COVID-19 is known to cause multi-organ dysfunction and even failure during acute infection, with several million patients experiencing prolonged symptoms after recovery. How and why symptoms linger, disappear, reappear, or manifest as new conditions, even in people with mild or asymptomatic cases, is still not fully understood.  

To shed light on this phenomenon, a recent study, which is under review for publication in the journal Nature, undertook an analysis of the types of cells that the SARS-CoV-2 virus can infect throughout the body, along with the persistence (duration), of the virus in those different cells, by performing comprehensive autopsies on patients who died during the first year of the pandemic in the U.S.

What They Did

Between April 26, 2020, and March 2, 2021, the research team performed autopsies on 44 people who had died from or with COVID-19 up to 230 days (just over seven and a half months) following their initial onset of symptoms. The study cohort was racially and ethnically diverse. Approximately 29.5% of the patients were female, with an average age of 59.2 years, and 95.5% had at least one underlying health issue. Chronic respiratory disease, hypertension, and/or obesity were the most common.  

The autopsy cases of SARS-CoV-2 infection were categorized as early, mid, or late according to how many days they had been experiencing symptoms at the time of death:

• Early (before or on day 14)
• Mid (days 15 to 30)
• Late (on or after day 31)

“Persistence” was defined as the presence of SARS-CoV-2 RNA among late cases. 

What They Found

The researchers found widespread infection and persistent SARS-CoV-2 RNA in all 44 cases, in distinct cell types at multiple sites across all sampled organs, and in 79 out of 85 body fluids tested for up to 230 days following symptom onset.

Overall, SARS-CoV-2 RNA was detected in:

• 97.7% of respiratory tissue (43/44 cases) 
• 90.9% of brain tissue (10/11)
• 86.4% of lymphoid tissue (38/44)
• 79.5% of cardiovascular tissue (35/44) 
• 72.7% of gastrointestinal tissue (32/44) 
• 68.2% of muscle, skin, adipose, and peripheral nervous tissue (30/44)
• 63.6% of renal and endocrine tissue (28/44) 
• 57.9% of ocular tissue and humors (22/28)
• 42.5% of reproductive tissue (17/40) 

Low RNA levels were also detected across multiple tissue categories in all late cases, despite being undetectable in blood plasma. The highest concentration was detected in the respiratory tract of early cases, though several mid and late cases also showed high levels in the sinuses, trachea, and lungs. 

The heart contained spike RNA in both early and late cases. It was detected in the brains of all six late cases, as well, crossing the blood-brain barrier. In about 50% of late cases, it was found in the tongue, the myocardium (the middle and thickest layer of the heart wall), and other diverse tissues.

Despite the widespread distribution of the virus in the body, however, scientists found little inflammation or direct viral cell abnormalities outside the lungs. 

What It Means

The findings show that though the highest concentration of SARS-CoV-2 is in the airways and lungs, the virus can travel early on–within the first week–and infect cells throughout the body, including the brain. Systemic infection can linger in the body for months, with RNA failing to clear from multiple organs for up to 230 days. Replication of the virus may occur even outside the lungs for three months (and as late as day 99), even in mild and asymptomatic cases. The fact that this can occur even without significant inflammation outside the respiratory tract raises more questions that warrant further study.

Still, the study results potentially clear up a sizable chunk of the mystery of long COVID, a condition that has baffled both scientists and healthcare professionals and caused suffering and disability to more than 10 million people in the U.S. alone. The authors hope that this new knowledge will lead to better solutions and greater relief. “Understanding the mechanisms by which the virus persists,” they wrote, “along with the body’s response to any viral reservoir, promises to help improve care for those afflicted.”

*Hasco, L. (2021, Dec. 27). Study Finds Coronavirus Can Persist for Months in Almost Every Organ System: A Step Towards Understanding Long COVID-19. Penn-Live Patriot News.   https://www.pennlive.com/nation-world/2021/12/study-finds-coronavirus-can-persist-for-months-in-almost-every-organ-system-a-step-towards-understanding-long-covid-19.html