ISARIC4C investigators sought to understand the effect of intestinal immune responses to SARS-CoV-2 on patient outcomes including magnitude of systemic antibody induction. Two prospective cohort studies, ISARIC4C and INSTINCT, were combined to acquire samples from 88 COVID-19 cases representing the full spectrum of disease severity and analysed viral RNA and host gut cytokine responses in the context of clinical and virological outcome measures. ISARIC4C investigators indicated that ROC analysis showed that expression of these gut cytokines at study enrolment in hospitalised COVID-19 cases associated negatively with overall clinical severity implicating a protective role in COVID-19. This suggests that a productive intestinal immune response may be beneficial in the response to a respiratory pathogen and a biomarker of a successful barrier response.