgM and IgG was 93.1%, 82.7% and 64.7%, respectively. The reason for the negative antibody findings in 12 patients might due to the lack of blood samples at the later stage of illness. The median seroconversion time for Ab, IgM and then IgG were day-11, day-12 and day-14, separately. The presence of antibodies was <40% among patients within 1-week since onset, and rapidly increased to 100.0% (Ab), 94.3% (IgM) and 79.8% (IgG) since day-15 after onset. In contrast, RNA detectability decreased from 66.7% (58/87) in samples collected before day-7 to 45.5% (25/55) during day 15-39. Combining RNA and antibody detections significantly improved the sensitivity of pathogenic diagnosis for COVID-19 (p<0.001), even in early phase of 1-week since onset (p=0.007). Moreover, a higher titer of Ab was independently associated with a worse clinical classification (p=0.006). CONCLUSIONS: The antibody detection offers vital clinical information during the course of SARS-CoV-2 infection. The findings provide strong empirical support for the routine application of serological testing in the diagnosis and management of COVID-19 patients. | Clin Infect Dis | 2020 | LitCov and CORD-19 | |
| 1569 | Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies The recent severe acute respiratory syndrome, known as Coronavirus Disease 2019 (COVID-19) has spread so much rapidly and severely to induce World Health Organization (WHO) to declare a state of emergency over the new coronavirus SARS-CoV-2 pandemic. While several countries have chosen the almost complete lock-down for slowing down SARS-CoV-2 spread, the scientific community is called to respond to the devastating outbreak by identifying new tools for diagnosis and treatment of the dangerous COVID-19. With this aim, we performed an in silico comparative modeling analysis, which allows gaining new insights into the main conformational changes occurring in the SARS-CoV-2 spike protein, at the level of the receptor-binding domain (RBD), along interactions with human cells angiotensin-converting enzyme 2 (ACE2) receptor, that favor human cell invasion. Furthermore, our analysis provides (1) an ideal pipeline to identify already characterized antibodies that might target SARS-CoV-2 spike RBD, aiming to prevent interactions with the human ACE2, and (2) instructions for building new possible neutralizing antibodies, according to chemical/physical space restraints and complementary determining regions (CDR) mutagenesis of the identified existing antibodies. The proposed antibodies show in silico high affinity for SARS-CoV-2 spike RBD and can be used as reference antibodies also for building new high-affinity antibodies against present and future coronaviruses able to invade human cells through interactions of their spike proteins with the human ACE2. More in general, our analysis provides indications for the set-up of the right biological molecular context for investigating spike RBD–ACE2 interactions for the development of new vaccines, diagnostic kits, and other treatments based on the targeting of SARS-CoV-2 spike protein. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00018-020-03580-1) contains supplementary material, which is available to authorized users. | Cell Mol Life Sci | 2020 | LitCov and CORD-19 | |
| 1570 | COVID-19 Vaccine Acceptance of Pregnant and Lactating Women (PLW) in Czechia: An Analytical Cross-Sectional Study Pregnant and lactating women (PLW) represent a particular population subset with increased susceptibility for COVID-19 morbidity and mortality, even though the evidence about the safety and efficacy of COVID-19 vaccines was delayed due to their initial exclusion from development trials. This unclear situation could have led to increased COVID-19 vaccine hesitancy levels among PLW; therefore, this study aimed to evaluate the attitudes of Czech PLW towards COVID-19 vaccines and the determinants of their attitudes. An analytical cross-sectional survey-based study was carried out in the University Hospital Brno (South Moravia, Czechia) between August and October 2021. The study utilised a self-administered questionnaire (SAQ) adapted from previous instruments used for the same purpose. The SAQ included closed-ended items covering demographic characteristics, clinical and obstetric characteristics, attitudes towards COVID-19 vaccination, and potential psychosocial predictors of vaccine acceptance. Out of the 362 included participants, 278 were pregnant (PW) and 84 were lactating women (LW). The overall COVID-19 vaccine acceptance (immediate and delayed) level was substantially high (70.2%), with a significant difference between PW (76.6%) and LW (48.8%). Out of the 70.2% who agreed to receive the vaccine, 3.6% indicated immediate acceptance, and 66.6% indicated delayed acceptance. Only 13.3% of the participants indicated their acceptance of their physician’s vaccination recommendation during pregnancy or while lactating, and 62.2% were against it. Our results agreed with the recent studies that revealed that PW tended to have a high level of COVID-19 vaccine acceptance, and they were also inclined to resist professional recommendations because they predominantly preferred to delay their vaccination. The pregnancy trimester, education level, employment status, and previous live births were significant determinants for COVID-19 vaccine acceptance. The most commonly preferred vaccine type was mRNA-based vaccines, followed by viral vector-based and inactivated virus vaccines. The first top priority of PLW was vaccine safety for their children, followed by vaccine safety for the PLW and vaccine effectiveness. Regarding psychosocial predictors, media/social media, trust in the government, the pharmaceutical industry, and healthcare professionals, partners, and a positive risk-benefit ratio were significant promoters for COVID-19 vaccine acceptance. Findings from this study suggest that promotional interventions targeting PLW should use web platforms and focus on vaccine safety evidence, the expected benefits of vaccines and potential harms of the infection. | Int J Environ Res Public Healt | 2021 | LitCov and CORD-19 | |
| 1571 | Predicting COVID-19 spread in the face of control measures in West Africa The novel coronavirus (COVID-19) pandemic is causing devastating demographic, social, and economic damage globally. Understanding current patterns of the pandemic spread and forecasting its long-term trajectory is essential in guiding policies aimed at curtailing the pandemic. This is particularly important in regions with weak economies and fragile health care systems such as West-Africa. We formulate and use a deterministic compartmental model to (i) assess the current patterns of COVID-19 spread in West-Africa, (ii) evaluate the impact of currently implemented control measures, and (iii) predict the future course of the pandemic with and without currently implemented and additional control measures in West-Africa. An analytical expression for the threshold level of control measures (involving a reduction in the effective contact rate) required to curtail the pandemic is computed. Considering currently applied health control measures, numerical simulations of the model using baseline parameter values estimated from West-African COVID-19 data project a 67% reduction in the daily number of cases when the epidemic attains its peak. More reduction in the number of cases will be achieved if additional public health control measures that result in a reduction in the effective contact rate are implemented. We found out that disease elimination is difficult when more asymptomatic individuals contribute in transmission or are not identified and isolated in a timely manner. However, maintaining a baseline level of asymptomatic isolation and a low transmission rate will lead to a significant reduction in the number of daily cases when the pandemic peaks. For example, at the baseline level of asymptomatic isolation, at least a 46% reduction in the transmission rate is required for disease elimination. Additionally, disease elimination is possible if asymptomatic individuals are identified and isolated within 5 days (after the incubation period). Combining two or more measures is better for disease control, e.g., if asymptomatic cases are contact traced or identified and isolated in less than 8 days, only about 29% reduction in the disease transmission rate is required for disease elimination. Furthermore, we showed that the currently implemented measures triggered a 33% reduction in the time-dependent effective reproduction number between February 28 and June 26, 2020. We conclude that curtailing the COVID-19 pandemic burden significantly in West-Africa requires more control measures than those that have already been implemented, as well as more mass testing and contact tracing in order to identify and isolate asymptomatic individuals early. | Math Biosci | 2020 | LitCov and CORD-19 | |
