key: cord-0890793-a1k2admy
authors: Liu, Esther C.; Lee, Jennifer H.; Loo, Angela; Mazur, Shawn; Sultan, Sam; Aull, Meredith; Lee, Jun B.; Muthukumar, Thangamani; Hartono, Choli
title: Casirivimab-Imdevimab (REGN-COV2) for Mild-to-Moderate SARS-CoV2 Infection in Kidney Transplant Recipients.
date: 2021-09-06
journal: Kidney Int Rep
DOI: 10.1016/j.ekir.2021.08.032
sha: 841ae3f1eb512f0d09f11ae56e5e984d4725270c
doc_id: 890793
cord_uid: a1k2admy

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Kidney transplant recipients are an immunocompromised population, many with comorbid diseases such as obesity, diabetes, and coronary artery disease, that may increase their risk for developing severe coronavirus disease 2019 (COVID-19) (1) . During the pandemic in New York City, kidney transplant recipients requiring hospitalization for COVID-19 had a higher rate of mortality compared to patients who could be treated in the ambulatory setting (2) . Accounting for differences in baseline risk factors for progression in immunocompromised patients, avoidance of hospitalization would be beneficial given the added costs, limited hospital resources during a surge, and higher risk of complications when they are hospitalized. Although COVID-19 vaccination efforts are currently widespread and highly recommended for the prevention of severe COVID-19 infection, some transplant programs delay administering vaccinations immediately post-transplant to avoid alloimmune stimulation. Another challenging aspect of vaccinating this population is that immunosuppressed kidney transplant recipients may have impaired antibody responses (3) . Emerging evidence of breakthrough infections among vaccinated kidney transplant recipients has been described and therefore it is important to evaluate the efficacy and safety of available COVID-19 treatment options (4). REGN-COV2, an antibody cocktail containing two SARS-COV2-neutralizing antibodies (casirivimab and imdevimab), has been shown to reduce COVID-19 viral load and received Emergency Use Authorization (EUA) by the US Food and Drug Administration for the treatment of mild-tomoderate COVID-19 infection in November 2020 (5, 6) . Casirivimab and imdevimab are two IgG1 antibodies that are noncompeting and they target the receptor-binding domain of the SARS-CoV-2 spike protein, therefore neutralizing viral entry into human cells via the angiotensinconverting enzyme 2 (ACE2) receptor (5) . We provided REGN-COV2 to our kidney transplant J o u r n a l P r e -p r o o f recipients with mild-to-moderate COVID-19 infection-defined as presence of mild symptoms, oxygen saturation greater than or equal to 94%, and no additional oxygen supplementation from baseline. Herein we report our center's experience. years (IQR 1-9). Pre-existing risk factors for severe disease were identified in our recipients and included age greater than 65 years, hypertension, coronary disease, and diabetes mellitus (table 1). The median time to REGN-COV2 infusion was 5 days (IQR 4-7). The most common symptoms reported include fever, fatigue/myalgia, diarrhea, and upper respiratory complaints (table 1) . At presentation, maintenance therapy included tacrolimus and mycophenolate mofetil. Three of 14 recipients also received corticosteroid maintenance therapy. Overall immunosuppression was reduced in 6 of our kidney transplant recipients after COVID19 diagnosis.

A single REGN-COV2 infusion of casirivimab 1200mg and imdevimab 1200mg was tolerated by our kidney transplant recipients. We did not encounter any cases of hypersensitivity reactions.

During infusion, 1 adverse event occurred where a recipient complained of burning sensation in the hands, which resolved following a dose of acetaminophen. Of the 14 treated recipients, 1 individual, aged 61, was hospitalized 6 days after infusion for worsening symptoms and de novo supplementation oxygen requirement. This patient received dexamethasone, remdesivir, tociluzumab, and required up to 15 liters oxygen. On day of discharge, oxygen requirement was weaned down to 2 liters oxygen via nasal cannula for ambulation. The patient continued to improve and no longer need oxygen supplement 2 weeks after discharge. A second recipient, age 79, was admitted after testing positive for COVID-19 and received the REGN-COV2 infusion from the emergency department. His risk factors for progression include advanced age, significant coronary disease, and hypertension. He required 2 liters oxygen supplementation via nasal cannula, remdesivir, and dexamethasone. He was discharged 12 days after admission without oxygen supplementation. We did not observe any cases of allograft rejection during the 30-day follow-up period. There was no mortality during the minimum 30-day follow-up period.

In a phase 3 study enrolling 4,057 COVID19 outpatients with one or more risk factors for developing severe disease, treatment with REGN-COV2 significantly reduced hospitalization or all-cause mortality, lowered viral load, and promptly resolved COVID-19 related symptoms (7) .

A recent report showed that the use of REGN-COV2 in solid organ transplant patients with mild-J o u r n a l P r e -p r o o f to-moderate COVID19 infection resulted in no progression of symptoms or the need for hospitalization (8) . In contrast, 2 of the 14 individuals at our center were hospitalized for additional management. Our analysis is limited by its small sample size to draw conclusions about efficacy but our findings demonstrate that it was safe for kidney transplant recipients with mild-to-moderate COVID-19 infections to receive REGN-COV2 therapy. Because our study lacked a control group, we examined our internal data for risk of hospitalization after COVID-19 diagnosis (9) . At our center, we observed a 65% hospitalization rate for COVID-19 infected kidney transplant patients when the REGN-COV2 infusions were not yet available (9) . We found that 31% of our hospitalized patients did not require respiratory support -it may be possible that these patients could have avoided hospitalization completely with REGN-COV2 administration (9) . Although we did not test our patients for presence of endogenous 

COVID-19 in solid organ transplant recipients: initial report from the US epicenter

Kidney allograft recipients, immunosuppression, and coronavirus disease-2019: a report of consecutive cases from a New York City transplant center

Postvaccine anti-SARS-CoV-2 spike protein antibody development in kidney transplant recipients

Severe consequences of COVID-19 infection among vaccinated kidney transplant recipients

REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19

Casirivimab and Imdevimab EUA Letter of Authorization

REGEN-COV antibody cocktail clinical outcomes study in COVID-19 outpatients

Casirivimab-imdevimab for treatment of COVID-19 in solid organ transplant recipients: An early experience

COVID-19 outcomes in patients waitlisted for kidney transplantation and kidney transplant recipients