Patrick C. Burke’s research while affiliated with Cleveland Clinic and other places

Background. The purpose of this study was to evaluate the effectiveness of the influenza vaccine during the 2024-2025 viral respiratory season. Methods. Employees of Cleveland Clinic in employment in Ohio on October 1, 2024, were included. The cumulative incidence of influenza among those in the vaccinated and unvaccinated states was compared over the following weeks. Protection provided by vaccination (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression. The analysis was adjusted for age, sex, job type, employment location, and eagerness to get vaccinated. Results. Among 53321 employees, 43771 (82.1%) had received the influenza vaccine by the end of the study. Influenza occurred in 324 (0.6%) during the study. In an analysis adjusted for age, sex, job type, employment location, and eagerness to get vaccinated, the risk of influenza was not significantly different between the vaccinated and unvaccinated states (HR, 1.09; 95% C.I., .76 - 1.55; P = 0.65), yielding a calculated vaccine effectiveness of -8.5% (95% C.I. -54.5 - 23.9%). Conclusions. This study has been unable to find that the influenza vaccine given to working-aged adults has provided protection overall against influenza during the 2024-2025 respiratory viral season thus far.

Background The purpose of this study was to evaluate whether the 2023-2024 formulation of the COVID-19 mRNA vaccine protects against COVID-19 caused by the JN.1 lineage of SARS-CoV-2. Methods Employees of Cleveland Clinic in employment when the JN.1 lineage of SARS-CoV2 became the dominant circulating strain, were included. Cumulative incidence of COVID-19 was examined prospectively. Protection provided by vaccination (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression. The analysis was adjusted for the propensity to get tested, age, sex, pandemic phase when the last prior COVID-19 episode occurred, and the number of prior vaccine doses. Results Among 47561 employees, COVID-19 occurred in 838 (1.8%) during the 16-week study period. In multivariable analysis, the 2023-2024 formula vaccinated state was associated with a significantly lower risk of COVID-19 while the JN.1 lineage was the dominant circulating strain (hazard ratio [HR], .77; 95% confidence interval [C.I.], .62-.94; P = .01), yielding an estimated vaccine effectiveness of 23% (95% C.I., 6%-38%). Compared to 0 or 1 prior vaccine doses, risk of COVID-19 was incrementally higher with 2 prior doses (HR, .1.46; 95% C.I., 1.12-1.90; P < .005), 3 prior doses (HR, 1.95; 95% C.I., 1.51-2.52; P < .001), and more than 3 prior doses (HR, 2.51; 95% C.I., 1.91-3.31; P < .001). Conclusions The 2023-2024 formula COVID-19 vaccine given to working-aged adults afforded a low level of protection against the JN.1 lineage of SARS-CoV-2, but a higher number of prior vaccine doses was associated with a higher risk of COVID-19. Summary Among 47561 working-aged Cleveland Clinic employees, the 2023-2024 formula COVID-19 vaccine was 23% effective against the JN.1 lineage of SARS-CoV-2, but a higher number of prior COVID-19 vaccine doses was associated with a higher risk of COVID-19.

Background The purpose of this study was to evaluate whether the 2023-2024 formulation of the COVID-19 mRNA vaccine protects against COVID-19. Methods Employees of Cleveland Clinic in employment when the 2023-2024 formulation of the COVID-19 mRNA vaccine became available to employees, were included. Cumulative incidence of COVID-19 over the following 17 weeks was examined prospectively. Protection provided by vaccination (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression, with time-dependent coefficients used to separate effects before and after the JN.1 lineage became dominant. The analysis was adjusted for the propensity to get tested, age, sex, pandemic phase when the last prior COVID-19 episode occurred, and the number of prior vaccine doses. Results Among 48210 employees, COVID-19 occurred in 2462 (5.1%) during the 17 weeks of observation. In multivariable analysis, the 2023-2024 formula vaccinated state was associated with a significantly lower risk of COVID-19 before the JN.1 lineage became dominant (HR, .58; 95% C.I., .49-.68, p-value < .001), and lower risk but one that did not reach statistical significance after (HR, .81; 95% C.I., .65-1.01, p-value 0.06). Estimated vaccine effectiveness (VE) was 42% (95% C.I., 32%-51%) before the JN.1 lineage became dominant, and 19% (C.I., -1%-35%) after. Risk of COVID-19 was lower among those previously infected with an XBB or more recent lineage, and increased with the number of vaccine doses previously received. Conclusions The 2023-2024 formula COVID-19 vaccine given to working-aged adults afforded modest protection overall against COVID-19 before the JN.1 lineage became dominant, and less protection after.