| 1572 | Disruption of CCR5 signaling to treat COVID-19-associated cytokine storm: Case series of four critically ill patients treated with leronlimab Coronavirus disease 2019 (COVID-19) is associated with considerable morbidity and mortality. The number of confirmed cases of infection with SARS-CoV-2, the virus causing COVID-19 continues to escalate with over 70 million confirmed cases and over 1.6 million confirmed deaths. Severe-to-critical COVID-19 is associated with a dysregulated host immune response to the virus, which is thought to lead to pathogenic immune dysregulation and end-organ damage. Presently few effective treatment options are available to treat COVID-19. Leronlimab is a humanized IgG4, kappa monoclonal antibody that blocks C–C chemokine receptor type 5 (CCR5). It has been shown that in patients with severe COVID-19 treatment with leronlimab reduces elevated plasma IL-6 and chemokine ligand 5 (CCL5), and normalized CD4/CD8 ratios. We administered leronlimab to 4 critically ill COVID-19 patients in intensive care. All 4 of these patients improved clinically as measured by vasopressor support, and discontinuation of hemodialysis and mechanical ventilation. Following administration of leronlimab there was a statistically significant decrease in IL-6 observed in patient A (p=0.034) from day 0–7 and patient D (p=0.027) from day 0–14. This corresponds to restoration of the immune function as measured by CD4+/CD8+ T cell ratio. Although two of the patients went on to survive the other two subsequently died of surgical complications after an initial recovery from SARS-CoV-2 infection. | J Transl Autoimmun | 2021 | LitCov and CORD-19 | |
| 1573 | SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes N/A | Nat Med | 2020 | LitCov and CORD-19 | |
| 1574 | Clinical characteristics and risk factors of patients with severe COVID-19 in Jiangsu province, China: a retrospective multicenter cohort study BACKGROUND: Coronavirus Disease-2019 (COVID-19) pandemic has become a major health event that endangers people health throughout China and the world. Understanding the factors associated with COVID-19 disease severity could support the early identification of patients with high risk for disease progression, inform prevention and control activities, and potentially reduce mortality. This study aims to describe the characteristics of patients with COVID-19 and factors associated with severe or critically ill presentation in Jiangsu province, China. METHODS: Multicentre retrospective cohort study of all individuals with confirmed Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infections diagnosed at 24 COVID-19-designated hospitals in Jiangsu province between the 10th January and 15th March 2020. Demographic, clinical, laboratory, and radiological data were collected at hospital admission and data on disease severity were collected during follow-up. Patients were categorised as asymptomatic/mild/moderate, and severe/critically ill according to the worst level of COVID-19 recorded during hospitalisation. RESULTS: A total of 625 patients, 64 (10.2%) were severe/critically ill and 561 (89.8%) were asymptomatic/mild/moderate. All patients were discharged and no patients died. Patients with severe/critically ill COVID-19 were more likely to be older, to be single onset (i.e. not belong to a cluster of cases in a family/community, etc.), to have a medical history of hypertension and diabetes; had higher temperature, faster respiratory rates, lower peripheral capillary oxygen saturation (SpO(2)), and higher computer tomography (CT) image quadrant scores and pulmonary opacity percentage; had increased C-reactive protein, fibrinogen, and D-dimer on admission; and had lower white blood cells, lymphocyte, and platelet counts and albumin on admission than asymptomatic/mild/moderate cases. Multivariable regression showed that odds of being a severe/critically ill case were associated with age (year) (OR 1.06, 95%CI 1.03–1.09), lymphocyte count (10(9)/L) (OR 0.25, 95%CI 0.08–0.74), and pulmonary opacity in CT (per 5%) on admission (OR 1.31, 95%CI 1.15–1.51). CONCLUSIONS: Severe or critically ill patients with COVID-19 is about one-tenths of patients in Jiangsu. Age, lymphocyte count, and pulmonary opacity in CT on admission were associated with risk of severe or critically ill COVID-19. | BMC Infect Dis | 2020 | LitCov and CORD-19 | |
| 1575 | Practices and Perceptions of Face Mask Use in a Pediatric Health System During the COVID-19 Pandemic N/A | Respir Care | 2021 | LitCov and CORD-19 | |
| 1576 | Association of a Public Health Campaign About COVID-19 Promoted by News Media and a Social Influencer With Self-reported Personal Hygiene and Physical Distancing in the Netherlands IMPORTANCE: In the absence of a vaccine and therapeutic agent, personal hygiene and physical distancing are essential measures to contain the coronavirus disease 2019 pandemic. OBJECTIVE: To determine whether a social media campaign, targeted at the gaps in behavior on personal hygiene and physical distancing and distributed nationwide via digital news media, may be an effective method to improve behavior and help to inhibit person-to-person transmission of severe acute respiratory syndrome coronavirus 2. DESIGN, SETTING, AND PARTICIPANTS: This survey study was designed to uncover self-reported gaps in behavior regarding personal hygiene and physical distancing in the Netherlands. A diagnostic survey was distributed by a large national newspaper (De Telegraaf) and a popular social influencer (Govert Sweep) on March 17, 2020, and was completed by 16 072 participants. Analysis of these outcomes showed that coughing and sneezing in the elbow was done well, but that handwashing, face touching, and physical distancing showed serious gaps compared with advised behavior. This diagnostic information was used to design infographics and a video targeted at repairing these gaps in behavior. The video and infographics were distributed on a national level on March 21, 2020, followed by a postcampaign survey to measure the results on March 24, 2020. Data analysis was performed from March to April 2020. EXPOSURE: Exposed participants were those who viewed the infographics and/or video. MAIN OUTCOMES AND MEASURES: Improvement on the extent of handwashing in all areas, handwashing duration of 20 seconds or longer, awareness on face touching, and physical distancing were measured according to responses on the postcampaign survey. RESULTS: A total of 17 189 participants (mean [SD] age, 47.61 [13.57] years; 9100 women [52.9%]) responded to the postcampaign survey. The news article in De Telegraaf was read more than 2 million times, and the influencer video was watched more than 80 000 times. Cross-sectional analysis of the postcampaign survey using logistic regression correcting for age, gender, and educational level showed that exposure to the video plus infographics (827 participants) (adjusted odds ratio [OR], 2.14; 95% CI, 1.83-2.50; P < .001) and to the infographics alone (11 348 participants) (adjusted OR, 1.31; 95% CI, 1.22-1.40; P < .001) were positively associated with washing hands in all areas compared with the unexposed group (4751 participants). In addition, exposure to the video plus infographics (adjusted OR, 1.86; 95% CI, 1.59-2.16; P < .001) and to the infographics alone (adjusted OR, 1.27; 95% CI, 1.19-1.36; P < .001) were positively associated with washing hands long enough compared with the unexposed group. Exposure to the video alone was not associated with improved handwashing. Compared with the unexposed group, exposure to the infographics alone and video plus infographics were associated with improvements in physical distancing when the participant had COVID-19 syptoms (infographics alone, adjusted OR, 1.10; 95% CI, 1.03-1.17; P = .006; video plus infographics, adjusted OR, 0.79; 95% CI, 0.69-0.91; P = .001) and face touching (infographics alone, adjusted OR, 1.29; 95% CI, 1.22-1.38; P < .001; infographics and video, adjusted OR, 1.49, 95% CI, 1.30-1.71; P < .001). CONCLUSIONS AND RELEVANCE: These findings suggest that a targeted behavioral change campaign, promoted by a news platform and social media, was associated with self-reported improvement in personal hygiene with the aim to prevent person-to-person transmission of severe acute respiratory syndrome coronavirus 2. This method of evidence-based campaigning may be an effective way to improve critical public health issues, such as the coronavirus disease 2019 pandemic. | JAMA Netw Open | 2020 | LitCov and CORD-19 | |
