Monday, September 20, 2021

JACC: Postacute Sequelae of SARS-CoV-2 Infection: A State-of-The Art Review



Since very early in the COVID outbreak, it became apparent that while most people would survive the infection - a significant portion of cases would experience severe illness - and require a lengthy recovery.  Some would be left with significant sequelae post-infection, while a relatively small percentage would succumb to the illness. 

Some `recovered' patients have been left with significant lung, heart, or kidney damage while others have experienced lingering neurological manifestations ranging 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.).

Some experts have suggested we may see huge increases in COVID-19 related heart failure and neurological diseases in the years ahead.

Emily A. Troyer, Jordan N. Kohn, and Suzi Hong 

Dubbed `Long COVID', or `Post-COVID Syndrome', this post-acute phase of the illness remains poorly defined, or understood.  Last week the CDC's MMWR carried a report (see Post-Acute Sequelae of SARS-CoV-2 Infection Among Adults Aged ≥18 Years — Long Beach, California, April 1–December 10, 2020) that found:

In a random sample of recovered COVID-19 patients in Long Beach, California, one third of participants reported post-acute sequelae 2 months after their positive test result, with higher rates reported among persons aged ≥40 years, females, persons with preexisting conditions, and Black persons.

Some of these sequelae are mild, and will probably dissipate over time, while others may become permanent disabilities or lead to premature death.  A few recent blogs on these concerns include:

CMAJ: Even Mild COVID-19 May Have Long-term Brain Impacts

CDC Science Update: COVID-19 and Persistent Symptoms

COCA Call (Tomorrow, June 17th): Evaluating and Caring for Patients with Post-COVID Conditions 

Today we have new review, published in the JACC (Journals of the American College of Cardiology) BTS, which examines the current knowledge on Postacute SARS-CoV-2 infection, including known impacts on the pulmonary, cardiac, neurological, renal, and endocrine systems.

This is a quite lengthy review which really requires reading in its entirety.  

I've only posted some brief excerpts from the opening and the discussion. Follow the link to read this review in full.  I'll have a brief postscript when you return. 

Postacute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A State-of-the-Art Review

State-Of-The-Art Review

David H. Jiang, Darius J. Roy, Brett J. Gu, Leslie C. Hassett, and Rozalina G. McCoy

J Am Coll Cardiol Basic Trans Science. Sep 15, 2021. Epublished DOI: 10.1016/j.jacbts.2021.07.002

Topic(s): Basic & Translational Research


• Long-term manifestation of PASC are experienced by 33% to 98% of patients who have recovered from initial COVID-19 illness.

• This review summarizes and synthesizes the emerging evidence about multisystem manifestations of PASC.

• Evidence points to disproportionate impact on racial/ethnic minorities, older patients, patients with preexisting conditions, and rural residents.

• Continued research is needed to better understand, anticipate, and mitigate the long-term effects of PASC on individual and population health.


The vast majority of patients (>99%) with severe acute respiratory syndrome coronavirus 2 survive immediate infection but remain at risk for persistent and/or delayed multisystem. This review of published reports through May 31, 2021, found that manifestations of postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) affect between 33% and 98% of coronavirus disease 2019 survivors and comprise a wide range of symptoms and complications in the pulmonary, cardiovascular, neurologic, psychiatric, gastrointestinal, renal, endocrine, and musculoskeletal systems in both adult and pediatric populations.

Additional complications are likely to emerge and be identified over time. Although data on PASC risk factors and vulnerable populations are scarce, evidence points to a disproportionate impact on racial/ethnic minorities, older patients, patients with preexisting conditions, and rural residents. Concerted efforts by researchers, health systems, public health agencies, payers, and governments are urgently needed to better understand and mitigate the long-term effects of PASC on individual and population health.


Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has created unprecedented challenges for public health and health care infrastructures around the world. As of June 18, 2021, there have been more than 177 million cases of COVID-19 worldwide, including 33 million in the United States, resulting in more than 3.8 million deaths globally and 600,000 deaths in the United States (1). Despite ongoing vaccination efforts, COVID-19 continues to spread around the world, driven by emergent variant strains and relaxation of prevention/mitigation strategies (2,3). With >99% of patients surviving the acute infectious period (4) and data on the long-term sequelae of COVID-19 disease beginning to emerge, there is an urgent need to better understand the lasting effects of COVID-19 on survivors (5). These long-term complications, collectively referred to as the postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) (6) and more colloquially as “long COVID” or “long haulers,” span multiple systems and may have significant effects on health, function status, and quality of life.

In this review, we summarize and synthesize the emerging evidence about symptoms and conditions comprising PASC, characterize what is known about the frequency and timing of their occurrence, and seek to identify individuals at highest risk. In the context of constrained resources and structural disparities within the US health care system, this review has several key objectives. First, it will help patients, clinicians, and health systems understand the epidemiology of PASC to inform timely evidence-based screening, diagnosis, and treatment and anticipate the resources required to care for patients with increasing burden of chronic health conditions. Second, it will be informative for payers as they anticipate resource use, costs of care, and consider optimal disease management, risk mitigation, and payment models. Lastly, it may help federal and state governments and public health agencies to coordinate their responses and ameliorate disparities in health care access, utilization, and health outcomes.

         (SNIP )


Although the end of the COVID-19 pandemic may be in sight with successful vaccination efforts, the fight against its long-term complications is just beginning. PASC affects children and adults irrespective of the severity of the COVID-19 infection itself, though it is more common among patients with more severe COVID-19.

It can cause a wide range of complications in the pulmonary, cardiovascular, neurologic, psychiatric, gastrointestinal, renal, endocrine, and musculoskeletal systems that may persist months or years beyond the initial infection. Racial and ethnic minorities, rural residents, older patients, and patients with preexisting conditions may be more likely to develop PASC, though more population-level data on PASC are urgently needed. A concerted approach between health care systems, payers, public health agencies, and governments will be necessary to understand, prevent, and mitigate the long-term impact of PASC on the nation’s health. 

(Continue . . . )

In the decade following the 1918 H1N1 pandemic- which killed tens of millions of people - the world experienced another type of epidemic; an explosion in cases of Encephalitis Lethargica, and Parkinson's disease, affecting millions (see The Lancet: COVID-19: Can We Learn From Encephalitis Lethargica?).

Its legacy was depicted in the 1990 fictionalized movie Awakenings, which was based on Oliver Sacks' 1973 memoir. In it, he described patients who had been comatose for 40 years who were treated with L-DOPA in the 1960s, and briefly recovered, only to slip back into a catatonic state.

Throughout history, there have been reports of similar outbreaks, resulting in severe neurological disease, including febris comatosa which sparked a severe epidemic in London between 1673 and 1675, and in 1890 in Italy, in the wake of the 1889–1890 influenza pandemic, a severe wave of somnolent illnesses (nicknamed the "Nona") appeared.

Among those who survived, Parkinsonism and other neurological sequelae was common.

While the exact cause of these epidemics remains unknown, a virus - or perhaps an autoimmune response to a viral infection - are both plausible suspects.

Over the past dozen years or so, we've seen ample evidence of neurological involvement from a variety of viral infections, including West Nile Virus (WNV), EV-D68, Zika Virus, and even seasonal influenza.

Taking the `long view', the individual and societal impact of COVID-19 could end up being far greater than is currently generally appreciated, and may not become fully apparent for years.   

More good reasons, as if we needed any, for doing whatever you can (i.e. get vaccinated, wear a facemask, avoid crowds, etc.) to avoid becoming infected with this pandemic virus.