key: cord-1002151-ui2m6f6r
authors: Satterfield, Benjamin A.; Bhatt, Deepak L.; Gersh, Bernard J.
title: Cardiac involvement in the long-term implications of COVID-19
date: 2021-10-22
journal: Nat Rev Cardiol
DOI: 10.1038/s41569-021-00631-3
sha: 5a1e498af134a70ae31d45d32ad0a919b47a67ca
doc_id: 1002151
cord_uid: ui2m6f6r

Throughout 2021, the medical and scientific communities have focused on managing the acute morbidity and mortality caused by the coronavirus disease 2019 (COVID-19) pandemic. With the approval of multiple vaccines, there is a light at the end of this dark tunnel and an opportunity to focus on the future, including managing the long-term sequelae in patients who have survived acute COVID-19. In this Perspectives article, we highlight what is known about the cardiovascular sequelae in survivors of COVID-19 and discuss important questions that need to be addressed in prospective studies to understand and mitigate these lasting cardiovascular consequences, including in post-acute COVID-19 syndrome. To provide the greatest benefit to these survivors, prospective studies should begin now, with resources made available to monitor and study this population in the coming years.

The coronavirus disease 2019 (COVID- 19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is associated with various disease manifestations across multiple organ systems, presenting with a spectrum of disease severity that is only partially explained by age, sex and comorbidities 1 . Of note, the manifestations of acute cardiovascular injury associated with SARS-CoV-2 infection are diverse, including acute myocardial infarction, myocarditis, stress cardiomyopathy, pericarditis, arrhythmias, multisystem inflammatory syndrome in both adults (MIS-A) and children (MIS-C), stroke, macrothrombotic disease including arterial and venous thromboembolism, microthrombotic disease and bleeding diathesis [2] [3] [4] (Fig. 1) . The pathogenic mechanisms underlying these clinical manifestations are not well understood and are likely to be multifactorial, including primary causes such as elevated local (endotheliitis) and systemic (cytokine storm) inflammation, resulting in coagulopathy, myocardial infarction, stroke, MIS-A, MIS-C and arrhythmias, direct viral cytopathic effects possibly resulting in myocarditis, and autoantibodies [5] [6] [7] . In addition, hypoxaemia can occur secondary to lung injury, and myocardial oedema can record the patients with COVID-19 who developed sequelae of the cardiovascular and other organ systems 12 . The high rate of these long-term complications potentially represents a substantial public health burden and well-designed studies are needed to follow-up individuals with post-acute COVID-19 syndrome, which should begin as soon as possible, with several already under way.

The disruption caused by the COVID-19 pandemic led to numerous clinical trials being delayed, cancelled or altered, which, in some cases, has resulted in the deployment of adaptive trial designs to meet the unique circumstances of the pandemic 13 . These trial designs have ultimately improved how clinical trials are performed, including the use of remote consent, telemedicine monitoring and novel trial protocols 11, 14, 15 . Effects on the 892 cardiovascular trials that were under way before the COVID-19 pandemic have been discussed previously 16 . More than 100 trials relating to COVID-19 with cardiovascular implications have been registered, including registries examining myocarditis, heart failure (HF), venous thromboembolism and general cardiac complications; additionally, there are 19 trials examining imaging, biomarkers and the natural history of cardiac sequelae as well as dozens of other trials on various cardiovascular medications, including the anti-inflammatory agent colchicine, inhibitors of the renin-angiotensinaldosterone system (RAAS), antiplatelet and anticoagulant agents, lipid-lowering therapies, and other drugs for pulmonary hypertension and HF ( Table 1 ). Many of these trials were small, had neutral outcomes and were largely underpowered. A few large trials with neutral outcomes included those that assessed the efficacy of ivermectin 17 and systemic anticoagulation 18 . Early in the pandemic, a theoretical concern arose that RAAS inhibition might worsen COVID-19, but subsequent studies have shown that this fear was unfounded and that removal of RAAS inhibition in patients with COVID-19 already receiving those medications is actually harmful 19 . For all clinical trials during this time, researchers have had to account for elevated rates of hospitalization and death, including a competing risk of death that can affect power calculations as well as under-reporting of events 20 .

develop secondary to the inflammatory states mentioned above [5] [6] [7] .