| 1577 | Venous thrombosis epidemiology, pathophysiology and anticoagulant therapies and trials in SARS-CoV-2 infection OBJECTIVE: Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus confers a risk of significant coagulopathy, with the resulting development of venous thromboembolism (VTE), potentially contributing to the morbidity and mortality. The purpose of the present review was to evaluate the potential mechanisms that contribute to this increased risk of coagulopathy and the role of anticoagulants in treatment. METHODS: A literature review of coronavirus disease 2019 (COVID-19) and/or SARS-CoV-2 and cell-mediated inflammation, clinical coagulation abnormalities, hypercoagulability, pulmonary intravascular coagulopathy, and anticoagulation was performed. The National Clinical Trials database was queried for ongoing studies of anticoagulation and/or antithrombotic treatment or the incidence or prevalence of thrombotic events in patients with SARS-CoV-2 infection. RESULTS: The reported rate of VTE among critically ill patients infected with SARS-CoV-2 has been 21% to 69%. The phenomenon of breakthrough VTE, or the acute development of VTE despite adequate chemoprophylaxis or treatment dose anticoagulation, has been shown to occur with severe infection. The pathophysiology of overt hypercoagulability and the development of VTE is likely multifactorial, with evidence supporting the role of significant cell-mediated responses, including neutrophils and monocytes/macrophages, endothelialitis, cytokine release syndrome, and dysregulation of fibrinolysis. Collectively, this inflammatory process contributes to the severe pulmonary pathology experienced by patients with COVID-19. As the infection worsens, extreme D-dimer elevations, significant thrombocytopenia, decreasing fibrinogen, and prolongation of prothrombin time and partial thromboplastin time occur, often associated with deep vein thrombosis, in situ pulmonary thrombi, and/or pulmonary embolism. A new phenomenon, termed pulmonary intravascular coagulopathy, has been associated with morbidity in patients with severe infection. Heparin, both unfractionated heparin and low-molecular-weight heparin, have emerged as agents that can address the viral infection, inflammation, and thrombosis in this syndrome. CONCLUSIONS: The overwhelming inflammatory response in patients with SARS-CoV-2 infection can lead to a hypercoagulable state, microthrombosis, large vessel thrombosis, and, ultimately, death. Early VTE prophylaxis should be provided to all admitted patients. Therapeutic anticoagulation therapy might be beneficial for critically ill patients and is the focus of 39 ongoing trials. Close monitoring for thrombotic complications is imperative, and, if confirmed, early transition from prophylactic to therapeutic anticoagulation should be instituted. The interplay between inflammation and thrombosis has been shown to be a hallmark of the SARS-CoV-2 viral infection. | J Vasc Surg Venous Lymphat Dis | 2020 | LitCov and CORD-19 | |
| 1578 | Change in serum IgG antibody during the recovery stage of Omicron variant infection in children: an analysis of 110 cases N/A | Zhongguo Dang Dai Er Ke Za Zhi | 2022 | LitCov | |
| 1579 | The Oxford Royal College of General Practitioners Clinical Informatics Digital Hub: Protocol to Develop Extended COVID-19 Surveillance and Trial Platforms BACKGROUND: Routinely recorded primary care data have been used for many years by sentinel networks for surveillance. More recently, real world data have been used for a wider range of research projects to support rapid, inexpensive clinical trials. Because the partial national lockdown in the United Kingdom due to the coronavirus disease (COVID-19) pandemic has resulted in decreasing community disease incidence, much larger numbers of general practices are needed to deliver effective COVID-19 surveillance and contribute to in-pandemic clinical trials. OBJECTIVE: The aim of this protocol is to describe the rapid design and development of the Oxford Royal College of General Practitioners Clinical Informatics Digital Hub (ORCHID) and its first two platforms. The Surveillance Platform will provide extended primary care surveillance, while the Trials Platform is a streamlined clinical trials platform that will be integrated into routine primary care practice. METHODS: We will apply the FAIR (Findable, Accessible, Interoperable, and Reusable) metadata principles to a new, integrated digital health hub that will extract routinely collected general practice electronic health data for use in clinical trials and provide enhanced communicable disease surveillance. The hub will be findable through membership in Health Data Research UK and European metadata repositories. Accessibility through an online application system will provide access to study-ready data sets or developed custom data sets. Interoperability will be facilitated by fixed linkage to other key sources such as Hospital Episodes Statistics and the Office of National Statistics using pseudonymized data. All semantic descriptors (ie, ontologies) and code used for analysis will be made available to accelerate analyses. We will also make data available using common data models, starting with the US Food and Drug Administration Sentinel and Observational Medical Outcomes Partnership approaches, to facilitate international studies. The Surveillance Platform will provide access to data for health protection and promotion work as authorized through agreements between Oxford, the Royal College of General Practitioners, and Public Health England. All studies using the Trials Platform will go through appropriate ethical and other regulatory approval processes. RESULTS: The hub will be a bottom-up, professionally led network that will provide benefits for member practices, our health service, and the population served. Data will only be used for SQUIRE (surveillance, quality improvement, research, and education) purposes. We have already received positive responses from practices, and the number of practices in the network has doubled to over 1150 since February 2020. COVID-19 surveillance has resulted in tripling of the number of virology sites to 293 (target 300), which has aided the collection of the largest ever weekly total of surveillance swabs in the United Kingdom as well as over 3000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology samples. Practices are recruiting to the PRINCIPLE (Platform Randomised trial of INterventions against COVID-19 In older PeopLE) trial, and these participants will be followed up through ORCHID. These initial outputs demonstrate the feasibility of ORCHID to provide an extended national digital health hub. CONCLUSIONS: ORCHID will provide equitable and innovative use of big data through a professionally led national primary care network and the application of FAIR principles. The secure data hub will host routinely collected general practice data linked to other key health care repositories for clinical trials and support enhanced in situ surveillance without always requiring large volume data extracts. ORCHID will support rapid data extraction, analysis, and dissemination with the aim of improving future research and development in general practice to positively impact patient care. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/19773 | JMIR Public Health Surveill | 2020 | LitCov and CORD-19 | |
| 1580 | Assessment of Structural Barriers and Racial Group Disparities of COVID-19 Mortality With Spatial Analysis IMPORTANCE: Although social determinants of health (SDOH) are important factors in health inequities, they have not been explicitly associated with COVID-19 mortality rates across racial and ethnic groups and rural, suburban, and urban contexts. OBJECTIVES: To explore the spatial and racial disparities in county-level COVID-19 mortality rates during the first year of the pandemic. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed data for all US counties in 50 states and the District of Columbia for the first full year of the COVID-19 pandemic (January 22, 2020, to February 28, 2021). Counties with a high concentration of a single racial and ethnic population and a high level of COVID-19 mortality rate were identified as concentrated longitudinal-impact counties. The SDOH that may be associated with mortality rate across these counties and in urban, suburban, and rural contexts were examined. The 3 largest racial and ethnic groups in the US were selected: Black or African American, Hispanic or Latinx, and non-Hispanic White populations. EXPOSURES: County-level characteristics and community health factors (eg, income inequality, uninsured rate, primary care physicians, preventable hospital stays, severe housing problems rate, and access to broadband internet) associated with COVID-19 mortality. MAIN OUTCOMES AND MEASURES: Data on county-level COVID-19 mortality rates (deaths per 100 000 population) reported by the US Centers for Disease Control and Prevention were analyzed. Four indexes were used to measure multiple dimensions of SDOH: socioeconomic advantage index, limited mobility index, urban core opportunity index, and mixed immigrant cohesion and accessibility index. Spatial regression models were used to examine the associations between SDOH and county-level COVID-19 mortality rate. RESULTS: Of the 3142 counties included in the study, 531 were identified as concentrated longitudinal-impact counties. Of these counties, 347 (11.0%) had a large Black or African American population compared with other counties, 198 (6.3%) had a large Hispanic or Latinx population compared with other counties, and 33 (1.1%) had a large non-Hispanic White population compared with other counties. A total of 489 254 COVID-19-related deaths were reported. Most concentrated longitudinal-impact counties with a large Black or African American population compared with other counties were spread across urban, suburban, and rural areas and experienced numerous disadvantages, including higher income inequality (297 of 347 [85.6%]) and more preventable hospital stays (281 of 347 [81.0%]). Most concentrated longitudinal-impact counties with a large Hispanic or Latinx population compared with other counties were located in urban areas (114 of 198 [57.6%]), and 130 (65.7%) of these counties had a high percentage of people who lacked health insurance. Most concentrated longitudinal-impact counties with a large non-Hispanic White population compared with other counties were in rural areas (23 of 33 [69.7%]), included a large group of older adults (26 of 33 [78.8%]), and had limited access to quality health care (24 of 33 [72.7%]). In urban areas, the mixed immigrant cohesion and accessibility index was inversely associated with COVID-19 mortality (coefficient [SE], –23.38 [6.06]; P < .001), indicating that mortality rates in urban areas were associated with immigrant communities with traditional family structures, multiple accessibility stressors, and housing overcrowding. Higher COVID-19 mortality rates were also associated with preventable hospital stays in rural areas (coefficient [SE], 0.008 [0.002]; P < .001) and higher socioeconomic status vulnerability in suburban areas (coefficient [SE], –21.60 [3.55]; P < .001). Across all community types, places with limited internet access had higher mortality rates, especially in urban areas (coefficient [SE], 5.83 [0.81]; P < .001). CONCLUSIONS AND RELEVANCE: This cross-sectional study found an association between different SDOH measures and COVID-19 mortality that varied across racial and ethnic groups and community types. Future research is needed that explores the different dimensions and regional patterns of SDOH to address health inequity and guide policies and programs. | JAMA Netw Open | 2022 | LitCov and CORD-19 | |
