Treatment With Monoclonal Antibodies Is Safe and Effective for Kidney Transplant Recipients With COVID-19

Background: Monoclonal antibodies have been the mainstay of treatment of COVID-19 in patients at high-risk of mortality from COVID-19. We aimed to study our experience with monoclonal antibodies (mAb) in kidney transplant recipients with COVID-19 at our center. Method(s): We reviewed 93 of our kidney transplant recipients who were infected with COVID-19 and received mAb treatment. The mAb infusion received was the one active against the variant that was circulating during that period (39 received either bamlanivimab or casirivimab/imdevimab, 41 received sotrovimab and 13 received bebtelovimab). All patients were on standard immunosuppression with tacrolimus and prednisone, and 88% were on mycophenolate prior to COVID-19 diagnosis, which was subsequently reduced or held for at least 2 weeks. Result(s): Of the 93 patients, median age was 54 (IQR 44-64), 44% were male, 42% were Hispanic, 36% were African American. 76% have received deceased donor kidney transplant, 94% had history of hypertension, 47% diabetes mellitus, 18% coronary artery disease. All the patients had mild symptoms without initial hypoxia requiring supplemental O2 and only 5 patients (5.4%) were admitted to the hospital. While 33 patients (35%) were unvaccinated at the time of COVID-19 diagnosis, 60 patients (65%) have received at least 2 doses of COVID vaccination at time of diagnosis and of those 27 patients (29%) have received a third dose. There was only one death (1%) in a patient that was re-hospitalized with severe COVID-19. There was no allograft loss. The rate of re-infection after mAb treatment was 6.5%. There was no serious adverse event related to the mAb infusion. Conclusion(s): Our experience suggests that monoclonal antibodies are a safe therapeutic to reduce the need for COVID-19 related hospitalization in this high-risk kidney transplant population, while one third of those were unvaccinated at the time of COVID-19 diagnosis.

Decreased Mortality From SARS-CoV-2 in Kidney Transplant Recipients Over the Course of the Pandemic

Background: We aimed to investigate the variation in mortality from SARS-CoV-2 infection in kidney transplant recipients Methods: Between March 16, 2020 and May 4, 2022, 537 patients were diagnosed with SARS-CoV-2 infection by RT-PCR. Result(s): 59% were male, median age 58 (IQR: 45-67), predominantly Hispanic (51.2%) and African American (29%). 75.4% received a deceased-donor renal transplant, 55% received anti-thymocyte induction. Most patients were on triple immunosuppression (96% on calcineurin inhibitors, 87% on anti-metabolite, and 99% on prednisone). While the mortality rate was 37 % (47/128) during first peak between March 16 and April 30, 2020, it has significantly decreased to 11% (7/61) from May 1, 2020 to end of December 2020 with social distancing and use of facemask. Between January 1, 2021 and November 5, 2021 with use of vaccination and monoclonal antibodies, the mortality rate further decreased to 7.7% (10/129). Between November 6, 2021 till May 4, 2022 which corresponds to the period when the Omicron variant and subvariants are prevalent, the mortality rate was 5.5% (12/219). Among those diagnosed during the period when Omicron was prevalent, 188/219 (85.8%) have received 2 doses of COVID vaccine and 82/219 (37.4%) have received a third dose. Since the beginning of use of monoclonal antibodies, 93 patients received a combination of casirivimab/imdevimab when initial SARS-CoV-2 variants were dominant and sotrovimab then bebtelovimab during the period of Omicron and its subvariants. Only one death occurred in patients who received monoclonal antibody treatment and that patient was hospitalized for severe COVID-19. We identified 23 re-infections. Most of re-infected patients have already received at least 2 doses of COVID vaccine but only 5 received a third dose. None of the re-infected patients was hospitalized and none of them died. Conclusion(s): In summary, mortality from SARS-CoV-2 infection in kidney transplant recipients has significantly decreased over time. This could be explained by initial exposure to higher viral load due to lack of personal protection and social distancing. However, since the judicious use of monoclonal antibodies and vaccination, in addition to social distancing protocols and use of facemask, the mortality in kidney transplant recipients has decreased over time.

