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Viral and host factors related to the clinical outcome of COVID-19

Our take —

In this study of 326 patients with laboratory-confirmed SAR-CoV-2 infection in Shanghai, severe disease was more likely to be associated with host factors than with viral characteristics. Older age, reduced levels of CD4+ and CD8+ T cells, and elevated levels of inflammation, specifically Interleukin-6 and Interleukin-8, were all statistically associated with clinical progression in multivariate adjustment; whereas, viral lineage and specific mutations were not.

Study design

Prospective Cohort

Study population and setting

This study included 326 patients with laboratory-confirmed SARS-CoV-2 admitted to the Shanghai Public Health Clinical Center in Shanghai, China from January 20 to February 25, 2020. Data collection included clinical and epidemiological characteristics, and serum cytokine measurements were obtained from 228 of these patients. Viral genome sequences from 112 patients were generated and used to analyse changes in the virus over time. The investigators characterized associations between clinical, immunological, and genomic parameters and disease severity (asymptomatic, mild, severe, and critical).

Summary of Main Findings

The median age was 51 years, and 53% were male. Among all 326 patients, 38% had at least one comorbidity upon admission. A majority (n=293) presented with mild disease. Two distinct groups, or clades, of the virus were identified, with one lineage linked to the Wuhan seafood market; both, however, exhibited similar virulence and clinical manifestations. Phylogenetic analysis indicates that the earliest possible spillover to humans occurred in late November 2019, and that there was limited variation in the virus genome in the sequences collected. Decreased levels of CD3+, CD4+, and CD8+ T cells were significantly associated with disease severity. Levels of IL-6 and IL-8 6 to 10 days post-symptom onset were significantly higher in critical cases relative to non-critical cases. The primary factors associated with disease severity in univariate analyses were higher age, lymphocyte count upon admission, presence of comorbidity, and male sex. In multivariate analysis, higher age and reduced lymphocyte count remained significantly associated with disease severity.

Study Strengths

This study examined a broad array of inflammatory biomarkers, including eleven cytokines and several lymphocyte subsets, as well as the genomic sequences from a relatively large sample of confirmed COVID-19 cases, and linked these characteristics with clinical progression.

Limitations

Variable selection method for multivariate analyses is unclear. The timing of the measurements of inflammatory biomarkers relative to the onset of clinical symptoms is unclear. Methodology for determining sequencing variants is simplistic and unclear.

Value added

This is one of the first studies to examine a broad array of inflammatory biomarkers, including eleven cytokines and several lymphocyte subsets, in conjunction with genomic sequences from a relatively large sample of confirmed COVID-19 cases, and to link these characteristics with clinical progression and epidemiological factors. It also provides phylogenetic evidence that mutations in the viral genome are not linked to clinical progression, suggesting that clinical progression is more closely linked with host factors than viral characteristics.