Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery

Yu-Miao Zhao, Yao-Min Shang, Wen-Bin Song, Qing-Quan Li, Hua Xie, Qin-Fu Xu, Jun-Li Jia, Li-Ming Li, Hong-Li Mao, Xiu-Man Zhou, Hong Luo, Yan-Feng Gao, Ai-Guo Xu, Yu-Miao Zhao, Yao-Min Shang, Wen-Bin Song, Qing-Quan Li, Hua Xie, Qin-Fu Xu, Jun-Li Jia, Li-Ming Li, Hong-Li Mao, Xiu-Man Zhou, Hong Luo, Yan-Feng Gao, Ai-Guo Xu

Abstract

Background: The long-term pulmonary function and related physiological characteristics of COVID-19 survivors have not been studied in depth, thus many aspects are not understood.

Methods: COVID-19 survivors were recruited for high resolution computed tomography (HRCT) of the thorax, lung function and serum levels of SARS-CoV-2 IgG antibody tests 3 months after discharge. The relationship between the clinical characteristics and the pulmonary function or CT scores were investigated.

Findings: Fifty-five recovered patients participated in this study. SARS-CoV-2 infection related symptoms were detected in 35 of them and different degrees of radiological abnormalities were detected in 39 patients. Urea nitrogen concentration at admission was associated with the presence of CT abnormalities (P = 0.046, OR 7.149, 95% CI 1.038 to 49.216). Lung function abnormalities were detected in 14 patients and the measurement of D-dimer levels at admission may be useful for prediction of impaired diffusion defect (P = 0.031, OR 1.066, 95% CI 1.006 to 1.129). Of all the subjects, 47 of 55 patients tested positive for SARS-CoV-2 IgG in serum, among which the generation of Immunoglobulin G (IgG) antibody in female patients was stronger than male patients in infection rehabilitation phase.

Interpretation: Radiological and physiological abnormalities were still found in a considerable proportion of COVID-19 survivors without critical cases 3 months after discharge. Higher level of D-dimer on admission could effectively predict impaired DLCO after 3 months discharge. It is necessary to follow up the COVID-19 patients to appropriately manage any persistent or emerging long-term sequelae.

Funding: Key Scientific Research Projects of Henan Higher Education Institutions.

Keywords: Covid-19; Follow-up study; Pulmonary function; Recovered patients; Serum marker.

Conflict of interest statement

The authors have no interests to declare.

© 2020 The Authors.

Figures

Fig. 1
Fig. 1
Enrolment of patients and follow-up at 3 months after hospital discharge. COVID-19: Coronavirus Disease 2019.
Fig. 2
Fig. 2
Follow-up thin-section CT imaging of 63-year-old man with confirmed COVID-19 pneumonia with dry cough. (A) First thin-section chest CT in hospital on February 2, 2020 (7 days after symptoms onset). CT imaging shows GGO associated with smooth interlobular and intralobular septal thickeing (crazy paving). (B) Crazy paving with some consolidations were observed over 7 days. (C) On March 4, 2020, scans showed that the previous lesion was absorbed and parenchymal bands with residual GGO were observed. (D) On May 2, 2020, intenstitial thickeing and residual GGO were observed. CXR: chest radiography.
Fig. 3
Fig. 3
Spearman's correlation analysis for CXR score 3 month after discharge with pulmonary function: DLCO% predicted (A), TLC% predicted (B), FEV1% predicted (C), and FVC% predicted (D).
Fig. 4
Fig. 4
Comparison of SARS-CoV-2 IgG antibody concentration between male and female patients in recovering status (A). Spearman's correlation analysis for CXR peak score with SARS-CoV-2 IgG antibody in recovered COVID-19 patients (B).

