Casirivimab/imdevimab treatment for outpatient COVID-19 during a SARS-CoV-2 B1.617.2 (Delta) surge at a community hospital

Methods

Results

Overall, 743 patients were abstracted for inclusion in the study. Of the patients included in the final analysis, patients had a median age of 57.0 (43.0–66.0) years, and 416 (56.0%) were female (Table 1). Those in the vaccinated group were older (60.0 vs. 55.0 years; p<0.001) and more likely to have chronic kidney disease (7.0%, n=22 vs. 3.4%, n=20; p=0.05), a history of immunosuppression (7.0%, n=11 vs. 1.4%, n=8; p<0.001), hypertension (39.9%, n=63 vs. 28.5%, n=167; p=0.006) and diabetes (18.4%, n=29 vs. 11.3%, n=66; p=0.02) as compared to their unvaccinated counterparts. Pulse rate was noted to be lower in those who were vaccinated as compared to those unvaccinated at the time of medication administration (77 vs. 80 beats per minute; p=0.01). No other differences in intake vital signs at the time of medication administration was observed between those who were vaccinated and unvaccinated (Table 2).

Following administration of casirivimab/imdevimab, 105 (14.1%) patients represented to either the ED or urgent care following infusion (Table 3). Vaccinated patients were more likely to represent after infusion as compared to those who were unvaccinated (32 vs. 73 patients; p=0.01). No difference was noted for the length of time since casirivimab/imdevimab administration and representation for further care between the two groups (3 vs. 3 days; p=0.92). Of those who represented for further care after casirivimab/imdevimab administration, 17 patients were admitted to the hospital with no difference between those who vaccinated and unvaccinated (6 vs. 11 patients; p=0.15). No difference was noted in the length of hospitalization between vaccinated and unvaccinated patients after receiving casirivimab/imdevimab (2 vs. 5 days; p=0.22).

Discussion

Overall, the rate of hospitalization due to severe COVID-19 after receiving casirivimab/imdevimab at a community hospital during the Delta variant surge was low. This finding was similar to previous literature describing hospitalization rates when other variants were predominant in the community [10], [11], [12], [13], [14]. Unlike several other MABs utilized previously, casirivimab/imdevimab is a dual MAB cocktail that targets nonoverlapping epitopes on the spike protein [7]. Due to this, casirivimab/imdevimab was found to be able to maintain its treatment effect between circulating variants seen within the different surges [15]. The current results further correlate with experimental data that showed that casirivimab/imdevimab retained efficacy against SARS-CoV-2 B.1.617.2 and was a viable treatment option for those at risk of disease progression [9].

Once becoming ill with COVID-19, the unvaccinated have been shown to have worse outcomes than those who were fully vaccinated against COVID-19 [16]. In the current study, the majority of those seeking MAB therapy for the treatment of COVID-19 were unvaccinated. This data is similar to prior studies from other locations within the United States in which those who were unvaccinated were more likely to receive monoclonal therapy as compared to those who were vaccinated [11, 12]. This data not only further emphasizes the need for vaccination as a primary means to reduce transmission and minimize the burden of disease on healthcare facilities but also shows the willingness of those who are unvaccinated to receive treatment with MABs.

Although data have shown that those who are fully vaccinated are less likely to require ED care or hospitalization for breakthrough COVID-19 infection, the data from the current study showed that those who were fully vaccinated were more likely to represent unexpectedly to the ED for further care following casirivimab/imdevimab infusion as compared to those who were unvaccinated [17]. Although it is difficult to ascertain the exact mechanism behind these findings, it is postulated that it could be related to the differences seen between the groups in the study. Those who were vaccinated were more likely to be older and have underlying comorbidities such as immunosuppression, chronic kidney disease, hypertension, and diabetes mellitus. Previous data have shown that those with breakthrough COVID-19 were more likely to be at advanced age and have multiple comorbidities [11]. Data have also shown that the viral load in these individuals can be as high as those who are unvaccinated [18, 19]. The possibility of a high viral load coupled with multiple underlying health issues may have exacerbated symptoms and caused a large number of vaccinated individuals to seek further care.

Another reason for the difference in representation found between those who were vaccinated and unvaccinated could be related to the behavioral differences, willingness to accept medical advice, and levels of medical mistrust between the two groups [20]. Medical mistrust has been defined as “distrust of healthcare providers, the healthcare system, medical treatments, and the government as a steward of public health” and has been conceptualized as a form of coping during a time of threat or uncertainty [21, 22]. 0Although those who were unvaccinated showed a willingness to accept treatment both in the current and previous studies, it could be postulated that patients with MAB treatment failure may have decided to not follow up with the institution that provided the treatment and sought care elsewhere.

Although those who were vaccinated were more likely to represent for unexpected care, no difference in hospitalization rates or length of stay was noted between those who were vaccinated and unvaccinated 28 days post-casirivimab/post-imdevimab infusion. This suggests that in the community setting, post-infection monoclonal therapies may prove effective for patients independent of their previous health decisions regarding COVID-19. Based upon these data, the authors suggest continued administration of monoclonal therapies to patients meeting EUA qualifiers irrespective of their previous vaccination status, and that vaccination status should not be utilized as a rule out for monoclonal therapy. Active surveillance of the variants of interest/concern is also needed to monitor the efficacy of each monoclonal therapy over time in order to minimize representations and hospitalizations of those receiving therapy.

From an osteopathic standpoint, this article highlights the need to assess and treat the whole person regardless of prior healthcare choices. Many individuals have shown vaccine hesitancy due to either mistrust of healthcare professionals, short-/long-term safety of the vaccine, religious reasons, and sociopolitical views. Given the fact that many individuals who sought care were unvaccinated, healthcare providers should not judge individuals based upon a subset of life choices and instead treat individuals with compassion and empathy based upon established guidelines and evidence-based medicine.

Conclusions

Although the rate of representation and hospitalization was low after receiving casirivimab/imdevimab for the outpatient treatment of mild-to-moderate COVID-19, those who were vaccinated were more likely to represent to either an ED or urgent care for unexpected care following medication administration. This is most likely due to the underlying risk factors associated with those choosing to receive a vaccine and not necessarily due to a treatment effect of the medication being administered.