Thread by @ZdenekVrozina

New study: SARS-CoV-2 doesn’t just lower white cell counts - it reshapes the T-cell landscape. Both the numbers and the quality of T-cells drop, especially in older and severely ill patients. And this has consequences. 🧵

https://twitter.com/harryspoelstra/status/1968399509974667698

Acute COVID-19 = a blow to T-cells. Patients had markedly lower absolute numbers of T-lymphocytes (CD4+, CD8+, naive and memory) compared to healthy controls. Classic lymphopenia - COVID cuts into the immune arsenal from the start. The immune system starts the fight with half its arsenal already gone.

Severity mirrors depth of the crash. The sickest patients had the lowest lymphocyte counts, especially CD8+ and naive T-cells. The steeper the disease, the deeper the T-cell depletion.

Age makes it worse. Naive CD8+ T-cells declined with age, the ratio of naive (CD45RA+) to memory (CD45RO+) T-cells also dropped in older patients. This reflects thymic shrinkage - older patients enter infection already depleted.

Functional subsets down too. CD4+CD28+ and CD8+CD28+ cells - key for strong activation and expansion - were reduced, pointing to exhaustion or dysfunction. Without CD28 co-signal, T-cells can recognize the virus but fail to switch on their turbo mode.

Treg paradox. Regulatory T-cells were relatively higher in proportion, but absolutely lower in number among the most severe cases. Smaller pie, bigger slice. The result? Immune imbalance - suppression and deficiency at once.

Antigen exposure pushes naive cells into memory. COVID drives a shift from naive (CD45RA+) to memory (CD45RO+) T-cells. Quick response today, but it burns tomorrow’s capacity - a costly trade-off in immunity!

CD8+ hit is critical. These are the main killers of infected cells, their loss in severe cases likely undermines viral control and fuels hyperinflammation.

CD28 signaling matters. Without costimulation, recognition doesn’t translate into full activation.
Put it together = the risk triad.
Age + loss of naive CD8 + fewer CD28+ T-cells = a recipe for severe disease. This biology explains why some patients spiral while others cope.

A T-cell panel (CD3, CD4, CD8 counts, naive/memory ratios, CD28 subsets) could help identify high-risk patients early - before their immune system fully crashes.

For older and immunocompromised, infection prevention is not optional. They enter COVID already disadvantaged, the virus then cuts away the last safety net.

But he warning is twofold.
In the elderly, COVID can wipe out the last reserve of naive T-cells, leaving them with little capacity to face new threats.
In children, each infection burns part of a vast reserve. It may not hurt today, but repeated hits could tax tomorrows immunity!

Public health.
Older and immunosuppressed individuals start from a worse baseline; infection then carves away what’s left. Prevention of infection is crucial, not optional! @szupraha @ZdravkoOnline

Sum:
Acute SARS-CoV-2 infection, especially in older or critically ill patients slashes both the quantity and quality of T-cells, with depletion of naive CD8 and CD28+ subsets and a skew toward memory phenotypes.

Limits.
Small sample (60 patients), single center, Omicron era. No long-term follow-up - unclear if and how quickly T-cell numbers recover. llmited control for time symptom onset, vacc/infection history, medications, comorbidities - all of which affect lymphocytes.

Lin et al. 2025, Study of Peripheral Blood T-Lymphocytes and Their Subpopulations in Patients with COVID-19, Biochemistry Research International. onlinelibrary.wiley.com/doi/epdf/10.11…