Antibody combo a promising pre-exposure prophylaxis for COVID-19 in haemodialysis patients

The combination of tixagevimab plus cilgavimab helps prevent COVID-19 infection in haemodialysis patients, with no safety signals, as shown in a study.

“A significant reduction in severity of illness, hospitalization rate, and mortality was found with pre-exposure prophylaxis with tixagevimab and cilgavimab in this real-world experience from Singapore,” the investigators reported.

Specifically, hospitalization rate decreased by 95.3 percent, from 42.5 percent to 2 percent (p<0.0001), following the administration of the antibody combination. The patients who contracted COVID-19 had mild symptoms, with only 1 percent being admitted to the intensive care unit. Finally, the mortality rate from COVID-19 infection dropped from 2.5 percent to 0 percent. [Cureus 2023;15:e41297]

In terms of safety, none of the patients who received tixagevimab plus cilgavimab had adverse events.

“Haemodialysis patients are deemed to be immunosuppressed and may not be able to mount an adequate response to vaccination against the SARS-CoV-2 virus. Due to the higher morbidity and mortality in this vulnerable group, pre-exposure prophylaxis with monoclonal antibodies was introduced as an additional measure for protection in selected community-based haemodialysis patients in Singapore,” the investigators said.

The findings of the present study, they added, suggest that the antibody combination affords “high-level safety for such patients who are vulnerable to severe or life-threatening infections.”

COVID-19 vax status not a factor

In the study, a total of 200 haemodialysis patients (mean age 62.9 years, 68 percent men) received tixagevimab plus cilgavimab, administered intramuscularly at ventro-gluteal and dorso-gluteal sites, as two separate consecutive injections. All recipients had received COVID-19 vaccinations prior to the antibody combination, with a range of one to five doses. A total of 198 patients (99 percent) completed two doses, while 189 (95 percent) completed three doses.

Fourteen patients (7 percent) contracted COVID-19 infection between 4 and 106 days after tixagevimab plus cilgavimab administration. Of these, 10 (71 percent) had mild symptoms while four (29 percent) had moderate symptoms requiring hospitalization, including two who had significant cardiovascular comorbidity and were admitted to the intensive care unit. The average length of hospital stay was 8.75 days. None of the patients died.

In comparison, in a historic control cohort of 4,425 patients from the same dialysis centres, 2,534 patients acquired COVID-19 infection. A total of 1,077 patients (42.5 percent) required hospitalization, of which 64 (2.5 percent) died due to the infection.

Of note, 98.6 percent of patients in the historic control cohort had completed one dose of COVID-19 vaccination and 97.9 percent had completed two doses. There was no significant difference in the number of patients with fully vaccinated status (defined as two vaccination doses) between the group that received tixagevimab plus cilgavimab and the historic control (p<0.167).

“Therefore, the higher COVID-19 infection, hospitalization, and mortality rate cannot be accounted for by any significant difference in the vaccination status,” the investigators stated.

Risk reduction in a vulnerable population

According to the investigators, the study has important implications, such that the data may be used to inform public health policy regarding the effective use of human monoclonal antibodies to counter the morbidity and mortality related to COVID-19. [JAMA 2022;327:384-385]

“Public perception of adopting such measures beyond vaccination can be positively influenced by real-world experience sharing of such programs. It also makes an evidence-based case to further the research and development of such therapeutics to effectively protect high-risk populations in the future with the emergence of SARS-CoV-2 variant strains,” they pointed out. [Cureus 2022;14:e32684; Front Immunol 2023;14:1139980; Viruses 2022;15:118]

Nevertheless, the fact that the study involved a real-world experience of a clinical audit and lacked randomization and blinding may have contributed to a degree of bias in case selection, the investigators acknowledged. Results were also limited to community-based haemodialysis centres under study in Singapore and may not be generalized to all settings. 

The investigators called for large prospective studies to establish a relationship between tixagevimab plus cilgavimab for pre-exposure prophylaxis and the morbidity or mortality outcomes of COVID-19 infection.