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Long-term consequences of COVID-19: research needs

2020; Elsevier BV; Volume: 20; Issue: 10 Linguagem: Inglês

10.1016/s1473-3099(20)30701-5

1474-4457

Dana Yelin, Eytan Wirtheim, Pauline Vetter, André C. Kalil, Judith Bruchfeld, Michael Runold, Giovanni Guaraldi, Cristina Mussini, Carlota Gudiol, Miquel Pujol, Alessandra Bandera, Luigia Scudeller, Mical Paul, Laurent Kaiser, Leonard Leibovici,

COVID-19 and healthcare impacts

Weeks and months after the onset of acute COVID-19, people continue to suffer. Paul Garner, a professor of epidemiology at Liverpool School of Tropical Medicine, UK, wrote on the 95th day after the onset of symptoms that "I am unable to be out of bed for more than three hours at a stretch, my arms and legs are permanently fizzing as if injected with Szechuan peppercorns, I have ringing in the ears, intermittent brain fog, palpitations, and dramatic mood swings."1Garner P COVID-19 at 14 weeks—phantom speed cameras, unknown limits, and harsh penalties.https://blogs.bmj.com/bmj/2020/06/23/paul-garner-covid-19-at-14-weeks-phantom-speed-cameras-unknown-limits-and-harsh-penalties/Date: 2020Date accessed: August 25, 2020Google Scholar Other people also describe similar complaints.2Rayner C Lokugamage AU Molokhia M COVID-19: prolonged and relapsing course of illness has implications for returning workers.https://blogs.bmj.com/bmj/2020/06/23/covid-19-prolonged-and-relapsing-course-of-illness-has-implications-for-returning-workers/Date accessed: August 25, 2020Google Scholar, 3Carfì A Bernabei R Landi F Persistent symptoms in patients after acute COVID-19.JAMA. 2020; 324: 603-605Crossref PubMed Scopus (2761) Google Scholar 78 of 100 patients in an observational cohort study who had recovered from COVID-19 had abnormal findings on cardiovascular MRI (median of 71 days after diagnosis) and 36 of those reported dyspnoea and unusual fatigue.4Puntmann VO Carerj ML Wieters I et al.Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19).JAMA Cardiol. 2020; (published online July 27.)https://doi.org/10.1001/jamacardio.2020.3557Crossref PubMed Scopus (1500) Google Scholar We are seeing patients in clinics dedicated to COVID-19 convalescents, and for some of these patients the return to their former health trajectory is slow and painful. These patients are not only those recovering from the severe form of the acute disease (ie, post intensive care syndrome), but also those who had mild and moderate disease. A summary of the most common complaints, based on our clinical impressions, is shown in the appendix (p 1). Rare long-term sequelae can result after other viral infections—eg, infectious mononucleosis, measles, and hepatitis B. Long-term sequelae of COVID-19 are unknown (as are many aspects of the acute disease). Long-term consequences were observed in survivors of severe acute respiratory syndrome (SARS)5Lam MH Wing YK Yu MW et al.Mental morbidities and chronic fatigue in severe acute respiratory syndrome survivors: long-term follow-up.Arch Intern Med. 2009; 169: 2142-2147Crossref PubMed Scopus (496) Google Scholar, 6Ngai JC Ko FW Ng SS To KW Tong M Hui DS The long-term impact of severe acute respiratory syndrome on pulmonary function, exercise capacity and health status.Respirology. 2010; 15: 543-550Crossref PubMed Scopus (355) Google Scholar but it is unknown whether lessons from SARS are applicable to COVID-19. Other concerns are rising: does acute COVID-19 cause diabetes?7Rubino F Amiel SA Zimmet P et al.New-onset diabetes in COVID-19.N Engl J Med. 2020; (published online June 12.)https://doi.org/10.1056/NEJMc2018688Crossref PubMed Scopus (555) Google Scholar Or other metabolic disorders? Will patients develop interstitial lung disease? We are still in the first months of the pandemic and we do not know what to tell our patients when they are asking about the course and prognosis of their ongoing complaints. The number of people affected by COVID-19 is unprecedented. We owe good answers on the long-term consequences of the disease to our patients and health-care providers. The obvious answer is in research. In the appendix (p 2) we have compiled a list of questions we think should