Decreased Mortality from Sars-CoV-2 Infection in Kidney Transplant Recipients Over the Course of the Pandemic

Purpose: We aimed to investigate the mortality from SARS-CoV-2 in kidney transplant recipients in the Bronx, New York since the beginning of the pandemic Methods: Between March 16, 2020 and November 5, 2021, 453 patients were diagnosed with SARS-CoV-2 infection. 316 were diagnosed by RT-PCR while the remaining 137 tested positive for anti-SARS-CoV-2 nucleocapsid IgG and did not have significant symptoms and had not been previously tested by RT-PCR Results: Of the 316 patients diagnosed by RT-PCR, 214 patients were hospitalized while 102 patients were managed at home as outpatient. 194 (61.3%) were male, median age 61 years old (IQR: 48-69), predominantly Hispanic (56.2%) and African American (29.5%). 75% received a deceased-donor renal transplant, 58% received anti-thymocyte induction. Most patients were on triple immunosuppression (95% on calcineurin inhibitors, 87% on anti-metabolite, and 97% on prednisone). Hypertension was the most common comorbidity followed by diabetes mellitus, heart disease and lung disease. A total of 65 patients (20.5%) died. The mortality rate was 37 % (47/128) in patients diagnosed between March 16 and April 30, 2020. From May 1, 2020 to end of December 2020 mortality rate has significantly decreased to 11% (7/61). Since the beginning of 2021 till November 5, 2021 the mortality rate is 7.7% (10/129). Twenty-seven patients were diagnosed with COVID-19 despite being partially of fully vaccinated (25 fully vaccinated, 2 after one dose of vaccine). 13/27 (48%) were managed at home while 14/27 (52%) were hospitalized and 2 (7%) of them died. Twenty-eight patients received treatment with casirivimab and imdevimab post diagnosis of SARS-CoV-2 starting 2021 and none of those patients have died. Conclusion(s): In summary, mortality from SARS-CoV-2 infection in kidney transplant recipients was higher earlier at the pandemic and has significantly decreased over time. This could be explained by initial exposure of the patients with higher viral load due to lack of personal protection and social distancing. However, since the judicious use of monoclonal antibodies and vaccination, in addition to social distancing protocols and use of facemask, the mortality in kidney transplant recipients has decreased over time.

Covid 19 re-infection versus re-activation in two renal transplant patients

Purpose: Rare cases of potential COVID 19 re-infection have been reported throughout the world. Methods: We describe two renal transplant recipients with possible SARS-COV-2 re-infection. Results: Patient #1 is a 63-year-old man with a history of renal transplant in February 2010, who initially experienced symptoms consistent with COVID-19 in April 2020 along with several family members. Due to limitations in outpatient testing, no SARS-CoV2 testing was able to be performed but he was treated as presumed COVID-19 infection due to high community prevalence and three weeks following his symptoms, SARS-CoV2 IgG was positive. The patient subsequently had four negative PCR tests from July-September 2020. In October, he was admitted for hypoxic respiratory failure and was found to be SARS-COV-2 positive by PCR and SARS-COV-IgG was negative (Figure 1). The patient was treated with Remdesivir and recovered. Patient #2 is a 64-year-old man with history of renal transplant in 2003, who was found to be SARS-COV-2 positive by RT-PCR in April 2020 after presenting with hypoxia. The patient had an uneventful hospital course and was discharged off supplemental oxygen. He had two negative SARS-COV-2 PCR tests in August and September and his SAR-COV-2 IgG was positive. In September, he was readmitted with hypoxic respiratory failure requiring intubation and ICU admission and was again found to be SARS-COV-2 positive by PCR. The patient had a complicated hospital course and expired on September 30th (Figure 1). Conclusions: Potential cases of SARS-COV-2 re-infection have been previously reported, but it is unclear whether these are true re-infections versus reactivation of a prior infection, prolonged viral shedding, or dynamic RT-PCR results. In our cases, we believe prolonged viral shedding from the initial infection or inaccurate testing is less likely given the prolonged time interval between the two events, the multiple negative tests in between, and the severity of the second episodes. While both of these patients were suspected of having re-infections, this could not be confirmed as genomic analysis was not performed. Future studies of similar cases are needed to determine factors contributing to re-infection.

