Manuela Di Fusco’s research while affiliated with Pfizer and other places

Background Long COVID includes new or persisting symptoms/signs/conditions impacting >1 organ/system following acute infection. The clinical presentation varies across patients and estimates of burden depend on the definition. Evidence on effectiveness of BNT162b2 BA.4/5 bivalent COVID-19 Vaccine (BNT162b2 bivalent) against long COVID remains scarce. This study assessed vaccine effectiveness (VE) of BNT162b2 bivalent for preventing long COVID symptoms among older adults.Table 1.Long COVID prevalence and vaccine effectiveness of BNT162b2 a against long COVID symptoms among older adults ≥50 years old Methods Symptomatic US adults ≥50 years old testing positive for SARS-CoV-2 via RT-PCR and rapid antigen at CVS Health were recruited between 03/02-05/18/2023 (CT.gov: NCT05160636). Participants reported presence or absence of each of 30 long COVID symptoms at 4 weeks, months 3 and 6 after testing. The CDC long COVID definition (new-onset or symptoms persisting ≥4 weeks after acute infection) was operationalized as the presence of ≥2 or ≥3 new or persistent symptoms consistent with long COVID from week 4 to month 6. The odds ratio (OR) of long COVID was computed for those who had received vs. had not received the BNT162b2 bivalent dose (vaccinated versus unvaccinated) before infection using mixed-effects logistic models, adjusting for multiple covariates. Absolute VE versus unvaccinated was calculated as (1‒OR)x100. Results Of 277 older adults aged ≥50 years recruited in the study, 172 received BNT162b2 and 105 did not. Mean time since last bivalent dose was 168 days. All study participants reported ≥1 long COVID symptoms through month 6. The prevalence of ≥2 and ≥3 long COVID symptoms at month 6 was 33.1% and 23%, respectively. Those who received the BNT162b2 bivalent dose were less likely than those who didn’t to report ≥2 symptoms (27.0% vs 44.4%; adjusted OR 0.50, 95% CI 0.28-0.88) and ≥3 symptoms (16.5% vs 34.9%; adjusted OR 0.43, 95% CI 0.24-0.79) from 4 weeks to 6 months since testing positive. Absolute VE ranged 50-57% (Table 1). Conclusion Despite high levels of immunity, especially among older adults, the post-pandemic burden of long COVID remains high, but is significantly lower for those vaccinated. Between 4 weeks and 6 months after testing positive, older adults vaccinated with BNT162b2 bivalent had approximately half the odds of long COVID than those unvaccinated. Disclosures Manuela Di Fusco, PhD, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) Abby Rudolph, PhD, Pfizer Inc: Employer|Pfizer Inc: Stocks/Bonds (Public Company) Laura L. Lupton, MD, MHSA, CVS Health: Employee|CVS Health: Stocks/Bonds (Public Company) Joseph C. Cappelleri, PhD, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) Alon Yehoshua, PharmD, MS, Pfizer Inc: Employer|Pfizer Inc: Stocks/Bonds (Public Company) Laura A. Puzniak, PhD. MPH, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) Santiago M.C. Lopez, MD, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) Xiaowu Sun, PhD, CVS Health: Employee|CVS Health: Stocks/Bonds (Public Company)

