key: cord-0075548-oy6a9u29 authors: Jasuja, Sanjiv; Jha, Vivekanand; Sagar, Gaurav; Bahl, Anupam; Verma, Shalini; Jasuja, Neharita; Kaur, Jasmeet title: Post vaccination analysis of anti-spike antibody responses in kidney transplant recipients with and without COVID-19 infection in a tertiary care center, India date: 2022-03-03 journal: Clin Kidney J DOI: 10.1093/ckj/sfac057 sha: 14468ba7f760f173eff2e42dfffb3f33e2a2efef doc_id: 75548 cord_uid: oy6a9u29 BACKGROUND: To investigate the anti-spike antibody response to vaccination in Kidney transplant recipients (KTRs) previously infected with SARS-CoV-2 as compared to KTRs with no history of COVID-19 from India. METHODS: SARS-CoV-2 spike immunoglobulin (Ig) G antibody response was measured in 105 post COVID-19 KTRs with PCR confirmed SARS-CoV-2 infection who received either no vaccination (cohort 1), single (cohort 2) or two doses (cohort 3) of vaccine and compared to 103 two-dose vaccinated COVID-19 naïve KTRs with no history of COVID-19 (cohort 4). RESULTS: Out of 103 COVID-19 naïve two-dose vaccinated KTRs, less than 50% became seropositive with anti-spike antibody titres > 50AU/mL subsequent to complete vaccination, the seroconversion rate being comparable in subjects receiving Covishield(TM) versus Covaxin(TM) vaccines. However, the seropositive KTRs vaccinated with Covishield(TM) had higher anti-spike antibody titres as compared to those who received Covaxin(TM). We observed higher anti-SARS-CoV-2 spike antibody levels in post COVID-19 KTRs after 1 dose of vaccine as compared with COVID-19 naïve two-dose vaccinated KTRs. Importantly, the second dose in post COVID-19 KTRs did not significantly increase anti-spike antibody levels compared with the single dose recipients. CONCLUSIONS: Our data presents that in KTRs with previous SARS-CoV-2 infection a single dose of vaccine (Covishield(TM)) may be effective in mounting optimal immune response. In contrast, COVID-19 naïve two-dose vaccinated KTRs respond poorly (<50%) to current recommendation of a two-dose regimen in India. . Studies have demonstrated increased morbidity and mortality in transplant patients [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] . In the absence of a definitive cure for COVID-19, vaccines are perhaps the most promising option available to control the pandemic. There are several SARS-CoV-2 vaccines currently available whose immunogenicity and safety have been assessed in various clinical trials [18] , however, no vaccine trial included transplant recipients. Recent investigations demonstrate that even though mRNA vaccines induce robust immune response in non-transplant individuals protecting against severe COVID-19, KTRs develop significantly lower antibody response post vaccination [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] . In contrast, studies evaluating the serologic response of transplant recipients to COVID-19 infection provide conflicting results reporting normal levels of anti-SARS-CoV-2 antibodies in KTRs subsequent to past COVID-19 infection [31] [32] [33] . However, majority of these studies explored the immune response to mRNA vaccines, currently not available in India; similar data following immunization with vaccines approved in India are not available. Importantly, the dynamics of vaccination with after natural infection in transplant recipients remain unexplored. In this study, we investigated the spectrum of antibody responses to SARS-CoV-2 in a cohort of KTRs with different vaccination status. were fully vaccinated with two doses of either of the approved vaccine (referred to as "COVID-19 naïve two-dose vaccinated"). The distribution of study cohorts is summarised in Figure 1 . Necessary institutional approvals were secured for carrying out the data analysis and manuscript development. Data were collected retrospectively from the medical records of the hospitals or patient"s follow-up submissions. Clinical data collected included demographics (age, height, weight, sex, duration from transplant to COVID-19, comorbidities, baseline immunosuppression regimen and details of vaccination. The primary objective of this study was to quantitatively evaluate the SARS-CoV-2 Anti-Spike IgG antibody response in previously infected KTRs with respect to their vaccination status, comparing to fully vaccinated uninfected KTRs. The secondary outcomes included evaluating association and correlation of anti-spike antibody levels with comorbidities and other baseline transplant characteristics. Anti-spike IgG antibodies to SARS-CoV-2 were assayed with AdviseDx SARS-CoV-2 IgG II assay (Abbott Diagnostics, Chicago, USA) using a chemiluminescent microparticle immunoassay (CMIA) intended for the qualitative and semi-quantitative detection of IgG antibodies to SARS-CoV-2 in human serum and plasma on the Alinity i system (Abbott Diagnostics, Chicago, USA). The analytical measurement interval (AMI) is stated as 22 to 40,000 AU/ml, and positivity cut-off is ≥50 AU/ml (manufacturer defined). According to the manufacturer, the observed LoQ (limit of quantification) on the Alinity i system was 7.2 AU/mL representing the lowest concentration at which a maximum allowable precision was met. The observed limit of detection (LoD) on the Alinity i system was 4.8 AU/mL and represents the lowest concentration at which the analytes can be detected [34] . However, in real world report generated in laboratory, low values are reported as undetectable or numeric value less than 7.2 AU/ml. Undetectable reports are considered zero (0.0) for calculation purpose. Bonferroni correction was applied keeping small sample size in consideration and multiple variable testing. The p-value less than 0.05 was considered as significant. The study subjects were categorized into 4 cohorts based on their COVID-19 infection and vaccination status ( To assess the immune response elicited upon vaccination against SARS-CoV-2, anti-SARS-CoV-2 spike protein IgG ("anti-spike antibody") levels were measured. 2125]AU/mL) were significantly lower than KTRs with past COVID-19 infection, irrespective of their vaccination status (p<0.001) ( Table 1 and Figure 2B ). Figure 2B ). Amongst the vaccinated cohort, the median time interval for assessment of the Out of the 103 COVID-19 naïve two-dose vaccinated subjects, 50 seropositive individuals with anti-spike antibody titre > 50 AU/mL were considered as "responders" and the remaining subject with anti-spike antibody titre < 50 AU/mL were identified as "non-responders". The demographics, baseline transplant characteristics, comorbidities, laboratory investigations along with vaccination details Table 2) . No significant association of anti-spike antibody levels assessed in KTRs from all cohorts with demographics, comorbidities, vaccination, and anti-spike antibody assessment details was observed (Table 3) . Similar results were obtained when we studied association of anti-spike antibody titres of only seropositive KTRs (anti-spike antibody levels > 50 AU/mL) with the baseline characteristics (Supplemental Table 1 We also analysed association of anti-spike antibody levels with demographics, vaccination details and comorbidities, and no significant association was observed. 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Hooda Director, Medical