Thread by @ZdenekVrozina

7-12% of patients recovering from moderate to severe COVID-19 show persistently low counts of B cells, CD4 T cells, and Tregs, even after clinical recovery.🧵

https://twitter.com/bagaidr/status/1976253010893287877

This sustained adaptive immune deficit may represent a important mechanism underlying Long COVID, resembling immunological patterns seen in chronic infections such as HIV and EBV.

The authors highlight a possible link with low serotonin levels, which support B and T cell proliferation - a hypothesis drawn from the work of Wong et al., 2023.

Insides.
Hidden immune deficit after recovery - most patients had normal total lymphocyte counts - so standard tests looked fine.

But deeper analysis revealed that some B and T cell subsets remained low, showing a hidden immunodeficiency.
Clinical recovery ≠ immunological recovery.

In moderate cases, CD4+ T cells and Tregs were tightly correlated (r = 0.72).
In severe cases, that link was lost, indicating a collapse of immune regulation - possibly due to Treg depletion or exhaustion.
This may explain persistent inflammation in some patients even after infection clears.

The authors highlight the idea that low serotonin after COVID impairs proliferation of B and CD4+ T cells, including Tregs.
Less serotonin - weaker immune recovery - sustained inflammatory fatigue axis in Long COVID.

Similarity to chronic infections - the pattern of ↓ B cells, ↓ CD4+ T cells, and ↓ Tregs resembles immune exhaustion profiles seen in HIV or EBV infections.
An HIV-like immune profile - not the virus itself, but a comparable state of adaptive immune depletion.

Authors note that Treg-supporting or immune checkpoint–modulating therapies might help restore balance.
They also caution that these patients may be more vulnerable to reinfections or autoimmunity!
A reminder that recovery is not always restoration.

NK cells - innate immunity still lagging behind. Even after 50 days, 8% of patients (both moderate and severe) had subnormal NK cell counts. Their persistent deficit could delay viral clearance and promote residual inflammation or antigen persistence.

Paradoxical recovery pattern - CD8+ T cells fully recovered in severe cases but remained low in 3–4% of moderate ones.
Immune reconstitution isn’t linear - severe inflammation may hyperactivate and temporarily expand CD8+ cells, while moderate cases show incomplete rebound.

All patients in this study were unvaccinated and infected during the Omicron wave 2023 - no prior infection, no vacc induced immunity.
Even under these conditions, 7–12% showed lasting immune depletion.
Omicron ≠ harmless.

COVID-19 recovery has two layers.
Clinical recovery - when symptoms fade and tests normalize.
Immunological recovery - when the adaptive and regulatory networks truly reset.
This study shows the two don’t always align.
Even after Omicron infection, some patients remain in a state of incomplete immune reconstitution - an HIV-like exhaustion pattern that may shape Long COVID biology. @szupraha @ZdravkoOnline @adamvojtech86

An at al., Persistent lymphocytopenia in convalescent patients with COVID-19: dysregulated B cell, CD4+ T cell, and treg compartments in 7–12% of moderate-severe cases. frontiersin.org/journals/cellu…