Longitudinal Sequelae of Severe COVID-19 3-12 Months Post Omicron Infection

Background Persistent and remitting-relapsing symptoms are frequently reported many months after SARS-CoV-2 infection. However, evidence of whether biological and clinical features of long COVID are associated with initial Omicron infection severity is lacking. MethodsA prospective observational cohort study of n=40 SARS-CoV-2 (Omicron B.1.1.529) infected individuals was performed, comprising n=20 non-hospitalised and n=20 hospitalised cases. ISARIC symptomology was collected at baseline, 3-, 6- and 12-months post infection. Total and neutralising IgG antibody and inflammatory proteome concentrations were determined in plasma at baseline and 3 months. Pairwise comparisons were made between non-hospitalised and hospitalised subgroup biological and symptom data to investigate differences over time. ClinicalTrials.gov NCT05548829.FindingsBy 3 months post infection, the non-hospitalised subgroup had higher median levels of Omicron variant specific ACE2 neutralising antibodies (BA.1, BA.2, BA.3), in particular females (p=0·06 - 0·09). A notable reduction in the levels of Omicron variant neutralizing antibodies was observed at 3 months in the hospitalised subgroup (p=0·09 - 0·16). Protracted elevation of inflammatory proteins type 1 keratin, prostasin and leukocyte associated immunoglobulin receptor 1 was observed in the hospitalised subgroup between baseline and 3 months post infection (padj <0·05). Fatigue, muscle pain, headache, and cough were the predominant symptoms at baseline, in both hospitalisation subgroups. Whilst these symptoms subsided over the 12 month follow up period in non-hospitalised, significantly more hospitalised individuals continued to experience muscle pain and shortness of breath (p<0·05).InterpretationThis is the first prospective study evidence of the link between Omicron hospitalisation and long term humoral immune response, inflammatory plasma proteome, and symptom persistence.