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Analysis of Dynamic Immune Processes Fills Gaps in Understanding of Severe COVID-19 Pathogenesis
pathogens. However, the role of these resident
immune cells, including alveolar macrophages and
lung TRMs, in dictating COVID-19 pathogenesis was
unclear. Furthermore, while immune responses in
COVID-19 have been studied in circulation, the role
of immune responses at the primary disease site
is less understood. Elucidating the immune mechanisms
behind COVID-19 is necessary to improve
treatment and prevention of the disease. Szabo, et al.
thus aimed to " define the dynamic immune processes
involved in pathogenesis of severe COVID-19 " using
IsoPlexis' functional profiling, which was supplemented
by phenotypic and transcriptomic profiling.1
The researchers obtained paired airway and blood
samples from 15 patients ages 14-84 with severe
COVID-19, all of whom required ventilation and intubation.
The samples were collected starting 24-36 hours
after intubation and continued daily for up to 10 days.1
The researchers used IsoPlexis' highly multiplexed
functional proteomics (CodePlex) to characterize the
cytokine and chemokine content of these samples and
compare them to samples from healthy subjects.
Highly Multiplexed Bulk Proteomics
Identifies Elevated Inflammatory Mediators
in Airway Samples of Severe COVID-19
IsoPlexis' Human Adaptive Immune panel for the
CodePlex Secretome chip identified significant
differences in the cytokine and chemokine content
of airway and blood cell samples from patients with
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severe COVID-19. Several analytes were elevated
in the airways, including monocyte/macrophage
chemoattractants MCP-1 (CCL2), MIP-1α (CCL3),
and MIP1β (CCL4), and T cell-associated cytokines
granzyme B, IL-7, and TNF-β. In the blood, MCP-1
(CCL2), MIP-1α (CCL3), granzyme B, IL-7, and TNF-β
were not detected, while MIP-1β (CCL4) was present
at variable levels across patients.1
severe COVID-19, both plasma and airway samples
contained low or variable levels of molecules
associated with T cell effector function, as well as
cytokines IL-6, IL-8, and TGF-β.1
The results showed
that proinflammatory chemokines and cytokines
were prominent in the airways, with only some of
these proteins present in the blood.1
The researchers also observed an accumulation
of monocytes/macrophages in the lungs of
severe COVID-19 patients, hypothesizing that the
production of airway monocyte chemoattractants
resulted in the infiltration of dysregulated monocytes
from the blood into the lung. " Overall, the results
suggested that the airways of severe COVID-19
patients are a highly inflammatory environment and
play a significant role in recruiting immune cells from
circulation to the site of infection. " 1
The researchers
concluded that the results " strongly implicate
myeloid cell recruitment as a major mechanism
perpetuating inflammation and pathogenesis of
severe COVID-19. " 1
In the patients with


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