Skip to main content

Some NLM-NCBI services and products are experiencing heavy traffic, which may affect performance and availability. We apologize for the inconvenience and appreciate your patience. For assistance, please contact our Help Desk at info@ncbi.nlm.nih.gov.

Elsevier - PMC COVID-19 Collection logoLink to Elsevier - PMC COVID-19 Collection
. 2021 Jan 8;397(10270):173–175. doi: 10.1016/S0140-6736(21)00039-8

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

Monica Cortinovis a, Norberto Perico a, Giuseppe Remuzzi a
PMCID: PMC7833833  PMID: 33428868

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 colleagues3 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

graphic file with name fx1_lrg.jpg

© 2021 Barcroft Media/Getty Images

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.

Acknowledgments

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.

References

  • 1.Zhou 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;395:1054–1062. doi: 10.1016/S0140-6736(20)30566-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Zhang 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;8:8. doi: 10.1038/s41413-020-0084-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Huang C, Huang L, Wang Y, et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2021 doi: 10.1016/S0140-6736(20)32656-8. published online Jan 8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Huang Y, Tan C, Wu J, et al. Impact of coronavirus disease 2019 on pulmonary function in early convalescence phase. Respir Res. 2020;21:163. doi: 10.1186/s12931-020-01429-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Zhao 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;25 doi: 10.1016/j.eclinm.2020.100463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Perico 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;17:46–64. doi: 10.1038/s41581-020-00357-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Porrini E, Ruggenenti P, Luis-Lima S, et al. Estimated GFR: time for a critical appraisal. Nat Rev Nephrol. 2019;15:177–190. doi: 10.1038/s41581-018-0080-9. [DOI] [PubMed] [Google Scholar]
  • 8.Marra 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;46:1393–1401. doi: 10.1097/CCM.0000000000003218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Marshall M. The lasting misery of coronavirus long-haulers. Nature. 2020;585:339–341. doi: 10.1038/d41586-020-02598-6. [DOI] [PubMed] [Google Scholar]
  • 10.Horton R. Offline: COVID-19 is not a pandemic. Lancet. 2020;396:874. doi: 10.1016/S0140-6736(20)32000-6. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Lancet (London, England) are provided here courtesy of Elsevier

RESOURCES