| 1581 | China's Public Health Policies in Response to COVID-19: From an "Authoritarian" Perspective Background: China is generally regarded internationally as an “authoritarian” state. Traditional definitions have assigned many negative connotations surrounding the term of authoritarian. We realize that it might not be considered value-neutral in other countries. But authoritarian in the Chinese context emphasizes more on centralized decision making, collectivism, coordinating all activities of the nation, and public support, which is considered a value-neutral term. Therefore, it is adopted in this paper. We would like to clarify this. Authoritarian governance is considered an important mechanism for developing China's economy and solving social problems. The COVID-19 crisis is no exception. Most of the current research on crisis management and government crises focuses on advanced, democratic countries. However, the consequences of crisis management by authoritarian governments have not been fully appreciated. Although prior research has addressed authoritarian initiatives to manage crises in China, authoritarian interventions have rarely been theorized in public health emergencies. Methods: Based on a literature review and theoretical analysis, we use a descriptive and qualitative approach to assess public health policies and mechanisms from an authoritarian perspective in China. In light of the key events and intervention measures of China's government in response to COVID-19, the strategic practices of the Communist Party of China (CPC) to construct, embody, or set political goals through authoritarian intervention in public health crisis management are discussed. Results: China's government responded to the COVID-19 pandemic with a comprehensive authoritarian intervention, notably by establishing a top-down leadership mechanism, implementing a resolute lockdown, rapidly establishing square cabin hospitals, enhancing cooperation between different government departments, mobilizing a wide range of volunteer resources, enforcing the use of health codes, imposing mandatory quarantine on those returning from abroad, and implementing city-wide nucleic acid testing. These measures ensured that China was able to contain the outbreak quickly and reflect on the unique role of the Chinese authoritarian system in responding to public health crises. Conclusions: Our paper contributes to expanding the existing understanding of the relationship between crisis management and authoritarian system. China's response to COVID-19 exemplifies the unique strengths of authoritarian institutions in public health crisis management, which is a helpful and practical tool to further enhance the CPC's political legitimacy. As a socialist model of crisis management with Chinese characteristics, it may offer desirable experiences and lessons for other countries still ravaged by the epidemic. | Front Public Health | 2021 | LitCov and CORD-19 | |
| 1582 | Glasgow Early Treatment Arm Favirpiravir (GETAFIX) for adults with early stage COVID-19: A structured summary of a study protocol for a randomised controlled trial OBJECTIVES: The GETAFIX trial will test the hypothesis that favipiravir is a more effective treatment for COVID-19 infection in patients who have early stage disease, compared to current standard of care. This study will also provide an important opportunity to investigate the safety and tolerability of favipiravir, the pharmacokinetic and pharmacodynamic profile of this drug and mechanisms of resistance in the context of COVID-19 infection, as well as the effect of favipiravir on hospitalisation duration and the post COVID-19 health and psycho-social wellbeing of patients recruited to the study. TRIAL DESIGN: GETAFIX is an open label, parallel group, two arm phase II/III randomised trial with 1:1 treatment allocation ratio. Patients will be randomised to one of two arms and the primary endpoint will assess the superiority of favipiravir plus standard treatment compared to standard treatment alone. PARTICIPANTS: This trial will recruit adult patients with confirmed positive valid COVID-19 test, who are not pregnant or breastfeeding and have no prior major co-morbidities. This is a multi-centre trial, patients will be recruited from in-patients and outpatients from three Glasgow hospitals: Royal Alexandra Hospital; Queen Elizabeth University Hospital; and the Glasgow Royal Infirmary. Patients must meet all of the following criteria: 1. Age 16 or over at time of consent 2. Exhibiting symptoms associated with COVID-19 3. Positive for SARS-CoV-2 on valid COVID-19 test 4. Point 1, 2, 3, or 4 on the WHO COVID-19 ordinal severity scale at time of randomisation. (Asymptomatic with positive valid COVID-19 test, Symptomatic Independent, Symptomatic assistance needed, Hospitalized, with no oxygen therapy) 5. Have >=10% risk of death should they be admitted to hospital as defined by the ISARIC4C risk index: https://isaric4c.net/risk 6. Able to provide written informed consent 7. Negative pregnancy test (women of childbearing potential*) 8. Able to swallow oral medication Patients will be excluded from the trial if they meet any of the following criteria: 1. Renal impairment requiring, or likely to require, dialysis or haemofiltration 2. Pregnant or breastfeeding 3. Of child bearing potential (women), or with female partners of child bearing potential (men) who do not agree to use adequate contraceptive measures for the duration of the study and for 3 months after the completion of study treatment 4. History of hereditary xanthinuria 5. Other patients judged unsuitable by the Principal Investigator or sub-Investigator 6. Known hypersensitivity to favipiravir, its metabolites or any excipients 7. Severe co-morbidities including: patients with severe hepatic impairment, defined as: • greater than Child-Pugh grade A • AST or ALT > 5 x ULN • AST or ALT >3 x ULN and Total Bilirubin > 2xULN 8. More than 96 hours since first positive COVID-19 test sample was taken 9. Unable to discontinue contra-indicated concomitant medications This is a multi-centre trial, patients will be recruited from in-patients and outpatients from three Glasgow hospitals: Royal Alexandra Hospital; Queen Elizabeth University Hospital; and the Glasgow Royal Infirmary. INTERVENTION AND COMPARATOR: Patients randomised to the experimental arm of GETAFIX will receive standard treatment for COVID-19 at the discretion of the treating clinician plus favipiravir. These patients will receive a loading dose of favipiravir on day 1 of 3600mg (1800mg 12 hours apart). On days 2-10, patients in the experimental arm will receive a maintenance dose of favipiravir of 800mg 12 hours apart (total of 18 doses). Patients randomised to the control arm of the GETAFIX trial will receive standard treatment for COVID-19 at the discretion of the treating clinician. MAIN OUTCOMES: The primary outcome being assessed in the GETAFIX trial is the efficacy of favipiravir in addition to standard treatment in patients with COVID-19 in reducing the severity of disease compared to standard treatment alone. Disease severity will be assessed using WHO COVID 10 point ordinal severity scale at day 15 +/- 48 hours. All randomised participants will be followed up until death or 60 days post-randomisation (whichever is sooner). RANDOMISATION: Patients will be randomised 1:1 to the experimental versus control arm using computer generated random sequence allocation. A minimisation algorithm incorporating a random component will be used to allocate patients. The factors used in the minimisation will be: site, age (16-50/51-70/71+), history of hypertension or currently obsess (BMI>30 or obesity clinically evident; yes/no), 7 days duration of symptoms (yes/no/unknown), sex (male/female), WHO COVID-19 ordinal severity score at baseline (1/2or 3/4). BLINDING (MASKING): No blinding will be used in the GETAFIX trial. Both participants and those assessing outcomes will be aware of treatment allocation. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): In total, 302 patients will be randomised to the GETAFIX trial: 151 to the control arm and 151 to the experimental arm. There will be an optional consent form for patients who may want to contribute to more frequent PK and PD sampling. The maximum number of patients who will undergo this testing will be sixteen, eight males and eight females. This option will be offered to all patients who are being treated in hospital at the time of taking informed consent, however only patients in the experimental arm of the trial will be able to undergo this testing. TRIAL STATUS: The current GETAFIX protocol is version 4.0 12(th) September 2020. GETAFIX opened to recruitment on 26(th) October 2020 and will recruit patients over a period of approximately six months. TRIAL REGISTRATION: GETAFIX was registered on the European Union Drug Regulating Authorities Clinical Trials (EudraCT) Database on 15(th) April 2020; Reference number 2020-001904-41 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001904-41/GB). GETAFIX was registered on ISRCTN on 7(th) September 2020; Reference number ISRCTN31062548 (https://www.isrctn.com/ISRCTN31062548). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (see Additional file 2). SUPPLEMENTARY INFORMATION: Supplementary information accompanies this paper at 10.1186/s13063-020-04891-1. | Trials | 2020 | LitCov and CORD-19 | |
