Feasibility analysis and mechanism exploration of Rhei Radix et Rhizome-Schisandrae Sphenantherae Fructus (RS) against COVID-19.

Introduction. As a novel global epidemic, corona virus disease 2019 (COVID-19) caused by SARS-CoV-2 brought great suffering and disaster to mankind. Recently, although significant progress has been made in vaccines against SARS-CoV-2, there are still no drugs for treating COVID-19. It is well known that traditional Chinese medicine (TCM) has achieved excellent efficacy in the treatment of COVID-19 in China. As a treasure-house of natural drugs, Chinese herbs offer a promising prospect for discovering anti-COVID-19 drugs.Hypothesis/Gap Statement. We proposed that Rhei Radix et Rhizome-Schisandrae Sphenantherae Fructus (RS) may have potential value in the treatment of COVID-19 patients by regulating immune response, protecting the cardiovascular system, inhibiting the production of inflammatory factors, and blocking virus invasion and replication processes.Aim. We aimed to explore the feasibility and molecular mechanisms of RS against COVID-19, to provide a reference for basic research and clinical applications.Methodology. Through literature mining, it is found that a Chinese herbal pair, RS, has potential anti-COVID-19 activity. In this study, we analysed the feasibility of RS against COVID-19 by high-throughput molecular docking and molecular dynamics simulations. Furthermore, we predicted the molecular mechanisms of RS against COVID-19 based on network pharmacology.Results. We proved the feasibility of RS anti-COVID-19 by literature mining, virtual docking and molecular dynamics simulations, and found that angiotensin converting enzyme 2 (ACE2) and 3C-like protease (3 CL pro) were also two critical targets for RS against COVID-19. In addition, we predicted the molecular mechanisms of RS in the treatment of COVID-19, and identified 29 main ingredients, 21 potential targets and 16 signalling pathways. Rhein, eupatin, (-)-catechin, aloe-emodin may be important active ingredients in RS. ALB, ESR1, EGFR, HMOX1, CTSL, and RHOA may be important targets against COVID-19. Platelet activation, renin secretion, ras signalling pathway, chemokine signalling pathway, and human cytomegalovirus infection may be important signalling pathways against COVID-19.Conclusion. RS plays a key role in the treatment of COVID-19, which may be closely related to immune regulation, cardiovascular protection, anti-inflammation, virus invasion and replication processes.

Immune responses and pathogenesis in persistently PCR-positive patients with SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 emerged in China in December 2019 and then rapidly spread worldwide. Why COVID-19 patients with the same clinical condition have different outcomes remains unclear. This study aimed to examine the differences in the phenotype and functions of major populations of immune cells between COVID-19 patients with same severity but different outcomes. Four common type adult inpatients with laboratory confirmed COVID-19 from Beijing YouAn Hospital, Capital Medical University were included in this study. The patients were divided into two groups based on whether or not COVID-19 polymerase chain reaction (PCR)-negative conversion occurred within 3 weeks. Peripheral blood samples were collected to compare the differences in the phenotype and functions of major populations of immune cells between the two groups of patients. The result shows that the proportions of CD3+ CD8+ CD38+ HLA-DR+ CD27- effector T killer cells generally declined, whereas that of CD3+ CD4+ CD8+ double-positive T cells (DPTs) increased in the persistently PCR-positive patients. In summary, considering the imbalance between effector T killer cells/CD3+CD4+CD8+ DPTs was a possible key factor for PCR-negative conversion in patients with COVID-19.

Population Bottlenecks and Intra-host Evolution During Human-to-Human Transmission of SARS-CoV-2.

The emergence of the novel human coronavirus, SARS-CoV-2, causes a global COVID-19 (coronavirus disease 2019) pandemic. Here, we have characterized and compared viral populations of SARS-CoV-2 among COVID-19 patients within and across households. Our work showed an active viral replication activity in the human respiratory tract and the co-existence of genetically distinct viruses within the same host. The inter-host comparison among viral populations further revealed a narrow transmission bottleneck between patients from the same households, suggesting a dominated role of stochastic dynamics in both inter-host and intra-host evolutions.

Epidemic and control of COVID-19 in Niger: quantitative analyses in a least developed country.

BACKGROUND: The COVID-19 pandemic is challenging the public health response system worldwide, especially in poverty-stricken, war-torn, and least developed countries (LDCs). METHODS: We characterized the epidemiological features and spread dynamics of COVID-19 in Niger, quantified the effective reproduction number (Rt ), evaluated the impact of public health control measures, and estimated the disease burden. RESULTS: As of 4 July 2020, COVID-19 has affected 29 communes of Niger with 1093 confirmed cases, among whom 741 (67.8%) were males. Of them 89 cases died, resulting in a case fatality rate (CFR) of 8.1%. Both attack rates and CFRs were increased with age (P < 0.0001). Health care workers accounted for 12.8% cases. Among the reported cases, 39.3% were isolated and treated at home, and 42.3% were asymptomatic. 74.6% cases were clustered in Niamey, the capital of Niger. The Rt fluctuated in correlation to control measures at different outbreak stages. After the authorities initiated the national response and implemented the strictest control measures, Rt quickly dropped to below the epidemic threshold (<1), and maintained low level afterward. The national disability-adjusted life years attributable to COVID-19 was 1267.38 years in total, of which years of life lost accounted for over 99.1%. CONCLUSIONS: Classic public health control measures such as prohibition of public gatherings, travelling ban, contact tracing, and isolation and quarantine at home, are proved to be effective to contain the outbreak in Niger, and provide guidance for controlling the ongoing COVID-19 pandemic in LDCs.

