New York University Study Dispels Previous Views On What Is Driving COVID-19 Deaths As It Finds That Higher Viral Loads In the Lungs Is One Of The Factors

COVID-19 Research: A new study by researchers from New York University Grossman School of Medicine, NYU Langone Health-USA has found that higher viral loads of the SARS-CoV-2 coronavirus in the lungs of those infected by the SARS-CoV-2 coronavirus is what is driving increased mortality risks especially in those hospitalized and requiring mechanical ventilation. The study also found that low anti-SARS-CoV-2 antibody and immune response was another contributing factor.

The study findings dispel initial theories that an overreaction of the body’s immune defense system or secondary opportunistic bacterial infections leading to pneumonia were what that was driving increased risk of mortality.
 
It is already known that respiratory failure is associated with increased mortality in COVID-19 patients however there are no validated lower airway biomarkers to predict clinical outcome.
 
The study team investigated whether bacterial respiratory infections were associated with poor clinical outcome of COVID-19 in a prospective, observational cohort of 589 critically ill adults, all of whom required mechanical ventilation. For a subset of 142 patients who underwent bronchoscopy, the team quantified SARS-CoV-2 viral load, analyzed the lower respiratory tract microbiome using metagenomics and metatranscriptomics and profiled the host immune response.
 
The COVID-19 Research findings showed that acquisition of a hospital-acquired respiratory pathogen was not associated with fatal outcome. Poor clinical outcome was associated with lower airway enrichment with an oral commensal (Mycoplasma salivarium).
 
Importantly increased SARS-CoV-2 abundance, low anti-SARS-CoV-2 antibody response and a distinct host transcriptome profile of the lower airways were most predictive of mortality.
 
The study findings provide evidence that secondary respiratory infections do not drive mortality in COVID-19 and clinical management strategies should prioritize reducing viral replication and maximizing host responses to SARS-CoV-2.
 
The study findings were published in the peer reviewed journal: Nature Microbiology. https://www.nature.com/articles/s41564-021-00961-5
 
The study findings are alarming and worth paying careful attention to considering the current Delta variant which is wreaking havoc globally are able to replicate rapidly and also contribute to high viral loads in those infected.
https://virological.org/t/viral-infection-and-transmission-in-a-large-well-traced-outbreak-caused-by-the-delta-sars-cov-2-variant/724
 
https://www.medrxiv.org/content/10.1101/2021.07.07.21260122v2
 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375250/
 
The study findings clearly showed that a buildup of coron avirus in the lungs is likely behind the steep mortality rates seen in the pandemic. The results contrast with previous suspicions that simultaneous infections, such as bacterial pneumonia or overreaction of, played major roles in heightened risk of death, the investigators say. 
 
The study findings showed that people who died of COVID-19 had on average 10 times the amount of virus, or viral load, in their lower airways as did severely ill patients who survived their illness.
 
Meanwhile, the investigators 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.
 
Lead author Dr Imran Sulaiman, MD, PhD, an adjunct professor in the Department of Medicine at NYU Langone Health told Thailand Medical News, “The study 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.”
 
Present guidelines from the U.S. Centers for Disease Control and Prevention, he notes, do not encourage use of antivirals such as remdesivir or other repurposed antiviral drugs for severely ill patients on mechanical ventilation. But Dr Sulaiman says the NYU Langone study results suggest that these medications may still remain a valuable tool in treating these patients.
 
Past claims that the virus may prompt the immune system to attack the body’s own lung tissue and lead to dangerous levels of inflammation were not validated in the study findings and were not a major contributor to COVID-19 deaths in the group studied. In fact, Dr Sulaiman notes that the strength of the immune response appeared proportionate to the amount of virus in the lungs.
 
The SARS-CoV-2 coronavirus has so far killed over 4.6 million humans worldwide, researchers say. Those placed on mechanical ventilators in order to breathe fare particularly poorly, with 70 percent nationwide succumbing to the illness. Notably, 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.
 
This study was designed to clarify the role of secondary infections, viral load, and immune cell populations in COVID-19 mortality, according to Dr Sulaiman. He says the investigation provides the most detailed survey of the lower airway environment in coronavirus patients.
 
The research team for the study collected bacterial and fungal samples from the lungs of 589 men and women who were hospitalized in NYU Langone facilities in Manhattan and on Long Island. All required mechanical ventilation. For a subset of 142 patients who also received a bronchoscopy procedure to clear their air passages, the investigators analyzed the amount of virus within their lower airways and identified the microbes present by studying small pieces of the germs’ genetic code.
 
The study team also surveyed the type of immune cells and compounds located in the lower airways.
 
Interestingly among the findings, the study revealed that those who died had on average 50 percent lower production of a type of immune chemical that targets the coronavirus compared with the COVID-19 patients who survived the illness.
 
These customized 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.
 
Study senior author Dr Leopoldo Segal, MD.,an associate professor in the Department of Medicine at NYU Langone further added,  “These study results suggest that a problem with the adaptive immune system is preventing it from effectively combating the coronavirus,” “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 defenses.”
 
Dr Segal however cautions that the investigators only studied coronavirus patients who survived their first two weeks of hospitalization. It is possible, he says, that bacterial infections or autoimmune reactions may play a greater role in COVID-19 mortality that occurs earlier.
 
Dr Segal says the research team next plans to observe how the microbe community and immune response in the lungs of coronavirus patients change over time.
 
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