| 1583 | Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection The global supply of COVID-19 vaccines remains limited. An understanding of the immune response that is predictive of protection could facilitate rapid licensure of new vaccines. Data from a randomized efficacy trial of the ChAdOx1 nCoV-19 (AZD1222) vaccine in the United Kingdom was analyzed to determine the antibody levels associated with protection against SARS-CoV-2. Binding and neutralizing antibodies at 28 days after the second dose were measured in infected and noninfected vaccine recipients. Higher levels of all immune markers were correlated with a reduced risk of symptomatic infection. A vaccine efficacy of 80% against symptomatic infection with majority Alpha (B.1.1.7) variant of SARS-CoV-2 was achieved with 264 (95% CI: 108, 806) binding antibody units (BAU)/ml: and 506 (95% CI: 135, not computed (beyond data range) (NC)) BAU/ml for anti-spike and anti-RBD antibodies, and 26 (95% CI: NC, NC) international unit (IU)/ml and 247 (95% CI: 101, NC) normalized neutralization titers (NF(50)) for pseudovirus and live-virus neutralization, respectively. Immune markers were not correlated with asymptomatic infections at the 5% significance level. These data can be used to bridge to new populations using validated assays, and allow extrapolation of efficacy estimates to new COVID-19 vaccines. | Nat Med | 2021 | LitCov and CORD-19 | |
| 1584 | MOG encephalomyelitis after vaccination against severe acute respiratory syndrome coronavirus type 2: case report and comprehensive review of the literature N/A | J Neurol | 2022 | LitCov | |
| 1585 | Incidence of venous thromboembolism in hospitalized patients with COVID-19 BACKGROUND: Coronavirus disease 2019 (COVID‐19) can lead to systemic coagulation activation and thrombotic complications. OBJECTIVES: To investigate the incidence of objectively confirmed venous thromboembolism (VTE) in hospitalized patients with COVID‐19. METHODS: Single‐center cohort study of 198 hospitalized patients with COVID‐19. RESULTS: Seventy‐five patients (38%) were admitted to the intensive care unit (ICU). At time of data collection, 16 (8%) were still hospitalized and 19% had died. During a median follow‐up of 7 days (IQR, 3‐13), 39 patients (20%) were diagnosed with VTE of whom 25 (13%) had symptomatic VTE, despite routine thrombosis prophylaxis. The cumulative incidences of VTE at 7, 14 and 21 days were 16% (95% CI, 10‐22), 33% (95% CI, 23‐43) and 42% (95% CI 30‐54) respectively. For symptomatic VTE, these were 10% (95% CI, 5.8‐16), 21% (95% CI, 14‐30) and 25% (95% CI 16‐36). VTE appeared to be associated with death (adjusted HR, 2.4; 95% CI, 1.02‐5.5). The cumulative incidence of VTE was higher in the ICU (26% (95% CI, 17‐37), 47% (95% CI, 34‐58), and 59% (95% CI, 42‐72) at 7, 14 and 21 days) than on the wards (any VTE and symptomatic VTE 5.8% (95% CI, 1.4‐15), 9.2% (95% CI, 2.6‐21), and 9.2% (2.6‐21) at 7, 14, and 21 days). CONCLUSIONS: The observed risk for VTE in COVID‐19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE. Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival. | J Thromb Haemost | 2020 | LitCov and CORD-19 | |
| 1586 | Tracking Public Attitudes Towards COVID-19 Vaccination on Tweets in Canada: Using Aspect-Based Sentiment Analysis BACKGROUND: The development and approval of COVID-19 vaccines have generated optimism for the end of the COVID-19 pandemic and a return to normalcy. However, vaccine hesitancy, often fueled by misinformation, poses a major barrier to achieving herd immunity. OBJECTIVE: We aim to investigate Twitter users’ attitudes toward COVID-19 vaccination in Canada after vaccine rollout. METHODS: We applied a weakly supervised aspect-based sentiment analysis (ABSA) technique, which involves the human-in-the-loop system, on COVID-19 vaccination–related tweets in Canada. Automatically generated aspect and opinion terms were manually corrected by public health experts to ensure the accuracy of the terms and make them more domain-specific. Then, based on these manually corrected terms, the system inferred sentiments toward the aspects. We observed sentiments toward key aspects related to COVID-19 vaccination, and investigated how sentiments toward “vaccination” changed over time. In addition, we analyzed the most retweeted or liked tweets by observing most frequent nouns and sentiments toward key aspects. RESULTS: After applying the ABSA system, we obtained 170 aspect terms (eg, “immunity” and “pfizer”) and 6775 opinion terms (eg, “trustworthy” for the positive sentiment and “jeopardize” for the negative sentiment). While manually verifying or editing these terms, our public health experts selected 20 key aspects related to COVID-19 vaccination for analysis. The sentiment analysis results for the 20 key aspects revealed negative sentiments related to “vaccine distribution,” “side effects,” “allergy,” “reactions,” and “anti-vaxxer,” and positive sentiments related to “vaccine campaign,” “vaccine candidates,” and “immune response.” These results indicate that the Twitter users express concerns about the safety of vaccines but still consider vaccines as the option to end the pandemic. In addition, compared to the sentiment of the remaining tweets, the most retweeted or liked tweets showed more positive sentiment overall toward key aspects (P<.001), especially vaccines (P<.001) and vaccination (P=.009). Further investigation of the most retweeted or liked tweets revealed two opposing trends in Twitter users who showed negative sentiments toward vaccines: the “anti-vaxxer” population that used negative sentiments as a means to discourage vaccination and the “Covid Zero” population that used negative sentiments to encourage vaccinations while critiquing the public health response. CONCLUSIONS: Our study examined public sentiments toward COVID-19 vaccination on tweets over an extended period in Canada. Our findings could inform public health agencies to design and implement interventions to promote vaccination. | J Med Internet Res | 2022 | LitCov and CORD-19 | |
| 1587 | Prevalence and risk factors for delirium in critically ill patients with COVID-19 (COVID-D): a multicenter cohort study BACKGROUND: To date, 750 000 patients with COVID-19 worldwide have required mechanical ventilation and thus are at high risk of acute brain dysfunction (coma and delirium). We aimed to investigate the prevalence of delirium and coma, and risk factors for delirium in critically ill patients with COVID-19, to aid the development of strategies to mitigate delirium and associated sequelae. METHODS: This multicentre cohort study included 69 adult intensive care units (ICUs), across 14 countries. We included all patients (aged ≥18 years) admitted to participating ICUs with severe acute respiratory syndrome coronavirus 2 infection before April 28, 2020. Patients who were moribund or had life-support measures withdrawn within 24 h of ICU admission, prisoners, patients with pre-existing mental illness, neurodegenerative disorders, congenital or acquired brain damage, hepatic coma, drug overdose, suicide attempt, or those who were blind or deaf were excluded. We collected de-identified data from electronic health records on patient demographics, delirium and coma assessments, and management strategies for a 21-day period. Additional data on ventilator support, ICU length of stay, and vital status was collected for a 28-day period. The primary outcome was to determine the prevalence of delirium and coma and to investigate any associated risk factors associated with development of delirium the next day. We also investigated predictors of number of days alive without delirium or coma. These outcomes were investigated using multivariable regression. FINDINGS: Between Jan 20 and April 28, 2020, 4530 patients with COVID-19 were admitted to 69 ICUs, of whom 2088 patients were included in the study cohort. The median age of patients was 64 years (IQR 54 to 71) with a median Simplified Acute Physiology Score (SAPS) II of 40·0 (30·0 to 53·0). 