Many studies have documented substantial increases in serum troponin levels as a manifestation of acute myocardial injury and, in general, these biomarkers have been shown to be correlated with the severity of acute illness [2] [3] [4] 8, 9 as well as SARS-CoV-2 viraemia 10 . However, among these patients, the degree of myocardial injury observed is inconsistent and the mechanisms are often unclear; whether the degree of troponin level elevation is simply reflective of more severe systemic illness or whether it is a causal factor of worsened prognosis has not yet been determined.

After acute illness, the long-term health implications in survivors of COVID-19 are uncertain, but evidence suggests that they might include cardiovascular, pulmonary, neurological and mental health complications as well as other less understood but debilitating symptoms and features of COVID-19 'long-hauler' syndrome (reviewed elsewhere 11 ). The rate of these complications is high but the true prevalence is uncertain. Groups such as the Electronic Medical Records and Genomics (eMERGE) consortium are developing electronic phenotyping algorithms to assist researchers in rapidly identifying from the electronic health Cardiac involvement in the long-term implications of COVID-19

Benjamin A. Satterfield , Deepak L. Bhatt and Bernard J. Gersh Abstract | Throughout 2021, the medical and scientific communities have focused on managing the acute morbidity and mortality caused by the coronavirus disease 2019 (COVID-19) pandemic. With the approval of multiple vaccines, there is a light at the end of this dark tunnel and an opportunity to focus on the future, including managing the long-term sequelae in patients who have survived acute COVID-19. In this Perspectives article, we highlight what is known about the cardiovascular sequelae in survivors of COVID-19 and discuss important questions that need to be addressed in prospective studies to understand and mitigate these lasting cardiovascular consequences, including in post-acute COVID-19 syndrome. To provide the greatest benefit to these survivors, prospective studies should begin now, with resources made available to monitor and study this population in the coming years.

In this Perspectives article, we highlight what is known about cardiovascular sequelae in survivors of COVID-19 and discuss important questions that need to be addressed in prospective studies to understand and mitigate these lasting cardiovascular consequences, including post-acute COVID-19 syndrome.

Cardiovascular complications in post-acute COVID-19 COVID-19 presents with a spectrum of severity. Throughout this manuscript, we discuss four degrees of severity, as typically used in the medical literature: asymptomatic, mild (having symptoms but not requiring hospitalization), moderate (requiring hospitalization but not intensive care) and severe (requiring intensive care). Some patients recover quickly, whereas others have a more prolonged course to recovery owing to lasting sequelae or the development of persistent symptoms (Fig. 2 [30] [31] [32] [33] [34] . This constellation of symptoms falls under the umbrella of COVID-19 long-hauler syndrome. The aetiology is poorly understood, the morbidity is substantial and the response to multidisciplinary rehabilitation is inconsistent. Whether these symptoms differ between those who initially presented with mild illness and those with moderate or severe illness is uncertain. Dyspnoea is the most frequent persistent symptom reported and is likely to be multifactorial in aetiology [33] [34] [35] [36] . Although we are focusing on cardiovascular complications, the effect of COVID-19 on respiratory function certainly contributes to the dyspnoea observed in these patients. Chest pain is the most common persistent cardiovascular symptom among patients surviving moderate-to-severe COVID-19; one study reported chest pain in 18% of survivors at 30 days and in 13% at 60 days 34 , whereas another study found chest pain in 21% of survivors at 60 days 33 . An additional study with longer follow-up found chest pain in 5% of survivors at 6 months 35 . Palpitations were also common, being present in 9% of survivors at 30 days 34 , 14% at 60 days 34 and 9% at 6 months 35 .

