Autopsy results from 44 people who died with COVID-19 show how the virus spreads through not just the respiratory system, but the entire body, including the brain, persisting for months in some patients.

A description of the results, published in the peer-reviewed journal Nature in December, highlights how far-reaching the burden of infection can be, with viral fragments found in 79 of 85 locations in the body across the 44 patients.

The small study forms “the most comprehensive analysis to date of the cellular tropism, quantification and persistence of SARS-CoV-2 across the human body, including the brain,” according to its authors.

The virus was able to spread to multiple organs and systems even in patients who died within a week of feeling their first symptoms, researchers found.

The 44 people whose autopsies contributed to this research were all unvaccinated individuals who had died with COVID-19. The median age of the individuals was 62.5 years, and 61.4 per cent had three or more comorbidities. The median span of time between the onset of symptoms and the patient being hospitalized was six days, with 18.5 days being the median interval between symptom onset and death.

Across the board, the autopsies showed that the virus was able to penetrate into numerous systems of the body, although researchers noted there was a significantly higher burden of SARS-CoV-2 RNA found in respiratory tissues. Researchers found the virus had invaded more than 35 cell types and membranes across different systems in the body.

Out of the 44 autopsies, 11 were whole-body and brain autopsies, providing the fullest picture of the viral spread in those individuals.

Of these 11, the two with the shortest duration between symptom onset and death—four days and five days—had the highest amount of viral RNA levels in their respiratory system, with high levels also found across the cardiovascular system and optic tissue, among others.

SARS-CoV-2 was found in at least one place in the central nervous system or brain tissue in 10 out of 11 of these autopsies, including five out of six of those who died more than a month after the first onset of symptoms.

Researchers noted that although there were significant viral traces found, the actual structural tissue of the brain was largely unchanged by the virus.

The individual who had the longest duration between symptom onset and death—230 days—had been hospitalized numerous times and ultimately died of lung transplant complications, not COVID-19, but was found to be positive for COVID-19 and have viral traces in numerous parts of their body, including the respiratory system, the heart, the tissue in the eyes and the brain.

The cause of death ranged across the individuals. Thirty-eight died of COVID-19, while six died of another core issue while having COVID-19. Of those who were killed by the virus, 35 had either acute pneumonia or severe lung damage at their time of death.

Two of the patients included had only mild symptoms of COVID-19 and had died of other causes, but still were found to have SARS-CoV-2 RNA spread widely throughout their bodies, suggesting that although the bulk of the autopsies focused on severe and fatal cases, the virus can penetrate far into the body even in mild cases.

The study is limited by its small scope and its focus on unvaccinated, older individuals who died with COVID-19, meaning these results may not reflect what occurs when younger, vaccinated individuals contract the virus.

Previous autopsy research has found evidence of COVID-19 across multiple systems, but some have theorized that viral traces found outside the respiratory system could’ve been due to residual blood left in tissues or cross-contamination. Researchers say that is not the case in this new study, which confirmed SARS-CoV-2 at the cellular level.

How long the virus persisted within the tissue was another aspect researchers were interested in. They found that among those who had a longer interval between symptom onset and death, the difference between the level of virus in the respiratory and non-respiratory tissues diminished significantly. This may be because different tissues are better at fighting the virus and identifying it, researchers theorized.

“Understanding mechanisms by which SARS-CoV-2 evades immune detection is essential to guide future therapeutic approaches to facilitate viral clearance,” the authors stated.