The COVID-19 outbreak was first identified in Wuhan, China. Despite the causal agent being closely related to a bat coronavirus (RaTG13), several questions remain regarding the origin, evolution and host interaction of COVID-19. Although the Seafood Market in Wuhan is suggested as the origin of the outbreak, some initial cases occurred in patients without contact with the market.
In their Nature study Xiaonan Zhang et al. from the Shanghai Public Health Clinical Center, Fudan University, Shanghai, China, analyzed the clinical, molecular and immunological characteristics of 326 confirmed COVID-19 patients in Shanghai between January 20th to February 25th, 2020. Patients were divided into 4 groups according to their presentation of infection; asymptomatic, mild (fever and pneumonia), critical (+dyspnea and lung opacity) or severe (+acute respiratory distress with oxygen support). Their clinical features were correlated with virus genome variation and host factors associated with disease severity.
The authors compared the genome of the virus isolated in Shanghai with the first-release genomes from Wuhan (Wuhan-Hu-1) and reported a similar viral genome between these two cities. Further analysis of COVID-19 genomic phylogeny indicated that the two major viral lineages share a common ancestor.
In addition, Zhang et al. showed progressive decline of CD3+, CD4+, and CD8+ T cells counts in COVID-19 infected patients. The lymphocytopenia observed in these patients was inversely correlated to serum IL-6 and IL-8 levels, and a significant high level of IL-6 was found in critical patients. These results indicate that loss of blood T lymphocytes and increased levels of serum IL-6 in COVID-19-infected patients can anticipate disease severity and mortality.
The authors discuss that the loss of CD3+ T lymphocytes may represent an underlying mechanism for disease progression, most likely caused by lymphocyte infiltration, induced by pro-inflammatory cytokines.
In summary, the study of Zhang et al. found evidence that COVID-19 severity is associated with depletion of CD3+ T lymphocytes, particularly the CD4+ and CD8+ fractions, and associated with high levels of IL-6 and IL-8. The study provides new insights into viral and host factors contributing to disease mechanisms and outcome that may help in designing new treatment strategies for COVID-19.