Background The CDC recently defined being “up-to-date” on COVID-19 vaccination as having received at least one dose of a COVID-19 bivalent vaccine. The purpose of this study was to compare the risk of COVID-19 among those “up-to-date” and “not up-to-date”. Methods Employees of Cleveland Clinic in Ohio, USA, in employment when the COVID-19 bivalent vaccine first became available, and still employed when the XBB lineages became dominant, were included. Cumulative incidence of COVID-19 since the XBB lineages became dominant was compared across the”up-to-date” and “not up-to-date” states, by treating COVID-19 bivalent vaccination as a time-dependent covariate whose value changed on receipt of the vaccine. Risk of COVID-19 by vaccination status was also evaluated using multivariable Cox proportional hazards regression adjusting for propensity to get tested for COVID-19, age, sex, most recent prior SARS-CoV-2 infection, and number of prior vaccine doses. Results COVID-19 occurred in 1475 (3%) of 48 344 employees during the 100-day study period. The cumulative incidence of COVID-19 was lower in the “not up-to-date” than the “up-to-date” state. On multivariable analysis, being “up-to-date” was not associated with lower risk of COVID-19 (HR, 1.05; 95% C.I., 0.88–1.25; P-value, 0.58). Results were very similar when those 65 years and older were only considered “up-to-date” after 2 doses of the bivalent vaccine. Conclusions Since the XBB lineages became dominant, adults “up-to-date” on COVID-19 vaccination by the CDC definition do not have a lower risk of COVID-19 than those “not up-to-date”, bringing into question the value of this risk classification definition.

Background. The CDC recently defined being 'up-to-date' on COVID-19 vaccination as having received at least one dose of a COVID-19 bivalent vaccine. The purpose of this study was to compare the risk of COVID-19 among those 'up-to-date' and 'not up-to-date' on COVID-19 vaccination. Methods. Employees of Cleveland Clinic in employment when the bivalent COVID-19 vaccine first became available, and still employed when the XBB lineages became dominant, were included. Cumulative incidence of COVID-19 since the XBB lineages became dominant was compared across the 'up-to-date' and 'not up-to-date' states, by treating COVID-19 bivalent vaccination as a time-dependent covariate whose value changed on receipt of the vaccine. Risk of COVID-19 by vaccination status was also compared using multivariable Cox proportional hazards regression adjusting for propensity to get tested for COVID-19, age, sex, and phase of most recent prior SARS-CoV-2 infection. Results. COVID-19 occurred in 1475 (3%) of 48344 employees during the 100-day study period. The cumulative incidence of COVID-19 was lower in the 'not up-to-date' than in the 'up-to-date' state. On multivariable analysis, not being 'up-to-date' with COVID-19 vaccination was associated with lower risk of COVID-19 (HR, 0.77; 95% C.I., 0.69-0.86; P-value, <0.001). Results were very similar when those 65 years and older were only considered 'up-to-date' after receiving 2 doses of the bivalent vaccine. Conclusions. Since the XBB lineages became dominant, adults 'not up-to-date' by the CDC definition have a lower risk of COVID-19 than those 'up-to-date' on COVID-19 vaccination, bringing into question the value of this risk classification definition.

