The longitudinal landscaping of inflammatory plasma factors reveals heterogeneous but core inflammatory modules in COVID-19 pneumonia

To define core inflammatory network responsible for severe COVID-19 pneumonia, we performed longitudinal quantitative analysis of 191 inflammatory factors in 955 plasma samples from 80 normal controls and 347 confirmed COVID-19 pneumonia patients, including 8 deceased patients. Differential expression analysis showed that 76% of plasma proteins (145 factors) were upregulated in severe COVID-19 patients compared with moderate patients, confirming overt inflammation in severe COVID-19 pneumonia. Global correlation analysis of the plasma factors revealed two core inflammatory modules, core I and II, comprising mainly myeloid cell and lymphoid cell compartments, respectively, with enhanced impact in a severity-dependent manner. We also observed elevated IFNA1 and suppressed IL12A, presenting a robust inverse correlation in severe patients, which was strongly associated with persistent hyperinflammation in 8.3% of moderate pneumonia patients and 59.4% of severe patients. Aberrant persistence of pulmonary and systemic inflammation might be associated with long COVID-19 sequelae