References

    1. Lu R., Zhao X., Li J. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395(10224):565–574.
    1. Du Toit A. Outbreak of a novel coronavirus. Nat Rev Microbiol. 2020;18(3):123.
    1. Li Q., Guan X., Wu P. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 2020;382(13):1199–1207.
    1. Holshue M.L., DeBolt C., Lindquist S. First Case of 2019 Novel Coronavirus in the United States. N Engl J Med. 2020;382(10):929–936.
    1. Bassetti M., Vena A., Giacobbe D.R. The novel Chinese coronavirus (2019-nCoV) infections: challenges for fighting the storm. Eur J Clin Invest. 2020;50(3):e13209.
    1. World Health Organization. COVID-19 dashboard. 2019. Accessed June 8, 2020. .
    1. Verdecchia P., Cavallini C., Spanevello A., Angeli F. COVID-19: ACE2centric infective disease? Hypertension. 2020
    1. Zhu H., Rhee J.W., Cheng P. Cardiovascular Complications in Patients with COVID-19: consequences of Viral Toxicities and Host Immune Response. Curr Cardiol Rep. 2020;22(5):32.
    1. Mo X., Jian W., Su Z. Abnormal pulmonary function in COVID-19 patients at time of hospital discharge. Eur Respir J. 2020
    1. Yu M., Liu Y., Xu D., Zhang R., Lan L., Xu H. Prediction of the Development of Pulmonary Fibrosis Using Serial Thin-Section CT and Clinical Features in Patients Discharged after Treatment for COVID-19 Pneumonia. Korean J Radiol. 2020;21(6):746–755.
    1. WHO. Clinical management of severe acute respiratory infection when COVID-19 disease is suspected: interim guidance, 13 March 2020. .
    1. National Health Commission of the People's Republic of China. Chinese management guideline for COVID-19 (Chinese version, Version 7.0). Accessed March 4. .
    1. Chung M., Bernheim A., Mei X. CT Imaging Features of 2019 Novel Coronavirus (2019-nCoV) Radiology. 2020;295(1):202–207.
    1. Antonio G.E., Wong K.T., Hui D.S. Thin-section CT in patients with severe acute respiratory syndrome following hospital discharge: preliminary experience. Radiology. 2003;228(3):810–815.
    1. Dai H., Zhang X., Xia J. High-resolution Chest CT Features and Clinical Characteristics of Patients Infected with COVID-19 in Jiangsu, China. Int J Infect Dis. 2020;95:106–112.
    1. Graham B.L., Steenbruggen I., Miller M.R. Standardization of Spirometry 2019 Update. An Official American Thoracic Society and European Respiratory Society Technical Statement. Am J Respir Crit Care Med. 2019;200(8):e70–e88.
    1. Qu J., Wu C., Li X. Profile of IgG and IgM antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Clin Infect Dis. 2020
    1. Jin Y., Wang M., Zuo Z. Diagnostic value and dynamic variance of serum antibody in coronavirus disease 2019. Int J Infect Dis. 2020;94:49–52.
    1. Hui D.S., Joynt G.M., Wong K.T. Impact of severe acute respiratory syndrome (SARS) on pulmonary function, functional capacity and quality of life in a cohort of survivors. Thorax. 2005;60(5):401–409.
    1. Hui D.S., Wong K.T., Ko F.W. The 1-year impact of severe acute respiratory syndrome on pulmonary function, exercise capacity, and quality of life in a cohort of survivors. Chest. 2005;128(4):2247–2261.
    1. Wang Q., Jiang H., Xie Y. Long-term clinical prognosis of human infections with avian influenza A(H7N9) viruses in China after hospitalization. EClinicalMedicine. 2020;20
    1. Simpson R., Robinson L. Rehabilitation After Critical Illness in People With COVID-19 Infection. Am J Phys Med Rehabil. 2020;99(6):470–474.
    1. Wei J., Lei P., Yang H. Analysis of thin-section CT in patients with coronavirus disease (COVID-19) after hospital discharge. Clin Imaging. 2020
    1. Balachandar V., Mahalaxmi I., Subramaniam M. Follow-up studies in COVID-19 recovered patients - is it mandatory? Sci Total Environ. 2020;729
    1. Guan W.J., Ni Z.Y., Hu Y. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382(18):1708–1720.
    1. Wang D., Hu B., Hu C. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020
    1. Chan K.S., Zheng J.P., Mok Y.W. SARS: prognosis, outcome and sequelae. Respirology. 2003;8 Suppl:S36-40.
    1. Xiong Y., Sun D., Liu Y. Clinical and High-Resolution CT Features of the COVID-19 Infection: comparison of the Initial and Follow-up Changes. Invest Radiol. 2020;55(6):332–339.
    1. Han X., Cao Y., Jiang N. Novel Coronavirus Pneumonia (COVID-19) Progression Course in 17 Discharged Patients: comparison of Clinical and Thin-Section CT Features During Recovery. Clin Infect Dis. 2020
    1. Ng C.K., Chan J.W., Kwan T.L. Six month radiological and physiological outcomes in severe acute respiratory syndrome (SARS) survivors. Thorax. 2004;59(10):889–891.
    1. Mineo G., Ciccarese F., Modolon C., Landini M.P., Valentino M., Zompatori M. Post-ARDS pulmonary fibrosis in patients with H1N1 pneumonia: role of follow-up CT. Radio Med. 2012;117(2):185–200.
    1. Wang Q., Zhang Z., Shi Y., Jiang Y. Emerging H7N9 influenza A (novel reassortant avian-origin) pneumonia: radiologic findings. Radiology. 2013;268(3):882–889.
    1. Wu A., Peng Y., Huang B. Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China. Cell Host Microbe. 2020;27(3):325–328.
    1. Gheblawi M., Wang K., Viveiros A. Angiotensin-Converting Enzyme 2: sARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System: celebrating the 20th Anniversary of the Discovery of ACE2. Cir Res. 2020;126(10):1456–1474.
    1. Das K.M., Lee E.Y., Singh R. Follow-up chest radiographic findings in patients with MERS-CoV after recovery. Indian J Radiol Imaging. 2017;27(3):342–349.
    1. Zheng Z., Peng F., Xu B. Risk factors of critical & mortal COVID-19 cases: a systematic literature review and meta-analysis. J Infect. 2020
    1. Zhang J., Wang X., Jia X. Risk factors for disease severity, unimprovement, and mortality in COVID-19 patients in Wuhan, China. Clin Microbiol Infect. 2020
    1. Zheng Y., Sun L.J., Xu M. Clinical characteristics of 34 COVID-19 patients admitted to intensive care unit in Hangzhou, China. J Zhejiang Univ Sci B. 2020;21(5):378–387.
    1. Gong J., Ou J., Qiu X. A Tool to Early Predict Severe Corona Virus Disease 2019 (COVID-19): a Multicenter Study using the Risk Nomogram in Wuhan and Guangdong, China. Clin Infect Dis. 2020
    1. Ngai J.C., Ko F.W., Ng S.S., To K.W., Tong M., Hui D.S. The long-term impact of severe acute respiratory syndrome on pulmonary function, exercise capacity and health status. Respirology. 2010;15(3):543–550.
    1. Zhou F., Yu T., Du R. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–1062.
    1. Zhang L., Yan X., Fan Q. d-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. J Thromb Haemost. 2020
    1. Zeng F., Dai C., Cai P. A comparison study of SARS-CoV-2 IgG antibody between male and female COVID-19 patients: a possible reason underlying different outcome between sex. J Med Virol. 2020

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