Variation of mortality from sars-cov-2 infection in kidney transplant recipients over the course of the pandemic

Purpose: We aimed to investigate the mortality from SARS-CoV-2 in kidney transplant recipients in the Bronx, New York, one of the epicenters of the pandemic over the period of the pandemic. Methods: Between March 16 and November 30, 2020, 158 patients were tested positive by SARS-CoV-2 RT-PCR. Results: 94 (59.5%) were male, at a median age of 62 years old (IQR: 51-71), predominantly Hispanic (54.4%) and African American (29.7%). 127 patients were admitted to the hospital and 29 were observed at home. 75.3% received a deceased-donor renal transplant, 57% received anti-thymocyte globulin induction. Most patients were on triple immunosuppression (94.3% on calcineurin inhibitors, 86.7% on anti-metabolite, 96.7% on prednisone). Hypertension was present in 96.2%, diabetes mellitus in 62.7%, heart disease in 19.6% and lung disease in 8.9% of the patients. The figure shows the number of RT-PCR positivity and mortality over the course of the pandemic starting on March 16, 2020. A total of 50 (31.6%) died as of November 30, 2020. The mortality rate was 40% (17/43) in patients diagnosed between March 16 and 31,2020, 39% (23/59) in patients diagnosed between April 1 and 15,2020 and 29% (7/24) in patients diagnosed between April 16 and 30, 2020. Since May 1st 2020, the mortality rate has significantly decreased to 9% (3/32). Conclusions: In summary, mortality from SARS-CoV-2 infection in kidney transplant recipients was higher during the first 6 weeks of the pandemic and has significantly decreased over time. This could be explained by initial exposure of the patients with higher viral load due to lack of personal protection and social distancing due to the fact that there is no current proven treatment for SARS-CoV-2 infection and clinical approach to patients has not been changed since the beginning of the pandemic.

Prevalence and dynamics of SARS-CoV-2 IGG in kidney transplant recipients

Purpose: We aimed to investigate the prevalence and dynamics of SARS-CoV-2 IgG in kidney transplant recipients in the Bronx, New York, one of the epicenters of the pandemic Methods: Between March 16 and November 30, 2020, 158 patients tested positive by SARS-CoV-2 RT-PCR. From May 3 to November 30, 2020, 1042 patients were screened for SARS-CoV-2 IgG antibodies and 164 (15.7%) were tested positive (Figure). Results: Sixty of the 164 patients were previously diagnosed COVID-19 by RTPCR, while the remaining 104 did not have significant symptoms and had not been previously tested by RT-PCR. Overall prevalence of COVID-19 diagnosis by RT-PCR and/or SARS-CoV-2 IgG in 1130 patients were 23.2%. Seventy RT-PCR positive patients were screened for SARS-CoV-2 IgG antibody at a median of 43 days postdiagnosis (IQR: 29-57) and 60 (85.7%) were positive. A total of 39 patients out 164 who previously tested positive for SARS-CoV-2 IgG (25 diagnosed with IgG and 14 with RT-PCR) were retested at a median time of 105 days (IQR: 83-116). Twenty patients (51.3%) became seronegative at a median time of 107 days (IQR: 87-134) from their first positive SARS-CoV-2 IgG. Six patients out of 14 (43%) who were diagnosed by positive RT-PCR became seronegative at a median time of 105 days (IQR: 83-166) from their first positive SARS-CoV-2 IgG while 14 patients out of 25 (56%) who were initially diagnosed by a positive SARS-CoV-2 IgG, became seronegative at a median time of 112 days (IQR: 91-138) from date of diagnosis Conclusions: . In summary, 40% of kidney transplant recipients were asymptomatic or mildly symptomatic and developed SARS-CoV-2 IgG without requiring testing by SARS-CoV-2 RT-PCR. However, half of the patients who initially developed antibodies lost them over time raising the questions of lasting immunity against SARS-CoV-2 and how effective are those antibodies.

Treatment with monoclonal antibodies minimize severity of covid-19 illness among kidney transplant recipients

Background: The mortality rate of kidney transplant recipients with COVID-19 is significantly higher than the general population, indicating a need for effective treatment to minimize potential severe symptoms in this population. We sought to evaluate the efficacy of monoclonal antibody therapy in decreasing the severity of COVID-19 symptoms among our kidney transplant recipients. Methods: We reviewed 17 kidney transplant recipients who were infected with SARS-CoV2 and received treatment with monoclonal antibody therapy. All patients were on standard immunosuppression with Tacrolimus and Prednisone, and 88% were on Mycophenolate prior to COVID diagnosis, which was subsequently reduced or held for at least 2 weeks. Results: Of the 17 patients reviewed, median age was 61 years (range 42 to 77 years), 47% were male, 59% were Hispanic, and 29% were African American. Additionally 94% had history of hypertension, 47% diabetes mellitus, 18% coronary artery disease, and median BMI was 28.8 (range 23.4 to 41.9). Eighteen percent were transplanted <1 year, 29% between 1-5 years, 24% 6-10 years, and the remaining >10 years. All patients had mild symptoms without evidence of hypoxia, and 94% received monoclonal antibody therapy within 7 days of diagnosis. Bamlanivimab 700mg was the most commonly administered agent at 59%, while 18% received Bamlanivimab 700mg and Etesevimab 1400mg. Casirivimab 1200 mg and imdevimab 1200 mg was used in 24%. Only 2 out of the 17 patients (11.8%) required hospitalization, and both were non-COVID-19 related reasons. Five out of 17 patients (29.4%) were evaluated in the Emergency Department but not admitted. All 17 patients (100%) recovered from their COVID-19 illness. There were no episodes of graft failure. Conclusions: Our experience suggests that monoclonal antibody therapies may be beneficial in preventing severe COVID-19 in renal transplant recipients and possibly reduce the need for COVID-19 related hospitalization in this high risk population. However, larger studies are needed to confirm these findings.