A variety of neurological, cardiac, pulmonary and other post-acute COVID-19 symptoms might have a theoretical aetiology in a persistently elevated inflammatory state, especially in those who developed cytokine storm or MIS-A or MIS-C during the acute phase of illness 37 .

Arrhythmias. The increased frequency of heart palpitations has raised a question about arrhythmias in survivors of COVID-19. Both bradyarrhythmias (including high-grade atrioventricular block) and tachyarrhythmias (including atrial fibrillation or flutter, ventricular tachycardia, and ventricular fibrillation) have been reported in acute COVID-19 (reFs 38, 39 ); however, these represent acute arrhythmias in the setting of acute illness and the chronicity of these new arrhythmias is uncertain. Acute arrhythmias were more common in patients with COVID-19 admitted to the ICU than in those admitted to general medical units, although the rates reported in the literature have varied from 18% to 44% [40] [41] [42] . New electrocardiographic changes and arrhythmias were detected in up to one-third of survivors of non-severe COVID-19 by systematic screening 43 . Interestingly, when examining arrhythmia frequency on a global level, regional differences have been reported in the frequency of different arrhythmias 44 . Atrial fibrillation is the most common arrhythmia reported in acute COVID-19 (reF. 45 ) and is often of new onset 46 . One study found that the rate of atrial fibrillation in patients with acute COVID-19 is similar to that observed in patients with influenza 47 , and the presence of atrial fibrillation portends a worse outcome 46 . Whether patients with newly diagnosed atrial fibrillation during acute COVID-19 will have recurrent episodes of atrial fibrillation and whether the rate of more malignant arrhythmias is increased in survivors of COVID-19 is uncertain. Reports have documented cases of postural orthostatic tachycardia syndrome as a cause of palpitations after recovery from acute COVID-19, as has been described after other viral illnesses 48 .

QT interval prolongation has been noted in patients hospitalized with COVID-19, including those showing progression to torsades de pointes 49 . Some degree of QT interval prolongation can occur in any patient with COVID-19 but this feature was often exacerbated early in the pandemic when medications with known QT-prolonging adverse effects, such as chloroquine, hydroxychloroquine and azithromycin, were used to treat patients 50, 51 .

Owing to concerns about myocardial injury caused by COVID-19, investigators started imaging survivors of COVID-19 using cardiac MRI. Initial studies demonstrated that, in both selected patients 52 (those with COVID-19 and elevated troponin levels during hospitalization) and unselected patients 53 (those with a range of asymptomatic, mild, moderate or severe COVID-19), a concerningly high frequency (up to 78%) of patients had abnormalities seen on cardiac MRI. These abnormalities included elevated T1 values (a marker of fibrosis or inflammation) in up to 73% of patients, increased T2 values (a marker of oedema) in up to 60% of patients and myocarditis-like late gadolinium enhancement (LGE) patterns in 32-45% of patients when cardiac MRI was performed within 37-71 days after COVID-19 diagnosis 52,53 . These findings raised the spectre of ongoing myocarditis and an eventual epidemic of long-term HF. However, these cardiac MRI findings did not correlate with biomarker data.

The concerning results from these studies led to additional investigations with cardiac MRI in patients with a range of COVID-19 severity. Results from these additional studies 30, [54] [55] [56] [57] [58] [59] [60] [61] [62] [63] [64] [65] [66] are summarized in Table 2 and were not always consistent with the initial studies. Although cardiac MRI still identified patients with myocarditis-like imaging patterns at levels higher than in the general population, the rates were less common than the initial studies suggested. A study by Joy et al. offered further reassurance; they examined 74 seropositive health-care workers who survived COVID-19 at a time point of 6 months after diagnosis 64 64 . The researchers also found no significant difference in the levels of N-terminal pro-B-type natriuretic peptide or high-sensitivity troponin between the groups.

