The smallpox antiviral tecovirimat has recently been purchased by the U.S. Strategic National Stockpile. Given significant uncertainty regarding both the contagiousness of smallpox in a contemporary outbreak and the efficiency of a mass vaccination campaign, vaccine prophylaxis alone may be unable to control a smallpox outbreak following a bioterror attack. Here, we present the results of a compartmental epidemiological model that identifies conditions under which tecovirimat is required to curtail the epidemic by exploring how the interaction between contagiousness and prophylaxis coverage of the affected population affects the ability of the public health response to control a large-scale smallpox outbreak. Each parameter value in the model is based on published empirical data. We describe contagiousness parametrically using a novel method of distributing an assumed R-value over the disease course based on the relative rates of daily viral shedding from human and animal studies of cognate orthopoxvirus infections. Our results suggest that vaccination prophylaxis is sufficient to control the outbreak when caused either by a minimally contagious virus or when a very high percentage of the population receives prophylaxis. As vaccination coverage of the affected population decreases below 70%, vaccine prophylaxis alone is progressively less capable of controlling outbreaks, even those caused by a less contagious virus (R0 less than 4). In these scenarios, tecovirimat treatment is required to control the outbreak (total number of cases under an order of magnitude more than the number of initial infections). The first study to determine the relative importance of smallpox prophylaxis and treatment under a range of highly uncertain epidemiological parameters, this work provides public health decision-makers with an evidence-based guide for responding to a large-scale smallpox outbreak.
1539 Background: Oncologists face a challenge in advising patients on the infection risk associated with antineoplastic and immunomodulating medications, as the extent of risk posed by each medication is not well understood. The rapid administration of COVID-19 immunizations across the population provides an opportunity to assess the influence of immunosuppressing medications on infection outcomes post-vaccination. This study evaluated the effect of antineoplastic and immunomodulating medications as classified by the World Health Organization Anatomical Therapeutic Chemical Classification System (WHO ATC) on post-vaccination risk of COVID-19 infection and antibody response to multiple SARS-CoV-2 epitopes using serial serologic assessments. Methods: At a large, tertiary healthcare system in San Diego, we conducted an observational cohort study from December 11, 2020, to September 22, 2022, comparing vaccinated adult patients taking WHO ATC-classified immunosuppressing medications (“immunosuppressed” group) with matched control patients not prescribed these medications (“immunocompetent” group) for the outcome of PCR+ COVID-19 infection. A subset of immunosuppressed and immunocompetent individuals was consented to provide serial assessments of antibody response to multiple SARS-CoV-2 epitopes using the Genalyte serologic platform. Results: 12,709 vaccinated immunosuppressed patients and 197,151 immunocompetent controls were identified for matched analysis. Receiving an immunosuppressing medication conferred increased risk of COVID-19 infection post-immunization (HR: 1.5, 95% CI: 1.38 – 1.63, p < 0.0001). Among immunosuppressing medications, PD1/PD-L1 inhibiting monoclonal antibodies and calcineurin inhibitors were associated with increased risk of COVID-19 infection (HR: 2.33, 95% CI: 1.35 – 4.04, p = 0.0038; HR 2.72, 95% CI: 1.78 – 4.16, respectively). Receiving three and four COVID-19 immunizations reduced this risk, except in patients taking calcineurin inhibitors. Among 87 consented participants, 218 samples from multiple timepoints revealed a decreased antibody response to both spike S1 and S2 subunits following third and fourth immunization. Despite decreased seroconversion, this study found medications like CD20 inhibiting monoclonal antibodies and folic acid analogs did not increase the post-immunization risk of COVID-19. Conclusions: These results help elucidate the relationship between antineoplastic and immunomodulating medications and COVID-19 immunization outcomes. In our patients, seroconversion efficacy did not always correspond to post-immunization infection, consistent with COVID-19 disease risk being multifactorial. The findings of this study inform oncologists’ shared decision-making process in advising patients of the risk of infection associated with immunomodulating medications and the potential impact on their vaccination response.
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