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Interpreting COVID-19 Data From IDWeek 2022: Prophylaxis, Treatment, and Opportunistic Infections in Immunocompromised Individuals

Cristina Mussini, MD

Head of Department of Infectious Diseases and Tropical Medicine
Full Professor of Infectious Diseases

Infectious Diseases Clinics, University Hospital
University of Modena and Reggio Emilia
Modena, Italy

Cristina Mussini, MD: consultant/advisor/speaker: AbbVie, Angelini, Gilead Sciences, GlaxoSmithKline, Janssen, MSD, Pfizer, Roche, ViiV Healthcare; researcher: Gilead Sciences, Janssen, MSD, ViiV Healthcare.

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Released: November 17, 2022

Key Takeaways

  • In an observational study of tixagevimab plus cilgavimab for COVID-19 pre-exposure prophylaxis in immunocompromised individuals, breakthrough infections occurred, including with hospitalizations.
  • The 74% mortality rate among solid organ transplant recipients with COVID-19–associated fungal infections highlights the importance of considering more frequent use of antifungal prophylaxis in this population.

At IDWeek 2022, COVID-19 continued to be a major research focus, with studies investigating many facets of infection understanding and management, including risk factors, prevention, diagnosis, treatment, and disease course. Several studies warrant particular attention regarding their potential impact on clinical practice, and I review 4 of them in this commentary. 

Baricitinib vs Tocilizumab for Severe COVID-19: Single-Center Retrospective Chart Review
Gonzalez and colleagues reported findings from a single-center retrospective chart review of hospitalized adults with polymerase chain reaction–confirmed SARS-CoV-2 and evidence of lower respiratory tract infection from July 2020 to December 2021. The investigators compared disease outcomes among those who received baricitinib (n = 175) vs those who received tocilizumab (n = 239). 

The results demonstrated that individuals who received tocilizumab had 86% higher odds of death compared with those who received baricitinib (odds ratio: 1.86; 95% CI: 1.17-2.96; P = .009). In addition, individuals who received tocilizumab had significantly higher hospital length of stay, ICU length of stay, and need for mechanical ventilation or organ support compared with individuals who received baricitinib.

Important limitations must be considered when interpreting the results of this study, including the fact that it was a retrospective analysis rather than a randomized comparison, as well as potential differences in severity of illness between the 2 treatment groups, as shown by ICU length of stay and need for mechanical ventilation or organ support. Moreover, the investigators noted that the analysis was unable to differentiate between individuals with delta vs omicron infections; thus, it is possible that differences in illness severity associated with each variant could have affected the study outcomes. Indeed, there were notable differences in baseline characteristics between the treatment groups, including longer median length of hospital stay, higher rate of additional source of infection, and higher rate of positive blood microbiology with tocilizumab vs baricitinib. Selection bias for different treatments always must be considered as a potential confounding factor in retrospective analyses.

Further data arguing against differential efficacy of the 2 treatments come from the results of an open-label randomized trial comparing tocilizumab (n = 126) with baricitinib (n = 125), each in combination with standard of care, in patients hospitalized with severe COVID-19. In the randomized study, the 2 treatments were equivalent, with baricitinib demonstrating noninferiority to tocilizumab for the primary outcome of mechanical ventilation or death by Day 28 (39.2% vs 44.4%; HR: 0.83; 95% CI: 0.56-1.21). 

SPRINTER: Inhaled Interferon Beta-1a (SNG001) in Patients Hospitalized With Moderate COVID-19
In the multinational, randomized, placebo-controlled phase III SPRINTER trial, adults hospitalized with COVID-19 and requiring supplemental oxygen were randomized to receive inhaled interferon beta-1a (SNG001; n = 309) vs placebo (n = 314), each in combination with standard of care. 

The results were disappointing in that SNG001 did not meet the primary endpoints of decreasing time to hospital discharge or time to recovery up to Day 28. Nevertheless, there was a trend toward decreased progression to severe disease or death within 35 days with SNG001 vs placebo, with an odds ratio of 0.71 (95% CI: 0.44-1.15) in the intention-to-treat population.

An important additional analysis included in this study was a post hoc assessment of long COVID (ie, symptoms at Day 60 and/or 90). Although the results suggested a possible benefit with SNG001 related to long COVID symptoms, most notably for fatigue/malaise, to me these symptoms are so subjective that it is difficult to know if the difference is clinically meaningful. 

Observational Study of Tixagevimab Plus Cilgavimab for COVID-19 Pre-exposure Prophylaxis in Immunocompromised Individuals
Lim and colleagues reported findings from an observational analysis of a Minnesota Department of Health voluntary tixagevimab plus cilgavimab patient registry conducted via a patient survey from December 2021 to June 2022. Among 296 participants, all of whom were vaccine eligible, only 69% were fully vaccinated, and 5.7% had not received even a single vaccine dose at the time they received tixagevimab plus cilgavimab.

The investigators found that 5.7% of patients had a breakthrough COVID-19 infection after receipt of tixagevimab plus cilgavimab, and 1.4% were hospitalized. There were no COVID-19–related deaths.

To me, the key take-home message from this study is that tixagevimab plus cilgavimab should be used as a supplement to and NOT a substitute for all recommended COVID-19 vaccine doses in immunocompromised individuals. 

Fungal Coinfections in Solid Organ Transplant Recipients With COVID-19
To address an important clinical need for more data on the incidence and management of COVID-19–associated fungal infections in immunocompromised individuals, investigators conducted a single-center retrospective study that included 23 adult solid organ transplant recipients diagnosed with COVID-19 from March 2020 to January 2022 who experienced a COVID-19–associated fungal infection (excluding Candida spp), 67% of which were probable COVID-19–associated pulmonary aspergillosis. The high proportion of pulmonary aspergillosis is consistent with the recently described entity termed “CAPA” for COVID-associated pulmonary aspergillosis and underscores the importance of taking this entity into account along with other potential fungal infections when evaluating patients in this group.

In 22 of 23 individuals, fungal markers were elevated, demonstrating that patients can be clinically followed by evaluating for these markers beginning early in diagnosis.

The results demonstrated an alarming 73.9% mortality rate. Of note, only 1 individual of 23 was receiving antifungal prophylaxis. To me, the strong message from this analysis is that we should be considering more frequent use of antifungal prophylaxis in this population, particularly for pulmonary aspergillosis.

Your Thoughts?
Will new COVID-19 data presented at IDWeek 2022 affect your clinical practice, and in what ways? Join the discussion and share your thoughts by posting a comment.

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