Background Fatigue is one of the most common symptoms experienced by patients with COVID-19, potentially interfering with daily activities. This study assessed the 6-month trajectory of fatigue from time of testing across age and BNT162b2 BA.4/5 bivalent COVID-19 Vaccine strata.Figure 1.Prevalence of symptoms of fatigue across groups defined by age and BNT162b2 COVID-19 Vaccination statusa) Overall cohort by BNT162b2 vaccination status Methods Symptomatic US adults testing positive for SARS-CoV-2 at CVS Health were recruited between 03/02-05/18/2023 (CT.gov: NCT05160636). Study participants self-reported symptoms of fatigue via an online survey during the acute (testing day, Week 1, Week 2) and long-term phase (Week 4, Month 3 and 6 after testing). The prevalence of fatigue was evaluated at each time point in the overall cohort and across groups defined by vaccination status and age (older adults: ≥50; younger adults: < 50). Between-group differences were tested by using chi-square statistics. b) Overall cohort by age Results The analyses included 643 study participants: 49% (316) vaccinated with BNT162b2 bivalent and 51% (327) unvaccinated; 43.1% (277) ≥50 and 56.9% (366) < 50 years old. A total of 424 (65.9%) participants self-reported symptoms of fatigue at time of testing. Their mean age was 46.5 years, 71.2% were female, 25.9% had ≥1 comorbidity, 43.2% had prior infection. The presence of fatigue was higher during the acute phase and remained prevalent during the long-term follow-up: 50.9% at Week 1, 41.1% at Week 2, 24.4% at Week 4, 19.6% at Month 3, and 18.5% at Month 6 (Figure 1a). While older and younger adults had similar prevalence of fatigue during the acute phase, at Week 4 the younger adults reported higher prevalence (28.7% vs 18.2%, p=0.007) (Figure 1b). In the overall cohort, and relatively consistently across age groups, those vaccinated with BNT162b2 reported significantly (p< 0.005) lower prevalence of fatigue at Week 4, Month 3 and 6 (Figures 1a, 1c, 1d). c) Younger adults (<50) Conclusion This study found that fatigue is a highly prevalent symptom affecting two-thirds of symptomatic adults at time of testing. While prevalence declined over time, fatigue symptoms persisted beyond the acute phase, with 1 in 5 still affected at Month 6. Compared with those vaccinated with BNT162b2 bivalent, the prevalence of fatigue was higher among unvaccinated throughout the follow-up, reaffirming the value of being up-to-date with COVID-19 vaccination. d) Older adults (≥50) Disclosures Manuela Di Fusco, PhD, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) Alexandra Berk, PhD, CVS Health: Employee|CVS Health: Stocks/Bonds (Public Company) Kristen E. Allen, MPH, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) Thomas M. Porter, MPH, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) Mary B. Alvarez, PharmD, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) Joseph C. Cappelleri, PhD, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) Mary M. Moran, MD, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) Xiaowu Sun, PhD, CVS Health: Employee|CVS Health: Stocks/Bonds (Public Company)

Background To assess the public health impact and economic value of an additional dose of BNT162b2 XBB.1.5-adapted COVID-19 vaccine 6 months after initial dose for those aged ≥65 years, compared to a single dose in the United States.Table 1.Clinical and Economic Outcomes of 2-dose vs 1-dose Strategy in the Population Aged ≥65 Years.LY = life year; QALY = quality adjusted life year; ICER = incremental cost effectiveness ratio Methods A combined Markov and decision tree model was used to estimate the public health impact of those aged ≥65 years receiving an additional BNT162b2 XBB.1.5-adapted dose over for a one-year time horizon (Oct 2023-Sept 2024). Age-stratified (65-74, 75+) annual attack, hospitalization, and vaccine coverage rates were informed by public health national surveillance data. Other age-stratified clinical, cost, and vaccine effectiveness parameters were informed by publications. Parameter uncertainty was examined through scenario and sensitivity analyses. Conservatively, indirect effects (e.g. reduced transmission) and broad societal benefits were not considered. Results For individuals aged 65 years and older, the model demonstrated that compared to a single dose, an additional dose of the BNT162b2 XBB.1.5-adapted COVID-19 Vaccine resulted in 338,148 fewer symptomatic cases, 19,947 fewer hospitalizations, and 591 fewer deaths. Cost of additional vaccinations were offset by costs averted (e.g., Long COVID (∼$1.3B), inpatient (∼$384M), indirect (∼$280M), and outpatient (∼$252M) costs), leading to a total cost savings of ∼$270.5M. The two-dose strategy for older adults improved health outcomes and lowered costs resulting in a dominant ICER (Table 1). The additional dose was predicted to be a budget-efficient solution for payers. Results were most sensitive to variation in the symptomatic rate of infection and the hospitalization rate. Conclusion An additional dose of BNT162b2 XBB.1.5-adapted COVID-19 vaccination for adults aged 65 years and older in the US may generate notable reductions in symptomatic cases, hospitalizations, and deaths and result in cost savings. The results demonstrate that administering an additional COVID-19 vaccine dose to older adults in the US should be an important public health goal, supporting current ACIP and CDC recommendations. Disclosures Alon Yehoshua, PharmD, MS, Pfizer Inc: Employer|Pfizer Inc: Stocks/Bonds (Public Company) Benjamin Yarnoff, PhD, Pfizer Inc: Grant/Research Support Manuela Di Fusco, PhD, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) Santiago M.C. Lopez, MD, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) Elizabeth A. Thoburn, MPH, Pfizer Inc: Employer|Pfizer Inc: Stocks/Bonds (Public Company) Abby Rudolph, PhD, Pfizer Inc: Employer|Pfizer Inc: Stocks/Bonds (Public Company) Kinga Marczell, PhD, Pfizer Inc: Grant/Research Support