1397 (66·9%) of 2088 patients were invasively mechanically ventilated on the day of ICU admission and 1827 (87·5%) were invasively mechanical ventilated at some point during hospitalisation. Infusion with sedatives while on mechanical ventilation was common: 1337 (64·0%) of 2088 patients were given benzodiazepines for a median of 7·0 days (4·0 to 12·0) and 1481 (70·9%) were given propofol for a median of 7·0 days (4·0 to 11·0). Median Richmond Agitation–Sedation Scale score while on invasive mechanical ventilation was –4 (–5 to –3). 1704 (81·6%) of 2088 patients were comatose for a median of 10·0 days (6·0 to 15·0) and 1147 (54·9%) were delirious for a median of 3·0 days (2·0 to 6·0). Mechanical ventilation, use of restraints, and benzodiazepine, opioid, and vasopressor infusions, and antipsychotics were each associated with a higher risk of delirium the next day (all p≤0·04), whereas family visitation (in person or virtual) was associated with a lower risk of delirium (p<0·0001). During the 21-day study period, patients were alive without delirium or coma for a median of 5·0 days (0·0 to 14·0). At baseline, older age, higher SAPS II scores, male sex, smoking or alcohol abuse, use of vasopressors on day 1, and invasive mechanical ventilation on day 1 were independently associated with fewer days alive and free of delirium and coma (all p<0·01). 601 (28·8%) of 2088 patients died within 28 days of admission, with most of those deaths occurring in the ICU. INTERPRETATION: Acute brain dysfunction was highly prevalent and prolonged in critically ill patients with COVID-19. Benzodiazepine use and lack of family visitation were identified as modifiable risk factors for delirium, and thus these data present an opportunity to reduce acute brain dysfunction in patients with COVID-19. FUNDING: None. TRANSLATIONS: For the French and Spanish translations of the abstract see Supplementary Materials section. | Lancet Respir Med | 2021 | LitCov and CORD-19 | |
| 1588 | Artificial Intelligence Distinguishes COVID-19 from Community Acquired Pneumonia on Chest CT BACKGROUND: Coronavirus disease has widely spread all over the world since the beginning of 2020. It is desirable to develop automatic and accurate detection of COVID-19 using chest CT. PURPOSE: To develop a fully automatic framework to detect COVID-19 using chest CT and evaluate its performances. MATERIALS AND METHODS: In this retrospective and multi-center study, a deep learning model, COVID-19 detection neural network (COVNet), was developed to extract visual features from volumetric chest CT exams for the detection of COVID-19. Community acquired pneumonia (CAP) and other non-pneumonia CT exams were included to test the robustness of the model. The datasets were collected from 6 hospitals between August 2016 and February 2020. Diagnostic performance was assessed by the area under the receiver operating characteristic curve (AUC), sensitivity and specificity. RESULTS: The collected dataset consisted of 4356 chest CT exams from 3,322 patients. The average age is 49±15 years and there were slightly more male patients than female (1838 vs 1484; p-value=0.29). The per-exam sensitivity and specificity for detecting COVID-19 in the independent test set was 114 of 127 (90% [95% CI: 83%, 94%]) and 294 of 307 (96% [95% CI: 93%, 98%]), respectively, with an AUC of 0.96 (p-value<0.001). The per-exam sensitivity and specificity for detecting CAP in the independent test set was 87% (152 of 175) and 92% (239 of 259), respectively, with an AUC of 0.95 (95% CI: 0.93, 0.97). CONCLUSIONS: A deep learning model can accurately detect COVID-19 and differentiate it from community acquired pneumonia and other lung diseases. | Radiology | 2020 | LitCov and CORD-19 | |
| 1589 | Heterogeneity in transmissibility and shedding SARS-CoV-2 via droplets and aerosols BACKGROUND: Which virological factors mediate overdispersion in the transmissibility of emerging viruses remains a long-standing question in infectious disease epidemiology. METHODS: Here, we use systematic review to develop a comprehensive dataset of respiratory viral loads (rVLs) of SARS-CoV-2, SARS-CoV-1 and influenza A(H1N1)pdm09. We then comparatively meta-analyze the data and model individual infectiousness by shedding viable virus via respiratory droplets and aerosols. RESULTS: The analyses indicate heterogeneity in rVL as an intrinsic virological factor facilitating greater overdispersion for SARS-CoV-2 in the COVID-19 pandemic than A(H1N1)pdm09 in the 2009 influenza pandemic. For COVID-19, case heterogeneity remains broad throughout the infectious period, including for pediatric and asymptomatic infections. Hence, many COVID-19 cases inherently present minimal transmission risk, whereas highly infectious individuals shed tens to thousands of SARS-CoV-2 virions/min via droplets and aerosols while breathing, talking and singing. Coughing increases the contagiousness, especially in close contact, of symptomatic cases relative to asymptomatic ones. Infectiousness tends to be elevated between 1 and 5 days post-symptom onset. CONCLUSIONS: Intrinsic case variation in rVL facilitates overdispersion in the transmissibility of emerging respiratory viruses. Our findings present considerations for disease control in the COVID-19 pandemic as well as future outbreaks of novel viruses. FUNDING: Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant program, NSERC Senior Industrial Research Chair program and the Toronto COVID-19 Action Fund. | Elife | 2021 | LitCov and CORD-19 | |
| 1590 | Psychological distress during the initial stage of the COVID-19 pandemic in an Italian population living with HIV: an online survey N/A | Infez Med | 2021 | LitCov and CORD-19 | |
| 1591 | COVID-19 and Stroke: Clinical Manifestations and Pathophysiological Insights Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health threat. Some COVID-19 patients have exhibited widespread neurological manifestations including stroke. Acute ischemic stroke, intracerebral hemorrhage, and cerebral venous sinus thrombosis have been reported in patients with COVID-19. COVID-19-associated coagulopathy is increasingly recognized as a result of acute infection and is likely caused by inflammation, including inflammatory cytokine storm. Recent studies suggest axonal transport of SARS-CoV-2 to the brain can occur via the cribriform plate adjacent to the olfactory bulb that may lead to symptomatic anosmia. The internalization of SARS-CoV-2 is mediated by the binding of the spike glycoprotein of the virus to the angiotensin-converting enzyme 2 (ACE2) on cellular membranes. ACE2 is expressed in several tissues including lung alveolar cells, gastrointestinal tissue, and brain. The aim of this review is to provide insights into the pathophysiological stroke mechanisms in COVID-19 patients. SARS-CoV-2 can down-regulate ACE2 and, in turn, over-activate the classical renin-angiotensin system (RAS) axis and decrease the activation of the alternative RAS pathway in the brain. The consequent imbalance in vasodilation, neuroinflammation, oxidative stress, and thrombotic response may contribute to the pathophysiology of stroke during SARS-CoV-2 infection. | J Stroke Cerebrovasc Dis | 2020 | LitCov and CORD-19 | |
| 1592 | Effectiveness of inactivated SARS-CoV-2 vaccines against the Delta variant infection in Guangzhou: a test-negative case-control real-world study The effectiveness of inactivated SARS-CoV-2 vaccines against the Delta variant, which has been associated with greater transmissibility and virulence, remains unclear. We conducted a test-negative case–control study to explore the vaccine effectiveness (VE) in real-world settings. We recruited participants aged 18–59 years who consisted of SARS-CoV-2 test-positive cases (n = 74) and test-negative controls (n = 292) during the outbreak of the Delta variant in May 2021 in Guangzhou city, China. Vaccination status was compared to estimate The VE of SARS-CoV-2 inactivated vaccines. A single dose of inactivated SARS-CoV-2 vaccine yielded the VE of only 13.8%. After adjusting for age and sex, the overall VE for two-dose vaccination was 59.0% (95% confidence interval: 16.0% to 81.6%) against coronavirus disease 2019 (COVID-19) and 70.2% (95% confidence interval: 29.6–89.3%) against moderate COVID-19 and 100% against severe COVID-19 which might be overestimated due to the small sample size. The VE of two-dose vaccination against COVID-19 reached 72.5% among participants aged 40–59 years, and was higher in females than in males against COVID-19 and moderate diseases. While single dose vaccination was not sufficiently protective, the two-dose dosing scheme of the inactivated vaccines was effective against the Delta variant infection in real-world settings, with the estimated efficacy exceeding the World Health Organization minimal threshold of 50%. | Emerg Microbes Infect | 2021 | LitCov and CORD-19 | |
