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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]

Vitamin D deficiency is common in adult renal transplant recipients, but data in children are scarce. Vitamin D is shown to have multiple effects on the cardiovascular system, renal function, and maintenance of bone health. We hypothesized that 25(OH)D deficiency is common in pediatric renal transplant recipients, and may be associated with hyperparathyroidism, short stature, renal function, and blood pressure control. We recruited 106 children during the winter/spring season who had a functioning renal transplant for at least 3 months. Twenty-five hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)D] were measured and correlated with clinical and biochemical parameters. Of the renal transplant patients, 38% were 25(OH)D deficient, 54% had insufficient levels, and only 8% had adequate 25(OH)D levels. Despite alfacalcidol supplementation in 59 (56%) patients, parathyroid hormone was increased in 58 (55%) and showed an inverse correlation with 25(OH)D ( p = 0.0003, r = 0.61) but not with 1,25(OH)D levels. Height standard deviation score (SDS) correlated with 25(OH)D ( p = 0.007, r = 0.42) and time post transplantation ( p = 0.02, r = 0.23); both were significant and independent predictors of height SDS. 25(OH)D inversely correlated with systolic BP SDS ( p = 0.02, r =−0.26); this association was lost on multiple regression analysis, but 25(OH)D was the only modifiable risk factor for hypertension. There was no correlation with estimated GFR or proteinuria. In conclusion, 25(OH)D deficiency is common in pediatric renal transplant recipients and correlates with hyperparathyroidism and short stature. 25(OH)D deficiency may be a modifiable risk factor for hypertension in transplant recipients. Further studies are required to test if routine supplementation with ergo or cholecalciferol is safe and effective in children after renal transplantation. [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.