Efficacy and safety of traditional Chinese medicine and antiviral antibody therapies for COVID-19: a network meta-analysis

Objective To systematically review the efficacy and safety of traditional Chinese medicine (TCM) and antiviral antibody therapy in the treatment of COVID-19. Methods PubMed, EMbase, The Cochrane Library, Web of Science, CNKI, WanFang Data, VIP and SinoMED databases were electronically searched to collect randomized controlled trials (RCTs) on efficacy and safety of traditional Chinese medicine and antiviral antibody therapies for COVID-19 from inception to June 2022. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies;then, network meta-analysis was performed by using Stata 14.0 software. Results A total of 44 RCTs were included. The results of network meta-analysis showed that, for mortality rate, the rank of cumulative probability was: TCM+ standard care (SC) (100%)>convalescent plasma (CP)+SC (42%)>SC (8%). In terms of hospital stay time, the rank of cumulative probability was: TCM+SC (95.5%)>SC (31.4%)>CP+SC (23.2%). In terms of time to viral clearance, the rank of cumulative probability was: TCM+SC (97.4%)>SC (37.4%)>CP+SC (15.2%). In the aspect of mechanical ventilation rate, the rank of cumulative probability was: TCM+SC (98.9%)>CP+SC (42.9%)>SC (8.3%). In the aspect of adverse reactions/events, the rank of cumulative probability was: TCM+SC (99.9%)>SC (47.9%)>CP+SC (2.2%). Conclusion The current evidence shows that TCM combined with SC is the most effective treatment in reducing mortality, shortening hospitalization time and viral negative conversion time, reducing mechanical ventilation rate, and the incidence of adverse reactions/events is low. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify above conclusion. Copyright © 2022 West China University of Medical Science. All rights reserved.

Stability of SARS-CoV-2-Encoded Proteins and Their Antibody Levels Correlate with Interleukin 6 in COVID-19 Patients.

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has become a severe global public health crisis. Therefore, understanding the molecular details of SARS-CoV-2 will be critical for fighting the virus's spread and preventing future pandemics. In this study, we globally profiled the stability of SARS-CoV-2-encoded proteins, studied their degradation pathways, and determined their correlation with the antibody responses in patient plasma. We identified 18 proteins with unstable half-lives and 6 relatively stable proteins with longer half-lives. The labile SARS-CoV-2 proteins were degraded mainly by the ubiquitin-proteasome pathway. We also observed a significant correlation between antibody levels and protein half-lives, which indicated that a stable antigen of SARS-CoV-2 could be more effective for eliciting antibody responses. In addition, levels of antiviral antibodies targeting NSP10 were found to be negatively correlated with systemic levels of interleukin 6 (IL-6) in patients. These findings may facilitate the development of novel therapeutic or diagnostic approaches. IMPORTANCE SARS-CoV-2, the etiological cause of COVID-19, carries 29 genes in its genome. However, our knowledge of the viral proteins in biological and biochemical aspects is limited. In this study, we globally profiled the stability of the viral proteins in living lung epithelial cells. Importantly, the labile SARS-CoV-2-encoded proteins were mainly degraded through the ubiquitin-proteasome pathway. Stable proteins, including spike and nucleocapsid, of SARS-CoV-2 were more effective in eliciting antibody production. The levels of antiviral antibodies targeting NSP10 were negatively correlated with systemic levels of IL-6 in COVID-19 patients.

B-Cell Responses in Hospitalized Severe Acute Respiratory Syndrome Coronavirus 2-Infected Children With and Without Multisystem Inflammatory Syndrome.

Multisystem inflammatory syndrome in children (MIS-C) can complicate infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but differences in the immune responses during MIS-C compared to coronavirus disease 2019 (COVID-19) are poorly understood. We longitudinally compared the amounts and avidity of plasma anti-nucleocapsid (N) and spike (S) antibodies, phenotypes of B cells, and numbers of virus-specific antibody-secreting cells in circulation of children hospitalized with COVID-19 (n = 10) and with MIS-C (n = 12). N-specific immunoglobulin G (IgG) was higher early after presentation for MIS-C than COVID-19 patients and avidity of N- and S-specific IgG at presentation did not mature further during follow-up as it did for COVID-19. Both groups had waning proportions of B cells in circulation and decreasing but sustained production of virus-specific antibody-secreting cells for months. Overall, B-cell responses were similar, but those with MIS-C demonstrated a more mature antibody response at presentation compared to COVID-19, suggesting a postinfectious entity.

Continued Virus-Specific Antibody-Secreting Cell Production, Avidity Maturation and B Cell Evolution in Patients Hospitalized with COVID-19.

Understanding the development and sustainability of the virus-specific protective immune response to infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remains incomplete with respect to the appearance and disappearance of virus-specific antibody-secreting cells (ASCs) in circulation. Therefore, we performed cross-sectional and longitudinal analyses of peripheral blood mononuclear cells and plasma collected from 55 hospitalized patients up to 4 months after onset of COVID-19 symptoms. Spike (S)- and nucleocapsid (N)-specific IgM and IgG ASCs appeared within 2 weeks accompanied by flow cytometry increases in double negative plasmablasts consistent with a rapid extrafollicular B cell response. Total and virus-specific IgM and IgG ASCs peaked at 3-4 weeks and were still being produced at 3-4 months accompanied by increasing antibody avidity consistent with a slower germinal center B cell response. N-specific ASCs were produced for longer than S-specific ASCs and avidity maturation was greater for antibody to N than S. Patients with more severe disease produced more S-specific IgM and IgG ASCs than those with mild disease and had higher levels of N- and S-specific antibody. Women had more B cells in circulation than men and produced more S-specific IgA and IgG and N-specific IgG ASCs. Flow cytometry analysis of B cell phenotypes showed an increase in circulating B cells at 4-6 weeks with decreased percentages of switched and unswitched memory B cells. These data indicate ongoing antigen-specific stimulation, maturation, and production of ASCs for several months after onset of symptoms in patients hospitalized with COVID-19.