Objectives To assess the public health and economic impact of vaccination with the Pfizer-BioNTech COVID-19 vaccine, KP.2, in 2024/2025 in the United States. Methods A combined cohort Markov-decision tree model was used to estimate the cost-effectiveness and budget impact of vaccination versus no vaccination in adults aged ≥18 years. The adult population was further stratified into 18-64 years and ≥65 years age groups. Public health surveillance data informed the annual proportion of individuals infected with and vaccinated against SARS-CoV-2 and the proportion of those infected who were hospitalized, stratified by age. Other age-stratified clinical, cost, and vaccine effectiveness parameters were informed by literature. The budget impact analysis was based on a hypothetical 1-million-member plan and used a payer perspective. Parameter uncertainty was tested in sensitivity analyses. Results Without vaccination, the model projected 21.4 million new symptomatic cases, 15,793 deaths, 629,098 hospitalizations, $115.5 billion in total costs, and 1 million QALYs lost among adults aged ≥18 years, with the greatest health burden observed among older adults aged ≥65 years (72$513 million, 9,173 LYs gained, 56,482 QALYs gained, and a dominant ICER. In the budget impact analysis, vaccination was estimated to result in total incremental cost savings for the population aged ≥65 years and a modest budget increase for the population aged 18–64 years. Conclusions Vaccination with the Pfizer BioNTech COVID-19 vaccine, KP.2, is a cost-effective measure from the societal perspective at a willingness-to-pay threshold of $50,000 that could reduce the health and economic burden of COVID-19.

Background: Long COVID remains a significant public health concern. This study investigated risk factors for long COVID in outpatient settings. Methods: A US-based prospective survey study (clinicaltrials.gov NCT05160636) was conducted in 2022 and replicated in 2023. Symptomatic adults testing positive for SARS-CoV-2 at CVS Pharmacies were recruited. CDC-based long COVID symptoms were collected at Week 4, Month 3, and Month 6 following SARS-CoV-2 testing. Logistic regression was used to develop a predictive model for long COVID using data from the 2022 cohort. The model was validated with data from the 2023 cohort. Model performance was evaluated with c-statistics. Results: Patients characteristics were generally similar between the 2022 (N = 328) and 2023 (N = 505) cohorts. The prevalence of long COVID defined as ≥3 symptoms at Month 6 was 35.0% and 18.2%, respectively. The risk factors associated with long COVID were older age, female sex, lack of up-to-date vaccination, number of acute symptoms on the day of SARS-CoV-2 testing, increase in symptoms at Week 1, underlying comorbidities and asthma/chronic lung disease. The c-statistic was 0.79, denoting good predictive power. Conclusions: A predictive model for long COVID was developed for an outpatient setting. This research could help differentiate at-risk groups and target interventions.