ABSTRACT
Background: Sex-disaggregated data suggest that men with coronavirus disease 2019 (COVID-19) are more likely to die than women. Whether circulating testosterone or sex hormone-binding globulin (SHBG) contributes to such sex differences remains unknown. Objective: To evaluate the associations of circulating total testosterone (TT), free testosterone (FT), and SHBG with COVID-19 mortality. Design: Prospective analysis. Setting: UK Biobank. Participants: We included 1306 COVID-19 patients (678 men and 628 women) who had serum TT and SHBG measurements and were free of cardiovascular disease or cancer at baseline (2006-2010). Main outcome measures: The death cases of COVID-19 were identified from National Health Service death records updated at 31 July 2020. Unconditional logistic regression was performed to estimate the odds ratio (OR) and 95% confidence intervals (CI) for mortality. Results: We documented 315 deaths of COVID-19 (194 men and 121 women). After adjusting for potential confounders, we did not find any statistically significant associations for TT (OR per 1-SD increase = 1.03, 95% CI: 0.85-1.25), FT (OR per 1-SD increase = 0.95, 95% CI: 0.77-1.17), or SHBG (OR per 1-SD increase = 1.09, 95% CI: 0.87-1.37) with COVID-19 mortality in men. Similar null results were observed in women (TT: OR per 1-SD increase = 1.10, 95% CI: 0.85-1.42; FT: OR per 1-SD increase = 1.10, 95% CI: 0.82-1.46; SHBG: OR per 1-SD increase = 1.16, 95% CI: 0.89-1.53). Conclusions: Our findings do not support a significant role of circulating testosterone or SHBG in COVID-19 prognosis.
Subject(s)
COVID-19 , Neoplasms , Cardiovascular DiseasesABSTRACT
BackgroundCoronavirus disease 2019 (COVID-19) deteriorates suddenly primarily due to excessive inflammatory injury, and insulin-like growth factor-1 (IGF-1) is implicated in endocrine control of the immune system. However, the effect of IGF-1 levels on COVID-19 prognosis remains unknown. ObjectiveTo investigate the association between circulating IGF-1 concentrations and mortality risk among COVID-19 patients. DesignProspective analysis. SettingUK Biobank. Participants1425 COVID-19 patients who had pre-diagnostic serum IGF-1 measurements at baseline (2006-2010). Main outcome measuresCOVID-19 mortality (available death data updated to 22 May 2020). Unconditional logistic regression was performed to estimate the odds ratio (OR) and 95% confidence intervals (CIs) of mortality across the IGF-1 quartiles. ResultsAmong 1425 COVID-19 patients, 365 deaths occurred due to COVID-19. Compared to the lowest quartile of IGF-1 concentrations, the highest quartile was associated with a 37% lower risk of mortality (OR: 0.63, 95% CI: 0.43-0.93, P-trend=0.03). The association was stronger in women and nonsmokers (both P-interaction=0.01). ConclusionsHigher IGF-1 concentrations are associated with a lower risk of COVID-19 mortality. Further studies are required to determine whether and how targeting IGF-1 pathway might improve COVID-19 prognosis.
Subject(s)
COVID-19ABSTRACT
Background: The incubation period of SARS-CoV-2 remains uncertain, which has important implications for estimating transmission potential, forecasting epidemic trends, and decision-making in prevention and control. Purpose: To estimate the central tendency and dispersion for incubation period of COVID-19 and, in turn, assess the effect of a certain length of quarantine for close contacts in active monitoring. Data Sources: PubMed, Embase, medRxiv, bioRxiv, and arXiv, searched up to April 26, 2020 Study Selection: COVID-19 studies that described either individual-level incubation period data or summarized statistics for central tendency and dispersion measures of incubation period were recruited. Data Extraction: From each recruited study, either individual-level incubation period data or summarized statistics for central tendency and dispersion measures were extracted, as well as population characteristics including sample size, average age, and male proportion. Data Synthesis: Fifty-six studies encompassing 4 095 cases were included in this meta-analysis. The estimated median incubation period for general transmissions was 5.8 days [95% confidence interval (95%CI), 5.3 to 6.2 d]. Median and dispersion were higher for SARS-CoV-2 incubation compared to other viral respiratory infections. Furthermore, about 20 in 10 000 contacts in active monitoring would develop symptoms after 14 days, or below 1 in 10 000 for young-age infections or asymptomatic transmissions. Limitation: Small sample sizes for subgroups; some data were possibly used repeatedly in different studies; limited studies for outside mainland China; non-negligible intra-study heterogeneity. Conclusion: The long, dispersive incubation period of SARS-CoV-2 contributes to the global spread of COVID-19. Yet, a 14-day quarantine period is sufficient to trace and identify symptomatic infections, which while could be justified according to a better understanding of the crucial parameters.
