Long-COVID following mild SARS CoV-2 infection: characteristic T cell alterations and response to antihistamines

Glynne, P.; Tahmasebi, N.; Gant, V. A.; Gupta, R.

Background: Long-COVID is characterised by the emergence of multiple debilitating symptoms following SARS CoV2 infection. Its aetiology is unclear, and it often follows a mild acute illness. Anecdotal reports of gradual clinical responses to histamine receptor antagonists (HRA) suggest a histamine-dependent mechanism distinct from anaphylaxis. Histamine is a paracrine regulator of T-cells: although T-cell perturbations are reported in acute COVID-19, the T-cell landscape in recovered patients and its relationship to long-COVID remains under-explored. Objective: To survey T-cell populations in patients recovered from mild COVID-19, comparing those with long-COVID and asymptomatic individuals, and to analyse these data in light of symptoms and response to HRA. Design: Prospective observational cohort study. Setting: Single-site outpatient clinic Participants: 65 (87 to 408 days post mild COVID-19). None had sought treatment for acute COVID-19. 16 recovered uneventfully (asymptomatic group), 49 presented with long-COVID (symptomatic group), of whom 25 received HRA. Measurements: Structured long-COVID symptom questionnaire; quantification of T-cell subsets using a standard diagnostic assay. Results: HRA significantly reduced mean symptom burden. T-cell profiles distinguished asymptomatic and long-COVID groups, but did not predict response to HRA. Long-COVID patients had reduced CD4+ and CD8+ effector memory (EM) cells and increased PD-1 expression on central memory (CM) cells. Asymptomatic controls had reduced CD8+ EM cells and increased CD28 expression on CM cells. Conclusion: HRA reduce long-COVID symptoms. T-cell perturbations persist for up to 400 days following mild acute COVID-19 irrespective of long-COVID symptoms. Limitations: Preliminary, single health system study.