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Multifaceted Examination and Assessment of COVID-19 Convalescent Patients in Wuhan, China: A Follow-Up Study of Survivors Three Months after Discharge
46 Pages Posted: 14 Oct 2020
More...Abstract
Background: Multiple organ damage and abnormal inflammation caused by COVID-19 have previously been reported in hospitalized patients. It remains unclear whether these patients can return to a healthy individual three months after discharge and whether there are related sequelae.
Methods: We followed up 95 severe/critical patients and 51 mild/moderate ones who recovered from COVID-19 and were discharged from hospital for 3 months. For comparison, 28 asymptomatic COVID-19 recovered individuals and 42 uninfected healthy donors (HDs) were included. At the visit, patients were interviewed and subjected to quality-of-life evaluation (St. George respiratory questionnaire [SGRQ]), pulmonary function tests, chest CT imaging, laboratory examination, detection of immune cells, and cytokine profiling.
Findings: At three months, all recovered patients tested negative for nucleic acid of SARS-CoV-2, and most were positive for serum SARS-COV-2 IgG, but few were still positive for serum IgM. The SGRQ scores for the quality-of-life were higher in recovered patients, especially those who had had severe/critical disease. Laboratory test revealed that CRP, LDH and D-dimer, three prevalent risk factors for COVID-19 prognosis in the acute phase, did not recover to the level of uninfected HDs in the convalescence. Immune cells virtually returned to normal levels in patients who recovered from COVID-19, but some pro-inflammatory cytokines, especially chemokines and factors related to vascular injury and angiogenesis, did not return to the level of HDs, and this was especially true of severe/critical recovered patients. CT of the lungs showed that ground-glass opacity (GGO) still lingered as the main manifestation, followed by strip-like fibrosis. Artificial intelligence (AI) analysis indicated that the lesions were most prominent in the lower lobe of right lung, and were mainly found in recovered severe/critical individuals. Abnormal lung function was mainly manifested as restrictive ventilation dysfunction and lowered diffusion capacity, which was more pronounced in severe/critical COVID-19 recovered patients. Overall, the recovery status of the patients varied with the severity of the disease.
Interpretation: Decreased physical quality of life, respiratory sequelae (restrictive ventilatory dysfunction, diffusion capacity disorder, and chest CT abnormalities), vascular injury and aberrant cytokine profiles still existed three months after discharge, and were more frequent and conspicuous in severe/critical COVID-19 rehabilitation patients compared to their mild/moderate and asymptomatic counterparts.
Trial Registration: This project was registered on the Clinical Trials website (No. NCT04456101)
Funding: This study was supported in part by the National Natural Science Special Foundation of China (82041018, 81800094), National Major Science and Technology Projects of China (CN):2019ZX09301001, Ministry of Science and Technology of the People's Republic of China (CN):2020YFC0844300, and the Fundamental Research Funds for the Central Universities, HUST: 2020kfyXGYJ011.
Declaration of Interests: The authors have no conflict of interest or financial relationships to disclose. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
Ethics Approval Statement: The protocol used in this project has been reviewed and approved by the institutional review boards of Medical Ethics Committee of Wuhan Union Hospital (NO.0271-01). All participants or their surrogates signed informed consent.
Keywords: COVID-19 recovered patients, three months after discharge, health-related quality of life, pulmonary function, chest computed tomography (CT), laboratory findings, immune cells, cytokines.
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