Follow up of patients with severe coronavirus disease 2019 (COVID-19): Pulmonary and extrapulmonary disease sequelae

Ayham Daher, Paul Balfanz, Christian Cornelissen, Annegret Müller, Ingmar Bergs, Nikolaus Marx, Dirk Müller-Wieland, Bojan Hartmann, Michael Dreher, Tobias Müller, Ayham Daher, Paul Balfanz, Christian Cornelissen, Annegret Müller, Ingmar Bergs, Nikolaus Marx, Dirk Müller-Wieland, Bojan Hartmann, Michael Dreher, Tobias Müller

Abstract

Background: Since December 2019 the novel coronavirus disease 2019 (COVID-19) has been burdening all health systems worldwide. However, pulmonary and extrapulmonary sequelae of COVID-19 after recovery from the acute disease are unknown.

Material and methods: Hospitalized COVID-19 patients not requiring mechanical ventilation were included and followed 6 weeks after discharge. Body plethysmography, lung diffusion capacity (DLco), blood gas analysis (ABG), 6-min walk test (6MWT), echocardiography, and laboratory tests were performed. Quality of life (QoL), depression, and anxiety were assessed using validated questionnaires.

Results: 33 patients with severe disease were included. Patients were discharged without prophylactic anticoagulation. At follow-up there were no thromboembolic complications in any patient. 11 patients (33%) had dyspnea, 11 (33%) had cough, and 15 (45%) suffered from symptoms of fatigue. Pulmonary function tests including ABG did not reveal any limitations (TLC: median=94% of predicted {IQR:85-105}; VC: 93% {78-101}; FEV1: 95% {72-103}; FEV1/FVC 79% {76-85}; PaO2: 72 mmHg {67-79}; PaCO2: 38 mmHg {35-38}), except for slightly reduced DLco (77% {69-95}). There were no echocardiographic impairments. 6MWT distance was reduced in most patients without oxygen desaturation. According to standardized questionnaires, patients suffered from reduced QoL, mainly due to decreased mobility (SGRQ activity score: 54 {19-78}). There were no indicators for depression or anxiety (PHQ-9: 7 {4-11}, GAD-7: 4 {1-9}, respectively).

Conclusions: Hospitalized patients with severe COVID-19, who did not require mechanical ventilation, are unlikely to develop pulmonary long-term impairments, thromboembolic complications or cardiac impairments after discharge but frequently suffer from symptoms of fatigue.

Keywords: COVID-19; Echocardiography; Fatigue; Follow up; Pulmonary functions; Quality of life.

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Copyright © 2020 Elsevier Ltd. All rights reserved.