| 1593 | Telehealth challenges during COVID-19 as reported by primary healthcare physicians in Quebec and Massachusetts BACKGROUND: The COVID-19 pandemic has driven primary healthcare (PHC) providers to use telehealth as an alternative to traditional face-to-face consultations. Providing telehealth that meets the needs of patients in a pandemic has presented many challenges for PHC providers. The aim of this study was to describe the positive and negative implications of using telehealth in one Canadian (Quebec) and one American (Massachusetts) PHC setting during the COVID-19 pandemic as reported by physicians. METHODS: We conducted 42 individual semi-structured video interviews with physicians in Quebec (N = 20) and Massachusetts (N = 22) in 2020. Topics covered included their practice history, changes brought by the COVID-19 pandemic, and the advantages and challenges of telehealth. An inductive and deductive thematic analysis was carried out to identify implications of delivering care via telehealth. RESULTS: Four key themes were identified, each with positive and negative implications: 1) access for patients; 2) efficiency of care delivery; 3) professional impacts; and 4) relational dimensions of care. For patients’ access, positive implications referred to increased availability of services; negative implications involved barriers due to difficulties with access to and use of technologies. Positive implications for efficiency were related to improved follow-up care; negative implications involved difficulties in diagnosing in the absence of direct physical examination and non-verbal cues. For professional impacts, positive implications were related to flexibility (teleworking, more availability for patients) and reimbursement, while negative implications were related to technological limitations experienced by both patients and practitioners. For relational dimensions, positive implications included improved communication, as patients were more at ease at home, and the possibility of gathering information from what could be seen of the patient’s environment; negative implications were related to concerns around maintaining the therapeutic relationship and changes in patients’ engagement and expectations. CONCLUSION: Ensuring that health services provision meets patients’ needs at all times calls for flexibility in care delivery modalities, role shifting to adapt to virtual care, sustained relationships with patients, and interprofessional collaboration. To succeed, these efforts require guidelines and training, as well as careful attention to technological barriers and interpersonal relationship needs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12875-021-01543-4. | BMC Fam Pract | 2021 | LitCov and CORD-19 | |
| 1594 | Divergent SARS CoV-2 Omicron-reactive T- and B cell responses in COVID-19 vaccine recipients The severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) Omicron variant (B.1.1.529) is spreading rapidly, even in vaccinated individuals, raising concerns about immune escape. Here, we studied neutralizing antibodies and T-cell responses targeting SARS-CoV-2 D614G (wildtype, WT), and the B.1.351 (Beta), B.1.617.2 (Delta), and B.1.1.529 (Omicron) variants of concern (VOC) in a cohort of 60 health care workers after immunization with ChAdOx-1 S, Ad26.COV2.S, mRNA-1273 or BNT162b2. High binding antibody levels against WT SARS-CoV-2 spike (S) were detected 28 days after vaccination with both mRNA vaccines (mRNA-1273 or BNT162b2), which significantly decreased after 6 months. In contrast, antibody levels were lower after Ad26.COV2.S vaccination but did not wane. Neutralization assays with infectious virus showed consistent cross-neutralization of the Beta and Delta variants, but neutralization of Omicron was significantly lower or absent (up to a 34-fold decrease compared to WT). Notably, BNT162b2 booster vaccination after either two mRNA-1273 immunizations or Ad26.COV.2 priming partially restored neutralization of the Omicron variant, but responses were still up to-17-fold decreased compared to WT. SARS-CoV-2-specific T-cells were detected up to 6 months after all vaccination regimens, with more consistent detection of specific CD4+ than CD8+ T-cells. No significant differences were detected between WT- and variant-specific CD4+ or CD8+ T-cell responses, including Omicron, indicating minimal escape at the T-cell level. This study shows that vaccinated individuals retain T-cell immunity to the SARS-CoV-2 Omicron variant, potentially balancing the lack of neutralizing antibodies in preventing or limiting severe COVID-19. Booster vaccinations are needed to further restore Omicron cross-neutralization by antibodies. | Sci Immunol | 2022 | LitCov and CORD-19 | |
| 1595 | Insights into antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine affecting the new SARS-CoV-2 Coronavirus disease 2019 (COVID-19) is a kind of viral pneumonia with an unusual outbreak in Wuhan, China, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is currently no licensed antiviral treatment available to prevent human CoV infection. The widespread clinical use and existing knowledge on antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine in the treatment of previous epidemic diseases, namely, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), may be helpful in the combat with novel SARS-CoV-2 infection. Recent clinical evidence didn’t confirm the beneficial role of lopinavir/ritonavir and chloroquine/hydroxychloroquine for COVID-19 patients and their use was reassessed. We provide an overview of the current evidence into the mechanisms of action of these available drugs which are repurposed for treatment of the new virus. Available data identifies remdesivir as an adenosine analogue that can target the RNA-dependent RNA polymerase and block viral RNA synthesis. It has been a promising antiviral drug against a wide array of RNA viruses. 3CLpro is a major CoV protease that cleaves the large replicase polyproteins during viral replication and can be targeted by the protease inhibitor lopinavir/ritonavir but the clinical effects are controversial. Chloroquine/Hydroxychloroquine could impair the replication of SARSCoV-2 by multiple mechanisms and their immunomodulatory properties could ameliorate clinical manifestations that are mediated by immune reactions of the host although its beneficial effects are under question and need to be proven at the clinical level. Existing in vitro and in vivo evidence delineate the molecular mechanisms of these drugs in CoV-infected cells. Numerous studies demonstrated the ability of remdesivir to inhibit SARS-CoV-2 replication but future research would be needed to understand the exact mode of action of lopinavir/ritonavir and chloroquine/hydroxychloroquine in SARS-CoV-2 infected cells and to use this knowledge in the treatment of the current COVID-19. | Biomed Pharmacother | 2020 | LitCov and CORD-19 | |
| 1596 | Evaluation of a multiplexed coronavirus antigen array for detection of SARS-CoV-2 specific IgG in COVID-19 convalescent plasma Mitigation of the COVID-19 pandemic requires an understanding of the antibody response to SARS-CoV-2. However, throughout the development of SARS-CoV-2 IgG antibody assays during the past year, cross-reactivity to other coronaviruses remained a question. To address these issues, we evaluated IgG in COVID-19 convalescent plasma samples for reactivity against three SARS-CoV-2 antigens including full-length spike, receptor binding domain, and the proximal extracellular fusion domain, and spike antigens from other coronaviruses (SARS-CoV, MERS-CoV, hCoV-HKU1, hCoV-OC43, hCoV-229E and hCoV-NL63) using the VaxArray Coronavirus SeroAssay which is a multiplexed antigen assay developed by InDevR Inc. These results were compared to two commercial SARS-CoV-2 IgG ELISAs targeting either the SARS-CoV-2 nucleocapsid or spike antigens and a live virus focus reduction neutralizing antibody test (FRNT). The VaxArray platform showed high specificity for detection of SARS-CoV-2 IgG, evident from lack of reactivity to SARS-CoV-2 antigens despite significant reactivity to endemic coronavirus antigens in pre-pandemic samples. SARS-CoV-2 IgG positive samples reacted weakly to SARS-CoV spike but not to MERS-CoV. While the VaxArray platform had overall comparable results to the spike and nucleocapsid IgG ELISAs, results were more similar to the spike antigen ELISA and the platform displayed a higher sensitivity and specificity than both ELISAs. Samples with FRNT titers below 1/23 reported negative on VaxArray, while positive samples on VaxArray had significantly higher neutralizing antibody titers. These results suggest that the VaxArray Coronavirus SeroAssay performs with high sensitivity and specificity for the detection of SARS-CoV-2 IgG, and positive results on the platform indicate SARS-CoV-2 neutralizing activity. | J Immunol Methods | 2021 | LitCov and CORD-19 | |
