Viral buildup in the lungs is the likely driver behind the steep mortality rates seen in the COVID-19 pandemic, according to a study published on Tuesday.
The researchers at New York University (NYU) Grossman School of Medicine, US, showed that people who died of COVID-19 had on average 10 times the amount of virus in their lower airways as did severely ill patients who survived their illness.
The finding, published in the journal Nature Microbiology, contradicts previous theories that simultaneous infections, such as bacterial pneumonia or overreaction of the body's immune defence system, played major roles in heightened risk of death.
The researchers found no evidence implicating a secondary bacterial infection as the cause of the deaths, although they cautioned that this may be due to the frequent course of antibiotics given to critically ill patients.
"Our findings suggest that the body's failure to cope with the large numbers of virus infecting the lungs is largely responsible for COVID-19 deaths in the pandemic," said study lead author Imran Sulaiman, an adjunct professor at NYU Langone Health.
The researchers noted that current guidelines from the Centers for Disease Control and Prevention do not encourage use of antivirals such as remdesivir for severely ill patients on mechanical ventilation.
However, the study results suggest that these medications may still remain a valuable tool in treating these patients, they noted.
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Despite previous concerns that the virus may prompt the immune system to attack the body's own lung tissue and lead to dangerous levels of inflammation, the researchers found no evidence that this was a major contributor to COVID-19 deaths in the group studied.
They noted that the strength of the immune response appeared proportionate to the amount of virus in the lungs.
The coronavirus has so far killed over 4 million people worldwide. Those placed on mechanical ventilators in order to breathe fare particularly poorly.
Experts attribute the high mortality seen in other viral pandemics such as the Spanish flu in 1918 and swine flu in 2009 to a secondary bacterial infection.
However, it remained unclear whether a similar issue afflicted people with COVID-19.
The latest study provides the most detailed survey of the lower airway environment in coronavirus patients, the researchers said.
They collected bacterial and fungal samples from the lungs of 589 men and women who were hospitalised in the US, all of whom required mechanical ventilation.
For a subset of 142 patients who also received a bronchoscopy procedure to clear their air passages, the researchers analysed the amount of virus within their lower airways and identified the microbes present by studying small pieces of the germs' genetic code.
They also surveyed the type of immune cells and compounds located in the lower airways.
The study revealed that those who died had on average 50 per cent lower production of a type of immune chemical that targets the coronavirus compared with the COVID-19 patients who survived the illness.
These customised proteins are part of the body's adaptive immune system, a subset of cells and chemicals that "remember" invading newly encountered microbes, leaving the body better prepared for future exposure.
"These results suggest that a problem with the adaptive immune system is preventing it from effectively combating the coronavirus," said study senior author Leopoldo Segal.
"If we can identify the source of this issue, we may be able to find an effective treatment that works by bolstering the body's own defences," said Segal, an associate professor at NYU.
He cautioned that the researchers only studied coronavirus patients who survived their first two weeks of hospitalisation.
It is possible that bacterial infections or autoimmune reactions may play a greater role in COVID-19 mortality that occurs earlier, Segal added.