Pragmatic Assessment of Influenza Vaccine Effectiveness in the Department of Defense (PAIVED): Updates from Year 4 of a Multi-site Trial

Background. The effectiveness of the influenza vaccine is varies with circulating strain concordance and timing of influenza spread in a community. The Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED) study is a multiyear, randomized clinical trial of three FDA-licensed vaccine types (egg-based, cellbased, and recombinant), designed to determine which influenza vaccine platform is most effective among adults in a military setting. Methods. Participants in the fourth year of PAIVED (2021-22 influenza season) were enrolled from September 2021 through January 2022 at 9 military facilities. Participants were asked each week about influenza-like illness (ILI) symptoms. If the participants reported ILI symptoms, research staff scheduled an acute and convalescent ILI visit. Additional details about the study are included in Figure 1. Results. In year 4, 4,688 participants were enrolled, among whom 63.8% were male, 56.5% were white, and the average age was 34 years (Tables 1 and 2). As of early April, 1,297 ILIs had been reported. Most participants reported a single ILI (987 (87%)), while 140 participants reported two ILIs and 10 reported three ILIs. The mean duration of the reported ILIs was 11 days, with a mean 5 days of limited activity. Three participants were hospitalized. Among the samples processed to date, influenza has been identified in four participants. Themost common pathogens in year 4 were SARS-CoV-2 and rhino/enterovirus (Figure 2). During all four years of PAIVED, we enrolled 15,449 participants, among whom 188 episodes of influenza have been identified so far (1.2%). Conclusion. The fourth year of PAIVED was characterized by early (preenrollment) spread of influenza in some areas, as well the nationwide spread of the SARS-CoV-2 Omicron variant in December. As the swabs are processed and participants? military health records are reviewed, we expect to identify more influenza cases;however, transmission patterns were far lower than historical averages due to pandemic precautions, making this surveillance data from identified strains more valuable. Comparative influenza vaccine effectiveness calculations will be performed to inform future vaccine purchasing decisions and we will compare serological response to the different vaccines. (Figure Presented).

Pathogen Co-infections and Trends in Influenza-like Illness in PAIVED

Background. The Pragmatic Assessment of Influenza Vaccine Effectiveness in the Department of Defense (DoD) (PAIVED) is a multicenter, multiservice study assessing influenza vaccine effectiveness in active-duty service members, retirees, and dependents. In its fourth season (2021/22), PAIVED offers a unique opportunity to examine influenza-like illness (ILI) trends prior to and during the COVID-19 pandemic in a prospectively followed, well-defined cohort. Methods. Over the past 4 influenza seasons, PAIVED has enrolled DoD beneficiaries who were randomized to receive egg-based, cell-based, or recombinant-derived influenza vaccine. Participants provided some basic demographic information and were then sent a weekly text or email that inquired about ILI symptoms, defined as 1) having cough or sore throat, plus 2) feeling feverish/having chills or having body aches/fatigue. Participants with ILI completed a daily symptom diary for one week and submitted a nasal swab for PCR-based pathogen detection. Results. Over the 4 seasons, 15,449 participants were followed for ILI (Table 1) with 3,407 participants reporting a total of 3,985 ILIs. For the 2021/22 season, ILI reports peaked in January (Figure 1). Overall, 4.7% of episodes had more than one pathogen identified (Table 2). Among the 122 coinfections identified to date, most were coinfections with rhinoviruses (91/122, 75%), including rhinovirus coinfections with seasonal coronaviruses (29, 24%), metapneumovirus (18, 15%), SARS-CoV-2 (17, 14%), and influenza (14, 11%). SARS-CoV-2 and influenza were found together in one sample. The lab data will continue to be processed for the current season (2021/22). Conclusion. ILI rates were lowest during the third year (2020/21), consistent with national influenza surveillance reports of influenza and outpatient ILI activity, suggesting that measures taken to reduce transmission of SARS-CoV-2 reduced the spread of other respiratory viruses. The emergence of the SARS-CoV-2 omicron variant in December 2021 was associated with higher ILI rates. Among those individuals for whom a sample was collected, coinfections were highest in 2018/19. Data collection and specimen analysis are ongoing for 2021/22. (Figure Presented).

Impact of COVID-19 Pandemic on Influenza-like Illness (ILI) Experience among Healthcare Workers in Military Treatment Facilities

