Comparison of the Respiratory Tractmicrobiome in Hospitalized COVID-19 Patients with Different Disease Severity (preprint)

Background: Little is known about the characteristics of respiratory tract microbiome in Coronavirus disease 2019 (COVID-19) inpatients with different severity. Methods: A cross-sectional study was conducted to characterize respiratory tract microbial communities of 69 COVID-19 inpatients from 64 nasopharyngeal swabs and 5 sputum specimens using 16S ribosomal RNA (rRNA) gene V3-V4 region sequencing. The bacterial profiles were used to find potential biomarkers by the two-step method, the combination of random forest model and the linear discriminant analysis effect size (LEfSe), and explore the connections with clinical characteristics by Spearman’s rank test. Results: : Compared with mild COVID-19 patients, severe patients had significantly decreased bacterial diversity ( P values were less than 0.05 in the alpha and beta diversity) and relative lower abundance of opportunistic pathogens, including Actinomyces , Prevotella , Rothia , Streptococcus , Veillonella . Eight potential biomarkers including Treponema, Lachnoanaerobaculum , Parvimonas, Selenomonas, Alloprevotella , Porphyromonas , Gemella and Streptococcus were found to distinguish the mild COVID-19 patients from the severe COVID-19 patients. The genera of Actinomyces and Prevotella were negatively correlated with age and inpatient days. Intensive Care Unit (ICU) admission, neutrophil count (GRA) and lymphocyte count (LYMPH) were significantly correlated with different genera in the two groups. In addition, there were a positive correlation between Klebsiella and white blood cell count (WBC) in two groups. Conclusion: The respiratory tract microbiome had significant difference in COVID-19 patients with different severity. The value of the respiratory tract microbiome as predictive biomarkers for COVID-19 severity merits further exploration.

Persistent SARS-COV-2 RNA positivity in a patient for 92 days after disease onset (preprint)

Background: Recently, patients with COVID-19 who showed persistently positive SARS-CoV-2 nucleic acid test results despite resolved clinical symptoms have attracted a lot of attention. We report the case of a patient with mild symptoms of coronavirus disease (COVID-19), who achieved clinical recovery but showed persistently positive SARS-CoV-2 nucleic acid test results until Day 92 after disease onset.Case presentation: The patient is a 50-year-old man with mild symptoms of coronavirus disease (COVID-19). He was quarantined for 105 days. Of these, inpatient quarantine lasted for 75 days. When the nucleic acid test results were negative for 3 consecutive days, the patient was discharged at Day 75 after disease onset. During this period, multiple samples were collected from the patient’s body surface, the surrounding environment, and physical surfaces, but none of these tested positive for SARS-CoV-2. These samples included those from anal swabs, hands, inner surface of mask, cell phone, bed rails, floor around the bed, and toilet bowl surface. However, nucleic acid retest results on Day 80 and Day 92 after disease onset were positive for SARS-CoV-2 nucleic acids. The patient continued with quarantine and observation at home. After the test results on Days 101 and 105 after disease onset were negative, quarantine was terminated at last.Conclusion: Per our knowledge, this is the longest known time that a patient has tested positive for SARS-CoV-2 nucleic acids. No symptoms were observed during follow-up. During hospitalization, the SARS-CoV-2 nucleic acid positivity was not observed in samples from the body surface and surrounding environment, and no verified transmission event occurred during the quarantine at home. After undergoing clinical recovery a minority of patients with COVID-19 have shown long-term positive results for the presence of the SARS-CoV-2 nucleic acid. This has provided new understanding and research directions for coronavirus infection. Long-term follow-up and quarantine measures have been employed for such patients. Further studies are required to analyze potential infectivity in such patients and determine whether more effective antiviral drugs or regimens to enable these patients to completely clear viral infection should be researched.