A specific group of patients who warrant special consideration are competitive athletes because even a mild decrease in cardiac function that might be asymptomatic in a normal individual can have a substantial effect on the ability of athletes to perform. This point also has implications for 'return to play' because even 66 . When examining healthy athletes as matched controls in addition to non-athlete healthy controls, these subsequent studies found that focal inferoseptal right ventricle insertion LGE is common among healthy athletesprobably caused by remodelling from athletic training -and that this finding should not be confused with myocarditis. The implications of these findings in athletes have been summarized and discussed in detail previously 67 .

One additional imaging measure worth noting is first-phase ejection fraction (EF1) measured by echocardiography, which is a sensitive measure of preclinical HF. Gu et al. examined EF1 in patients with COVID-19 in both Wuhan, China, and London, UK, and found that EF1 was a better predictor of survival than other echocardiographic findings, laboratory findings, age or comorbidities 68 .

Taken together, a variety of laboratory and imaging abnormalities are seen in post-acute COVID-19, although many of the cardiac MRI findings are not detected at a significantly higher rate than among healthy controls in some studies. Of note, the only study that focused beyond the 1-3-month period after diagnosis found no significant differences in any cardiac MRI parameters between survivors of COVID-19 and controls. Furthermore, none of these studies found correlations between abnormal cardiac MRI findings and biomarker or tissue abnormalities. Indeed, the latest studies are much more reassuring, suggesting that the earlier findings were probably overinterpreted, and follow-up of asymptomatic patients with COVID-19 and imaging abnormalities has largely shown preserved left ventricular function 43, 59, 61 . Long-term studies will be needed to monitor functional status and observe these imaging abnormalities. In summary, the spectre of a looming HF epidemic caused by COVID-19-induced myocarditis seems much less likely than was feared approximately 1 year ago. Multiple registries are actively collecting information on these patients. Laboratory and imaging abnormalities seen in post-acute COVID-19 are summarized in box 1.

Multiple early studies demonstrated that patients with COVID-19 and acute myocardial injury, defined as an elevated serum troponin level, have substantially higher mortality than similar patients with COVID-19 and normal troponin levels 3, 8, 9, 52 . Indeed, among the standard biomarkers of troponin I, B-type natriuretic peptide, C-reactive protein, ferritin and d-dimer, only the troponin I level was found to be associated with 30-day in-hospital mortality 69 . Elevated levels of troponin and C-reactive protein can occur even in patients with mild COVID-19 who did not require hospitalization 53 . Although some cases of elevated troponin levels were linked to obvious causes, such as acute coronary syndrome or pulmonary embolism 8, 9 , in many other cases the cause was unclear.

Many of the cardiac MRI studies described above focused primarily on patients with COVID-19 in whom the initial presentation was mild, but some evidence exists that left and right ventricular dysfunction might persist in patients with COVID-19 who have a more severe initial clinical course, with evidence of acute myocardial injury. Additionally, patients with COVID-19 and elevated C-reactive protein or d-dimer levels or lymphopenia had higher myocardial T2 values than those without these abnormal laboratory values; similarly, patients with severe COVID-19 had higher myocardial T2 values than those with mild or moderate COVID-19 (reF. 63 ). However, one study found that neither the admission level nor the peak level of troponin could be used to predict the development of myocarditis-like findings on cardiac MRI 48 .

Although cardiac MRI abnormalities have been observed in patients with COVID-19, rarely was an endomyocardial biopsy sample obtained, which is the gold standard for the diagnosis of myocarditis. Another approach to estimating the frequency of myocarditis cases is to look at autopsy findings. One study examined 22 published studies and identified 277 autopsied hearts from patients who died from COVID-19 (reF. 70 ). This study reported that 7.2% of the patients who died from COVID-19 had histological evidence of myocarditis; however, most of these samples showed only small foci of inflammatory infiltrates of questionable clinical relevance in the myocardium. Multifocal or diffuse infiltrates with cardiomyocyte injury that would be expected to cause substantial cardiac dysfunction were found in only 1.4% of the autopsied hearts. Although the cohort of patients who died from COVID-19 was older and had multiple comorbidities -being distinct from the population of young, relatively healthy survivors in which some concerning reports of myocarditis have been published -a myocarditis rate of 1.4-7.2% is far below that reported in the initial imaging studies and is in accordance with the 2.3% rate of myocarditis reported in a large imaging study by Daniels et al. 66 .