References

    1. Lu R., Zhao X., Li J., Niu P., Yang B., Wu H., Wang W., Song H., Huang B., Zhu N., Bi Y., Ma X., Zhan F., Wang L., Hu T., Zhou H., Hu Z., Zhou W., Zhao L., Chen J., Meng Y., Wang J., Lin Y., Yuan J., Xie Z., Ma J., Liu W.J., Wang D., Xu W., Holmes E.C., Gao G.F., Wu G., Chen W., Shi W., Tan W. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395(10224):565–574.
    1. Zhou P., Yang X.L., Wang X.G., Hu B., Zhang L., Zhang W., Si H.R., Zhu Y., Li B., Huang C.L., Chen H.D., Chen J., Luo Y., Guo H., Jiang R.D., Liu M.Q., Chen Y., Shen X.R., Wang X., Zheng X.S., Zhao K., Chen Q.J., Deng F., Liu L.L., Yan B., Zhan F.X., Wang Y.Y., Xiao G.F., Shi Z.L. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270–273.
    1. Zhu N., Zhang D., Wang W., Li X., Yang B., Song J., Zhao X., Huang B., Shi W., Lu R., Niu P., Zhan F., Ma X., Wang D., Xu W., Wu G., Gao G.F., Tan W. A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med. 2020;382(8):727–733.
    1. Mizumoto K., Kagaya K., Zarebski A., Chowell G. Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan. Euro Surveill. 2020;25(10) 2020.
    1. Kimball A., Hatfield K.M., Arons M., James A., Taylor J., Spicer K., Bardossy A.C., Oakley L.P., Tanwar S., Chisty Z., Bell J.M., Methner M., Harney J., Jacobs J.R., Carlson C.M., McLaughlin H.P., Stone N., Clark S., Brostrom-Smith C., Page L.C., Kay M., Lewis J., Russell D., Hiatt B., Gant J., Duchin J.S., Clark T.A., Honein M.A., Reddy S.C., Jernigan J.A. Asymptomatic and presymptomatic SARS-CoV-2 infections in residents of a long-term care skilled nursing facility - king county, Washington, march 2020, MMWR. Morb. Mortal. Wkly. Rep. 2020;69(13):377–381.
    1. Sakurai A., Sasaki T., Kato S., Hayashi M., Tsuzuki S.I., Ishihara T., Iwata M., Morise Z., Doi Y. Natural history of asymptomatic SARS-CoV-2 infection. N. Engl. J. Med. 2020;383(9):885–886.
    1. Tabata S., Imai K., Kawano S., Ikeda M., Kodama T., Miyoshi K., Obinata H., Mimura S., Kodera T., Kitagaki M., Sato M., Suzuki S., Ito T., Uwabe Y., Tamura K. Clinical characteristics of COVID-19 in 104 people with SARS-CoV-2 infection on the Diamond Princess cruise ship: a retrospective analysis. Lancet Infect. Dis. 2020;20(9):1043–1050.
    1. Wu Z., McGoogan J.M. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese center for disease control and prevention. Jama. 2020;323(13):1239–1242.
    1. Richardson S., Hirsch J.S., Narasimhan M., Crawford J.M., McGinn T., Davidson K.W., Barnaby D.P., Becker L.B., Chelico J.D., Cohen S.L., Cookingham J., Coppa K., Diefenbach M.A., Dominello A.J., Duer-Hefele J., Falzon L., Gitlin J., Hajizadeh N., Harvin T.G., Hirschwerk D.A., Kim E.J., Kozel Z.M., Marrast L.M., Mogavero J.N., Osorio G.A., Qiu M., Zanos T.P. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York city area. Jama. 2020;323(20):2052–2059.
    1. Lewnard J.A., Liu V.X., Jackson M.L., Schmidt M.A., Jewell B.L., Flores J.P., Jentz C., Northrup G.R., Mahmud A., Reingold A.L., Petersen M., Jewell N.P., Young S., Bellows J. Incidence, clinical outcomes, and transmission dynamics of severe coronavirus disease 2019 in California and Washington: prospective cohort study. BMJ. 2020;369:m1923.
    1. Wang D., Hu B., Hu C., Zhu F., Liu X., Zhang J., Wang B., Xiang H., Cheng Z., Xiong Y., Zhao Y., Li Y., Wang X., Peng Z. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in wuhan, China. Jama. 2020;323(11):1061–1069.
