key: cord-0855229-iy9uz57c authors: Angarone, Michael; Kumar, Rebecca N.; Stosor, Valentina title: Organ transplant patients, COVID‐19, and neutralizing monoclonal antibodies: The glass is half full date: 2021-10-06 journal: Transpl Infect Dis DOI: 10.1111/tid.13724 sha: 1838113518e0446a1f8e2cdd4cb2fd8dc1c669a6 doc_id: 855229 cord_uid: iy9uz57c nan Organ transplant recipients are among the most vulnerable populations for severe infections with SARS-CoV-2 both because of the effects of immunosuppression and the high burden of other high-risk co-morbid medical conditions. 1 The severity and devastating impact of COVID-19 on transplant patients is evidenced by high rates of hospitalization and mechanical ventilation and high mortality. These poor outcomes coupled with the suboptimal immunogenicity of SARS-CoV-2 vaccines in the transplant population underscore the urgency for effective therapies for COVID- 19. 2 To date, the only recommended therapeutic agents for COVID -19 in the ambulatory setting are neutralizing monoclonal antibodies directed to SARS-CoV-2 spike protein. [3] [4] [5] [6] Four monoclonal antibody preparations have been made available through emergency use authorization by the Food and Drug Administration (FDA) for the treatment of mild to moderate COVID-19 in persons at high risk for progression to severe COVID-19, including solid organ transplant (SOT) recipients; the approved agents include bamlanivimab (revoked April 16, 2021), 3, 8 casirivimab-imdevimab, 4 bamlanivimab-etesevimab, 5 and sotrovimab. 6 The emergency use authorizations were based on early clinical trials data demonstrating reductions in SARS-CoV-2 viral load, [3] [4] [5] 9, 10 hospitalizations, emergency department (ED) and/or medically attended visits, [3] [4] [5] [6] [9] [10] [11] [12] and deaths 5 in persons who receive therapy early in the course of clinical symptoms compared to placebo. However, transplant recipients were not among the early trial participants. Thus, although transplant patients with mild to moderate COVID-19 are eligible for neutralizing monoclonal antibody therapies, data regarding their safety and efficacy are lacking. In this issue of Transplant Infectious Disease, Kutzler et al. present the outcomes and tolerability of bamlanivimab for mild to moderate COVID-19 in SOT recipients. 13 Eighteen adult SOT recipients (15 kidney recipients, two liver recipients, and one heart recipient) were included in this retrospective, observational cohort. The average age was 52 years, and 72% of the patients were male and predominately Caucasian (67%). Other comorbidities included an average BMI of 32 kg/mm 3 , hypertension (8.39%), and diabetes (44%). The majority had symptomatic SARS-CoV-2 infection, with fatigue and cough being the most common symptom. Bamlanivimab was given 5 ± 2 days from a positive test for SARS-CoV-2. Four (22%) patients required either hospitalization or emergency room visit within 32 days of treatment. Three Bamlanivimab is inactive and bamlanivimab-etesevimab is less active against all of these variants due to the presence of the E484K substitution. [18] [19] [20] The variants, B.1.617 and P.1, carry two substitutions, E484Q/K and L452R, that lead to the loss of neutralizing activity of bamlanivimab-etesevimab and reduced activity of casirivimab. 18, 19 Because of theoretical concerns for treatment failure, the FDA emergency use authorization for bamlanivimab has been revoked, and bamlanivimab-etesevimab is no longer recommended. 7, 8 However, casirivimab and imdevimab bind at nonoverlapping regions of the receptor binding domain, and casirivimab-imdevimab retains activity against these variants. [18] [19] [20] Sotrovimab, designed to bind at a more conserved region of the receptor binding domain, also remains active against all circulating SARS-CoV-2 variants. 6 The concern for emerging treatment resistant variants is even higher in organ recipients with COVID-19. With higher levels of virus in respiratory secretions and more prolonged viral shedding than the general population, 21 Coronavirus disease 2019 in solid organ transplant: a multicenter cohort study. Clinical Infectious Diseases Immunogenicity of SARS-CoV-2 BNT162b2 vaccine in solid organ transplant recipients Emergency use authorization (EUA) of bamlanivimab Emergency use authorization (EUA) of casirivimab and imdevimab Emergency use authorization (EUA) of bamlanivimab and etesevimab Emergency use authorization (EUA) of sotrovimab General management of nonhospitalized patients with acute COVID-19 COVID-19) update: FDA revokes emergency use authorization for monoclonal antibody bamlanivimab. U.S. Food and Drug Administration REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19 Effect of bamlanivimab as monotherapy or in combination with etesevimab on viral load in patients with mild to moderate COVID-19: a randomized clinical trial SARS-CoV-2 neutralizing antibody LY-CoV555 in outpatients with Covid-19 Early Covid-19 treatment with SARS-CoV-2 neutralizing antibody sotrovimab Initial experience of bamlanivimab monotherapy use in solid organ transplant recipients Bamlanivimab for treatment of COVID-19 in solid organ transplant recipients: early singlecenter experience Bamlanivimab for mild to moderate COVID-19 in kidney transplant recipients Monoclonal antibody therapy for COVID-19 in solid organ transplant recipients SARS-CoV-2 variant classifications and definitions Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization Increased resistance of SARS-CoV-2 variant P.1 to antibody neutralization Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 SARS-CoV-2 viral dynamics in immunocompromised patients Bamlanivimab treatment leads to rapid selection of immune escape variant carrying E484K mutation in a B.1.1.7 infected and immunosuppressed patient Effect of bamlanivimab vs placebo on incidence of COVID-19 among residents and staff of skilled nursing and assisted living facilities: a randomized clinical trial Subcutaneous REGEN-COV antibody combination for Covid-19 prevention Northwestern University Feinberg School of Medicine. Valentina Stosor https://orcid.org/0000-0002-0388-5460