Recovery from moderate-to-severe acute COVID-19. The available evidence suggests that patients with COVID-19 requiring hospitalization, regardless of age, have worse long-term outcomes than those who did not require hospitalization 71, 72 . However, data on these outcomes are still scarce and more information is urgently needed. The percentage of patients who have persistently elevated troponin levels, the timeline for eventual normalization of troponin levels, and the clinical relevance of persistently elevated troponin levels with left ventricular dysfunction or other prognostic indicators all remain uncertain. Acutely decreased left ventricular systolic function associated with moderate-to-severe COVID-19 occurs from a variety of causes, including myocarditis, stress-induced cardiomyopathy, critical illness cardiomyopathy and acute myocardial infarction. Anecdotal experience as well as a small number of published studies [73] [74] [75] [76] suggest that, in many of these cases, the ventricular dysfunction is only temporary and returns to normal within days to weeks. However, this recovery has not been well documented in the literature and the long-term prognosis for either those with recovery of left ventricular function or those without is not known. Patients with COVID-19 and evidence of acute cardiac injury should be monitored for long-term prognosis. Compared with those who never required hospitalization, more baseline laboratory and imaging information is available in survivors of moderate-to-severe COVID-19, but there is a dearth of long-term follow-up data specifically on the development of HF and arrhythmias. These patients should be 48, 82 .

The COVID-19 pandemic greatly disrupted how patients and the health-care system interacted, especially during the first months of the pandemic. Many patients delayed urgent and emergent care, including for acute cardiovascular conditions. Hospitalizations temporarily decreased 83 , but, in the case of acute coronary syndromes, the pandemic often simply led to a delayed presentation to hospital 84 , which is associated with worse outcomes 85 . Indeed, a multicentre, international registry of patients with COVID-19 and suspected acute coronary syndrome who underwent invasive coronary angiography found that symptom-to-admission times were greatly increased and that in-hospital mortality was higher among patients with any type of acute coronary syndrome than in recent pre-pandemic times; cardiogenic shock was also much more common 86 . The North American COVID-19 and STEMI (NACMI) registry similarly found that patients with ST-segment elevation myocardial infarction and COVID-19 were at higher risk of a composite end point of in-hospital death, stroke, recurrent myocardial infarction or repeat revascularization than they were before the pandemic 87 . These patients also presented with higher rates of cardiogenic shock and were less likely to receive invasive angiography than control patients from the pre-COVID era 87 .

Although not yet documented, these survivors of an acute coronary syndrome are very likely to have a higher rate of long-term complications, including HF and arrhythmias, even in those who did present to hospital, owing to increased door-to-balloon times 88, 89 . Furthermore, postponed outpatient preventive care appointments might have contributed to worse long-term outcomes, although this effect will be difficult to quantify 90 . 101 . More recent data suggest that the incidence might be tenfold higher, but this complication is still rare, and most cases are mild 102, 103 . The severity of the complication tends to be mild to moderate and is diagnosed clinically and with cardiac MRI, although rare reports of fulminant myocarditis with histopathology have been reported 104 . The long-term implications in these patients are not yet known, but this small risk is thought to be far outweighed by the benefit of vaccination against COVID-19. One study estimated that COVID-19 vaccination of the group of individuals who were most likely to experience post-vaccination myocarditis (adolescent and young adult men) would prevent >10 times the number of hospitalizations and 3-4 times the number of ICU admissions owing to COVID-19 than would result from cases of vaccine-associated myocarditis 105 .

