Robust antibody responses rely on affinity maturation, which predominantly occurs in germinal centres (GCs) located in secondary lymphoid organs (SLOs). This preprint describes the absence of GCs in patients with fatal COVID-19, suggesting that SARS-CoV-2 might impair humoral immune responses by disrupting SLO architecture. The authors report a specific block in BCL-6+ T follicular helper (TFH) cell differentiation and an increase in T helper 1 (TH1) cells, as well as aberrant TNF production, at the site of TFH cell differentiation. Increased levels of SARS-CoV-2-specific circulating plasmablasts, likely of extrafollicular origin, were found to correlate with systemic inflammation. It remains unclear whether the loss of GCs also occurs in COVID-19 survivors and whether this may cause an inefficient and short-lived antibody response.