AUTHOR=Onyango Therese Bredholt , Zhou Fan , Bredholt Geir , Brokstad Karl A. , Lartey Sarah , Mohn Kristin G.-I. , Özgümüs Türküler , Kittang Bård Reiakvam , Linchausen Dagrun Waag , Shafiani Shahin , Elyanow Rebecca , Blomberg Bjørn , Langeland Nina , Cox Rebecca Jane , Bergen COVID-19 Research Group , Bansal Amit , Madsen Anders , Tøndel Camilla , Fjelltveit Elisabeth Berg , Søyland Hanne , Sandnes Helene Heitmann , Olofsson Jan Stefan , Vahokoski Juha , Risa Kristin , Hansen Lena , Trieu Mai-Chi , Sævik Marianne , Ertesvåg Nina Urke TITLE=SARS-CoV-2 specific immune responses in overweight and obese COVID-19 patients JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1287388 DOI=10.3389/fimmu.2023.1287388 ISSN=1664-3224 ABSTRACT=

Obesity is a known risk factor for severe respiratory tract infections. In this prospective study, we assessed the impact of being obese or overweight on longitudinal SARS-CoV-2 humoral and cellular responses up to 18 months after infection. 274 patients provided blood samples at regular time intervals up to 18 months including obese (BMI ≥30, n=32), overweight (BMI 25-29.9, n=103) and normal body weight (BMI 18.5-24.9, n=134) SARS-CoV-2 patients. We determined SARS-CoV-2 spike-specific IgG, IgA, IgM levels by ELISA and neutralising antibody titres by neutralisation assay. RBD- and spike-specific memory B cells were investigated by ELISpot, spike- and non-spike-specific IFN-γ, IL-2 and IFN-γ/IL-2 secreting T cells by FluoroSpot and T cell receptor (TCR) sequencing was performed. Higher BMI correlated with increased COVID-19 severity. Humoral and cellular responses were stronger in overweight and obese patients than normal weight patients and associated with higher spike-specific IgG binding titres relative to neutralising antibody titres. Linear regression models demonstrated that BMI, age and COVID-19 severity correlated independently with higher SARS-CoV-2 immune responses. We found an increased proportion of unique SARS-CoV-2 specific T cell clonotypes after infection in overweight and obese patients. COVID-19 vaccination boosted humoral and cellular responses irrespective of BMI, although stronger immune boosting was observed in normal weight patients. Overall, our results highlight more severe disease and an over-reactivity of the immune system in overweight and obese patients after SARS-CoV-2 infection, underscoring the importance of recognizing overweight/obese individuals as a risk group for prioritisation for COVID-19 vaccination.