Long-COVID following mild SARS CoV-2 infection - the response to antihistamines

Key Messages

This prospective study of 49 long-COVID patients revealed that treating with a combination of antihistamines, including famotidine, is helpful in managing long COVID symptoms that arose in patients after contracting mild COVID-19.

Long-COVID patients took a combination of H1 receptor antihistamines (loratadine 10 mg twice daily or fexofenadine 180 mg twice daily) and H2 receptor antihistamines (famotidine 40 mg once daily or nizatidine 300 mg once daily).

The treatment regimen was for a minimum of 4 weeks, and the patients reported significantly reduced symptoms.


Publication Date: June 7, 2021
Peer Reviewed: No
Publication Type: Original | Clinical Prospective
DOI: https://www.doi.org/10.1101/2021.06.06.21258272

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

Paul Glynne, Natasha Tahmasebi, Vanya Gant, Rajeev Gupta


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.

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.

Prospective observational cohort study.

Single-site outpatient clinic

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.

Structured long-COVID symptom questionnaire; quantification of T-cell subsets using a standard diagnostic assay.

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.

HRA reduce long-COVID symptoms. T-cell perturbations persist for up to 400 days following mild acute COVID-19 irrespective of long-COVID symptoms.