Although no data are so far available on long-term cardiovascular sequelae, given the disease manifestations and pathogenesis observed during acute COVID-19, we can make educated determinations of certain cardiovascular complications that should undergo prospective monitoring in survivors of COVID-19 (box 2). Specific areas to investigate should include correlations between imaging abnormalities and pathology or histology, clinical syndromes and the development of long-term comorbidities. These studies should aim to determine the mechanisms and aetiology of different manifestations of viral presence in the heart. We might reasonably predict increased rates of progression to atherosclerotic cardiovascular disease, HF and/or valvular disease owing to lasting inflammatory effects, and these outcomes should be specifically assessed. Although cardiopulmonary symptoms are common in post-acute COVID-19, determining whether these symptoms are linked to objective evidence of cardiovascular disease by electrocardiography, echocardiography or advanced imaging will be important. Determining whether the presence of these symptoms is associated with worse prognosis will also be key. End points of these clinical studies should include functional status and symptoms, survival and cardiac morbidity (that is, the development of HF or arrhythmias). These end points should be assessed by imaging with cardiac MRI, echocardiography and/or PET as well as by the use of stress testing, biomarker measuring and event monitoring.

Given that few data are available on how these cardiovascular complications should be managed, we recommend that clinical judgement be used to determine follow-up and management in a manner similar to if they had occurred due to other, better-studied aetiologies. One useful guide for clinicians could be a position paper from the ESC 106 .

More than 18 months have passed since the WHO announced the pandemic nature of COVID-19. In that time, we have learned that cardiac injury is common during acute COVID-19 and that it is associated with worse short-term outcomes, that the aetiology of cardiac injury is multifactorial and that imaging abnormalities are common irrespective of the severity of the acute illness. However, much remains to be learned about the natural history and clinical importance of these findings in survivors of acute COVID-19, especially those with post-acute COVID-19 syndrome. We need more information on correlations between imaging findings and pathology and histology. We do not understand the aetiology of different manifestations of SARS-CoV-2 presence in cardiac tissues. The window of opportunity is quite narrow as cases of acute COVID-19 infection decrease with the roll-out of vaccination programmes. Governments, academic centres and private-public collaborations must invest the time and resources into this endeavour to understand the complex and disparate natural history of cardiovascular disease in the large number of survivors of COVID-19 as well as to prepare for the next potential pandemic.

Benjamin A. Satterfield 1 , Deepak L. Bhatt 2 and Bernard J. Gersh 1 ✉

• In patients with coronavirus disease 2019 (COVID-19) and elevated troponin levels, how long does troponin take to normalize? • In patients with COVID-19 and newly reduced left ventricular ejection fraction (LVEF), how many normalize and how long does this normalization take? • Is there an association between normalization of troponin levels and normalization of LVEF if both were abnormal during acute COVID-19? • In patients with acute COVID-19 who present with reduced LVEF or abnormal first-phase ejection fraction but in whom these parameters subsequently normalize, is there an increased risk of developing heart failure in the coming years? • In patients with a myocarditis-like late gadolinium enhancement pattern or abnormal T1 or T2 values on cardiac MRI, is there an increased risk of developing heart failure in the coming years? • Are survivors of COVID-19 at increased risk of diastolic dysfunction over the long term? www.nature.com/nrcardio

Sex differences in COVID-19 case fatality: do we know enough?

Acute myocardial injury in patients hospitalized with COVID-19 infection: a review

Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19)

Cardiovascular complications in COVID-19

COVID-19 and acute myocardial injury and infarction: related mechanisms and emerging challenges

Jr What we (don't) know about myocardial injury after COVID-19

Mechanisms of myocardial injury in COVID-19

Characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019

Acute myocardial injury is common in patients with COVID-19 and impairs their prognosis

Increased prevalence of myocardial injury in patients with SARS-CoV-2 viremia

Post-acute COVID-19 syndrome

Leveraging the electronic health record to address the COVID-19 pandemic

Regulation of cardiovascular therapies during the COVID-19 public health emergency

The COVID-19 pandemic: a catalyst to improve clinical trials

COVID-19: an unintended force for medical revolution

The landscape of cardiovascular clinical trials in the United States initiated before and during COVID-19

Effect of ivermectin on time to resolution of symptoms among adults with mild COVID-19: a randomized clinical trial

