Background. Prior to the introduction of vaccines, COVID-19 hospitalizations of non-institutionalized persons in Connecticut disproportionately affected communities of color and individuals of low socioeconomic status (SES). Whether the magnitude of these disparities changed 7-9 months after vaccine rollout during the Delta wave is not well documented. Methods. All initially hospitalized patients with laboratory-confirmed COVID-19 during July-September 2021, were obtained from the Connecticut COVID-NET database, including patients’ geocoded residential addresses. Census tract measures of poverty and crowding were determined by linking geocoded residential addresses to the 2014-2018 American Community Survey. Age-adjusted incidence and relative rates of COVID-19 hospitalization were calculated and compared to those from July-December 2020. Vaccination levels by age and race/ethnicity at the beginning and end of the study period were obtained from Connecticut’s COVID vaccine registry and age-adjusted average values were determined. Results. There were 708 COVID-19 hospitalizations among community residents of the two counties, July-September 2021. Age-adjusted incidence was highest among non-Hispanic Blacks and Hispanic/Latinx compared to non-Hispanic Whites ((RR 4.10 (95% CI 3.41-4.94) and 3.47 (95% CI 2.89-4.16)). While RR decreased significantly among Hispanic/Latinx and among the lowest SES groups, it increased among non-Hispanic Blacks (from RR 3.1 (95% CI 2.83-3.32) to RR 4.10). Average age-adjusted vaccination rates among those >12 years were lowest among non-Hispanic Blacks compared to Hispanic/Latinx and non-Hispanic Whites (50.6% vs 64.7% and 66.6%). Conclusions. While racial/ethnic and SES disparities in COVID-19 hospitalization have mostly decreased over time, disparities among non-Hispanic Blacks increased, possibly due to differences in vaccination rates.

Background: Influenza is a persistent public health problem associated with severe morbidity and mortality. Drug use is related to myriad health complications, but the relationship between drug use and severe influenza outcomes is not well understood. The study objective was to evaluate the relationship between drug use and severe influenza-associated outcomes. Methods: Data were collected by the Influenza Hospitalization Surveillance Network (FluSurv-NET) from the 2016-2017 through 2018-2019 influenza seasons. Among persons hospitalized with influenza, descriptive statistics and logistic regression models were used to analyze differences in demographic characteristics, risk and behavioral factors, and severe outcomes (intensive care unit [ICU] admission, mechanical ventilation, or death) between people who used drugs (PWUD), defined as having documented drug use within the past year, and non-PWUD. Results: Among 48,430 eligible hospitalized influenza cases, 2,019 were PWUD and 46,411 were non-PWUD. PWUD were younger than non-PWUD and more likely to be male, non-Hispanic Black or Hispanic/Latino, smoke tobacco, abuse alcohol, and have chronic conditions including asthma, chronic liver disease, chronic lung disease, or immunosuppressive conditions. PWUD had greater odds of ICU admission and mechanical ventilation, but not death compared with non-PWUD. Opioid use specifically was associated with increased risk of ICU admission and mechanical ventilation. Conclusion: PWUD had greater odds of ICU admission and mechanical ventilation than non-PWUD hospitalized with influenza. These results support targeted initiatives to prevent influenza and associated severe outcomes among this population.

