NEW YORK, Aug. 31, 2021 /PRNewswire/ -- A buildup of
coronavirus in the lungs is likely behind the steep mortality rates
seen in the pandemic, a new study finds. The results contrast with
previous suspicions that simultaneous infections, such as bacterial
pneumonia or overreaction of the body's immune defense system,
played major roles in heightened risk of death, the investigators
say.
Led by researchers at NYU Grossman School of Medicine, the new
study 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.
"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," says study lead author
Imran Sulaiman, MD, PhD, an adjunct
professor in the Department of Medicine at NYU Langone Health.
Current guidelines from the Centers for Disease Control and
Prevention, he notes, do not encourage use of antivirals such as
remdesivir for severely ill patients on mechanical ventilation. But
Sulaiman says the NYU Langone study results suggest that these
medications may still remain a valuable tool in treating these
patients.
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 investigators found no evidence that
this was a major contributor to COVID-19 deaths in the group
studied. In fact, Sulaiman notes 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, 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.
The new study, publishing online Aug.
31 in the journal Nature Microbiology, was
designed to clarify the role of secondary infections, viral load,
and immune cell populations in COVID-19 mortality, according to
Sulaiman. He says the investigation provides the most detailed
survey of the lower airway environment in coronavirus patients.
For the investigation, the researchers 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 authors also surveyed
the type of immune cells and compounds located in the lower
airways.
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.
"These results suggest that a problem with the adaptive immune
system is preventing it from effectively combating the
coronavirus," says study senior author Leopoldo Segal, MD. "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," says Segal, an
associate professor in the Department of Medicine at NYU
Langone.
He 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.
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.
Funding for the study was provided by National Institutes of
Health grants R37 CA244775, R01 HL125816, R21 AI158997, R01
AI143861, R01 AI143861-02S, R01 DK110014, P20 CA252728, and P30
CA016087; and CDC Foundation grant UWSC1085.1. Further funding was
provided by Ingelheim Pharma GmbH & Co. Bristol-Myers Squibb, Celgene Corporation, Genentech
Inc., Gilead, GlaxoSmithKline plc, Janssen Pharmaceutical Companies
of Johnson & Johnson, Novartis Institutes for Biomedical
Research, Pfizer Inc., and Sanofi.
In addition to Sulaiman and Segal, other NYU Langone researchers
included Luis Angel, MD;
Jun-Chieh Tsay, MD; Benjamin Wu, MD; Kelsey
Krolikowski, BA; Yonghua Li,
MD, PhD; Rosemary Schluger,
RN; Stephen Yeung, PhD;
Ralf Duerr, MD, PhD; Sara Thannickal; Chang
Wang, MS; George Jour, MD;
Guomiao Shen, PhD; Joseph Carpenito,
BS; Xiuxiu Liu, MD; Kun Ji, MD;
Destiny Collazo, BA; Anthony Labarbiera, BA; Nancy Amoroso, MD; Shari
Brosnahan, MD; Vikramjit
Mukherjee, MD; David Kaufman,
MD; Jan Bakker, MD, PhD;
Anthony Lubinsky, MD; Deepak
Pradhan, MD; Daniel Sterman,
MD; Michael Weiden, MD; Adriana Heguy; PhD; Ludovic Desvignes, PhD; Shohei Koide, PhD; Kenneth Stapleford, PhD; Kamal Khanna, PhD; Ann
Marie Schmidt, MD; Bo
Shopsin, MD, PhD; Peter Meyn;
Chan Wang, PhD; and Huilin Li, PhD. Other study coinvestigators were
Matthew Chung, PhD; Stephanie Banakis, MS; and Elodie Ghedin, PhD, at the National Institute of
Allergy and Infectious Diseases in Bethesda, Md.; Lizzette Perez-Perez, MSc; and Emmie De Wit,
PhD, at the National Institute of Allergy and Infectious Diseases
in Hamilton, Mont.; Laura Evans, MD, MSc, at the University of Washington in Seattle; Timothy Uyeki, MD, at the Centers for Disease
Control and Prevention in Atlanta,
Ga.; and Jose Clememte, PhD;
Bin Zhang, PhD; and Christian Forst,
PhD, at Icahn School of Medicine at Mount
Sinai in New York City.
Media Inquiries
Shira Polan
212-404-4279
shira.polan@nyulangone.org
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SOURCE NYU Langone Health