Effect of intermediate-dose vs standard-dose prophylactic anticoagulation on thrombotic events, extracorporeal membrane oxygenation treatment, or mortality among patients with COVID-19 admitted to the intensive care unit: the INSPIRATION randomized clinical trial

Effects of reninangiotensin-aldosterone system inhibitors on disease severity and mortality in patients with COVID-19: a meta-analysis

The consequences of the COVID-19 pandemic on non-COVID-19 clinical trials

Long-term clinical outcomes in survivors of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus outbreaks after hospitalisation or ICU admission: a systematic review and meta-analysis

Impact of severe acute respiratory syndrome (SARS) on pulmonary function, functional capacity and quality of life in a cohort of survivors

Mental morbidities and chronic fatigue in severe acute respiratory syndrome survivors: long-term follow-up

Depression as a mediator of chronic fatigue and post-traumatic stress symptoms in middle east respiratory syndrome survivors

Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome

Pulmonary function and exercise capacity in survivors of severe acute respiratory syndrome

Stress and psychological distress among SARS survivors 1 year after the outbreak

A proposed framework and timeline of the spectrum of disease due to SARS-CoV-2 infection: Illness beyond acute infection and public health implications

Management of post-acute Covid-19 in primary care

Cardiac involvement in patients recovered from COVID-2019 identified using magnetic resonance imaging

Long COVID guidelines need to reflect lived experience

Sequelae in adults at 6 months after COVID-19 infection

Persistent symptoms in patients after acute COVID-19

Follow-up of adults with noncritical COVID-19 two months after symptom onset

6-Month consequences of COVID-19 in patients discharged from hospital: a cohort study

Sequelae, persistent symptomatology and outcomes after COVID-19 hospitalization: the ANCOHVID multicentre 6-month follow-up study

Post-COVID syndrome: an insight on its pathogenesis

Arrhythmia in COVID-19. SN Compr

Cardiac arrhythmias in COVID-19

Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirusinfected pneumonia in Wuhan, China

Clinical characteristics of Covid-19 in

Atrial arrhythmias in COVID-19 patients

Cardiovascular sequalae in uncomplicated COVID-19 survivors

Worldwide survey of COVID-19-associated arrhythmias

COVID-19 and cardiac arrhythmias: a global perspective on arrhythmia characteristics and management strategies

Contribution of atrial fibrillation to in-hospital mortality in patients with COVID-19

Atrial fibrillation in patients hospitalized with COVID-19: incidence, predictors, outcomes and comparison to influenza

Postural orthostatic tachycardia syndrome (POTS) and other autonomic disorders after COVID-19 infection: a case series of 20 patients

Cardiac corrected QT interval changes among patients treated for COVID-19 infection during the early phase of the pandemic

Hydroxychloroquine/azithromycin therapy and QT prolongation in hospitalized patients with COVID-19

Use of chloroquine and hydroxychloroquine in COVID-19 and cardiovascular implications: understanding safety discrepancies to improve interpretation and design of clinical trials

COVID-19: myocardial injury in survivors

Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease

Cardiovascular magnetic resonance findings in competitive athletes recovering from COVID-19 infection

Cardiac magnetic resonance findings in patients recovered from COVID-19: initial experiences in elite athletes

Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance

Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, posthospital discharge

Cardiac involvement in consecutive elite athletes recovered from Covid-19: a magnetic resonance study

Evaluation for myocarditis in competitive student athletes recovering from coronavirus disease 2019 with cardiac magnetic resonance imaging

COVID-19 myocardial pathology evaluation in AthleTEs with cardiac magnetic resonance (COMPETE CMR)

Prevalence of inflammatory heart disease among professional athletes with prior COVID-19 infection who received systematic returnto-play cardiac screening

SARS-CoV-2 cardiac involvement in young competitive athletes

Cardiac T1 and T2 mapping showed myocardial involvement in recovered COVID-19 patients initially considered devoid of cardiac damage

Prospective case-control study of cardiovascular abnormalities 6 months following mild COVID-19 in healthcare workers

