IDWeek 2023 in Boston
At IDWeek, investigators presented data regarding COVID-19 natural history and treatment in immunocompromised persons. Although not formally peer-reviewed, these works underwent expert assessment. Registered attendees can access IDWeek content online.
Summary of data
Heavily immunocompromised persons, particularly with inborn or acquired immunodeficiencies related to medications, blood cancers or organ transplantation, continue to experience adverse COVID-19 outcomes. These include persistent infections associated with development of antiviral resistance mutations. Small-scale studies reinforce that authorized antiviral therapies can reduce severe disease. Frontiers including combination antivirals or adjunctive cellular therapies may hold promise for those at risk for protracted disease, yet dedicated trials are lacking.
High-risk phenotypes for severe COVID-19
Several studies confirmed risks among immunocompromised populations in the “modern” COVID-19 era, i.e., Omicron subvariant infections following ≥3 vaccinations. The large retrospective U.K. INFORM study (Poster #398) found among 12 million persons, 4% were immunocompromised yet represented 25% of COVID-19-related outcomes. There was >10-times higher relative risk among solid organ transplant recipients and persons with blood cancers on active therapy (absolute risks were ~1% versus 0.1% in the non-immunosuppressed group).
Protracted COVID-19 and treatment-emergent viral mutations
Multiple works evaluated SARS-CoV-2 shedding in immunocompromised persons while monitoring for viral evolution. Raglow et al. (Abstract #1097) prospectively evaluated 150 immunocompromised persons (90% symptomatic, 70% ≥3 vaccines, 74% antiviral-treated). Prolonged viable virus shedding was uncommon, albeit seen for >30 days in several B-cell-depleted persons, associated with de novo spike protein mutations. The prospective LUNAR study (Poster #512) of sotrovimab use (N=195 persons, 99% ≥1 vaccine, BA.5 subvariant infections) observed excellent viral response, yet 8/23 (35%) with paired data at day 30 showed treatment-emergent mutations reducing neutralizing activity of the monoclonal antibody.
Johnson et al. (Poster #495) retrospectively studied treatment-emergent resistance mutations in 21 immunocompromised persons and found three cases of de novo mutations associated with resistance to the antiviral remdesivir (Veklury). One isolate from a patient with myeloma showed additional mutations confirming reduced susceptibility to nirmatrelvir/ritonavir (Paxlovid) on infection day 88. Similarly, Chang et al. (Poster #464) performed prospective repeated nasal swabs in immunocompromised persons including two with blood cancers who developed >10 de novo mutations during infections lasting >100 days. This included one participant with lymphoma who had received four remdesivir courses and demonstrated mutations associated with remdesivir resistance.
Real-world effectiveness of various antivirals in immunocompromised persons
Multiple studies assessed outcomes following antiviral therapy courses with heavy immunocompromised populations, including comparison of different regimens.
Moussa et al. (Poster #528) performed a single-center, retrospective, matched study of molnupiravir versus nirmatrelvir/ritonavir in persons with cancer. Chronic comorbidities and lower respiratory symptoms were more common in the molnupiravir group; ~80% of persons were fully vaccinated. Non-statistically significant higher rates of severe outcomes were seen in the molnupiravir group. Rebound syndromes were somewhat more common following molnupiravir (9% vs. 3%), yet there were dramatically fewer adverse events (0% vs. 31%).
Arvanitis et al. (Poster #508) performed a single-center retrospective analysis of COVID-19 outcomes in 26 nirmatrelvir/ritonavir-treated versus untreated patients with cancer. The nirmatrelvir/ritonavir group, which had higher vaccination rates and fewer comorbidities, ultimately experienced a decreased hospitalization rate (27% vs. 65%) and mortality (8% vs. 23%) versus the untreated group.
Hirai et al. (Poster #474) retrospectively assessed outcomes among 51 immunosuppressed patients with COVID-19 following early remdesivir versus combined remdesivir plus mAb therapy (N=35). Quicker fever response and virological response were seen in the combination group, with no progression to severe disease or death (0% vs. 4% in the monotherapy group).
Adjunctive and alternative therapies in the most complex COVID-19 cases
Dr. Dioverti (Session #100) presented an overview of refractory COVID-19 in immunocompromised persons with a focus on combination therapies. Six retrospective series (N=83 patients, majority B-cell-depleted) were summarized, including regimens of combined remdesivir plus nirmatrelvir/ritonavir or molnupiravir (+/- antibody therapies), or prolonged (≥15 day) nirmatrelvir/ritonavir. Results were generally favorable. One patient with acute myeloid leukemia and persistent COVID-19 complicated by hypoxia and orthostasis (despite treatment with mAb, remdesivir and convalescent plasma) received three infusions of HLA-matched virus-specific T-cells and showed resolution of symptoms and viral clearance.
Registered attendees can access IDWeek content online.