be answered. This list is based on the authors' views and experience rather than on the literature, which is scant. For efficient research and for research that our patients (and we) can trust, some common problems in the description and research of acute COVID-19 should be avoided. The main problem is fragmentation. For example, Wynants and colleagues8Wynants L Van Calster B Collins GS et al.Prediction models for diagnosis and prognosis of COVID-19 infection: systematic review and critical appraisal.BMJ. 2020; 369m1328Crossref PubMed Scopus (1933) Google Scholar described 47 models for predicting COVID-19 infection and 16 prognostic models for COVID-19 patients. Most of these models had a high risk of bias and most of them did not have external validation. Additionally, randomised controlled trials on interventions to treat the acute disease were stopped before enlisting the planned sample size. Although much effort was invested in these studies, we have learned little. Fragmentation also happens by discipline,6Ngai JC Ko FW Ng SS To KW Tong M Hui DS The long-term impact of severe acute respiratory syndrome on pulmonary function, exercise capacity and health status.Respirology. 2010; 15: 543-550Crossref PubMed Scopus (355) Google Scholar, 7Rubino F Amiel SA Zimmet P et al.New-onset diabetes in COVID-19.N Engl J Med. 2020; (published online June 12.)https://doi.org/10.1056/NEJMc2018688Crossref PubMed Scopus (555) Google Scholar and the follow-up (for clinical and research purposes) should be multinational, multidisciplinary, comprehensive, and homogenous. Careful recording of symptoms and patient examination should allow understanding of which part of the sequelae is common to all severe infections, which symptoms might be explained by the anxiety caused by a new disease and by the isolation,9Vindegaard N Benros ME COVID-19 pandemic and mental health consequences: systematic review of the current evidence.Brain Behav Immun. 2020; (published online May 30.)https://doi.org/10.1016/j.bbi.2020.05.048Crossref PubMed Scopus (2050) Google Scholar and which symptoms are secondary to a complicated form of COVID-19 (eg, pulmonary involvement during the acute disease). If indeed COVID-19 is causing long-term sequelae then are the mechanisms underlying the long-term consequences immunological? Or caused by new or relapsing inflammation, ongoing infection, or side-effects of immunomodulatory treatment? Such data can serve to point at candidate management strategies to be tested in trials. Support for research is needed on the trajectory of people recovering from COVID-19. To avoid the problems we have witnessed in the research of the acute phase of the disease, a clear definition of patient inclusion criteria, a common protocol, and uniform definitions of outcomes and ways to measure them are required. Additionally, data should be collected in real time and computational tools are needed to be able to do this (appendix p 3). The participation of an international and interdisciplinary group of researchers is essential. Multisite and multinational projects are needed because a description from one group or one site cannot discern between universal features and features of the local health system or the local population. By comparing data from different sites and countries we can learn which characteristics of the disease are universal and which are local. In addition to improving the care of our patients with long-term consequences of COVID-19, we hope to be able to join such necessary research efforts soon. We declare no competing interests. Download .pdf (.36 MB) Help with pdf files Supplementary appendix Long COVID: tackling a multifaceted condition requires a multidisciplinary approachIn their Comment,1 Dana Yelin and colleagues highlight the persistent, heterogeneous, and recurring symptoms of long COVID. A Lancet Editorial2 asks for better research and care to avoid years of struggle for individuals with long COVID. We write following an international, multi-stakeholder forum, in which peoples' voices were central, to expand the call to action and to identify how we can prevent long COVID from becoming the long-lasting legacy of COVID-19. Full-Text PDF