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The rise of SARS-CoV-2 variants has made the pursuit to define correlates of protection more troublesome, despite the availability of the World Health Organisation (WHO) International Standard for anti-SARS-CoV-2 Immunoglobulin sera, a key reagent used to standardise laboratory findings into an international unitage. Using pseudotyped virus, we examine the capacity of convalescent sera, from a well-defined cohort of healthcare workers (HCW) and Patients infected during the first wave from a national critical care centre in the UK to neutralise B.1.1.298, variants of interest (VOI) B.1.617.1 (Kappa), and four VOCs, B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma) and B.1.617.2 (Delta), including the B.1.617.2 K417N, informally known as Delta Plus. We utilised the WHO International Standard for anti-SARS-CoV-2 Immunoglobulin to report neutralisation antibody levels in International Units per mL. Our data demonstrate a significant reduction in the ability of first wave convalescent sera to neutralise the VOCs. Patients and HCWs with more severe COVID-19 were found to have higher antibody titres and to neutralise the VOCs more effectively than individuals with milder symptoms. Using an estimated threshold for 50% protection, 54 IU/mL, we found most asymptomatic and mild cases did not produce titres above this threshold. [ABSTRACT FROM AUTHOR]

Competing Interests: All authors declare no competing interests. We acknowledge support from the NIHR/UKRI grant, COV0170 Humoral Immune Correlates of COVID-19 (HICC; based at the Laboratory of Viral Zoonotics, University of Cambridge), the Royal Papworth Hospital NHS Trust (RPH; supporting HB), and the EU FETopen Grant Virofight (supporting RW and SE). AN is supported by Project OVEL (BBSRC, UKRI). We thank the RPH Trust and clinical studies team, health-care workers, and outpatients who participated in this study. We also thank members of the HICC consortium. AN and DC contributed equally to this work. HB and JLH contributed equally to this work.