Long-Term Infection of SARS-CoV-2 Evoked a Potential CD4+ T Cell Differentiation in Non-Critical Pneumonia Patients: A Prospective Study
21 Pages Posted: 24 Mar 2020More...
Background: The outbreak of SARS-CoV-2-associated pneumonia, a disease called COVID-19, caused global concern. New cases of COVID-19 were gradually reduced under the strict quarantine measures in China. Many patients were still being hospitalized while some patients had been discharged continually. To investigate the differences between hospitalized patients and discharged ones may help to better understand the disease progression and guide the therapeutical strategy in the clinic.
Methods: We collected 334 confirmed COVID-19 patients including 212 still in hospital with a positive nucleic acid test on halfway for SARS-CoV-2 and 122 discharged from hospital from February 27, 2020, to March 1, 2020. We analyzed the disease duration from symptom onset to recovery, the time-points of undetectable viral nucleic acid from collected discharged cases. Furthermore, we addressed the viral loads of hospitalized patients and compared the viral loads, immune cells, and cytokine changes between the hospitalized and discharged patients.
Findings: In general, the hospitalized patients had a longer illness time compared with the discharged SARS-CoV-2 infected patients. Further analysis of viral loads by RT-PCR explored a long-term infection of SARS-CoV-2 that existed with the median time of 18·5 days. Serum analysis showed that both IgG and IgM were positive in all detected patients after infection of two weeks, while no significant difference was detected between hospitalized and discharged patients. CD4+ T and NK cells from hospitalized patients significantly increased, compared with the ones from discharged patients, while the CD8+ T cell decreased. Further analysis of the cytokines showed that IL-6, TNF-α, IFN-γ, IL-2, IL-4, and IL-10 from hospitalized patients were all significantly higher than the ones from discharged patients, indicating a potential of CD4+ T cell differentiation into Th1, Th2, Th17/Tfh, and Treg cells.
Interpretation: In this study, we highlighted that long-term viral infection exists in non-critical patients, and could induce the adaptive immune responses with increased CD4+ T cells and decreased CD8+ T cells. The increased CD4+ T cells had the potential to differentiate into Th1, Th2, Treg, or Th17/Tfh cells. Furthermore, we found that antibodies were produced in these patients, B cell responses were also initiated around two weeks after infection.
Funding Statement: This study was funded by the grants from the project of Thousand Youth Talents for DH; and from the China National Natural Science Foundation (Nos. 31770983 and 81974249 to DH).
Declaration of Interests: The authors declare no competing interests.
Ethics Approval Statement: This case series was approved by the Institutional Ethics Committee of Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. Written informed consent was waived by the Ethics Commission of the designated hospital for emerging infectious diseases.
Keywords: SARS-CoV-2, long-term infection, adaptive immune responses, CD4+ T cell differentiation
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