Lower CD3 and CD4 counts in kidney transplant recipients who did not respond to COVID-19 vaccination

Background: Kidney transplant recipient's response rate to COVID-19 vaccination is reportedly less than 54% after the 2nd dose, significantly lower than general population and dialysis patients, reported as between 85-90% and 95-100%, respectively. Methods: We studied SARS-CoV-2 anti-spike IgG levels in our kidney transplant recipients after their COVID-19 vaccination using the OrthoV IgG platform. Results: 69 kidney transplant recipients received a SARS-CoV-2 vaccine (47 Pfizer, 20 Moderna and 2 Johnson and Johnson) at a median 36 months after transplantation (range, 3 months to 22 years). 61% were male, 39% Black, 29% Hispanic with a median age of 60 (range 22-82). 72% were deceased-donor kidney transplant recipients. 23 patients had previous history of COVID-19 diagnosed by SARS-CoV-2 PCR and/or antinucleocapsid antibody and 21 of those patients (91%) developed anti-spike IgG after 1st or 2nd dose with a median level of 13.2 (11.2-16.2). 46 patients without history of previous COVID-19, 17 (37%) developed anti-spike IgG at a median of 28 days (range 10-72) after the second vaccine dose with a median level of 5.7 (1.22-15.4). Patients who didn't develop anti-spike IgG tended to be older, of African-American descent, on MMF > 1 g/day, have lower CD3 and CD4 counts. Conclusions: In summary, most kidney transplant recipients without history of COVID-19 did not produce anti-spike IgG after being fully vaccinated and it is associated with augmented immunosuppression, lower T cell counts, African-American race and older age.

Clinical outcomes of hospitalized kidney transplant recipients with COVID-19 in a predominantly minority population

Background: COVID-19 has been associated with increased morbidity in kidney transplant recipients. We aimed to identify risk factors for mortality in hospitalized kidney transplant recipients with COVID-19 Methods: We retrospectively reviewed the medical records of 75 kidney transplant recipients admitted for COVID-19 at our institution. Results: Among the 75 patients, 28 (37%) died at a median 8 days (range, 1-36) after admission to the hospital. The Table summarizes the demographics and initial labs values of both groups. Most of our patients were Hispanic (54%) and African American (32%) and 97% had hypertension and 65% had diabetes mellitus. There was no difference between the two groups in terms of sex, type of transplant, time from transplant, immunosuppressive medications, medical comorbidities, presenting symptoms, temperature, or pulse oximetry values on admission. Non-survivors were older and had higher BMI. On admission most patients were lymphopenic, had low CD3/CD4/CD8 counts and had higher inflammatory markers (ferritin, d-dimer, CRP, procalcitonin, interleukine-6 levels). Non-survivors had statistically significant higher procalcitonin, IL-6 and pro-BNP levels on admission. More non-survivors required ICU stay (64% vs. 13%, p < 0.001), intubation (57% vs. 11%, p < 0,001) and renal replacement therapy (32% vs. 17%, p=0.17) compared to survivors. There was no difference in secondary bacterial infections, CMV viremia, DVT or stroke between the two groups. In a multivariate analysis, BMI (OR 1.15, CI 1.04-1.30, p= 0.017 per unit increase), higher procalcitonin (OR 4.16, 1.09-18.87, p=0.046) and proBNP levels (OR 1.017, 1.002-1.034, p=0.039, per 100 unit increase) on admission were associated with increased mortality. Conclusions: COVID-19 is associated with increased mortality (37%) in our kidney transplant recipients and higher BMI, procalcitonin and proBNP levels at admission are associated with mortality.