    1. Chen T., Wu D., Chen H., Yan W., Yang D., Chen G., Ma K., Xu D., Yu H., Wang H., Wang T., Guo W., Chen J., Ding C., Zhang X., Huang J., Han M., Li S., Luo X., Zhao J., Ning Q. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020;368:m1091.
    1. Arentz M., Yim E., Klaff L., Lokhandwala S., Riedo F.X., Chong M., Lee M. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington state. Jama. 2020;323(16):1612–1614.
    1. Cao J., Tu W.J., Cheng W., Yu L., Liu Y.K., Hu X., Liu Q. Clinical features and short-term outcomes of 102 patients with corona virus disease 2019 in wuhan, China. Clin. Infect. Dis. 2020
    1. Danzi G.B., Loffi M., Galeazzi G., Gherbesi E. Acute pulmonary embolism and COVID-19 pneumonia: a random association? Eur. Heart J. 2020;41(19):1858.
    1. Zhang Y., Xiao M., Zhang S., Xia P., Cao W., Jiang W., Chen H., Ding X., Zhao H., Zhang H., Wang C., Zhao J., Sun X., Tian R., Wu W., Wu D., Ma J., Chen Y., Zhang D., Xie J., Yan X., Zhou X., Liu Z., Wang J., Du B., Qin Y., Gao P., Qin X., Xu Y., Zhang W., Li T., Zhang F., Zhao Y., Li Y., Zhang S. Coagulopathy and antiphospholipid antibodies in patients with covid-19. N. Engl. J. Med. 2020;382(17):e38.
    1. Mao L., Jin H., Wang M., Hu Y., Chen S., He Q., Chang J., Hong C., Zhou Y., Wang D., Miao X., Li Y., Hu B. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in wuhan, China. JAMA Neurol. 2020;77(6):1–9.
    1. Klok F.A., Kruip M., van der Meer N.J.M., Arbous M.S., Gommers D., Kant K.M., Kaptein F.H.J., van Paassen J., Stals M.A.M., Huisman M.V., Endeman H. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb. Res. 2020;191:145–147.
    1. Oxley T.J., Mocco J., Majidi S., Kellner C.P., Shoirah H., Singh I.P., De Leacy R.A., Shigematsu T., Ladner T.R., Yaeger K.A., Skliut M., Weinberger J., Dangayach N.S., Bederson J.B., Tuhrim S., Fifi J.T. Large-vessel stroke as a presenting feature of covid-19 in the young. N. Engl. J. Med. 2020;382(20)
    1. Toscano G., Palmerini F., Ravaglia S., Ruiz L., Invernizzi P., Cuzzoni M.G., Franciotta D., Baldanti F., Daturi R., Postorino P., Cavallini A., Micieli G. Guillain-barré syndrome associated with SARS-CoV-2. N. Engl. J. Med. 2020;382(26):2574–2576.
    1. Wang Y., Liu Y., Liu L., Wang X., Luo N., Li L. Clinical outcomes in 55 patients with severe acute respiratory syndrome coronavirus 2 who were asymptomatic at hospital admission in shenzhen, China. J. Infect. Dis. 2020;221(11):1770–1774.
    1. Hu Z., Song C., Xu C., Jin G., Chen Y., Xu X., Ma H., Chen W., Lin Y., Zheng Y., Wang J., Hu Z., Yi Y., Shen H. Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China, Science China. Life Sci. 2020;63(5):706–711.
    1. WHO Director-General's Opening Remarks at the Media Briefing on COVID-19 - 24 February 2020. 2020. (Accessed June 26 2020)
    1. Mo X., Jian W., Su Z., Chen M., Peng H., Peng P., Lei C., Chen R., Zhong N., Li S. Abnormal pulmonary function in COVID-19 patients at time of hospital discharge. Eur. Respir. J. 2020;55(6)
    1. Ahmed H., Patel K., Greenwood D., Halpin S., Lewthwaite P., Salawu A., Eyre L., Breen A., O'Connor R., Jones A., Sivan M. 2020. Long-term clinical outcomes in survivors of coronavirus outbreaks after hospitalisation or ICU admission: a systematic review and meta-analysis of follow-up studies. 2020.04.16.20067975.
    1. Kroenke K., Spitzer R.L., Williams J.B. The PHQ-9: validity of a brief depression severity measure. J. Gen. Intern. Med. 2001;16(9):606–613.
    1. Kroenke K., Spitzer R.L., Williams J.B., Löwe B. The patient health questionnaire somatic, anxiety, and depressive symptom scales: a systematic review. Gen. Hosp. Psychiatr. 2010;32(4):345–359.
