ABSTRACT
COVID-19 is characterized by dysregulated immune responses, metabolic dysfunction and adverse effects on the function of multiple organs. To understand host responses to COVID-19 pathophysiology, we combined transcriptomics, proteomics, and metabolomics to identify molecular markers in peripheral blood and plasma samples of 66 COVID-19-infected patients experiencing a range of disease severities and 17 healthy controls. A large number of expressed genes, proteins, metabolites, and extracellular RNAs (exRNAs) exhibit strong associations with various clinical parameters. Multiple sets of tissue-specific proteins and exRNAs varied significantly in both mild and severe patients suggesting a potential impact on tissue function. Chronic activation of neutrophils, IFN-I signaling, and a high level of inflammatory cytokines were observed in patients with severe disease progression. In contrast, COVID-19-infected patients experiencing milder disease symptoms showed robust T-cell responses. Finally, we identified genes, proteins, and exRNAs as potential biomarkers that might assist in predicting the prognosis of SARS-CoV-2 infection. These data refine our understanding of the pathophysiology and clinical progress of COVID-19. SYNOPSIS image Proteomics, metabolomics and RNAseq data map immune responses in COVID-19 patients with different disease severity, revealing molecular makers associated with disease progression and alterations of tissue-specific proteins. A multi-omics profiling of the host response to SARS-CoV2 infection in 66 clinically diagnosed and laboratory confirmed COVID-19 patients and 17 uninfected controls. Significant correlations between multi-omics data and key clinical parameters. Alteration of tissue-specific proteins and exRNAs. Enhanced activation of immune responses is associated with COVID-19 pathogenesis. Biomarkers to predict COVID-19 clinical outcomes pending clinical validation as prospective marker.
ABSTRACT
Background. The course of disease in mild and moderate COVID-19 has many implications for mobile patients, such as the risk of spread of the infection, precautions taken, and investigations targeted at preventing transmission. Methods. Three hundred thirty-one adults were hospitalized from January 21 to February 22, 2020, and classified as severe (10%) or critical (4.8%) cases;1.5% died. Two hundred eighty-two (85.2%) mild or moderate cases were admitted to regular wards. Epidemiological, demographic, clinical, chest computed tomography (CT) scan, laboratory, treatment, and outcome data from patient records were analyzed retrospectively. Results. Patients were symptomatic for 9.82 +/- 5.75 (1-37) days. Pulmonary involvement was demonstrated on a chest CT scan in 97.9% of cases. It took 16.81 +/- 8.54 (3-49) days from the appearance of the first symptom until 274 patients tested virus-negative in naso- and oropharyngeal (NP) swabs, blood, urine, and stool, and 234 (83%) patients were asymptomatic for 9.09 +/- 7.82 (1-44) days. Subsequently, 131 patients were discharged. One hundred sixty-nine remained in the hospital;these patients tested virus-free and were clinically asymptomatic because of widespread persisting or increasing pulmonary infiltrates. Hospitalization took 16.24 +/- 7.57 (2-47) days;the time interval from the first symptom to discharge was 21.37 +/- 7.85 (3-52) days. Conclusions. With an asymptomatic phase, disease courses are unexpectedly long until the stage of virus negativity. NP swabs are not reliable in the later stages of COVID-19. Pneumonia outlasts virus-positive tests if sputum is not acquired. Imminent pulmonary fibrosis in high-risk groups demands follow-up examinations. Investigation of promising antiviral agents should heed the specific needs of mild and moderate COVID-19 patients.