Treatment Database

Second-generation H1 receptor antagonists targeting mast cell activation (MCAS) as a driver of Long COVID symptoms. A prospective observational study by Glynne et al. (J Investig Med 2022) of 65 Long COVID patients found significant reduction in mean symptom burden with H1 receptor antagonists, accompanied by characteristic T-cell alterations. An Italian prospective study (n=14 treated vs 13 controls, 20 days) found 29% of treated patients achieved full resolution vs 0% controls. Clinical experience from Glynne et al.'s practice (>200 patients) suggests 65–70% respond, with skin and GI symptoms improving first, followed by brain fog and fatigue. In the STIMULATE-ICP trial (Lancet Infect Dis 2026; open-label, 12 NHS clinics, nearly 800 participants across four arms), famotidine plus loratadine for 12 weeks reduced fatigue slightly more than no study drug (Fatigue Assessment Scale −1.48 points; 95% CI −2.88 to −0.08), below the 3-point difference considered clinically meaningful, and the difference was gone by 24 weeks. Mechanism includes blocking H1-mediated cytokine signaling and potentially blocking HRH1 as an alternative SARS-CoV-2 entry receptor.