Dysregulation of the immune response affects the outcome of critical COVID-19 patients.

Critical cases of coronavirus disease 2019 (COVID-19) are associated with a high risk of mortality. It remains unclear why patients with the same critical condition have different outcomes. We aimed to explore relevant factors that may affect the prognosis of critical COVID-19 patients. Six critical COVID-19 inpatients were included in our study. The six patients were divided into two groups based on whether they had a good or poor prognosis. We collected peripheral blood samples at admission and the time point of exacerbation to compare differences in the phenotypes and functions of major populations of immune cells between the groups. On admission, compared to patients with poor prognoses, those with good prognoses had significantly higher counts of monocytes (P < .05), macrophages (P < .05), higher frequency of CD3+ CD4+ CD45RO+ CXCR3+ subsets (P < .05), higher frequency of CD14+ CD11C+ HLA-DR+ subset of dendritic cells (P < .05), and a lower count of neutrophils (P < .05). At the time point of exacerbation, the proportions of naïve CD4+ T cells (P < .05), Tregs, and Th2 cells in the poor prognosis group were relatively higher than those in the good prognosis group, and CD4+ memory T cells were relatively lower (P < .05). According to our results, the poor prognosis group showed a worse immune response than the good prognosis group at the time of admission and at exacerbation. Dysregulation of the immune response affects the outcome of critical COVID-19 patients.

Epidemiological and clinical characteristics of 47 corona virus disease 2019 non-survivors in Huoshenshan Hospital

Objective To provide a basis for further optimizing the diagnosis and treatment strategies of severe and critical corona virus disease 2019 (COVID-19) by investigating and analyzing the epidemiological and clinical characteristics of the death cases. Methods The epidemiological and clinical characteristics of 47 death cases obtained from Huoshenshan Hospital in Whuhan, Hubei Province were retrospectively analyzed. Results All the patients developed initial symptoms in Wuhan. The time from onset to admission was (12.60±5.60) days. Most of them were male (68.09%) with non-nosocomial infection (91.49%), advanced age (>60 years, 89.36%). Over half of the cases (51.06%) reported a history of contact with suspected or confirmed patients, and comorbidity of chronic diseases (70.21%). Multiple organ dysfunction syndrome (MODS) occurred in 29 cases (61.70%) with heart failure (51.06%) and renal failure (36.17%). The main clinical symptoms included fever, fatigue, dyspnea and cough. At admission,most cases were severe (55.32%) or critical (42.55%), and the in-hospital survival was longer for the severe than for the critical (P=0.02). 76.59% of the patients received invasive mechanical ventilation, and they had a longer in-hospital survival than those with non-invasive mechanical ventilation (P<0.05). Conclusions This group of cases occurred during the peak of the COVID-19 outbreak in China, characterized by male, elder and history of chronic diseases. Acute respiratory distress syndrome (ARDS) caused by COVID-19 was responsible for patients' death, and MODS manifestated by heart and kidney failure also implicated in the process. Disease severity and invasive mechanical ventilation were related to in-hospital survival.

Potential of Arbidol for Post-exposure Prophylaxis of COVID-19 Transmission: A Preliminary Report of a Retrospective Cohort Study.

The efficient transmission of severe acute respiratory syndrome-2 coronavirus (SARS-CoV-2) from patients to health care workers or family members has been a worrisome and prominent feature of the ongoing outbreak. On the basis of clinical practice and in-vitro studies, we postulated that post-exposure prophylaxis (PEP) using Arbidol is associated with decreased infection among individuals exposed to confirmed cases of COVID-19 infection. We conducted a retrospective cohort study on family members and health care workers who were exposed to patients confirmed to have SARS-CoV-2 infection by real-time RT-PCR and chest computed tomography (CT) from January 1 to January 16, 2020. The last follow-up date was Feb. 26, 2020. The emergence of fever and/or respiratory symptoms after exposure to the primary case was collected. The correlations between post-exposure prophylaxis and infection in household contacts and health care workers were respectively analyzed. A total of 66 members in 27 families and 124 health care workers had evidence of close exposure to patients with confirmed COVID-19. The Cox regression based on the data of the family members and health care workers with Arbidol or not showed that Arbidol PEP was a protective factor against the development of COVID-19 (HR 0.025, 95% CI 0.003-0.209, P=0.0006 for family members and HR 0.056, 95% CI 0.005-0.662, P=0.0221 for health care workers). Our findings suggest Arbidol could reduce the infection risk of the novel coronavirus in hospital and family settings. This treatment should be promoted for PEP use and should be the subject of further investigation.