Long-term follow-up of recovered patients with COVID-19

By early January, 2021, COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had resulted in more than 83 million confirmed cases and more than 1·8 million deaths. The clinical spectrum of SARS-CoV-2 infection is wide, encompassing asymptomatic infection, fever, fatigue, myalgias, mild upper respiratory tract illness, severe life-threatening viral pneumonia requiring admission to hospital, and death.1Zhou F Yu T Du R et al.Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.Lancet. 2020; 395: 1054-1062Summary Full Text Full Text PDF PubMed Scopus (18725) Google Scholar Physicians are observing persisting symptoms and unexpected, substantial organ dysfunction after SARS-CoV-2 infection in an increasing number of patients who have recovered, as previously observed in the SARS outbreak.2Zhang P Li J Liu H et al.Long-term bone and lung consequences associated with hospital-acquired severe acute respiratory syndrome: a 15-year follow-up from a prospective cohort study.Bone Res. 2020; 8: 8Crossref PubMed Scopus (294) Google Scholar However, COVID-19 is a new disease and uncertainty remains regarding the possible long-term health sequelae. This is particularly relevant for patients with severe symptoms, including those who required mechanical ventilation during their hospital stay, for whom long-term complications and incomplete recovery after discharge would be expected. Unfortunately, few reports exist on the clinical picture of the aftermath of COVID-19. The study by Chaolin Huang and colleagues3Huang C Huang L Wang Y et al.6-month consequences of COVID-19 in patients discharged from hospital: a cohort study.Lancet. 2021; (published online Jan 8.)https://doi.org/10.1016/S0140-6736(20)32656-8Summary Full Text Full Text PDF PubMed Scopus (2818) Google Scholar in The Lancet is relevant and timely. They describe the clinical follow-up of a cohort of 1733 adult patients (48% women, 52% men; median age 57·0 years, IQR 47·0–65·0) with COVID-19 who were discharged from Jin Yin-tan Hospital (Wuhan, China). 6 months after illness onset, 76% (1265 of 1655) of the patients reported at least one symptom that persisted, with fatigue or muscle weakness being the most frequently reported symptom (63%, 1038 of 1655). More than 50% of patients presented with residual chest imaging abnormalities. Disease severity during the acute phase was independently associated with the extent of lung diffusion impairment at follow-up (odds ratio 4·60, 95% CI 1·85–11·48), with 56% (48 of 86) of patients requiring high-flow nasal cannula, non-invasive ventilation, and invasive mechanical ventilation during their hospital stay having impaired pulmonary diffusion capacity.3Huang C Huang L Wang Y et al.6-month consequences of COVID-19 in patients discharged from hospital: a cohort study.Lancet. 2021; (published online Jan 8.)https://doi.org/10.1016/S0140-6736(20)32656-8Summary Full Text Full Text PDF PubMed Scopus (2818) Google Scholar These findings are consistent with those from earlier small studies that reported lingering radiological and pulmonary diffusion abnormalities in a sizeable proportion of COVID-19 patients up to 3 months after hospital discharge.4Huang Y Tan C Wu J et al.Impact of coronavirus disease 2019 on pulmonary function in early convalescence phase.Respir Res. 2020; 21: 163Crossref PubMed Scopus (341) Google Scholar, 5Zhao YM Shang YM Song WB et al.Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery.EClinicalMedicine. 2020; 25100463Summary Full Text Full Text PDF Scopus (577) Google Scholar Evidence from previous coronavirus outbreaks suggests that some degree of lung damage could persist, as shown in patients who recovered from SARS, 38% of whom had reduced lung diffusion capacity 15 years after infection.2Zhang P Li J Liu H et al.Long-term bone and lung consequences associated with hospital-acquired severe acute respiratory syndrome: a 15-year follow-up from a prospective cohort study.Bone Res. 2020; 8: 8Crossref PubMed Scopus (294) Google Scholar Although SARS-CoV-2 primarily affects the lungs, several other organs, including the kidney, can also be affected.6Perico L Benigni A Casiraghi F Ng LFP Renia L Remuzzi G Immunity, endothelial injury and complement-induced coagulopathy in COVID-19.Nat Rev Nephrol. 2020; 17: 46-64Crossref PubMed Scopus (395) Google Scholar Therefore, Huang and colleagues assessed the sequelae of extrapulmonary manifestations of COVID-19. Unexpectedly, 13% (107 of 822) of the patients who did not develop acute kidney injury during their hospital stay and presented with normal renal function, based on estimated glomerular filtration rate (eGFR) during the acute phase, exhibited a decline in eGFR (<90 mL/min per 1·73 m2) at follow-up.3Huang C Huang L Wang Y et al.6-month consequences of COVID-19 in patients discharged from hospital: a cohort study.Lancet. 