Monday, February 07, 2022

Nature: Long-term Cardiovascular Outcomes of COVID-19


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Despite ample evidence to the contrary, much of society continues to view SARS-CoV-2 infection as a simple respiratory infection - not unlike influenza - that really only seriously affects the elderly, and those with severe comorbidities.   

While it is true that 98%-99% of people survive the acute phase of COVID - and most deaths have occurred among the elderly, or those with serious comorbidities -  the extrapulmonary manifestations of SARS-CoV-2 infection are many, varied, and only partially appreciated.

Last week, in American Heart Assoc: Stroke Risk Among Older Adults Highest in First 3 Days After COVID-19 Diagnosis, we looked at a study that found the risk of stroke increased 10-fold in the week following infection. Although it declined over time, even a month later it was still 9% higher than normal. 

We've seen many other neurological manifestations associated with COVID illness (see JAMA: Neurologic Manifestations Of Patients With Severe Coronavirus Disease), including:

Neurological manifestations ranged from relatively mild (headaches, dizziness, anosmia, mild confusion, etc.) to more profound (seizures, stupor, loss of consciousness, etc.) to potentially fatal (ischemic stroke, cerebral hemorrhage, muscle injury (rhabdomyolysis), etc.). 

We've seen other studies that have linked COVID infection to cardiac damage and in 2020, JAMA published an original investigation which found a substantial increase in out-of-hospital cardiac arrests in New York City during the peak of their first COVID-19 wave, finding:

From March 1 to April 25, 2020, New York City, New York (NYC), reported 17 118 COVID-19–related deaths. On April 6, 2020, out-of-hospital cardiac arrests peaked at 305 cases, nearly a 10-fold increase from the prior year.

In the summer of 2020 (see JAMA: Two Studies Linking SARS-CoV-2 Infection To Cardiac Injury), we examined the results of 39 autopsies on COVID cases, that showed even when pneumonia is the presumed cause of death - and even without overt histopathic evidence of acute myocarditis - the heart often shows a high viral load of SARS-COV-2

A second, and arguably even more worrisome study, found a remarkable incidence of cardiac injury and myocardial inflammation among a relatively young cohort (avg. age 49 & without pre-existing cardiac hx) of COVID patients who mainly recovered at home but continued to experience a variety of symptoms following their illness. 

An accompanying editorial (see Coronavirus Disease 2019 (COVID-19) and the Heart—Is Heart Failure the Next Chapter? by Clyde W. Yancy, MD, MSc1,2; Gregg C. Fonarow, MD3,4) raised serious concerns over the long-term impact of COVID on public health.

We've seen similar questions raised over over post-infection neurological manifestations (see Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms by Emily A. Troyer, Jordan N. Kohn, and Suzi Hong). 

These cardiac and neurological sequelae are only part of a much larger spectrum of Postacute Sequelae of SARS-CoV-2 InfectionDubbed `Long COVID', or `Post-COVID Syndrome', this post-acute phase of the illness remains poorly defined and  understood.  

All of which brings us to a new study, published today in the Journal Nature, that takes an early look at the long-term (12 month) impact of COVID illness on cardiovascular health, even among those who weren't  ill enough to require hospitalization. 

This is a lengthy, and detailed, report that deserves to be read in its entirety.  I've reproduced the abstract and some excerpts below, but you'll want to follow the link to download the full study.  I'll have a brief postscript after the break.

Open Access
Published: 07 February 2022
Long-term cardiovascular outcomes of COVID-19
Yan XieEvan XuBenjamin BoweZiyad Al-Aly

Nature Medicine (2022)Cite this article


The cardiovascular complications of acute coronavirus disease 2019 (COVID-19) are well described, but the post-acute cardiovascular manifestations of COVID-19 have not yet been comprehensively characterized. Here we used national healthcare databases from the US Department of Veterans Affairs to build a cohort of 153,760 individuals with COVID-19, as well as two sets of control cohorts with 5,637,647 (contemporary controls) and 5,859,411 (historical controls) individuals, to estimate risks and 1-year burdens of a set of pre-specified incident cardiovascular outcomes. 

We show that, beyond the first 30 d after infection, individuals with COVID-19 are at increased risk of incident cardiovascular disease spanning several categories, including cerebrovascular disorders, dysrhythmias, ischemic and non-ischemic heart disease, pericarditis, myocarditis, heart failure and thromboembolic disease. 

These risks and burdens were evident even among individuals who were not hospitalized during the acute phase of the infection and increased in a graded fashion according to the care setting during the acute phase (non-hospitalized, hospitalized and admitted to intensive care). 

