Inflammatory and immune response signatures associated with COVID-19 severity

Abstract Severe COVID-19 is characterised by an overactive pro-inflammatory response of the immune system which is associated with new persistent symptoms. Differences in the persistence of symptoms, plasma inflammatory proteins and antibodies between hospitalised and non-hospitalised cases were investigated in the current study. n=120 participants were recruited with informed consent, of whom n=60 were hospitalised with severe disease. Blood samples and detailed symptom data were collected 3 months after a positive PCR test for SARS-CoV-2. Plasma samples were analysed by OLINK Explore 384 inflammation panel and ACE2 neutralisation and IgG assays. R software was used to identify statistically significant differences in protein concentration in hospitalised cases, relative to non-hospitalised cases. Differences in anti-SARS-CoV-2 IgG antibody concentration, ACE2 neutralisation and symptoms were also analysed between hospitalisation subgroups. 14 proteins including angiopoietin-like protein 2 and C-X-C motif chemokine 17 were significantly elevated (by greater than +/− 0.20 log2 fold change; p < 0.05) at 3 months in the hospitalised study group, relative to non-hospitalised cases. The concentrations of BA.2 and BA.3 specific anti-SARS-CoV-2 IgG and spike receptor binding domain neutralising antibodies were more frequently detected in non-hospitalised cases. The hospitalised cohort more frequently reported persistence of muscle pain, headache, fatigue and shortness of breath. Characteristic changes in the plasma proteome and symptom clusters that persist 3 months after infection have been observed in hospitalised COVID-19 cases. This data could help inform clinical care requirements for longer term COVID-19 recovery. Supported by grants from UKRI, SFI and HSC R&D Office