Subject(s)
COVID-19 , Respiratory Tract InfectionsABSTRACT
Background: An outbreak caused by the 2019 novel coronavirus (2019-nCoV) has spread globally. However, the viral dynamics, co-infection and their associations with clinical severity, have not been well explored.Methods: We longitudinally enrolled 23 (Five severe-type, ten common-type and eight asymptomatic-type patients) hospitalized 2019-nCov-infected patients in Jiangsu between January 21 and February 11, 2020. Medical records and pharyngeal swab specimens, were collected to analyze the association between viral dynamic and disease severity.Results: Five severe-type, ten common-type and eight asymptomatic-type patients were enrolled. Linear mixed effects models revealed that the common and severe-type patients had a higher level of viral load (3.08 points, 95% CI, 0.51-5.65, P = 0.019; 6.07 points, 95% CI, 2.79-9.35, P < 0.001) and maintained a higher peak viral load ( P = 0.066 and 0.022, respectively), when compared with the asymptomatic group. Viral load shedding among older patients (aged ≥ 60) processed slower than that among younger patients ( P = 0.047). RNA virome sequencing identified two co-infected RNA viruses, Human endogenous retrovirus H (HERV) and Human picobirnavirus (HPBV). Of note, HPBV was detected in one severe-type and two common-type patients, while was not detected in all the asymptomatic cases.Conclusion: Higher viral load was positively associated with disease severity. This finding highlights the importance of monitoring the viral kinetics to identify patients at greater risk of progressing to severe pneumonia.
Subject(s)
COVID-19 , Coinfection , PneumoniaABSTRACT
Neutralizing antibody is one of the most effective interventions for acute pathogenic infection. Currently, over three million people have been identified for SARS-CoV-2 infection but SARS-CoV-2-specific vaccines and neutralizing antibodies are still lacking. SARS-CoV-2 infects host cells by interacting with angiotensin converting enzyme-2 (ACE2) via the S1 receptor-binding domain (RBD) of its surface spike glycoprotein. Therefore, blocking the interaction of SARS-CoV-2-RBD and ACE2 by antibody would cause a directly neutralizing effect against virus. In the current study, we selected the ACE2 interface of SARS-CoV-2-RBD as the targeting epitope for neutralizing antibody screening. We performed site-directed screening by phage display and finally obtained one IgG antibody (4A3) and several domain antibodies. Among them, 4A3 and three domain antibodies (4A12, 4D5, and 4A10) were identified to act as neutralizing antibodies due to their capabilities to block the interaction between SARS-CoV-2-RBD and ACE2-positive cells. The domain antibody 4A12 was predicted to have the best accessibility to all three ACE2-interfaces on the spike homotrimer. Pseudovirus and authentic SARS-CoV-2 neutralization assays showed that all four antibodies could potently protect host cells from virus infection. Overall, we isolated multiple formats of SARS-CoV-2-neutralizing antibodies via site-directed antibody screening, which could be promising candidate drugs for the prevention and treatment of COVID-19.
Subject(s)
Acute Disease , Severe Acute Respiratory Syndrome , Tumor Virus Infections , COVID-19ABSTRACT
Since December 2019, the outbreak of COVID-19 in Wuhan has spread rapidly due to population movement during the Spring Festival holidays. Since January 23rd, 2020, the strategies of containment and contact tracing followed by quarantine and isolation has been implemented extensively in mainland China, and the rates of detection and confirmation have been continuously increased, which have effectively suppressed the rapid spread of the epidemic. In the early stage of the outbreak of COVID-19, it is of great practical significance to analyze the transmission risk of the epidemic and evaluate the effectiveness and timeliness of prevention and control strategies by using mathematical models and combining with a small amount of real-time updated multi-source data. On the basis of our previous research, we systematically introduce how to establish the transmission dynamic models in line with current Chinese prevention and control strategies step by step, according to the different epidemic stages and the improvement of the data. By summarized our modelling and assessing ideas, the model formulations vary from autonomous to non-autonomous dynamic systems, the risk assessment index changes from the basic regeneration number to the effective regeneration number, and the epidemic development and assessment evolve from the early SEIHR transmission model-based dynamics to the recent dynamics which are mainly associated with the variation of the isolated and suspected population sizes.
ABSTRACT
Background: Previous studies have showed clinical characteristics of patients with the 2019 novel coronavirus disease (COVID-19) and the evidence of person-to-person transmission. Limited data are available for asymptomatic infections. This study aims to present the clinical characteristics of 24 cases with asymptomatic infection screened from close contacts and to show the transmission potential of asymptomatic COVID-19 virus carriers. Methods: Epidemiological investigations were conducted among all close contacts of COVID-19 patients (or suspected patients) in Nanjing, Jiangsu Province, China, from Jan 28 to Feb 9, 2020, both in clinic and in community. Asymptomatic carriers were laboratory-confirmed positive for the COVID-19 virus by testing the nucleic acid of the pharyngeal swab samples. Their clinical records, laboratory assessments, and chest CT scans were reviewed. Findings: None of the 24 asymptomatic cases presented any obvious symptoms before nucleic acid screening. Five cases (20.8%) developed symptoms (fever, cough, fatigue and etc.) during hospitalization. Twelve (50.0%) cases showed typical CT images of ground-glass chest and five (20.8%) presented stripe shadowing in the lungs. The remaining seven (29.2%) cases showed normal CT image and had no symptoms during hospitalization. These seven cases were younger (median age: 14.0 years; P = 0.012) than the rest. None of the 24 cases developed severe COVID-19 pneumonia or died. The median communicable period, defined as the interval from the first day of positive nucleic acid tests to the first day of continuous negative tests, was 9.5 days (up to 21 days among the 24 asymptomatic cases). Through epidemiological investigation, we observed a typical asymptomatic transmission to the cohabiting family members, which even caused severe COVID-19 pneumonia. Interpretation: The asymptomatic carriers identified from close contacts were prone to be mildly ill during hospitalization. However, the communicable period could be up to three weeks and the communicated patients could develop severe illness. These results highlighted the importance of close contact tracing and longitudinally surveillance via virus nucleic acid tests. Further isolation recommendation and continuous nucleic acid tests may also be recommended to the patients discharged.