Based on Transcriptome Sequencing: Clinicians Need to Pay Attention to Fever Caused by Common Respiratory Pathogens During the Global Outbreak of COVID-19 (preprint)

Objectives:During the COVID-19 pandemic, clinicians and public health decision-makers especially focus on fever patients. Other common pathogens that may cause fever are easily overlooked. We aimed to describe the pathogen infection and epidemic trend of non-SARS-CoV-2 occurring in hospitalized patients.Methods:An observational cohort study of 733 consecutive patients admitted to Hospital Clinic of the Second Xiangya Hospital for COVID-19. All samples of a pharyngeal swab from patients with fever have been tested for nucleic acid and immune antigens of SARS-CoV-2 and Influenza A/B virus. 649 fever patients have been tested for nucleic acid in ten respiratory pathogens. Macrotranscriptome sequencing was performed on 26 samples.Results:Of a total of 733 patients with fever, 2.05% patients had confirmed SARS-CoV-2 infections. Fever patients with common respiratory pathogens in fever patients was 8.78%. There is no integration phenomenon between SARS-Cov-2 and the human genome. SARS-CoV-2 positive samples will also be infected with other viruses, especially adenovirus. Macrotranscript analysis showed that there was no significant difference in the species and genus levels of pathogens between Covid-19 patients and other fever patients. The main pathways that affect human metabolism after SARS-Cov-2 infection are the Calvin-Benson-Bassham cycle, pyrimidine deoxyribonucleotides de novo biosynthesis I and D-galactose degradation V.Conclusions:Most patients have a fever caused by common respiratory pathogens. Clinicians still need to pay more attention to infections of common respiratory pathogens in addition to SARS-CoV-2. China's public health measures to stop the spread of the epidemic have proven effective.

A Novel Protein Drug, Novaferon, as the Potential Antiviral Drug for COVID-19 (preprint)

Abstract Background Novaferon, a novel protein drug approved for the treatment of chronic hepatitis B in China, exhibits potent antiviral activities. We aimed to determine the anti-SARS-CoV-2 effects of Novaferon in vitro, and conducted a randomized, open-label, parallel group study to explore the antiviral effects of Novaferon for COVID-19. Methods In laboratory, the inhibition of Novaferon on viral replication in cells infected with SARS-CoV-2, and on SARS-CoV-2 entry into healthy cells was determined. Antiviral effects of Novaferon were evaluated in COVID-19 patients with treatment of Novaferon, Novaferon plus Lopinavir/Ritonavir, or Lopinavir/Ritonavir. The primary endpoint was the SARS-CoV-2 clearance rates on day 6 of treatment, and the secondary endpoint was the time to the SARS-CoV-2 clearance in COVID-19 patients Results Novaferon inhibited the viral replication in infected cells (EC50=1.02 ng/ml), and protected healthy cells from SARS-CoV-2 infection (EC50=0.1 ng/ml). Results from the 89 enrolled COVID-19 patients showed that both Novaferon and Novaferon plus Lopinavir/Ritonavir groups had significantly higher SARS-CoV-2 clearance rates on day 6 than the Lopinavir/Ritonavir group (50.0% vs.24.1%, p = 0.0400, and 60.0% vs.24.1%, p = 0.0053). Median time to SARS-CoV-2 clearance were 6 days, 6 days, and 9 days for three groups respectively, suggesting a 3-dayreduction of time to SARS-CoV-2 clearance in both Novaferon and Novaferon plus Lopinavir/Ritonavir groups compared with Lopinavir/Ritonavir group. Conclusions Novaferon exhibited anti-SARS-CoV-2 effects in vitro and in COVID-19 patients. These data justified the further evaluation of Novaferon. Key words: COVID-19, SARS-CoV-2, Novaferon, Antiviral drug, Lopinavir/Ritonavir

Clinical Characteristics of 20,662 Patients with COVID-19 in mainland China: A Systemic Review and Meta-analysis (preprint)

Coronavirus disease 2019 (COVID-19) is a global pandemic and has been widely reported; however, a comprehensive systemic review and meta-analysis has not been conducted. We systematically investigated the clinical characteristics of COVID-19 in mainland China to guide diagnosis and treatment. We searched the PubMed, Embase, Scopus, Web of Science, Cochrane Library, bioRxiv, medRxiv, and SSRN databases for studies related to COVID-19 published or preprinted in English or Chinese from January 1 to March 15, 2020. Clinical studies on COVID-19 performed in mainland China were included. We collected primary outcomes including signs and symptoms, chest CT imaging, laboratory tests, and treatments. Study selection, data extraction, and risk of bias assessment were performed by two independent reviewers. Qualitative and quantitative synthesis was conducted, and random-effects models were applied to pooled estimates. This study is registered with PROSPERO (number CRD42020171606). Of the 3624 records identified, 147 studies (20,662 patients) were analyzed. The mean age of patients with COVID-19 was 49.40 years, 53.45% were male, and 38.52% had at least one comorbidity. Fever and cough were the most common symptoms, followed by fatigue, expectoration, and shortness of breath. Most patients with COVID-19 had abnormal chest CT findings with ground glass opacity (70.70%) or consolidation (29.91%). Laboratory findings shown lymphopenia, increased lactate dehydrogenase, increased infection-related indicators, and fibrinolytic hyperactivity. Antiviral therapy, antibiotic therapy, and corticosteroids were administered to 89.75%, 79.13%, and 35.64% of patients, respectively. Most clinical characteristics of COVID-19 are non-specific. Patients with suspected should be evaluated by virological assays and clinically treated.