| 1597 | Public Knowledge, Attitude and Perception towards COVID-19 Vaccination in Saudi Arabia Coronavirus disease-19 (COVID-19) is a highly contagious infection that mainly affects the respiratory system of patients. To date, more than 10 million people have been affected by this virus, and Saudi Arabia has also reported over 210 million cases. At present, there is no established treatment for COVID-19. Vaccination is one of the ways to defeat the pandemic. Recent reports have indicated rare but serious adverse events after vaccination, causing an anxious response from the general public worldwide. Therefore, this study was aimed at evaluating the knowledge, attitude, and perception of the COVID-19 vaccine among the Saudi population. This study is a cross-sectional, web-based online survey conducted using a snowball sampling technique. A self-administered questionnaire prepared in Arabic and English was used to collect feedback from the general population on their knowledge, attitudes, and perceptions about the COVID-19 vaccine. Participants (n = 2022) from different regions of the country replied to the questions. The responses to the questions were recorded on a spreadsheet and analyzed using the SPSS software. Statistical analysis was performed using one-way ANOVA and non-parametric tests to draw conclusions about the results. Multivariate stepwise regression analysis was performed to determine the association between the knowledge, attitude, and perception scores and the demographic variables. p < 0.05 was used to indicate the significance of the data. The data from the study indicated that most of the participants were males (81%), between 18 and 59 years of age (85.9%), Saudi nationals (98.3%), and possessed graduation or above as a qualification (62.9%). The results suggest that a major portion of respondents have satisfactory knowledge (76%), a positive attitude (72.4%), and perception (71.3%) towards the use of COVID-19 vaccines. Their responses can be categorized as between ‘good’ and ‘fair’. However, 30–40% of respondents lacked information about COVID-19 vaccination availability for under 18-year-olds as well as for pregnant women, in addition to the lack of knowledge about the serious unreported adverse reactions and long-term protection offered by the vaccine against coronavirus. The correlation analysis between the variables (p > 0.05) indicated that the response to the KAP domains has no direct relationship. The survey results suggest that most of the Saudi population has sound knowledge and a positive attitude and perception. Since the COVID-19 vaccines have been approved for use in pregnancy and above 12-year-old children by health authorities, the lack of information shown by a significant percentage of participants requires strategies to update this information. Awareness programs targeting all sections of the population must be continued to provide all the updates, including vaccinations for pregnant women and children. | Int J Environ Res Public Healt | 2021 | LitCov and CORD-19 | |
| 1598 | COVID-19: angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection COVID-19 pandemic is caused by the novel coronavirus SARS-CoV-2. Angiotensin-converting enzyme 2 (ACE2) is not only an enzyme but also a functional receptor on cell surfaces through which SARS-CoV-2 enters the host cells and is highly expressed in the heart, kidneys, and lungs and shed into the plasma. ACE2 is a key regulator of the renin–angiotensin–aldosterone system (RAAS). SARS-CoV-2 causes ACE/ACE2 balance disruption and RAAS activation, which leads ultimately to COVID-19 progression, especially in patients with comorbidities, such as hypertension, diabetes mellitus, and cardiovascular disease. Therefore, ACE2 expression may have paradoxical effects, aiding SARS-CoV-2 pathogenicity, yet conversely limiting viral infection. This article reviews the existing literature and knowledge of ACE2 in COVID-19 setting and focuses on its pathophysiologic involvement in disease progression, clinical outcomes, and therapeutic potential. | Eur J Clin Microbiol Infect Di | 2021 | LitCov and CORD-19 | |
| 1599 | Health Center Testing for SARS-CoV-2 During the COVID-19 Pandemic-United States, June 5-October 2, 2020 Long-standing social inequities and health disparities have resulted in increased risk for coronavirus disease 2019 (COVID-19) infection, severe illness, and death among racial and ethnic minority populations. The Health Resources and Services Administration (HRSA) Health Center Program supports nearly 1,400 health centers that provide comprehensive primary health care* to approximately 30 million patients in 13,000 service sites across the United States.† In 2019, 63% of HRSA health center patients who reported race and ethnicity identified as members of racial ethnic minority populations (1). Historically underserved communities and populations served by health centers have a need for access to important information and resources for preventing exposure to SARS-CoV-2, the virus that causes COVID-19, to testing for those at risk, and to follow-up services for those with positive test results.§ During the COVID-19 public health emergency, health centers¶ have provided and continue to provide testing and follow-up care to medically underserved populations**; these centers are capable of reaching areas disproportionately affected by the pandemic.†† HRSA administers a weekly, voluntary Health Center COVID-19 Survey§§ to track health center COVID-19 testing capacity and the impact of COVID-19 on operations, patients, and personnel. Potential respondents can include up to 1,382 HRSA-funded health centers.¶¶ To assess health centers' capacity to reach racial and ethnic minority groups at increased risk for COVID-19 and to provide access to testing, CDC and HRSA analyzed survey data for the weeks June 5-October 2, 2020*** to describe all patients tested (3,194,838) and those who received positive SARS-CoV-2 test results (308,780) by race/ethnicity and state of residence. Among persons with known race/ethnicity who received testing (2,506,935), 36% were Hispanic/Latino (Hispanic), 38% were non-Hispanic White (White), and 20% were non-Hispanic Black (Black); among those with known race/ethnicity with positive test results, 56% were Hispanic, 24% were White, and 15% were Black. Improving health centers' ability to reach groups at increased risk for COVID-19 might reduce transmission by identifying cases and supporting contact tracing and isolation. Efforts to improve coordination of COVID-19 response-related activities between state and local public health departments and HRSA-funded health centers can increase access to testing and follow-up care for populations at increased risk for COVID-19. | MMWR Morb Mortal Wkly Rep | 2020 | LitCov and CORD-19 | |
| 1600 | COVID-19 in patients with thoracic malignancies (TERAVOLT): first results of an international, registry-based, cohort study BACKGROUND: Early reports on patients with cancer and COVID-19 have suggested a high mortality rate compared with the general population. Patients with thoracic malignancies are thought to be particularly susceptible to COVID-19 given their older age, smoking habits, and pre-existing cardiopulmonary comorbidities, in addition to cancer treatments. We aimed to study the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on patients with thoracic malignancies. METHODS: The Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry is a multicentre observational study composed of a cross-sectional component and a longitudinal cohort component. Eligibility criteria were the presence of any thoracic cancer (non-small-cell lung cancer [NSCLC], small-cell lung cancer, mesothelioma, thymic epithelial tumours, and other pulmonary neuroendocrine neoplasms) and a COVID-19 diagnosis, either laboratory confirmed with RT-PCR, suspected with symptoms and contacts, or radiologically suspected cases with lung imaging features consistent with COVID-19 pneumonia and symptoms. Patients of any age, sex, histology, or stage were considered eligible, including those in active treatment and clinical follow-up. Clinical data were extracted from medical records of consecutive patients from Jan 1, 2020, and will be collected until the end of pandemic declared by WHO. Data on demographics, oncological history and comorbidities, COVID-19 diagnosis, and course of illness and clinical outcomes were collected. Associations between demographic or clinical characteristics and outcomes were measured with odds ratios (ORs) with 95% CIs using univariable and multivariable logistic regression, with sex, age, smoking status, hypertension, and chronic obstructive pulmonary disease included in multivariable analysis. This is a preliminary analysis of the first 200 patients. The registry continues to accept new sites and patient data. FINDINGS: Between March 26 and April 12, 2020, 200 patients with COVID-19 and thoracic cancers from eight countries were identified and included in the TERAVOLT registry; median age was 68·0 years (61·8–75·0) and the majority had an Eastern Cooperative Oncology Group performance status of 0–1 (142 [72%] of 196 patients), were current or former smokers (159 [81%] of 196), had non-small-cell lung cancer (151 [76%] of 200), and were on therapy at the time of COVID-19 diagnosis (147 [74%] of 199), with 112 (57%) of 197 on first-line treatment. 152 (76%) patients were hospitalised and 66 (33%) died. 13 (10%) of 134 patients who met criteria for ICU admission were admitted to ICU; the remaining 121 were hospitalised, but were not admitted to ICU. Univariable analyses revealed that being older than 65 years (OR 1·88, 95% 1·00–3·62), being a current or former smoker (4·24, 1·70–12·95), receiving treatment with chemotherapy alone (2·54, 1·09–6·11), and the presence of any comorbidities (2·65, 1·09–7·46) were associated with increased risk of death. However, in multivariable analysis, only smoking history (OR 3·18, 95% CI 1·11–9·06) was associated with increased risk of death. INTERPRETATION: With an ongoing global pandemic of COVID-19, our data suggest high mortality and low admission to intensive care in patients with thoracic cancer. Whether mortality could be reduced with treatment in intensive care remains to be determined. With improved cancer therapeutic options, access to intensive care should be discussed in a multidisciplinary setting based on cancer specific mortality and patients' preference. FUNDING: None. | Lancet Oncol | 2020 | 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.