Insights into SARS-CoV-2 Biodistribution: Autopsy Study Findings
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Chapter 1: Understanding Autopsies and Their Significance
An autopsy, which translates to "the act of seeing for oneself" in Greek, serves as the definitive method for determining the cause of death and understanding the effects of diseases on the human body. While numerous autopsy studies have focused on Covid-19 patients, researchers from the U.S. National Institute of Health (NIH)—led by Daniel Chertow, Ph.D., MPH, alongside over 30 collaborators—pointed out significant limitations in previous research, including the failure to assess all organs or to confirm the replication of SARS-CoV-2.
To address these gaps, Dr. Chertow and his team conducted comprehensive autopsy examinations on Covid-19 patients, employing advanced biochemical assays on multiple organ systems to elucidate the disease's impact on the body. Their research has been released as a preprint and submitted to a respected journal within the Nature Portfolio for peer review, and it is expected to pass given the substantial expertise of the contributing scientists.
What They Did
From April 26, 2020, to March 2, 2021, Dr. Chertow and his team performed autopsies on 44 individuals who had tested positive for Covid-19 in Maryland, USA. The cohort included 30% females, with an average age of 59 years; demographics showed 41% were African American, 41% White, 16% Hispanic, and 2.3% Asian. Notably, 95.5% of the patients had pre-existing conditions, commonly hypertension, obesity, and chronic respiratory and cardiovascular ailments. The timeline from symptom onset to hospitalization averaged nine days, with death occurring around 35 days post-symptom onset. In 89% of cases, death was attributed to Covid-19 or related complications.
The team categorized the autopsy cases into 'early' (39%), 'mid' (30%), and 'late' (32%), based on the duration of illness prior to death. They meticulously preserved tissue samples from various organs using high-quality materials and techniques.
To quantify the nucleocapsid (N) gene of SARS-CoV-2, they employed digital droplet polymerase chain reaction (ddPCR), chosen for its lower mutation rate, ensuring accurate results despite potential variations in virus strains. Real-time PCR, used to measure gene expression, helped assess subgenomic RNA (sgRNA), indicative of recent viral replication. Tissues exhibiting high levels of N gene copies and sgRNA expression underwent further analysis to confirm the presence of live viruses.
What They Discovered
The findings from Dr. Chertow’s study can be complex, so below is a summarized overview of their key results.
Presence of Nucleocapsid (N) Gene Fragments
The team detected SARS-CoV-2 gene fragments in all 44 autopsied cases across 79 of 85 anatomical sites and body fluids using ddPCR. In early-stage cases, significant levels of N gene copies were found in nearly all tissues, particularly in respiratory organs. As cases progressed, the average N gene copies decreased in most tissues, except for reproductive organs, indicating potential persistence of viral fragments.
sgRNA as an Indicator of Recent Viral Activity
sgRNA expression, a sign of active viral replication, was present in all tissue types, particularly in early cases. This expression was notably highest in respiratory tissues, suggesting that SARS-CoV-2 could remain active in the body for extended periods.
Tissue Damage Associated with Covid-19
Dr. Chertow and his team observed tissue damage patterns in 37 out of 39 cases linked to Covid-19, including alveolar damage indicative of pneumonia. Evidence of pulmonary blood clots and myocardial damage was also noted, showcasing direct complications of the disease.
Chapter 2: Implications of Findings
Dr. Chertow's research provides critical insights into the biodistribution of SARS-CoV-2, suggesting that the virus can invade various organ systems, especially during the early stages of infection. Their analysis reveals that while the virus is present in multiple organs, it does not necessarily induce inflammation or significant tissue damage outside of the respiratory system.
This research highlights the importance of understanding the long-term consequences of viral persistence in organs beyond the lungs. The findings raise questions about the potential for subclinical effects or chronic complications associated with SARS-CoV-2 in extrapulmonary organs, such as the brain, which is known to be an immune-privileged site.
In conclusion, while Dr. Chertow's study offers groundbreaking insights into SARS-CoV-2's behavior within the human body, it also underscores the need for further research to fully understand the ramifications of these findings on public health and future therapeutic strategies.