Viral genomic, metagenomic and human transcriptomic characterization and prediction of the clinical forms of COVID-19

Abstract

COVID-19 is characterized by respiratory symptoms of various severities, ranging from mild upper respiratory signs to acute respiratory failure/acute respiratory distress syndrome associated with a high mortality rate. However, the pathophysiology of the disease is largely unknown. Shotgun metagenomics from nasopharyngeal swabs were used to characterize the genomic, metagenomic and transcriptomic features of patients from the first pandemic wave with various forms of COVID-19, including outpatients, patients hospitalized not requiring intensive care, and patients in the intensive care unit, to identify viral and/or host factors associated with the most severe forms of the disease. Neither the genetic characteristics of SARS-CoV-2, nor the detection of bacteria, viruses, fungi or parasites were associated with the severity of pulmonary disease. Severe pneumonia was associated with overexpression of cytokine transcripts activating the CXCR2 pathway, whereas patients with benign disease presented with a T helper “Th1-Th17” profile. The latter profile was associated with female gender and a lower mortality rate. Our findings indicate that the most severe cases of COVID-19 are characterized by the presence of overactive immune cells resulting in neutrophil pulmonary infiltration which, in turn, could enhance the inflammatory response and prolong tissue damage. These findings make CXCR2 antagonists, in particular IL-8 antagonists, promising candidates for the treatment of patients with severe COVID-19.

Molecular signature of postmortem lung tissue from COVID-19 patients suggests distinct trajectories driving mortality

“…Studies during previous SARS and Middle East respiratory syndrome (MERS) epidemics showed that individuals receiving invasive mechanical ventilation were more likely to develop secondary infections and have a higher fatality rate ( Feldman and Anderson, 2021 ). Recent investigations indicate that coinfections and/or superinfections occur at varying frequencies in oral, blood and urine samples from COVID-19 patients ( Charalampous et al, 2020 ; Langford et al, 2020 ; Mostafa et al, 2020 ; Alhumaid et al, 2021 ; Ripa et al, 2021 ; Rodriguez et al, 2021 ; Silva et al, 2021 ; Vijay et al, 2021 ). However, little is known about the prevalence of these pathogens and their exact molecular relevance in the human lung tissue during COVID-19 infection.…”

Molecular signature of postmortem lung tissue from COVID-19 patients suggests distinct trajectories driving mortality

“…Studies during previous SARS and MERS epidemics showed individuals receiving invasive mechanical ventilation were more likely to develop secondary infections and have a higher fatality rate (Feldman & Anderson, 2021). Recent investigations indicate that coinfections and/or superinfections occur at varying frequencies in oral, blood, and urine samples from COVID-19 patients (Alhumaid et al, 2021; Charalampous et al, 2020; Langford et al, 2020; Mostafa et al, 2020; Ripa et al, 2021; Rodriguez et al, 2021; Silva et al, 2021; Vijay et al, 2021). However, little is known about the prevalence of these pathogens and their exact molecular relevance in the human lung tissue during COVID-19 infection.…”

Genomic characterization of the dominating Beta, V2 variant carrying vaccinated (Oxford−AstraZeneca) and nonvaccinated COVID‐19 patient samples in Bangladesh: A metagenomics and whole‐genome approach

“…to evolve and interact together along with SARS-CoV-2. 18 Worryingly, the coexistence of other microbial pathogens and underlying intricate molecular pathogenesis leading to exorbitant indisposition in severely ill COVID-19 patients. 19 In this scenario, empiric broad-spectrum use of antibiotics has been prescribed for the majority of the COVID-19 patients irrespective of the cause.…”

“…This technology allows to detect and describe a wide range of known and unknown emerging pathogens, including their virulence and/or AMR profiles. 18 This study thus was carried out to precisely analyze the meta-transcriptomic sequencing data to reveal the genomic and metagenomic features among vaccinated and nonvaccinated populations, though the complete host−pathogen interaction may not be elucidated.…”