Immunomodulators for severe coronavirus disease-2019 in transplant patients: Do they increase the risk of secondary infection?

BACKGROUND: Current guidelines recommend immunomodulators, tocilizumab or baricitinib, for the management of severe coronavirus disease-2019 (COVID-19) in patients with increasing oxygen requirements. Given their immunosuppressive effects, there is a concern for higher rates of infection among transplant recipients. METHODS: A retrospective cohort study of transplant patients with severe COVID-19 between April 2020 and January 2022 was performed at the Mayo Clinic. The primary outcome was incidence of secondary infections after COVID-19 diagnosis. Secondary outcomes were 90-day mortality, ventilatory days, and thromboembolic events. RESULTS: A total of 191 hospitalized transplant patients were studied, including 77 (40.3%) patients who received an immunomodulator. Overall, 89% were solid organ transplant recipients, with kidney as the most common transplanted organ (50.3%). The majority (89.0%) required oxygen supplementation on admission, and 39.8% of these patients required mechanical ventilation during the hospital course. There was no significant difference in the incidence of secondary infections between those who received or did not receive an immunomodulator (p = .984). Likewise, there was no difference in 90-day mortality between patients who received or did not receive an immunomodulator (p = .134). However, higher mortality was observed among patients that developed a secondary infection (p < .001). CONCLUSION: The use of immunomodulators in transplant patients with severe COVID-19 was not significantly associated with an increased risk of secondary infections. Secondary infections were associated with higher risk of all-cause mortality. Future studies of larger cohorts are needed to explore the effect of immunomodulators on survival among transplant patients with COVID-19.

Rebound Phenomenon after Nirmatrelvir/Ritonavir Treatment of Coronavirus Disease-2019 in High-Risk Persons.

In a cohort of 483 high-risk patients treated with nirmatrelvir/ritonavir for coronavirus disease-2019, two patients (0.4%) required hospitalization by day 30. Four patients (0.8%) experienced rebound of symptoms, which were generally mild, at median of 9 days after treatment, and all resolved without additional COVID-19-directed therapy.