Our results provide evidence that the risk and 1-year burden of cardiovascular disease in survivors of acute COVID-19 are substantial. Care pathways of those surviving the acute episode of COVID-19 should include attention to cardiovascular health and disease.


Cerebrovascular disorders

People who survived the first 30 d of COVID-19 exhibited increased risk of stroke (hazard ratio (HR) = 1.52 (1.43, 1.62); burden 4.03 (3.32, 4.79) per 10,00 persons at 12 months; for all HRs and burdens, parenthetical ranges refer to 95% confidence intervals (CIs)) and transient ischemic attacks (TIA) (HR = 1.49 (1.37, 1.62); burden 1.84 (1.38, 2.34)). The risks and burdens of a composite of these cerebrovascular outcomes were 1.53 (1.45, 1.61) and 5.48 (4.65, 6.35). 


There were increased risks of atrial fibrillation (HR = 1.71 (1.64, 1.79); burden 10.74 (9.61, 11.91)), sinus tachycardia (HR = 1.84 (1.74, 1.95); burden 5.78 (5.07, 6.53)), sinus bradycardia (HR = 1.53 (1.45, 1.62); burden 4.62 (3.90, 5.38)), ventricular arrhythmias (HR = 1.84 (1.72, 1.98); burden 4.18 (3.56, 4.85)); and atrial flutter (HR = 1.80 (1.66, 1.96); burden 3.10 (2.55, 3.69)). The risks and burdens of a composite of these dysrhythmia outcomes were 1.69 (1.64, 1.75), and 19.86 (18.31, 21.46).

Inflammatory disease of the heart or pericardium

Inflammatory disease of the heart or pericardium included pericarditis (HR = 1.85 (1.61, 2.13)); burden 0.98 (0.70, 1.30) and myocarditis (HR = 5.38 (3.80, 7.59); burden 0.31 (0.20, 0.46)). The risks and burdens of a composite of these inflammatory diseases of the heart or pericardium were 2.02 (1.77, 2.30) and 1.23 (0.93, 1.57).

Ischemic heart disease

Ischemic heart disease included acute coronary disease (HR = 1.72 (1.56, 1.90); burden 5.35 (4.13, 6.70)), myocardial infarction (HR = 1.63 (1.51, 1.75); burden 2.91 (2.38, 3.49)), ischemic cardiomyopathy (HR = 1.75 (1.44, 2.13); burden 2.34 (1.37, 3.51)) and angina (HR = 1.52 (1.42, 1.64); burden 2.50 (2.00, 3.03)). The risks and burdens of a composite of these ischemic heart disease outcomes were 1.66 (1.52, 1.80) and 7.28 (5.80, 8.88).

Other cardiovascular disorders

Other cardiovascular disorders included heart failure (HR = 1.72 (1.65, 1.80); burden 11.61 (10.47, 12.78)), non-ischemic cardiomyopathy (HR = 1.62 (1.52, 1.73); burden 3.56 (2.97, 4.20)), cardiac arrest (HR = 2.45 (2.08, 2.89); burden 0.71 (0.53, 0.93)) and cardiogenic shock (HR = 2.43 (1.86, 3.16); burden 0.51 (0.31, 0.77)). The risks and burdens of a composite of these other cardiovascular disorders were 1.72 (1.65, 1.79) and 12.72 (11.54, 13.96).

Thromboembolic disorders

Thromboembolic disorders included pulmonary embolism (HR = 2.93 (2.73, 3.15); burden 5.47 (4.90, 6.08)); deep vein thrombosis (HR = 2.09 (1.94, 2.24); burden 4.18 (3.62, 4.79)) and superficial vein thrombosis (HR = 1.95 (1.80, 2.12); burden 2.61 (2.20, 3.07)). The risks and burdens of a composite of these thromboembolic disorders were 2.39 (2.27, 2.51) and 9.88 (9.05, 10.74).

          (Continue . . . )

It should be noted that the COVID-positive cohort for this study came from patients infected during the first year of the pandemic (1 March 2020 to 15 January 2021), and therefore would not include any Delta, or Omicron, cases.  The authors acknowledge:

Finally, as the pandemic, with all its dynamic features, continues to progress, as the virus continues to mutate and as new variants emerge, as treatment strategies of acute and post-acute COVID-19 evolve and as vaccine uptake improves, it is possible that the epidemiology of cardiovascular manifestations in COVID-19 might also change over time21.
Many people dismiss COVID infection as trivial since it is mostly mild, and point to the high survival rate - even among those hospitalized - as if that tells the whole story. 

But as these studies continue to show - the long-term impacts of COVID infection can be serious and should not be underestimated - making this is an illness you really want to prevent if possible.