Background. Healthcare workers (HCWs) are at heightened risk of exposure to respiratory pathogens, and occupy an important epidemiologic position in the COVID-19 pandemic. PAIVED, a multicenter, multiservice study assessing influenza vaccine effectiveness in the Department of Defense over four consecutive influenza seasons (2018-22), provides an opportunity to describe influenza like illness (ILI) experience and assess the impact of SARS-CoV-2 in HCWs compared to non-HCWs. Methods. PAIVED participants were randomized to receive either egg-based, cell-based, or recombinant-derived influenza vaccine and then surveyed weekly for ILI. At enrollment, participants provided key demographic data including whether they were HCWs with direct patient contact. ILI was defined a priori as 1) having cough or sore throat plus 2) feeling feverish/having chills or having body aches/fatigue. Participants with ILI completed a symptom diary for seven days and submitted a nasal swab for pathogen detection. Study recruitment was conducted from September-January over four consecutive years. Results. Of 13188 eligible participants enrolled, 4819 (36%) were HCWs. Overall, HCWs were more likely to be female (43% vs 31%), active duty military (86% vs 69%), and to identify as white (61% vs 56%). HCWs more commonly reported ILI than non-HCWs (25% vs 21%, p< 0.01). Of those experiencing ILI, SARS-CoV-2 was identified in a higher proportion of HCWs than non-HCWs (17% vs 12%, p< 0.01). Influenza was isolated in similar proportion of HCWs and non-HCWs (5% vs 4%). Each group reported similar ILI duration and severity (p< 0.01). Conclusion. In a prior analysis of the 2019-20 PAIVED season, HCWs were more likely than non-HCWs to report ILI, have shorter illness duration, and isolate influenza A (H1N1). The propensity for HCWs to report ILI persisted over the four years. While SARS-CoV-2 emerged as a major pathogen in both groups, HCWs were more likely to have it identified as a cause of ILI, suggesting increased risk of symptomatic SARS-CoV-2 in our HCW population. Influenza incidence was lower than that of SARS-COV-2, and did not differ between HCWs and non-HCWs. Mean duration of illness did not differ between groups over four years;this equalization may relate to the higher incidence of SARS-CoV-2 in HCWs.

Seasonality of Microbiology of Combat-related Wound Infections in Afghanistan

Background: We examined the seasonality of wounds and wound infections, including occurrence of multidrug resistance, among combat casualties injured in Afghanistan. Methods: The Trauma Infectious Disease Outcomes Study is a retrospective observational study of infectious complications among military personnel wounded during deployment (06/09-12/14). Wound cultures obtained ≤7 days following injury in Afghanistan were assessed. Epidemiologic, clinical, and microbiologic data were analyzed by injury season [winter (1 Dec-28/29 Feb), spring (1 Mar-31 May), summer (1 Jun-31 Aug), and fall (1 Sep-30 Nov)]. Multidrug-resistant (MDR) determinations for Gram-negative and Gram-positive organisms were per standardized definitions. Results: The study population included 316 patients with a median of 3.5 (IQR 3-5) days from injury to initial culture. Gram-negatives (N=188, 59.5%) were more commonly isolated from wound cultures in summer (N=81, 43.1%) and fall (N=57, 30.3%) versus winter (N=18, 9.6%) and spring (N=32, 17%) (p< 0.001). The MDR Gram-negatives (N=69, 21.8%) were more common in summer (N=26, 37.7%), and fall (N=26, 37.7%) versus winter (N=3, 4.3%) and spring (N=14, 20.3%) (p=0.028). Wound infections were diagnosed in 198 (63%) patients. The pattern for infecting Gram-negative isolates (N=143, 72.2%, Table 1) was similar to that of overall Gram-negative isolates: summer (79.5%) and fall (83.6%;p< 0.001);MDR Gram-negatives (summer, 25.6%) and (fall, 41.8%;p=0.015). Escherichia coli and Enterobacter spp. were the most common infecting Gram-negative bacilli with no significant difference across the seasons. There was a higher proportion of infecting Acinetobacter baumannii isolates in the summer and fall compared to winter and spring. Infecting Gram-positive isolates (N=128, 65%) were not significantly different by season. Anaerobes associated with infections were also identified (N=30, 15%) with a higher proportion in the winter compared to summer, fall, and spring (p=0.036). Conclusion: Gram-negatives, including MDR Gram-negative infecting organisms, were more common in summer/fall months in service members injured in Afghanistan. This may have implications for empiric antibiotic coverage during these months. Disclosures: David R. Tribble, DrPH, AstraZeneca: The HJF, in support of the USU IDCRP, was funded to conduct or augment unrelated Phase III Mab and vaccine trials as part of US Govt. COVID19 response.

Emergence of the SARS-CoV-2 Omicron Variant in the Pragmatic Assessment of Influenza Vaccine Effectiveness in the Department of Defense (PAIVED) Study

