Characterization of Microbial Co-infections in the Respiratory Tract of hospitalized COVID-19 patients (preprint)

Summary Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of Coronavirus disease 2019 (COVID-19). However, microbial composition of the respiratory tract and other infected tissues, as well as their possible pathogenic contributions to varying degrees of disease severity in COVID-19 patients remain unclear. Method Between January 27 and February 26, 2020, serial clinical specimens (sputum, nasal and throat swab, anal swab and feces) were collected from a cohort of hospitalized COVID-19 patients, including 8 mildly and 15 severely ill patients (requiring ICU admission and mechanical ventilation), in the Guangdong province, China. Total RNA was extracted and ultra-deep metatranscriptomic sequencing was performed in combination with laboratory diagnostic assays. Co-infection rates, the prevalence and abundance of microbial communities in these COVID-19 patients were determined. Findings Notably, respiratory microbial co-infections were exclusively found in 84.6% of severely ill patients (11/13), among which viral and bacterial co-infections were detected by sequencing in 30.8% (4/13) and 69.2% (9/13) of the patients, respectively. In addition, for 23.1% (3/13) of the patients, bacterial co-infections with Burkholderia cepacia complex (BCC) and Staphylococcus epidermidis were also confirmed by bacterial culture. Further, a time-dependent, secondary infection of B. cenocepacia with expressions of multiple virulence genes in one severely ill patient was demonstrated, which might be the primary cause of his disease deterioration and death one month after ICU admission. Interpretation Our findings identified distinct patterns of co-infections with SARS-CoV-2 and various respiratory pathogenic microbes in hospitalized COVID-19 patients in relation to disease severity. Detection and tracking of BCC-associated nosocomial infections are recommended to improve the pre-emptive treatment regimen and reduce fatal outcomes of hospitalized patients infected with SARS-CoV-2. Funding National Science and Technology Major Project of China, National Major Project for Control and Prevention of Infectious Disease in China, the emergency grants for prevention and control of SARS-CoV-2 of Ministry of Science and Technology and Guangdong province, Guangdong Provincial Key Laboratory of Genome Read and Write, Guangdong Provincial Academician Workstation of BGI Synthetic Genomics, and Shenzhen Engineering Laboratory for Innovative Molecular Diagnostics.

Efficacy and Safety of Traditional Chinese Medicine in COVID-2019: A Study Protocol for an Open-Label, Multicenter Randomized Controlled Trial (preprint)

Introduction: The outbreak of a novel coronavirus (SARS-CoV-2) and associated COVID-19 disease in late December 2019 has led to a global pandemic. It directly leads to high morbidity and mortality, but also results in a devastating effect on the global economy. Unfortunately, there are no effective therapies or vaccines for it. Hence, we designed a randomized trial to evaluate the efficacy and safety of Traditional Chinese Medicine for treating patients with COVID-19.Methods and analysis: This is an open-label, multicenter randomized controlled clinical trial. One hundred and twelve patients infected by SARS-CoV-2 will be randomly assigned to the experimental or the control group in an equal ratio. The patients in control group will accept routine supportive clinically care including the therapies of anti-viral, anti-bacterial and ameliorating the related symptoms, while patients in the experimental group will be asked to take traditional Chinese medicine depending on the different stages of the disease for consecutive 14 days in addition to supportive care. All data will be gathered at baseline and on days 3, 7, 10 and 14. The primary outcome measures will be the time of Reverse Transcription PCR testing of respiratory tract sample turns to be negative. Secondary outcome measures will include Murray lung injury score, MuLBSTA score and TCM ( Traditional Chinese Medicine ) Syndrome Scoring System. A laboratory test will be taken before and after treatment to assess the safety of TCM.Discussion: The study may help to identify the the efficacy and safety of Traditional Chinese Medicine in treating COVID-2019.Trial registration: Chinese Clinical Trial Registry, ChiCTR2000030759.Registered on March 13th 2020-Retrospectively registered, http://www.chictr.org.cn/.