2021; (published online Jan 8.)https://doi.org/10.1016/S0140-6736(20)32656-8Summary Full Text Full Text PDF PubMed Scopus (2818) Google Scholar However, this finding must be interpreted with caution. Because repeated GFR measurement using a gold-standard technique—such as plasma clearance of iohexol or iothalamate—would presumably have been unfeasible in such a large cohort of patients, GFR-estimating equations, such as that used in the present study, do not enable a sound assessment of renal function, which can be overestimated or underestimated compared with measured GFR.7Porrini E Ruggenenti P Luis-Lima S et al.Estimated GFR: time for a critical appraisal.Nat Rev Nephrol. 2019; 15: 177-190Crossref PubMed Scopus (182) Google Scholar Importantly, deep venous thrombosis was not diagnosed in any of the patients who underwent ultrasonography at follow-up.3Huang C Huang L Wang Y et al.6-month consequences of COVID-19 in patients discharged from hospital: a cohort study.Lancet. 2021; (published online Jan 8.)https://doi.org/10.1016/S0140-6736(20)32656-8Summary Full Text Full Text PDF PubMed Scopus (2818) Google Scholar This is an encouraging finding, in light of the frequent development of venous thromboembolism in patients with COVID-19 who are critically ill while in hospital.6Perico L Benigni A Casiraghi F Ng LFP Renia L Remuzzi G Immunity, endothelial injury and complement-induced coagulopathy in COVID-19.Nat Rev Nephrol. 2020; 17: 46-64Crossref PubMed Scopus (395) Google Scholar Even though the study offers a comprehensive clinical picture of the aftermath of COVID-19 in patients who have been admitted to hospital, only 4% (76 of 1733) were admitted to an intensive care unit (ICU),3Huang C Huang L Wang Y et al.6-month consequences of COVID-19 in patients discharged from hospital: a cohort study.Lancet. 2021; (published online Jan 8.)https://doi.org/10.1016/S0140-6736(20)32656-8Summary Full Text Full Text PDF PubMed Scopus (2818) Google Scholar rendering the information about the long-term consequences in this particular cohort inconclusive. However, previous research on patient outcomes after ICU stays suggests that several patients with COVID-19 who were critically ill during their hospital stay will subsequently face impairments regarding their cognitive and mental health or physical function far beyond their hospital discharge.8Marra A Pandharipande PP Girard TD et al.Co-occurrence of post-intensive care syndrome problems among 406 survivors of critical illness.Crit Care Med. 2018; 46: 1393-1401Crossref PubMed Scopus (274) Google Scholar Outpatient clinics that are dedicated to following up on lasting disabilities in the large number of patients who previously had COVID-19 are opening in many hospitals, especially in areas where large SARS-CoV-2 outbreaks have occurred. However, this initiative implies a further burden on the health-care system in terms of human and economic resources, in addition to conventional health-care services. Unfortunately, these clinics are largely unaffordable in most low-income or middle-income countries that have also been severely affected by the COVID-19 pandemic. However, the success of this approach to monitoring and treating patients with COVID-19 who have recovered creates an opportunity to concomitantly conduct integrated multidisciplinary research studies during 1–2 years of follow-up, as is currently happening in the UK and USA.9Marshall M The lasting misery of coronavirus long-haulers.Nature. 2020; 585: 339-341Crossref PubMed Scopus (181) Google Scholar These studies will improve our understanding of the natural history of COVID-19 sequelae and the factors or mediators involved, and enable us to assess the efficacy of therapeutic interventions to mitigate the long-term consequences of COVID-19 on multiple organs and tissues. This is consistent with the syndemic nature of the COVID-19 pandemic,10Horton R Offline: COVID-19 is not a pandemic.Lancet. 2020; 396: 874Summary Full Text Full Text PDF PubMed Scopus (632) Google Scholar and has implications for the long-term follow-up of COVID-19 sequelae, which in most instances should be interpreted against a background of an array of non-communicable diseases and social and income inequalities that exacerbate the adverse effects of each of these diseases in many communities. GR reports personal fees and non-financial support from Alexion Pharmaceuticals Inc, Janssen Pharmaceutical, Akebia Therapeutics, Alnylam, Boehringer Ingelheim, Inception Sciences Canada, Omeros, and Catalyst Biosciences, all outside of the submitted work. MC and NP declare no competing interests. RETRACTED: 6-month consequences of COVID-19 in patients discharged from hospital: a cohort studyAt 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery. Full-Text PDF