Tuesday, July 28, 2020

JAMA: Two Studies Linking SARS-CoV-2 Infection To Cardiac Injury


While there is a certain amount of comfort to be taken from data that suggests COVID-19 is a relatively low mortality - high morbidity pandemic - and that nearly 99% of all those infected survive - evidence of serious post-infection sequelae from SARS-CoV-2 infection continues to mount. 

Very early on COVID-19 was linked to prolonged hospitalizations, and there are numerous anecdotal reports of patients continuing to suffer from fatigue, shortness of breath, chest pains, cognitive issues, and other debilitating symptoms weeks or even months after being discharged. 

Three weeks ago, Dr. Anthony Fauci expressed concerns that many COVID patients are suffering from a post-viral syndrome - similar to ME/CFS - which has disabled and traumatized well over a million Americans over the past 3 decades (see NIH About CFS/ME). 

How prevalent this post-viral syndrome might be among COVID survivors may not be fully appreciated for years, but it has the potential to have a significant impact.

Somewhat easier to identify are those COVID survivors who have had strokes, blood clots, heart attacks, or have suffered permanent lung damage during the course of their illness. 

Some past studies on these adverse outcomes include:

Last month JAMA published an original investigation which found a 3-fold increase in out-of-hospital cardiac arrests in New York City during the peak of their COVID-19 epidemic, 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.
Admittedly many of these cases likely already had underlying cardiac problems, but COVID-19 appears to have a direct, and often serious impact on cardiac function.  In May, the American Heart Association's journal Circulation published:
Among patients with COVID-19, there is a high prevalence of cardiovascular disease, and >7% of patients experience myocardial injury from the infection (22% of critically ill patients). Although angiotensin-converting enzyme 2 serves as the portal for infection, the role of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers requires further investigation. COVID-19 poses a challenge for heart transplantation, affecting donor selection, immunosuppression, and posttransplant management. There are a number of promising therapies under active investigation to treat and prevent COVID-19.
Added to this, follow-up exams and cohort studies are starting to show hidden organ damage among COVID survivors - even among relatively young patients who experienced only mild or moderate illness - raising concerns of increased disability and/or shortened lifespans among some survivors. 

Yesterday JAMA published two on-point studies, both of which raise serious questions over the long-term impact of SARS-CoV-2 infection on the cardiovascular system. 

The first provides 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. 

July 27, 2020

Author Affiliations Article Information
JAMA Cardiol. Published online July 27, 2020. doi:10.1001/jamacardio.2020.3551

Key Points

Question Can severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) be documented in cardiac tissue of coronavirus disease 2019 (COVID-19) autopsy cases?

Findings In this cohort study of 39 autopsy cases of patients with COVID-19, cardiac infection with SARS-CoV-2 was found to be frequent but not associated with myocarditislike influx of inflammatory cells into the myocardium.

Meaning Among individuals with cardiac infection, overt myocarditis was not observed in the acute phase, but the long-term consequences of this cardiac infection needs to be studied.

The second, and arguably more worrisome study, finds 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. 
-Original Investigation
July 27, 2020

Valentina O. Puntmann, MD, PhD1; M. Ludovica Carerj, MD1,2; Imke Wieters, MD3; et alMasia Fahim3; Christophe Arendt, MD1,4; Jedrzej Hoffmann, MD1,5; Anastasia Shchendrygina, MD, PhD1,6; Felicitas Escher, MD7; Mariuca Vasa-Nicotera, MD5; Andreas M. Zeiher, MD5; Maria Vehreschild, MD3; Eike Nagel, MD1
Author Affiliations Article Information
JAMA Cardiol. Published online July 27, 2020. doi:10.1001/jamacardio.2020.3557

Key Points

Question What are the cardiovascular effects in unselected patients with recent coronavirus disease 2019 (COVID-19)?

Findings In this cohort study including 100 patients recently recovered from COVID-19 identified from a COVID-19 test center, cardiac magnetic resonance imaging revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), which was independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis.

Meaning These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.
Both studies can be read in their entirety at the provided links, along with an accompanying editorial entitled:
July 27, 2020

Clyde W. Yancy, MD, MSc1,2; Gregg C. Fonarow, MD3,4
JAMA Cardiol. Published online July 27, 2020. doi:10.1001/jamacardio.2020.3575
While it isn't known whether the cardiac changes observed in these patients (including reduced left ventricular injection fraction) are permanent, the fear of cardiologists is they could presage a new wave of pandemic-related heart failure down the road. 

And it is worth noting we've seen similar concerns raised 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).

COVID-19 isn't the first viral or bacterial infection with a relatively low CFR, that can produce delayed, and often surprising, sequelae. 
  • Last month, in The Lancet: COVID-19: Can We Learn From Encephalitis Lethargica?, we looked at the decade-epidemic of neurological disease that began around the time of the 1918 pandemic, and persisted until the late 1920s.  While its cause remains unknown, a viral infection is strongly suspected. 
  • Vector-borne viruses like West Nile, Chikungunya, and Zika can sometimes lead to devastating  neuroinvasive complications (such as meningitis or encephalitis) or paralysis (Guillain Barre Syndrome).
  • Even relatively mild non-polio enteroviruses - like EV-71 and EV-D68 - can lead to Acute Flaccid Paralysis (AFM), particularly in children and adolescents. 
  • And while rare, untreated strep throat can lead to Rheumatic fever and heart damage, Glomerulonephritis (kidney damage), and Sydenham Chorea (neurological damage).
The tendency from the start of this pandemic has been to underestimate the impact of SARS-CoV-2 infection, and to arbitrarily divide outcomes into just two categories; deaths and recoveries.  

As a result - even as the evidence to the contrary continues to pour in - many people point to the statistics and dismiss COVID-19 as only a threat to the elderly and infirmed, and that for everyone else, it isn't any worse than the `flu'. 

Although most people still appear to recover from COVID-19 without medical intervention and without lasting damage, some (as yet, unquantified) percentage may find themselves saddled with serious, long-term health consequences as a result their SARS-COV-2 infection. 

While that burden may not become fully apparent for years, it is something that individuals, and society as a whole, will have to deal with long after the pandemic has ended.