key: cord-0942630-c82sdf36 authors: Zervou, Fainareti N.; Ali, Nicole M.; Neumann, Henry J.; Madan, Rebecca Pellett; Mehta, Sapna A. title: SARS‐CoV‐2 antibody responses in solid organ transplant recipients date: 2021-09-22 journal: Transpl Infect Dis DOI: 10.1111/tid.13728 sha: e306e3482ef58fcdaaaf9ffa9a8f7cf5e92a8004 doc_id: 942630 cord_uid: c82sdf36 Antibody responses among immunocompromised solid organ transplant recipients (SOT) infected with Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) may be diminished compared to the general population and have not been fully characterized. We conducted a cohort study at our transplant center to investigate the rate of seroconversion for SARS‐CoV‐2 IgG antibodies among SOT recipients who were diagnosed with Coronavirus disease 2019 (COVID‐19) and underwent serum SARS‐CoV‐2 IgG enzyme‐linked immunosorbent assay (ELISA) testing. The 61 patients who were included in the final analysis underwent initial SARS‐CoV‐2 IgG testing at a median of 62 days (Interquartile range 55.0–75.0) from symptom onset. Note that, 51 of 61 patients (83.6%) had positive SARS‐CoV‐2 IgG results, whereas 10 (16.4%) had negative IgG results. Six (60%) out of 10 seronegative patients underwent serial IgG testing and remained seronegative up to 17 weeks post‐diagnosis. Use of belatacept in maintenance immunosuppression was significantly associated with negative IgG antibodies to SARS‐CoV‐2 both in univariate and multivariate analyses (Odds ratio 0.04, p = .01). In conclusion, the majority of organ transplant recipients with COVID‐19 in our study developed SARS‐CoV‐2 antibodies. Further longitudinal studies of the durability and immunologic role of these IgG responses and the factors associated with lack of seroconversion are needed. In addition to serological testing, we reviewed electronic medical records of all cohort patients for the following information: age; gender; race; ethnicity; transplanted organ; date of transplantation; body mass index (defined as the patient's weight in kilograms divided by the square of height in meters); co-morbidities including diabetes mellitus, hypertension, and hyperlipidemia; chronic kidney disease of the native or transplanted kidney; chronic obstructive pulmonary disease; asthma; cirrhosis of the native or transplanted liver; coronary artery disease; active or history of malignancy; smoking history; maintenance immunosuppression; a dose of prednisone if used for maintenance immunosuppression; and date of symptom onset. Laboratory data were reviewed, including absolute lymphocyte count and gamma globulin levels during symptomatic illness (defined as the first 2 weeks of symptoms). Gamma globulin levels were defined as low if <768 mg/dl which is the lower limit of normal as per our microbiology lab's reference. Charts were also reviewed to evaluate the need for mechanical ventilation, extracorporeal membrane oxygenation, and death. Severe acute respiratory syndrome coronavirus-2 IgG ELISA SARS-CoV-2 IgG ELISA (Abbott Laboratories, Abbott Park, IL) was approved by the US Food and Drug Administration under an emergency use authorization and became available at our institution on May 15, 2020. The assay was performed in accordance with the manufacturer's instructions. This qualitative, chemiluminescent assay detects IgG antibodies against the SARS-CoV-2 nucleocapsid protein in human serum and plasma. The response is measured in relative light units and compared to a calibrator to determine the calculated index (specimen/calibrator), and a positive or negative result is reported. An index of 1.4 or greater correlates with a positive result as per manufacturer specification. The primary study outcome of interest was the percentage of SOT inhibitors, and high-dose steroids as part of maintenance immunosuppression or for COVID-19 treatment were not found to be significantly associated with the development of SARS-CoV-2 antibodies (Table 3) . However, the use of belatacept as maintenance immunosuppression was significantly associated with a lack of seroconversion (p = .01). Three out of 10 patients (30%) with negative IgG testing were on belat- positive IgG testing up to 2 months after symptom onset. 