The outcome of SARS-CoV-2 infection seems to depend more on the quality of early innate immunity (pDC + NK cells) than on the strength of the antibody response.
A 2026 immunology study helps explain why.🧵
A 2026 immunology study helps explain why.🧵
The authors compared two immune profiles:
Hospitalized COVID-19 patients
PCR-confirmed infection, mild to severe disease
Healthcare workers without proof of infection
PCR-negative and seronegative (IgM/IgG), unvaccinated (2020)
Hospitalized COVID-19 patients
PCR-confirmed infection, mild to severe disease
Healthcare workers without proof of infection
PCR-negative and seronegative (IgM/IgG), unvaccinated (2020)
The study was conducted before vaccines were available.
So
any antibodies detected came only from infection
absence of antibodies means no detectable systemic infection,
not absolute proof that the virus never entered the body
So
any antibodies detected came only from infection
absence of antibodies means no detectable systemic infection,
not absolute proof that the virus never entered the body
What exposure actually means here
The control group (low susceptibility) was defined as healthcare workers who
reported at least three high-risk exposures,
remained repeatedly PCR-negative and IgM/IgG-negative,
described exposures such as -
aerosol-generating procedures,
close contact without a mask,
contact with confirmed COVID-19 patients.
The control group (low susceptibility) was defined as healthcare workers who
reported at least three high-risk exposures,
remained repeatedly PCR-negative and IgM/IgG-negative,
described exposures such as -
aerosol-generating procedures,
close contact without a mask,
contact with confirmed COVID-19 patients.
We do not know whether these healthcare workers
were briefly infected below detection thresholds,
had only local mucosal replication,
or were never infected at all.
That uncertainty is real - and acknowledged.
were briefly infected below detection thresholds,
had only local mucosal replication,
or were never infected at all.
That uncertainty is real - and acknowledged.
The study contrasts -
a profile seen in established, systemic COVID-19,
vs
a profile seen when exposure does not progress to detectable infection.
That distinction matters.
a profile seen in established, systemic COVID-19,
vs
a profile seen when exposure does not progress to detectable infection.
That distinction matters.
Immune pattern in hospitalized COVID-19 -
patients with active COVID-19 showed
↓ plasmacytoid dendritic cells (pDCs),
↓ functional NK cell subsets,
↑ plasmablast expansion,
↑ neutralizing antibodies.
This looks like
delayed early control - high viral burden - strong but late antibody response.
patients with active COVID-19 showed
↓ plasmacytoid dendritic cells (pDCs),
↓ functional NK cell subsets,
↑ plasmablast expansion,
↑ neutralizing antibodies.
This looks like
delayed early control - high viral burden - strong but late antibody response.
Immune pattern in healthcare workers without proof of infection -
relatively preserved pDC levels,
more intact NK cell profiles,
very low plasmablast activity,
no detectable antibodies.
Interpretation -
whatever happened early, it did not escalate into systemic infection.
relatively preserved pDC levels,
more intact NK cell profiles,
very low plasmablast activity,
no detectable antibodies.
Interpretation -
whatever happened early, it did not escalate into systemic infection.
The sickest patients often had more antibodies, not fewer.
That doesn’t mean antibodies are useless.
It means - antibodies reflect how much infection already happened
That doesn’t mean antibodies are useless.
It means - antibodies reflect how much infection already happened
This study suggests -
early innate immunity (interferon signaling via pDCs, NK function)
may shape whether infection escalates.
early innate immunity (interferon signaling via pDCs, NK function)
may shape whether infection escalates.
Antibodies describe the past infection. Early innate immunity shapes whether infection escalates at all.
That’s the signal - with all limitations openly stated.
That’s the signal - with all limitations openly stated.
Laura Martín-Pedraza at al., Contrasting immune responses in COVID-19: insights from healthcare workers and infected patients on plasmablast, pDC, and NK cell dynamics. Frontiers in Immunology 2026. frontiersin.org/journals/immun…
Why this matters for reinfections?
Every new exposure -
re-tests early innate immune responses,
may fail if interferon/NK responses are impaired.
That helps explain why
reinfections are common,
antibody presence ≠ sterilizing immunity,
early immune dysfunction may accumulate risk.
Every new exposure -
re-tests early innate immune responses,
may fail if interferon/NK responses are impaired.
That helps explain why
reinfections are common,
antibody presence ≠ sterilizing immunity,
early immune dysfunction may accumulate risk.
Why this matters biologically?
SARS-CoV-2 is not a passive virus.
It actively interferes with early antiviral defenses.
SARS-CoV-2 is not a passive virus.
It actively interferes with early antiviral defenses.
The virus is known to
suppress type I interferon signaling,
impair plasmacytoid dendritic cell (pDC) function,
and promote NK cell dysfunction and exhaustion during infection.
suppress type I interferon signaling,
impair plasmacytoid dendritic cell (pDC) function,
and promote NK cell dysfunction and exhaustion during infection.
So the immune pattern seen in reinfected -
reflects mechanisms the virus itself exploits once infection escalates.
reflects mechanisms the virus itself exploits once infection escalates.
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