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

Abstract

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. 1 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. 2 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 colleagues 3 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. 3 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.4, 5 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. 2 Although SARS-CoV-2 primarily affects the lungs, several other organs, including the kidney, can also be affected. 6 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. 3 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. 7 Importantly, deep venous thrombosis was not diagnosed in any of the patients who underwent ultrasonography at follow-up. 3 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. 6 © 2021 Barcroft Media/Getty Images 2021 Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. 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), 3 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. 8 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. 9 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, 10 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.