New Delhi: A new study conducted by scientists from the National Institutes of Health (NIH) in the US has found that SARS-CoV-2 causes systemic infection and can persist in the body for months. Systemic infection affects the entire body, rather than a single organ or body part.


The results of the study, yet to be peer-reviewed, were recently released online in a manuscript under review for publication in the journal, Nature. The study was performed at the NIH in Bethesda, Maryland.


Acute Covid-19 infection causes multi-organ dysfunction. When patients experience prolonged symptoms, it is termed Post-Acute Sequelae of SARS-CoV-2 (PASC) or long Covid.


Not much information is available on the burden of infection outside the respiratory tract, and how much time is required by the body for viral clearance. The scientists from NIH conducted this study to find the answers to these questions. 


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SARS-CoV-2 Can Disseminate During Early Infection & Infect Cells Throughout Body


Though the burden of SARS-CoV-2 is the highest in the airways and lungs, the virus can disseminate early during infection and infect cells throughout the entire body, including widely throughout the brain, the US scientists found. The virus is capable of replicating outside the respiratory tract, and can spread to the cardiovascular organs, lymphoid tissues, gastrointestinal tract, renal and endocrine glands, and reproductive tissues.


The authors call the study the most comprehensive analysis to date of SARS-CoV-2 cellular tropism (host tissues that support growth of a particular pathogen), quantification, and persistence across the body and brain.


The study said that delayed viral clearance could be one of the reasons behind persistent symptoms in long Covid sufferers.


The authors noted in the study that understanding the mechanisms by which SARS-CoV-2 persists, and the cellular host responses to viral persistence promises to improve clinical management of long Covid.


The US scientists performed extensive autopsies on a diverse population of 44 individuals who died from or with Covid-19 up to 230 days following initial symptom onset. The autopsies were performed to map and quantify SARS-CoV-2 distribution, replication, and cell-type specificity across the human body, including the brain, the study said. Autopsies of only fatal cases were conducted, and not of those with long Covid.


The study found that SARS-CoV-2 virus is widely distributed, even among patients who died with asymptomatic to mild Covid-19.


Also, the virus replicates in multiple pulmonary and extrapulmonary tissues at early stages of infection.


The scientists detected persistent SARS-CoV-2 RNA at multiple sites, including regions throughout the brain, for up to 230 days following the onset of symptoms.


SARS-CoV-2 was detected in all 44 cases, and across 79 of 85 anatomical locations, and body fluids sampled. The scientists detected the highest burden of SARS-CoV-2 RNA in the respiratory tract of early cases.


There were very few instances of inflammation or direct cytopathology (structural changes in host cells caused by viral invasion) outside of the lungs, despite extensive distribution of SARS-CoV-2 in the body.


The persistence of viral RNA and single guide RNA (sgRNA) may represent infection with defective virus, which has been described in persistent infection with measles virus, the authors said.


Early Viremic Phase


The authors noted that their findings support an early viremic phase, which seeds the virus throughout the body following pulmonary infection. Viremic phase is associated with Viremia, and is the spread of the virus into blood from the initial site of infection.


One of the patients was a juvenile with no evidence of multisystem inflammatory syndrome, suggesting that infected children without severe Covid-19 can also experience systemic infection with SARS-CoV-2.


A less robust innate and adaptive immune response outside the respiratory tract could be responsible for a less efficient viral clearance in extrapulmonary tissues.


SARS-CoV-2 was detected in the brains of all six late cases, and across most locations evaluated in the brains of five patients, including a patient who died 230 days after infection, the study said.


Out of 44 patients, SARS-CoV-2 RNA was detected in the respiratory tissues of 43 patients, in the cardiovascular tissues of 35, lymphoid tissues of 38, gastrointestinal tissues of 32, renal and endocrine tissue of 28, reproductive tissue of 30, and brain tissue of 10, the study found.