Background The purpose of this study was to evaluate whether a bivalent COVID-19 vaccine protects against COVID-19. Methods Employees of Cleveland Clinic in employment when the bivalent COVID-19 vaccine first became available, were included. Cumulative incidence of COVID-19 over the following 26 weeks was examined. Protection provided by vaccination (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression, with change in dominant circulating lineages over time accounted for by time-dependent coefficients. The analysis was adjusted for the pandemic phase when the last prior COVID-19 episode occurred, and the number of prior vaccine doses. Results Among 51017 employees, COVID-19 occurred in 4424 (8.7%) during the study. In multivariable analysis, the bivalent vaccinated state was associated with lower risk of COVID-19 during the BA.4/5 dominant (HR, .71; 95% C.I., .63-.79) and the BQ dominant (HR, .80; 95% C.I., .69-.94) phases, but decreased risk was not found during the XBB dominant phase (HR, .96; 95% C.I., .82-.1.12). Estimated vaccine effectiveness (VE) was 29% (95% C.I., 21%-37%), 20% (95% C.I., 6%-31%), and 4% (95% C.I., -12%-18%), during the BA.4/5, BQ, and XBB dominant phases, respectively. Risk of COVID-19 also increased with time since most recent prior COVID-19 episode and with the number of vaccine doses previously received. Conclusions The bivalent COVID-19 vaccine given to working-aged adults afforded modest protection overall against COVID-19 while the BA.4/5 lineages were the dominant circulating strains, afforded less protection when the BQ lineages were dominant, and effectiveness was not demonstrated when the XBB lineages were dominant.

Background. The purpose of this study was to evaluate whether a bivalent COVID-19 vaccine protects against COVID-19. Methods. Employees of Cleveland Clinic in employment on the day the bivalent COVID-19 vaccine first became available to employees, were included. The cumulative incidence of COVID-19 was examined over the following weeks. Protection provided by vaccination (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression. The analysis was adjusted for the pandemic phase when the last prior COVID-19 episode occurred, and the number of prior vaccine doses received. Results. Among 51011 employees, 20689 (41%) had had a previous documented episode of COVID-19, and 42064 (83%) had received at least two doses of a COVID-19 vaccine. COVID-19 occurred in 2452 (5%) during the study. Risk of COVID-19 increased with time since the most recent prior COVID-19 episode and with the number of vaccine doses previously received. In multivariable analysis, the bivalent vaccinated state was independently associated with lower risk of COVID-19 (HR, .70; 95% C.I., .61-.80), leading to an estimated vaccine effectiveness (VE) of 30% (95% CI, 20-39%). Compared to last exposure to SARS-CoV-2 within 90 days, last exposure 6-9 months previously was associated with twice the risk of COVID-19, and last exposure 9-12 months previously with 3.5 times the risk. Conclusions. The bivalent COVID-19 vaccine given to working-aged adults afforded modest protection overall against COVID-19, while the virus strains dominant in the community were those represented in the vaccine.

Background The purpose of this study was to evaluate whether boosting previously infected or vaccinated healthcare personnel with a vaccine developed for an earlier variant of SARS-CoV-2 protects against the Omicron variant. Methods Employees of Cleveland Clinic previously infected with or vaccinated against COVID-19, and working in Ohio the day the Omicron variant was declared a variant of concern, were included. The cumulative incidence of COVID-19 was examined over two months during an Omicron variant surge. Protection provided by boosting (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression. Analyses were adjusted for time since proximate SARS-CoV-2 exposure as a time-dependent covariate. Results Among 39 766 employees, 8037 (20%) previously infected and the remaining previously vaccinated, COVID-19 occurred in 6230 (16%) during the study. Risk of COVID-19 increased with time since proximate SARS-CoV-2 exposure, and boosting protected those >6 months since prior infection or vaccination. In multivariable analysis, boosting was independently associated with lower risk of COVID-19 among those vaccinated but not previously infected (HR, .43; 95% CI, .41-.46) as well as those previously infected (HR, .66; 95% CI, .58-.76). Among those previously infected, receiving 2 compared to 1 dose of vaccine was associated with higher risk of COVID-19 (HR, 1.54; 95% CI, 1.21-1.97). Conclusions Administering a COVID-19 vaccine not designed for the Omicron variant, >6 months after prior infection or vaccination, protects against Omicron variant infection in those previously infected or vaccinated. There is no evidence of an advantage to administering more than 1 dose of vaccine to previously infected persons.

