Thursday, December 15, 2022

Nature: SARS-CoV-2 Infection and Persistence in the Human Body and Brain at Autopsy


Despite more than 1 million American deaths, and millions more affected by `Long COVID', many continue to believe that the SARS-CoV-2 virus is `no worse than the flu' , and mostly a danger to the elderly, or those with serious comorbidities. 

While it's true roughly 99% of people survive the acute phase of COVID, the long-term impacts of having had COVID are far from trivial for millions of people. A few (of many) studies include:

Neurology: Incidence of Epilepsy and Seizures Over the First 6 Months After a COVID-19 Diagnosis: A Retrospective Cohort Study
The Lancet: Neurological and Psychiatric Risk Trajectories After SARS-CoV-2 Infection

MMWR: Post–COVID-19 Symptoms and Conditions Among Children and Adolescents

Nature: Long-term Cardiovascular Outcomes of COVID-19
Nature: Long-term Neurologic Outcomes of COVID-19
Making matters worse, these risks appear to increase with every infection (see Nature: Acute and Postacute Sequelae Associated with SARS-CoV-2 Reinfection).  Which the exact mechanism behind these `Long-COVID' symptoms isn't known, the extrapulmonary spread of the virus - particularly to the brain and the heart - is strongly suspected to contribute. 

Nature: Enhanced Replication of SARS-CoV-2 Omicron BA.2 in Human Forebrain and Midbrain Organoids

Nat. Comms: Neuropathology and Virus in Brain of SARS-CoV-2 Infected Non-human Primates

Association of Cardiac Infection With SARS-CoV-2 in Confirmed COVID-19 Autopsy Cases - JAMA

All of which brings us to a study, published in Nature yesterday, which documents the spread, and persistence, of the SARS-COV-2 virus at autopsy in 44 cases.  First the link, and abstract (but you'll want to read the report in its entirety), followed by a press release from NIAID. 

Published: 14 December 2022
SARS-CoV-2 infection and persistence in the human body and brain at autopsy

Sydney R. SteinSabrina C. RamelliAlison GrazioliJoon-Yong ChungManmeet SinghClaude Kwe YindaClayton W. WinklerJunfeng SunJames M. DickeyKris YlayaSung Hee KoAndrew P. Platt,Peter D. BurbeloMartha QuezadoStefania PittalugaMadeleine PurcellVincent J. MunsterFrida BelinkyMarcos J. Ramos-BenitezEli A. BoritzIzabella A. LachDaniel L. HerrJoseph Rabin,
Kapil K. SahariaNIH COVID-19 Autopsy Consortium, …
Daniel S. Chertow Show authors

Nature (2022) Cite this article


Coronavirus disease 2019 (COVID-19) is known to cause multi-organ dysfunction1,2,3 during acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some patients experiencing prolonged symptoms, termed post-acute sequelae of SARS-CoV-2 (refs. 4,5). However, the burden of infection outside the respiratory tract and time to viral clearance are not well characterized, particularly in the brain3,6,7,8,9,10,11,12,13,14

Here we carried out complete autopsies on 44 patients who died with COVID-19, with extensive sampling of the central nervous system in 11 of these patients, to map and quantify the distribution, replication and cell-type specificity of SARS-CoV-2 across the human body, including the brain, from acute infection to more than seven months following symptom onset. 

We show that SARS-CoV-2 is widely distributed, predominantly among patients who died with severe COVID-19, and that virus replication is present in multiple respiratory and non-respiratory tissues, including the brain, early in infection. 

Further, we detected persistent SARS-CoV-2 RNA in multiple anatomic sites, including throughout the brain, as late as 230 days following symptom onset in one case. Despite extensive distribution of SARS-CoV-2 RNA throughout the body, we observed little evidence of inflammation or direct viral cytopathology outside the respiratory tract. Our data indicate that in some patients SARS-CoV-2 can cause systemic infection and persist in the body for months.

          (Continue . . . )

NIAID Now | December 14, 2022

Early Findings of Widespread, Long-Lasting Virus Helped Inform Research

Autopsies of 44 people who died from COVID-19 in the first year of the pandemic showed researchers that disease-causing SARS-CoV-2 virus spread throughout the body – beyond just a respiratory disease – and remained in tissue for months. The study, from the National Institutes of Health and published in Nature, helped scientists broaden their perspectives on where SARS-CoV-2 could cause infection and persist, including the brain. The work also supported the rationale for a clinical trial evaluating the antiviral drug Paxlovid for the treatment of post-acute sequelae of COVID-19, also known as Long COVID.

Findings from the autopsies, which took place between April 2020 and March 2021, confirmed that SARS-CoV-2 primarily infected and damaged the airway and lungs. But scientists also found virus fragments (viral RNA) in 79 of 85 body locations, with some virus found up to 230 days after patient’s symptoms began. Scientists found virus in cardiovascular, lymphoid, gastrointestinal, renal, endocrine, reproductive, muscle, brain and other tissue – although none of these areas sustained significant inflammation compared to what they found in the respiratory tract. Scientists from NIH’s National Institute of Allergy and Infectious Diseases and Clinical Center led the work, closely collaborating with National Cancer Institute (NCI) pathologists, four other NIH institutes, the University of Maryland, and Maryland health care facilities in Salisbury and Towson.

“We show SARS-CoV-2 disseminates across the human body and brain early in infection at high levels and provide evidence of virus replication at multiple extrapulmonary sites during the first two weeks following symptom onset,” their study states. Virus can spread throughout the body and viral RNA may remain detectable for months even in cases with mild or no symptoms, they say.

Senior study author Dr. Daniel Chertow said prior to the work, “the thinking in the field was that SARS-CoV-2 was predominantly a respiratory virus.” Finding the viral fragments in tissue throughout the body – and sharing those findings with colleagues a year ago – helped scientists explore a relationship between the viral fragments and Long COVID.

Long COVID gets its name from the persistent symptoms some people experience after having COVID-19; symptoms can be debilitating, and the cause is not known. Though the study in Nature did not specifically explore Long COVID, finding the viral RNA throughout the body raised speculation that those fragments might contribute to the persistent symptoms, according to Dr. Chertow. Treating people with an effective COVID-19 antiviral such as Paxlovid could, therefore, eliminate the persistent symptoms.

The Paxlovid trial, now underway at Duke University, is part of the NIH-funded RECOVER project – Researching COVID to Enhance Recovery – and includes an extension of the autopsy work, according Dr. Stephen Hewitt of NCI, who collaborated on the paper in Nature, and serves on a steering committee for the RECOVER project.

He said one branch of RECOVER includes tissue pathology studies, and obtaining material from autopsies is in progress; these autopsies include people who both were vaccinated and infected with variants of concern – data not available in the earlier study that Dr. Chertow’s group led.

“We’re hoping to replicate the data on viral persistence

It may take another 5 or 10 years before we can accurately assess the impact of COVID infection on society's health and well being. But current evidence suggests that COVID - even when it only produces mild acute illness - is an infection best avoided whenever possible.
 and study the relationship with Long COVID,” Dr. Hewitt said, adding that the project is scheduled to last four years. “Less than a year in we have about 85 cases, and we are working to expand these efforts.”

S Stein, et al. SARS-CoV-2 infection and persistence throughout the human body and brain at autopsy. Nature DOI: 10.1038/s41586-022-05542-y (2022).

It may take another 5 or 10 years before we can accurately assess the impact of COVID infection on society's health and well being. But current evidence suggests that COVID - even when it only produces mild acute illness - is an infection best avoided whenever possible.