Cardiovascular evaluation after COVID-19 in 137 collegiate athletes: results of an algorithm-guided screening

Prevalence of clinical and subclinical myocarditis in competitive athletes with recent SARS-CoV-2 infection: results from the Big Ten COVID-19 Cardiac Registry

Return to play for athletes after COVID-19 infection: the fog begins to clear

First-phase ejection fraction, a measure of preclinical heart failure, is strongly associated with increased mortality in patients with COVID-19

Troponin and other biomarker levels and outcomes among patients hospitalized with COVID-19: derivation and validation of the HA2T2 COVID-19 mortality risk score

Myocarditis is rare in COVID-19 autopsies: cardiovascular findings across 277 post-mortem examinations

Predictors of COVID-19 severity: a literature review

Clinical outcomes in young US adults hospitalized with COVID-19

Left ventricular dysfunction in COVID-19: a diagnostic issue

COVID-19-associated stress (Takotsubo) cardiomyopathy

Takotsubo cardiomyopathy caused by emotional stressors in the coronavirus disease 2019 (COVID-19) pandemic era

SARS-CoV-2 triggered Takotsubo in 38 patients

Prevalence and outcomes of acute ischemic stroke among patients ≤50 years of age with laboratory confirmed COVID-19 infection

Prevalence and predictors of venous thromboembolism or mortality in hospitalized COVID-19 patients

Ventricular arrhythmia burden during the coronavirus disease 2019 (COVID-19) pandemic

Pulmonary embolism in COVID-19 patients: prevalence, predictors and clinical outcome

Pulmonary thrombosis in Covid-19: before, during and after hospital admission

Long-COVID postural tachycardia syndrome: an American Autonomic Society statement

Fewer hospitalizations for acute cardiovascular conditions during the COVID-19 pandemic

Acute coronary syndromes undergoing percutaneous coronary intervention in the COVID-19 era: comparable case volumes but delayed symptom onset to hospital presentation

COVID-19 and cardiovascular disease

TCT CONNECT-215 demographics and in-hospital outcomes of COVID-19 patients undergoing an invasive strategy for acute coronary syndrome: the global multi-centre prospective COVID-ACS registry

Initial findings from the North American COVID-19 myocardial infarction registry

Impact of the COVID-19 Pandemic on door-to-balloon time for primary percutaneous coronary intervention -results from the Singapore Western STEMI network

Effect of the COVID-19 pandemic on treatment delays in patients with ST-segment elevation myocardial infarction

Delayed care with harmful health consequencesreported experiences from national surveys during coronavirus disease 2019

Racial and ethnic health disparities related to COVID-19

Racial disparities in coronavirus disease 2019 (COVID-19) outcomes

The disproportionate impact of COVID-19 on racial and ethnic minorities in the United States

COVID-19 and black, Asian, and minority ethnic communities: a complex relationship without just cause

Prevalence of Overweight, Obesity, and Severe Obesity Among Adults Age 20 and Over: United States

Estimates of diabetes and its burden in the United States

Chronic Kidney Disease in the United States

Myocarditis and pericarditis are rare following live viral vaccinations in adults

Patients with acute myocarditis following mRNA COVID-19 vaccination

Myocarditis following immunization with mRNA COVID-19 vaccines in members of the US military

Myocarditis with COVID-19 mRNA Vaccines

Myocarditis after Covid-19 vaccination in a large health care organization

Myocarditis after BNT162b2 mRNA vaccine against Covid-19 in Israel

Myocarditis after Covid-19 mRNA vaccination

Association of myocarditis with BNT162b2 messenger RNA COVID-19 vaccine in a case series of children

Late phase of COVID-19 pandemic in general cardiology. A position paper of the ESC Council for Cardiology Practice

B.A.S. researched data for the article and wrote the manuscript. D.L.B. and B.J.G. discussed the content of the article and reviewed/edited it before submission.

The authors declare no competing interests.

Nature Reviews Cardiology thanks Steffen Massberg, Richard Vander Heide and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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