A bibliometric analysis of linguistic research on COVID-19

Research on COVID-19 has drawn the attention of scholars around the world since the outbreak of the pandemic. Several literature reviews of research topics and themes based on scientometric indicators or bibliometric analyses have already been conducted. However, topics and themes in linguistic-specific research on COVID-19 remain under-studied. With the help of the CiteSpace software, the present study reviewed linguistic research published in SSCI and A&HCI journals to address the identified gap in the literature. The overall performance of the documents was described and document co-citations, keyword co-occurrence, and keyword clusters were visualized via CiteSpace. The main topic areas identified in the reviewed studies ranged from the influences of COVID-19 on language education, and speech-language pathology to crisis communication. The results of the study indicate not only that COVID-19-related linguistic research is topically limited but also that insufficient attention has been accorded by linguistic researchers to Conceptual Metaphor Theory, Critical Discourse Analysis, Pragmatics, and Corpus-based discourse analysis in exploring pandemic discourses and texts.

No association between circulating levels of testosterone and sex hormone-binding globulin and risk of COVID-19 mortality in UK biobank (preprint)

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.

Pre-diagnostic circulating concentrations of insulin-like growth factor-1 and risk of COVID-19 mortality: results from UK Biobank (preprint)

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.

High viral load suggests increased COVID-19 severity in a longitudinal cohort (preprint)

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.

Isolating multiple formats of human monoclonal neutralizing antibodies against SARS-CoV-2 by in vitro site-directed antibody screening (preprint)

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.

Implications of the virus-encoded miRNA and host miRNA in the pathogenicity of SARS-CoV-2 (preprint)

The outbreak of COVID-19 caused by SARS-CoV-2 has rapidly spread worldwide and has caused over 1,400,000 infections and 80,000 deaths. There are currently no drugs or vaccines with proven efficacy for its prevention and little knowledge was known about the pathogenicity mechanism of SARS-CoV-2 infection. Previous studies showed both virus and host-derived MicroRNAs (miRNAs) played crucial roles in the pathology of virus infection. In this study, we use computational approaches to scan the SARS-CoV-2 genome for putative miRNAs and predict the virus miRNA targets on virus and human genome as well as the host miRNAs targets on virus genome. Furthermore, we explore miRNAs involved dysregulation caused by the virus infection. Our results implicated that the immune response and cytoskeleton organization are two of the most notable biological processes regulated by the infection-modulated miRNAs. Impressively, we found hsa-miR-4661-3p was predicted to target the S gene of SARS-CoV-2, and a virus-encoded miRNA MR147-3p could enhance the expression of TMPRSS2 with the function of strengthening SARS-CoV-2 infection in the gut. The study may provide important clues for the mechisms of pathogenesis of SARS-CoV-2.

Detection of 2019 novel coronavirus in semen and testicular biopsy specimen of COVID-19 patients (preprint)

Background: As of March 11, 2020, the COVID-19 outbreak was declared as a pandemic. Expending our understanding of the transmission routes of the viral infection is crucial in controlling the outbreak. It is unclear whether the 2019 novel coronavirus (2019-nCoV) can directly infect the testes or male genital tract and be sexually transmitted from males. Methods: From January 31 to March 14, 2020, 12 patients in recovery and one patient died of COVID-19 were included in this descriptive study. The clinical characteristics, laboratory findings, chest CT scans and outcome data were recorded. To examine whether there is sexual transmission from male, we employed realtime polymerase chain reaction testing (RT-PCR) to detect 2019-nCov in semen or testicular biopsy specimen. Findings: The age range of the 12 patients in recovery was 22-38 years. None of the patients developed severe COVID-19 pneumonia. As of March 14, 2020, ten patients discharged from the hospital while the rest 2 had developed into recovery stage. All of the patients in recovery tested negative for 2019-nCoV RNA in semen samples. Another died patient was 67 years old, who died in March 10, 2020 and tissue sample via testicular biopsy was tested negative for viral RNA. Conclusion: No positive RT-PCR result was found in the semen or testicular biopsy specimen. The results from this study show no evidence of sexual transmission of 2019-nCov from males.

Screening and management of asymptomatic infection of corona virus disease 2019 (COVID-19) / 中华预防医学杂志

To date, the controlling of outbreak of corona virus disease 2019 (COVID-19) has entered into a critical period in China. Recently, work resumption and public place is planning to open outside of Hubei, suggesting an uncertain and complex development of the epidemic in the next stage. Few days ago, we conducted a study on the epidemiological and clinical characteristics of asymptomatic infections of COVID-19, and found them might be the infection source. We believe that the findings are critical for developing public health intervention strategies for controlling COVID-19 infection in the future. Screening among the high-risk population and improving the sensitivity of measurement may contribute to the detection and management of asymptomatic infection.

Clinical Characteristics of 24 Asymptomatic Infections with COVID-19 Screened among Close Contacts in Nanjing, China (preprint)

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.