    1. Jones P.W., Quirk F.H., Baveystock C.M. The St george's respiratory questionnaire. Respir. Med. 1991;85(Suppl B):25–31. ; discussion 33-7.
    1. Jones P.W., Quirk F.H., Baveystock C.M., Littlejohns P. A self-complete measure of health status for chronic airflow limitation. The St. George's Respiratory Questionnaire. Am. Rev. Respir. Dis. 1992;145(6):1321–1327.
    1. Brooks R. EuroQol: the current state of play. Health Pol. 1996;37(1):53–72.
    1. Wanger J., Clausen J.L., Coates A., Pedersen O.F., Brusasco V., Burgos F., Casaburi R., Crapo R., Enright P., van der Grinten C.P., Gustafsson P., Hankinson J., Jensen R., Johnson D., Macintyre N., McKay R., Miller M.R., Navajas D., Pellegrino R., Viegi G. Standardisation of the measurement of lung volumes. Eur. Respir. J. 2005;26(3):511–522.
    1. Miller M.R., Hankinson J., Brusasco V., Burgos F., Casaburi R., Coates A., Crapo R., Enright P., van der Grinten C.P., Gustafsson P., Jensen R., Johnson D.C., MacIntyre N., McKay R., Navajas D., Pedersen O.F., Pellegrino R., Viegi G., Wanger J. Standardisation of spirometry. Eur. Respir. J. 2005;26(2):319–338.
    1. Chetta A., Zanini A., Pisi G., Aiello M., Tzani P., Neri M., Olivieri D. Reference values for the 6-min walk test in healthy subjects 20-50 years old. Respir. Med. 2006;100(9):1573–1578.
    1. Casanova C., Celli B.R., Barria P., Casas A., Cote C., de Torres J.P., Jardim J., Lopez M.V., Marin J.M., Montes de Oca M., Pinto-Plata V., Aguirre-Jaime A. The 6-min walk distance in healthy subjects: reference standards from seven countries. Eur. Respir. J. 2011;37(1):150–156.
    1. Xu Z., Shi L., Wang Y., Zhang J., Huang L., Zhang C., Liu S., Zhao P., Liu H., Zhu L., Tai Y., Bai C., Gao T., Song J., Xia P., Dong J., Zhao J., Wang F.S. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir. Med. 2020;8(4):420–422.
    1. Tian S., Xiong Y., Liu H., Niu L., Guo J., Liao M., Xiao S.Y. Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies. Mod. Pathol. 2020;33(6):1007–1014.
    1. Huang Y., Tan C., Wu J., Chen M., Wang Z., Luo L., Zhou X., Liu X., Huang X., Yuan S., Chen C., Gao F., Huang J., Shan H., Liu J. Impact of coronavirus disease 2019 on pulmonary function in early convalescence phase. Respir. Res. 2020;21(1):163.
    1. Ware L.B. Autopsy in ARDS: insights into natural history. Lancet Respir. Med. 2013;1(5):352–354.
    1. Moldofsky H., Patcai J. Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study. BMC Neurol. 2011;11:37.
    1. Ellul M.A., Benjamin L., Singh B., Lant S., Michael B.D., Easton A., Kneen R., Defres S., Sejvar J., Solomon T. Neurological associations of COVID-19. Lancet Neurol. 2020;19(9):767–783.
    1. Szekely Y., Lichter Y., Taieb P., Banai A., Hochstadt A., Merdler I., Gal Oz A., Rothschild E., Baruch G., Peri Y., Arbel Y., Topilsky Y. The spectrum of cardiac manifestations in coronavirus disease 2019 (COVID-19) - a systematic echocardiographic study. Circulation. 2020;142(4):342–353.
    1. Iba T., Levy J.H., Levi M., Thachil J. Coagulopathy in COVID-19. J. Thromb. Haemostasis. 2020;18(9):2103–2109.
    1. Iba T., Levy J.H., Connors J.M., Warkentin T.E., Thachil J., Levi M. The unique characteristics of COVID-19 coagulopathy. Crit. Care. 2020;24(1):360.
    1. Tang N., Li D., Wang X., Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. 2020;18(4):844–847.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe