Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.

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Post-acute COVID-19 syndrome.

### What you need to know

Post-acute covid-19 (“long covid”) seems to be a multisystem disease, sometimes occurring after a relatively mild acute illness.1 Clinical management requires a whole-patient perspective.2 This article, intended for primary care clinicians, relates to the patient who has a delayed recovery from an episode of covid-19 that was managed in the community or in a standard hospital ward. Broadly, such patients can be divided into those who may have serious sequelae (such as thromboembolic complications) and those with a non-specific clinical picture, often dominated by fatigue and breathlessness. The specialist rehabilitation needs of a third group, covid-19 patients whose acute illness required intensive care, have been covered elsewhere.3

In the absence of agreed definitions, for the purposes of this article we define post-acute covid-19 as extending beyond three weeks from the onset of first symptoms and chronic covid-19 as extending beyond 12 weeks. Since many people were not tested, and false negative tests are common,4 we suggest that a positive test for covid-19 is not a prerequisite for diagnosis.

### How common is it?

Around 10% of patients who have tested positive for SARS-CoV-2 virus remain unwell beyond three weeks, and a smaller proportion for months (see box 1).7 This is based on the UK COVID Symptom Study, in which people enter their ongoing symptoms on a smartphone app. This percentage is lower than that cited in many published observational …

https://www.bmj.com/content/bmj/370/bmj.m3026.full.pdf

Management of post-acute covid-19 in primary care.

Mechanisms of SARS-CoV-2 Transmission and Pathogenesis.

Since its emergence in Wuhan, China, covid-19 has spread and had a profound effect on the lives and health of people around the globe. As of 4 July 2021, more than 183 million confirmed cases of covid-19 had been recorded worldwide, and 3.97 million deaths. Recent evidence has shown that a range of persistent symptoms can remain long after the acute SARS-CoV-2 infection, and this condition is now coined long covid by recognized research institutes. Studies have shown that long covid can affect the whole spectrum of people with covid-19, from those with very mild acute disease to the most severe forms. Like acute covid-19, long covid can involve multiple organs and can affect many systems including, but not limited to, the respiratory, cardiovascular, neurological, gastrointestinal, and musculoskeletal systems. The symptoms of long covid include fatigue, dyspnea, cardiac abnormalities, cognitive impairment, sleep disturbances, symptoms of post-traumatic stress disorder, muscle pain, concentration problems, and headache. This review summarizes studies of the long term effects of covid-19 in hospitalized and non-hospitalized patients and describes the persistent symptoms they endure. Risk factors for acute covid-19 and long covid and possible therapeutic options are also discussed.

https://www.bmj.com/content/bmj/374/bmj.n1648.full.pdf

Long covid-mechanisms, risk factors, and management.

Long COVID or post-COVID-19 syndrome first gained widespread recognition among social support groups and later in scientific and medical communities. This illness is poorly understood as it affects COVID-19 survivors at all levels of disease severity, even younger adults, children, and those not hospitalized. While the precise definition of long COVID may be lacking, the most common symptoms reported in many studies are fatigue and dyspnoea that last for months after acute COVID-19. Other persistent symptoms may include cognitive and mental impairments, chest and joint pains, palpitations, myalgia, smell and taste dysfunctions, cough, headache, and gastrointestinal and cardiac issues. Presently, there is limited literature discussing the possible pathophysiology, risk factors, and treatments in long COVID, which the current review aims to address. In brief, long COVID may be driven by long-term tissue damage (e.g. lung, brain, and heart) and pathological inflammation (e.g. from viral persistence, immune dysregulation, and autoimmunity). The associated risk factors may include female sex, more than five early symptoms, early dyspnoea, prior psychiatric disorders, and specific biomarkers (e.g. D-dimer, CRP, and lymphocyte count), although more research is required to substantiate such risk factors. While preliminary evidence suggests that personalized rehabilitation training may help certain long COVID cases, therapeutic drugs repurposed from other similar conditions, such as myalgic encephalomyelitis or chronic fatigue syndrome, postural orthostatic tachycardia syndrome, and mast cell activation syndrome, also hold potential. In sum, this review hopes to provide the current understanding of what is known about long COVID.

Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments.

Importance Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide. Case reports of hospitalized patients suggest that COVID-19 prominently affects the cardiovascular system, but the overall impact remains unknown. Objective To evaluate the presence of myocardial injury in unselected patients recently recovered from COVID-19 illness. Design, Setting, and Participants In this prospective observational cohort study, 100 patients recently recovered from COVID-19 illness were identified from the University Hospital Frankfurt COVID-19 Registry between April and June 2020. Exposure Recent recovery from severe acute respiratory syndrome coronavirus 2 infection, as determined by reverse transcription–polymerase chain reaction on swab test of the upper respiratory tract. Main Outcomes and Measures Demographic characteristics, cardiac blood markers, and cardiovascular magnetic resonance (CMR) imaging were obtained. Comparisons were made with age-matched and sex-matched control groups of healthy volunteers (n = 50) and risk factor–matched patients (n = 57). Results Of the 100 included patients, 53 (53%) were male, and the mean (SD) age was 49 (14) years. The median (IQR) time interval between COVID-19 diagnosis and CMR was 71 (64-92) days. Of the 100 patients recently recovered from COVID-19, 67 (67%) recovered at home, while 33 (33%) required hospitalization. At the time of CMR, high-sensitivity troponin T (hsTnT) was detectable (greater than 3 pg/mL) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (greater than 13.9 pg/mL) in 5 patients (5%). Compared with healthy controls and risk factor–matched controls, patients recently recovered from COVID-19 had lower left ventricular ejection fraction, higher left ventricle volumes, and raised native T1 and T2. A total of 78 patients recently recovered from COVID-19 (78%) had abnormal CMR findings, including raised myocardial native T1 (n = 73), raised myocardial native T2 (n = 60), myocardial late gadolinium enhancement (n = 32), or pericardial enhancement (n = 22). There was a small but significant difference between patients who recovered at home vs in the hospital for native T1 mapping (median [IQR], 1119 [1092-1150] ms vs 1141 [1121-1175] ms;P = .008) and hsTnT (4.2 [3.0-5.9] pg/dL vs 6.3 [3.4-7.9] pg/dL;P = .002) but not for native T2 mapping. None of these measures were correlated with time from COVID-19 diagnosis (native T1:r = 0.07;P = .47; native T2:r = 0.14;P = .15; hsTnT:r = −0.07;P = .50). High-sensitivity troponin T was significantly correlated with native T1 mapping (r = 0.33;P  Conclusions and Relevance In this study of a cohort of German patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis. These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.

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Masia Fahim

Papers

Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19).