Molnupiravir for Treatment of COVID-19 in Solid Organ Transplant Recipients.

Solid organ transplant recipients (SOTRs) are at a higher risk of progression of coronavirus disease 2019 (COVID-19).1,2 With the emergence of new viral-variants, the currently available antisevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies are losing their efficacy.3 Outpatient treatment of COVID-19 in SOTRs is limited by complicated logistics of administration of Remdesivir and drug–drug interactions with Nirmatrelvir/ritonavir. Molnupiravir acts as a substrate for SARS-CoV-2 RNA polymerase and impairs SARS-CoV-2 replication and infection.4 It retains antiviral activity against all known variants of SARS-CoV-2.3 In a recent clinical trial, patients treated with molnupiravir resulted in faster time to recovery and reduced viral detection and load.5 We present our data regarding the characteristics and outcomes of adult SOTRs with mild-to-moderate COVID-19 who were treated with oral dosage of 800 mg of molnupiravir twice a day for 5 d during the period from June 2022 to October 2022 and with at least 14 d of follow-up. During the study period, 98 SOTRs were diagnosed with COVID-19 in our institution. They received Bebtelovimab 54 (55%), molnupiravir 23 (23%), and no treatment for asymptomatic illness 21 (21%). Among 23 patients who received molnupiravir, they were at a mean of 5.5 y (range, 0.3–17.2) away from the transplant, with median duration of symptoms of 1.9 d (range, 1–4) and had variable vaccination status. Seven patients (30%) had received Tixagevimab/Cilgavimab, given at a mean of 170 d (range, 82–256) before the current diagnosis of COVID-19. Nine (39%) had a remote history of previous COVID-19. Eleven (48%) patients were on Tacrolimus monotherapy, and in the rest 12 (52%), mycophenolate was stopped for duration of COVID-19 symptoms. Considerations for use of molnupirivir were inability/unwilling to be scheduled for SARS-CoV-2 monoclonal antibodies infusion, 3 (13%); prior use of Tixagevimab/Cilgavimab prophylaxis, 7 (30%) and more recently starting October 2022; and less predictable activity of Bebtelovimab, 13 (57%) (Table 1). Pregnancy status of all women in childbearing age was reviewed before prescribing molnupiravir, and all recipients were advised on the use of barrier contraception. TABLE 1. - Characteristics and outcomes of solid organ transplant recipients treated with molnupiravir (N = 23) Age, mean (range), y 60 (41–73) Male sex, n(%) 13 (56%) Race Caucasian 14 (61%) African American 5 (22%) Hispanic 2 (8.6%) Asian 2 (8.6%) Type of organ transplant, n (%) Kidney 9 (39%) Heart 6 (26%) Liver-kidney 4(17%) Liver 3(13%) Heart-kidney 1 (4%) Time from transplant, mean (range), y 5.5 (0.3–17.2) Duration of symptoms before treatment, mean (range), d 1.9 (1–4) COVID-19 vaccination status, n (%) Unvaccinated 2 (8.7%) 1- 1-dose 1 (4%) 2- 2-doses 10 (43%) 3- 3-doses 9 (39%) Induction immunosuppression T-cell depletion 14 (61%) Steroids 7 (30%) Basiliximab 2 (8.6%) Lowered/stopped mycophenolate 12/12 (100) of eligible patients Follow-up period, mean (range), d 69 (15–178) Resolution of acute symptoms excluding cough, mean (range), d 3.6 (3–7) Progression of COVID-19 symptoms, n (%) 0 (0%) Hospitalizations not related to COVID-19 within 14 d of treatment, n (%) 1 (4%) arm swelling Associated graft rejection/dysfunction during the follow-up period, n (%) 0 (0%) Need for intensive care, n (%) 0 (0%) Death during at least 14-d follow-up, n (%) 0 (0%) Rebound of COVID-19 symptoms 0 (0%) COVID-19, coronavirus disease 2019. During the mean follow-up period of 69 d (range, 16–178), none of the patients reported progression of symptoms, and 1 patient (4%) was hospitalized for non-COVID illness. Molnupiravir was tolerated in all the patients with none of the recipients requiring discontinuation of therapy secondary to intolerance. No rebound COVID-19 symptoms were noted. No episodes of organ rejection associated with alteration of immunosuppression and COVID-19 were noted after completion of antiviral therapy during the study period. These acceptable outcomes are likely associated with very early initiation of antiviral therapy, overall lower immune suppression in setting of time away from transplant, and no recent treatment of allograft rejection, along with previous variable natural and acquired immunity. Limitations of our retrospective results include no comparator arm, diversity of patient population, and a small sample size. Although there is a chance these patients may have improved without any therapeutic intervention, but based on the unknown risk of progression and associated morbidity, all symptomatic SOTRs with COVID-19 are currently offered treatment along with optimization of immunosuppression. In the current setting of uncertain and limited choices, when initiated early in the disease course, molnupiravir may offer a safe and efficacious therapeutic option for the treatment of mild-to-moderate COVID-19 in certain SOTRs. To attain desired outcomes in the outpatient management of COVID-19, transplant centers should devise mechanisms for early diagnosis, prompt treatment, and mitigation strategies to provide equitable access to treatment for all transplant recipients.