10 Only three patients in our cohort who were seropositive had undergone repeat IgG testing, with two remaining seropositive 28 days later and one becoming seronegative on repeat testing at an interval of 43 days from diagnosis and 12 days from first positive IgG testing. We are therefore are unable to make meaningful conclusions regarding the durability of IgG from our study. Among 10 patients who had a negative IgG test at a median of 56.5 days after RT-PCR diagnosis, six had serial repeat testing and remained seronegative up to 17 weeks after diagnosis. In our study, belatacept use was the only risk factor significantly associated with the lack of IgG antibodies to SARS-CoV-2. Although there is ambiguity surrounding the role of antibodies to SARS-CoV-2 in COVID-19, our study is the first to find a potential association between the use of belatacept and lack of seroconversion. Prior literature has described the impact of abatacept, a predecessor of belatacept, on post-vaccination serologic responses and also the potential for belatacept to prevent antibody formation. 22 Limitations of our relatively small study include that the fact most patients underwent IgG testing >4 weeks after symptom onset due to the lack of available COVID-19 serologic assays earlier during the study period. Therefore we were unable to study the overall kinetics of serological conversion. It is possible, for example, that some seroneg- Further longitudinal studies with earlier and serial testing of antibody responses and whether IgG seropositivity confers immunity to SARS-CoV-2 reinfection are needed, particularly in immunocompromised patients. Covid-19 and kidney transplantation COVID-19 in solid organ transplant recipients: initial report from the US epicenter COVID-19 in solid organ transplant: a multi-center cohort study Kidney allograft recipients, immunosuppression, and coronavirus disease-2019: a report of consecutive cases from a New York City transplant center COVID-19 mortality in transplant recipients High mortality among kidney transplant recipients diagnosed with coronavirus disease 2019: results from the Brazilian multicenter cohort study Antibody responses to SARS-CoV-2 in patients with COVID-19 Antibody detection and dynamic characteristics in patients with COVID-19 Longitudinal change of SARS-Cov2 antibodies in patients with COVID-19 Clinical outcomes and serologic response in solid organ transplant recipients with COVID-19: a case series from the United States In-depth virological assessment of kidney transplant recipients with COVID-19 Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications. medRxiv A national survey of screening and management of hypogammaglobulinemia in Canadian transplantation centers Does increasing immunoglobulin levels impact survival in solid organ transplant recipients with hypogammaglobulinemia? What is the impact of hypogammaglobulinemia on the rate of infections and survival in solid organ transplantation? A meta-analysis Humoral response to natural influenza infection in solid organ transplant recipients Antibody maturation and viremia after primary cytomegalovirus infection, in immunocompetent patients and kidney-transplant patients Lower detection rates of SARS-COV2 antibodies in cancer patients versus health care workers after symptomatic COVID-19 Anti-SARS-CoV-2 antibody response in patients with chronic lymphocytic leukemia A tertiary center experience of multiple myeloma patients with COVID-19: lessons learned and the path forward Prevalence and predictors of SARS-CoV-2 antibodies among solid organ transplant recipients with confirmed infection Poor Anti-SARS-CoV-2 humoral and T cell responses after 2 injections of mRNA vaccine in kidney transplant recipients treated with belatacept Effect of abatacept on the immunogenicity of 23-valent pneumococcal polysaccharide vaccination (PPSV23) in rheumatoid arthritis patients Lymphopenia in severe coronavirus disease-2019 (COVID-19): systematic review and meta-analysis Anti-SARS-CoV IgG response in relation to disease severity of severe acute respiratory syndrome SARS-CoV-2 antibody responses in solid organ transplant recipients We thank all NYU Langone Transplant Institute staff and NYU Langone Health laboratory technologists for their selfless devotion to patient care during the COVID-19 pandemic. The authors declare that they have no conflict of interest. None.