Abstract
Understanding the processes of immune regulation in patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for improving treatment. Here, we performed longitudinal whole-transcriptome RNA sequencing on peripheral blood mononuclear cell (PBMC) samples from 18 patients with coronavirus disease 2019 (COVID-19) during their treatment, convalescence, and rehabilitation. After analyzing the regulatory networks of differentially expressed messenger RNAs (mRNAs), microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) between the different clinical stages, we found that humoral immunity and type I interferon response were significantly downregulated, while robust T-cell activation and differentiation at the whole transcriptome level constituted the main events that occurred during recovery from COVID-19. The formation of this T cell immune response might be driven by the activation of activating protein-1 (AP-1) related signaling pathway and was weakly affected by other clinical features. These findings uncovered the dynamic pattern of immune responses and indicated the key role of T cell immunity in the creation of immune protection against this disease.
Highlights
INTRODUCTION SinceDecember 2019, a new zoonotic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has swept the world, causing a variety of clinical syndromes collectively termed coronavirus disease 2019 (COVID-19).[1,2,3] The World Health Organization declared a pandemic in March 2020
According to the guidelines for diagnosis and management of COVID-19 (6th edition) issued by the National Health Commission of China, 5 patients developed severe pneumonia by imaging examination, with the percutaneous oxygen saturation (SpO2) less than 93% or respiratory rate (RR) exceeding 30 breaths/min in the resting state, and were diagnosed as severe COVID-19; 7 patients had fever, dyspnea, and other respiratory symptoms, with computed tomography (CT) imaging findings of pneumonia, but did not meet the severe criteria, and were classified as having moderate COVID-19; the remaining 6 patients were diagnosed as mild based on their milder clinical symptoms and no obvious pneumonia (Fig. 1a)
From February 24 to April 2, 2020, all the patients were discharged from the hospital in batches and entered the rehabilitation stage based on the following criteria: the respiratory symptoms had improved significantly, SpO2 and RR returned to normal in severe patients, CT imaging of the lungs showed obvious absorption of inflammation, and the nucleic acid tests were negative on 2 consecutive occasions (Fig. 1b, Supplementary Table 1)
Summary
December 2019, a new zoonotic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has swept the world, causing a variety of clinical syndromes collectively termed coronavirus disease 2019 (COVID-19).[1,2,3] The World Health Organization declared a pandemic in March 2020. The symptoms of COVID-19 are fever, dry cough, fatigue, diarrhea, conjunctivitis, and pneumonia.[1] Most people do seem to be less affected, either remaining totally asymptomatic or having only mild symptoms. Some people develop a severe pneumonia, acute respiratory distress syndrome (ARDS) or multiple organ failure.[2,4] It is currently believed that severe COVID-19 pathogenesis may be mediated by a unique immune response disorder, and the host antiviral immune response affects the severity of the disease and the clinical outcome.[5,6]
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