Viral reactivation in the lungs of patients with severe pneumonia is associated with increased mortality, a multicenter, retrospective study.

PURPOSE: Viral reactivation is widespread in patients with severe pneumonia, yet the landscape of viral reactivation in the lungs is not well-known. This study aims to assess the landscape and clinical features of viral reactivation in the early onset of severe pneumonia in ICU patients. METHODS: The clinical data from 97 patients were collected retrospectively from the intensive care units of five teaching hospitals between June 2018 and July 2021. Metagenomic next-generation sequencing (mNGS) of the bronchoalveolar lavage fluid (BALF) was performed at the onset of severe pneumonia. RESULTS: Cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), and Epstein-Barr virus (EBV) were the most common reactivated viruses in the lower respiratory tract of patients with severe pneumonia. After adjusting for the risk of confounding and competition of age, sex, sequential organ failure assessment, acute physiology chronic health assessment II and immunosuppression status, viral reactivation resulted in an overall 2.052-fold increase in 28-day all-cause mortality (95% CI: 1.004-4.194). CONCLUSION: This study showed that CMV, HSV-1, and EBV were the most common reactivated viruses in the lungs of patients with severe pneumonia. The existence of viral reactivations was associated with an increased risk of mortality. The simultaneous reactivation of multiple viruses needs to be considered in the design of clinical trials. This article is protected by copyright. All rights reserved.

Worldwide tracing of mutations and the evolutionary dynamics of SARS-CoV-2 (preprint)

Understanding the mutational and evolutionary dynamics of SARS-CoV-2 is essential for treating COVID-19 and the development of a vaccine. Here, we analyzed publicly available 15,818 assembled SARS-CoV-2 genome sequences, along with 2,350 raw sequence datasets sampled worldwide. We investigated the distribution of inter-host single nucleotide polymorphisms (inter-host SNPs) and intra-host single nucleotide variations (iSNVs). Mutations have been observed at 35.6% (10,649/29,903) of the bases in the genome. The substitution rate in some protein coding regions is higher than the average in SARS-CoV-2 viruses, and the high substitution rate in some regions might be driven to escape immune recognition by diversifying selection. Both recurrent mutations and human-to-human transmission are mechanisms that generate fitness advantageous mutations. Furthermore, the frequency of three mutations (S protein, F400L; ORF3a protein, T164I; and ORF1a protein, Q6383H) has gradual increased over time on lineages, which provides new clues for the early detection of fitness advantageous mutations. Our study provides theoretical support for vaccine development and the optimization of treatment for COVID-19. We call researchers to submit raw sequence data to public databases.