Background. Novel SARS-CoV-2 (SCV2) variants may differ in epidemiology and clinical impact. PAIVED, a randomized trial comparing the efficacy of 3 different platforms of inactivated influenza vaccines in adult military health system beneficiaries, actively surveils participants for influenza-like illness (ILI), including COVID-19, and conducts targeted investigations among those who develop ILI. The current season (2021/22) offered an opportunity to assess symptomatology associated with emerging SCV2 variants in this prospective cohort. Methods. Following receipt of influenza vaccine, PAIVED participants receive a weekly email or text message querying for ILI symptoms. Those who reported ILI completed a validated symptom diary (FLU-PRO Plus) daily for 7 days and collected a nasal swab. Nasal specimens underwent multiplex PCR testing, followed by SCV2 genome sequencing as applicable. PAIVED study participants from the 2021-22 influenza season who reported an ILI, had confirmed infection with SCV2 for which sequence data is available, and completed at least one FLU-PRO Plus survey were included in this analysis. Results. To date, 293 participants (7% of active cohort;22.5% reporting ILI) tested positive for SCV2;sequencing has identified 23 Delta and 200 Omicron variants (199 BA.1, 1 BA.2). Among the 212 participants with sequenced SCV2 and symptom data, 55% were male, 57% were white, and 85% were active-duty military (Table 1). Overall, peak symptom severity was classified as mild to moderate in 79.3% of cases, fever duration averaged 2.5+/-2.2 days, and there were activity limitations for a mean of 5.2+/-3.8 days. No differences in maximum symptom scores (total or by domain) were detected for participants infected with Omicron compared to Delta. Figure 1 depicts variation in mean symptom scores by day of ILI, grouped by variant Conclusion. Omicron emerged as the predominant SCV2 variant causing ILI in our cohort this season, typically manifesting with mild symptoms. Further exploration of potential differences in ILI experience between SCV2 variants and other ILI causes, plus the impact and timing of vaccination, will add insight into the relative contribution of such factors on symptomatology.

SARS-CoV-2 (COVID-19) Testing Experience within a Military Treatment Facility

Background. The Walter Reed National Military Medical Center (WRNMMC) established a consolidated COVID-19 screening area (CSA) beginning in March 2020 to provide beneficiary and staff testing via a drive-through site. Testing was available to all patients and WRNMMC staff regardless of beneficiary status. Presented is a descriptive analysis of our testing operations and positivity rates within a closed medical system from March 2020 to April 2021. Methods. For quality and process improvement, we compiled daily testing logs from March 2020 to April 2021 from the CSA. These logs included patient demographics, reason for testing, test result, testing platform, and occupational status at the hospital. We determined positivity rates in various subgroups -asymptomatic, symptomatic, pre-operative, in order to track testing use and access. Additionally, we compared the overall positivity rate to the surrounding civilian community by pulling data from the Maryland Department of Health's COVID database. Results. Over the course of nearly 14 months of testing availability, 34,694 beneficiaries were screened with 41,582 individual tests. After May 2020, the monthly overall positivity rate varied from 1.99% to 11.92%, peaking in December 2020 (with high rates in November 2020, 7.52% and January 2021, 9.53%), correlating with or exceeding elevated positivity rates in Montgomery County (November 2020: 4.91%;December 2020: 6.48%;January 2021: 6.51%). When examining only symptomatic individuals, the positivity rate is notably much higher, with monthly rates varying from 6.40% to 21.10%, with a similar peak in December 2020. After full implementation of pre-operative screening for procedures with aerosolization potential in June 2020, the range of positivity rates was 0.28%-1.66%. Since vaccination for COVID-19 became widely available beginning in Feb 2021, the preoperative positivity rate has remained below 0.85%. Conclusion. Our institutional experience is unique in its ability to offer universal access to COVID-19 testing for beneficiaries and staff of the DoD under direction of the ID service. Our process serves as a model for public and occupational health response, and may guide lab resource and real-time staffing management in support of COVID-19 diagnostics at a medical center.

Bamlanivimab (BAM) for SARS-CoV-2 Infection: Rates and Risk Factors for Hospitalization after Monoclonal Antibody Administration in a High-Risk Population

Background. In response to the ongoing COVID-19 pandemic, an emergency use authorization (EUA) was issued for neutralizing antibody therapies including BAM. Licensing trials suggest that use of BAM reduces hospitalizations when compared with placebo (1.6% vs 6.3%). However, the real world impact of BAM is not well-described. In this study, risk factors, outcomes, and hospitalization rates among high-risk outpatients presenting with mild-to-moderate COVID-19 who received BAM were examined. Methods. This is a single center retrospective analysis of all patients who received BAM monotherapy between 11/11/2020 and 3/16/2021. Electronic health records were reviewed for baseline demographics, EUA indications, comorbidities, and outcomes to include infusion reactions, hospitalizations, and deaths occurring within 29 days of BAM administration. Moderate COVID-19 was defined as having any infiltrate on chest imaging prior to BAM administration. Chi-squared or Fisher's exact tests were used to compare categorical values as appropriate, and Mann-Whitney U for continuous variables. Results. Of the 101 patients who received BAM (median age 64 years;21% black;4% Hispanic;55% male), 13 were subsequently admitted. 22 patients (22%) had moderately severe disease as evidenced by abnormal imaging. Severity on presentation, number of indications for therapy, hypertension, stroke, diabetes, and number of co-morbidities were significantly associated with subsequent admission (table 1). No patients had adverse infusion reactions. Of those hospitalized, 8 (61.5%) were for COVID-19, the median duration of hospitalization was 2 days, and 4 received guideline-directed treatment for COVID-19 (table 2). Conclusion. In a high-risk population, hospitalization rates were higher than those observed in clinical trials, with 8% of subjects being admitted for COVID-19. Disease severity on presentation, multiple indications for therapy, and the presence of multiple co-morbidities were all associated with subsequent admission. Reassuringly, BAM was well tolerated, and in those requiring admission, hospitalizations were short, resource utilization was low, and there were no deaths.