Background The purpose of this study was to evaluate whether boosting healthcare personnel, already reasonably protected by prior infection or vaccination, with a vaccine developed for an earlier variant of COVID-19 protects against the Omicron variant. Methods Employees of Cleveland Clinic who were previously infected with or vaccinated against COVID-19, and were working in Ohio the day the Omicron variant was declared a variant of concern, were included. The cumulative incidence of COVID-19 was examined over two months during an Omicron variant surge. Protection provided by boosting (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression. Analyses were adjusted for time since proximate overt immunologic challenge (POIC) as a time-dependent covariate. Results Among 39 766 employees, 8037 (20%) previously infected and the remaining previously vaccinated, COVID-19 occurred in 6230 (16%) during the study. Risk of COVID-19 increased with time since POIC. In multivariable analysis, boosting was independently associated with lower risk of COVID-19 among those with vaccine-induced immunity (HR, .43; 95% CI, .41-.46) as well as those with natural immunity (HR, .66; 95% CI, .58-.76). Among those with natural immunity, receiving 2 compared to 1 dose of vaccine was associated with higher risk of COVID-19 (HR, 1.54; 95% CI, 1.21-1.97). Conclusions Administering a COVID-19 vaccine not designed for the Omicron variant, 6 months or more after prior infection or vaccination, protects against Omicron variant infection in both previously infected and previously vaccinated individuals. There is no evidence of an advantage to administering more than 1 dose of vaccine to previously infected persons. Summary Among 39 766 Cleveland Clinic employees already protected by prior infection or vaccination, vaccine boosting after 6 months was associated with significantly lower risk of COVID-19. After COVID-19 infection, there was no advantage to more than one dose of vaccine.

Background The purpose of this study was to evaluate the necessity of COVID-19 vaccination in persons with prior COVID-19. Methods Employees of Cleveland Clinic working in Ohio on Dec 16, 2020, the day COVID-19 vaccination was started, were included. Anyone who tested positive for COVID-19 at least once before the study start date was considered previously infected. One was considered vaccinated 14 days after receiving the second dose of a COVID-19 mRNA vaccine. The cumulative incidence of COVID-19, symptomatic COVID-19, and hospitalizations for COVID-19, were examined over the next year. Results Among 52238 employees, 4718 (9%) were previously infected, and 36922 (71%) were vaccinated by the study’s end. Cumulative incidence of COVID-19 was substantially higher throughout for those previously uninfected who remained unvaccinated than for all other groups, lower for the vaccinated than unvaccinated, and lower for those previously infected than those not. Incidence of COVID-19 increased dramatically in all groups after the Omicron variant emerged. In multivariable Cox proportional hazards regression, both prior COVID-19 and vaccination were independently associated with significantly lower risk of COVID-19. Among previously infected subjects, a lower risk of COVID-19 overall was not demonstrated, but vaccination was associated with a significantly lower risk of symptomatic COVID-19 in both the pre-Omicron (HR 0.60, 95% CI 0.40–0.90) and Omicron (HR 0.36, 95% CI 0.23–0.57) phases. Conclusions Both previous infection and vaccination provide substantial protection against COVID-19. Vaccination of previously infected individuals does not provide additional protection against COVID-19 for several months, but after that provides significant protection at least against symptomatic COVID-19.