key: cord-1037960-aw50cxz8 authors: Benning, Louise; Morath, Christian; Bartenschlager, Marie; Reineke, Marvin; Töllner, Maximilian; Nusshag, Christian; Kälble, Florian; Reichel, Paula; Schaier, Matthias; Schnitzler, Paul; Zeier, Martin; Süsal, Caner; Bartenschlager, Ralf; Speer, Claudius title: Natural SARS-CoV-2 infection results in higher neutralization response against variants of concern compared to two-dose BNT162b2 vaccination in kidney transplant recipients date: 2021-12-23 journal: Kidney Int DOI: 10.1016/j.kint.2021.12.009 sha: 26cb774b0038bb086902982932a13e3025171cb0 doc_id: 1037960 cord_uid: aw50cxz8 nan To the Editor: Seroconversion rates in kidney transplant recipients (KTR) after two-dose BNT162b2 mRNA vaccination are in the range of 3-59% and thus significantly lower compared to the greater than 90% achieved in healthy controls 1 . In convalescent COVID-19 patients, antibody levels decline only slightly after 6-8 months, whereas vaccine-induced immunity appears to decrease more rapidly [2] [3] [4] . Recent data suggest that SARS-CoV-2 variants of concern (VoCs) partially escape humoral immune responses induced by natural infection with a non-escaping variant or vaccination 5 . However, little is known about protection against VoCs in KTR who recovered from COVID-19 or were immunized with two doses of BNT162b2. We compared humoral immunity in 18 KTR hospitalized for COVID-19 infection with immunity in 25 KTR with seroconversion after two-dose BNT162b2 vaccination. Nucleocapsid antibodies were measured after the second vaccination in vaccinated or at hospitalization in COVID-19 infected patients to exclude prior SARS-CoV-2 infection. Baseline characteristics including immunosuppressive regimens are given in Supplementary Table S1 . COVID-19 disease severity ranged from moderate to critical, with two COVID-19-related deaths (Supplementary Table S2 ). Immunosuppressive antimetabolite medication was stopped in all COVID-19 patients and 9/18 (50%) patients received corticosteroids only (Supplementary Table S3 Our data show that there is no significant difference between convalescent or vaccinated KTR for commercially available tests such as anti-S1 IgG, neutralizing antibodies determined by a surrogate However, these estimates are derived from the general population and may not be applicable to immunosuppressed patients. Our data suggest that 60-80 days after SARS-CoV-2 infection, most convalescent KTR showed strong neutralization against all tested VoCs. In contrast, at least one third of vaccinated KTR showed insufficient neutralization against the VoCs B.1.351 or B.1.617.2 even though antibodies were detectable in commercially available tests. Therefore, a third booster dose seems reasonable even in vaccinated KTR with seroconversion to protect against breakthrough infections caused by VoCs. variant of concern in 16 SARS-CoV-2 convalescent kidney transplant recipients 2-3 months after hospitalization compared to 12 and 13 two-dose BNT162b2 vaccinated kidney transplant recipients with and without mycophenolate mofetil maintenance therapy, respectively. MFI, mean fluorescence intensity; MMF, mycophenolate mofetil; ns, non-significant; RBD, receptor-binding domain; VoCs, variants of concern; * P < 0.05; ** P < 0.01; *** P < 0.001 J o u r n a l P r e -p r o o f Review of Early Immune Response to SARS-CoV-2 Vaccination Among Patients With CKD Waning antibodies to SARS-CoV-2 -Don't panic Robust neutralizing antibodies to SARS-CoV-2 infection persist for months Antibody persistence in the first 6 months following SARS-CoV-2 infection among hospital workers: a prospective longitudinal study SARS-CoV-2 variants of concern partially escape humoral but not T cell responses in COVID-19 convalescent donors and vaccine recipients Neutralization of SARS-CoV-2 variants by convalescent and BNT162b2 vaccinated serum Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum Intensity of mycophenolate mofetil treatment is associated with an impaired immune response to SARS-CoV-2 vaccination in kidney transplant recipients Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection