Lack of antibodies against seasonal coronavirus OC43 nucleocapsid protein identifies patients at risk of critical COVID-19

Dugas, M.; Grote-Westrick, T.; Merle, U.; Fontenay, M.; Kremer, A. E.; Vollenberg, R.; Lorentzen, E.; Tiwari-Heckler, S.; Duchemin, J.; Ellouze, S.; Vetter, M.; Fuerst, J.; Brix, T.; Denkinger, C. M.; Mueller-Tidow, C.; Schmidt, H.; Tepasse, P.-R.; Kuehn, J.

The vast majority of COVID-19 patients experience a mild disease. However, a minority suffers from severe disease with substantial morbidity and mortality. We report results from a non-interventional validation study comprising 248 patients (132 males, 116 females) with confirmed SARS-CoV-2 infections from three tertiary care referral centers in Germany and France. Overall median age was 60 years. The ICU group comprised more males, whereas the outpatient group contained a higher percentage of females. For each patient, the serum or plasma sample obtained closest after symptom onset was examined. Patients with critical disease had significantly lower levels of anti-HCoV OC43 nucleocapsid protein (NP)-specific antibodies compared to other COVID-19 patients (p=0.025). OC43 negative inpatients had an increased risk of critical disease (adjusted odds ratio 2.81 [95% CI 1.10 - 7.87]), higher than the risk by increased age or BMI, and lower than the risk by male sex. Frequency of critical disease in COVID-19 inpatients was significantly different according to OC43 status (p=0.009): 23 of 32 (72%) OC43 negative, 46 of 92 (50%) OC43 below or with cutoff, 5 of 18 (28%) OC43 positive inpatients required ICU therapy, respectively. Our results indicate that prior infections with seasonal human coronaviruses can protect against a severe course of COVID-19. Therefore, anti-OC43 antibodies should be measured for COVID-19 inpatients and considered as part of the risk assessment for each patient. Hence, we expect individuals tested negative for anti-OC43 antibodies to particularly benefit from vaccination against SARS-CoV-2, especially with other risk factors prevailing.