Background: Despite the WHO recommendation that pregnant women be prioritised for seasonal influenza vaccination, coverage in the Western Pacific Region remains low. Our goal was to provide additional data for the Western Pacific region about the value of maternal influenza vaccination to pregnant women and their families. Methods: We conducted a 16-year retrospective cohort to evaluate risks associated with influenza-associated maternal acute respiratory infection (ARI) in New Zealand. ARI hospitalisations during the May-September influenza season were identified using select ICD-10-AM primary and secondary discharge codes from chapter J00-J99 (diseases of the respiratory system). Cox proportional hazards models were used to calculate crude and adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Results: We identified 822,391 pregnancies among New Zealand residents between 2003 and 2018; 5,095 (0.6%) had >1 associated ARI hospitalisation during the influenza season; these pregnancies were at greater risk of preterm birth (aHR 1.5, 95% CI 1.3-1.7), and low birthweight (aHR 1.7, 95% CI 1.5-2.0) than pregnancies without such hospitalisations. We did not find an association between maternal ARI hospitalisation and fetal death (aHR 1.1, 95% CI 0.6-1.4) during the influenza season. Maternal influenza vaccination was associated with reduced risk of preterm birth (aHR 0.8, 95% CI 0.7-0.9), and low birthweight (aHR 0.9, 95%CI 0.8-0.9), and fetal death (aHR 0.5%, 95% CI 0.3-0.7). Conclusion: In this population-based cohort, being hospitalised for an ARI during the influenza season while pregnant was a risk-factor for delivering a preterm or a low birthweight infant and vaccination reduced this risk.

Background: Acute respiratory infections (ARIs) result in millions of illnesses and hundreds of thousands of hospitalizations annually in the US. The responsible viruses include influenza, parainfluenza, human metapneumovirus, coronaviruses, respiratory syncytial virus (RSV), and human rhinoviruses. This study estimated the population-based hospitalization burden of 18 respiratory viruses (RV) over 4 years, from 7/1/2015 to 6/30/2019 among adults ≥18 years of age for Allegheny County (Pittsburgh), Pennsylvania. Methods: We used population-based statewide hospital discharge data, health system electronic medical record (EMR) data for RV tests, census data, and a published method to calculate burden. Results: Among 26,211 eligible RV tests, 67.6% were negative for any virus. The viruses detected were rhinovirus/enterovirus (2,552; 30.1%), influenza A (2,299; 27.1%), RSV (1,082; 12.7%), human metapneumovirus (832; 9.8%), parainfluenza (601; 7.1%), influenza B (565; 6.7%), non-SARS-CoV-2 coronavirus (420; 4.9% 1.5 years of data available), and adenovirus (136; 1.6%). Most tests were among female (58%) and white (71%) patients with 60% of patients ≥65 years, 24% 50-64 years and 16% 18-49 years. The annual burden, ranged from 137-174/100,000 population for rhinovirus/enterovirus; 99-182/100,000 for influenza A; 56-81/100,000 for RSV. Among adults <65 years, rhinovirus/enterovirus hospitalization burden was higher than influenza A; whereas the reverse was true for adults ≥65 years. RV hospitalization burden increased with increasing age. Conclusions: These virus-specific ARI population-based hospital burden estimates showed significant non-influenza burden. These estimates can serve as the basis for several areas of research that are essential for setting funding priorities and guiding public health policy.

Pandemic influenza viruses may emerge from animal reservoirs and spread among humans in the absence of cross-reactive antibodies in the human population. Immune response to highly conserved T cell epitopes in vaccines may still reduce morbidity and limit the spread of the new virus even when cross-protective antibody responses are lacking. We used an established epitope content prediction and comparison tool, EpiCC, to assess the potential for emergent H1N1 G4 swine influenza A virus (G4) to impact swine and human populations. We identified and computed the total cross-conserved T cell epitope content in HA sequences of human seasonal and experimental influenza vaccines, swine influenza vaccines from Europe and the United States (US) against G4. The overall T cell epitope content of US commercial swine vaccines was poorly conserved with G4, with an average T cell epitope coverage of 35.7%. EpiCC scores for the comparison between current human influenza vaccines and circulating human influenza strains were also very low. In contrast, the T cell epitope coverage of a recent European swine influenza vaccine (HL03) was 65.8% against G4. Poor T cell epitope cross-conservation between emergent G4 and swine and human influenza vaccines in the US may enable G4 to spread in swine and spillover to human populations in the absence of protective antibody response. One European influenza vaccine, HL03, may protect against emergent G4. This study illustrates the use of the EpiCC tool for prospective assessment of existing vaccine strains against emergent viruses in swine and human populations.

Background Human Parainfluenza viruses (HPIV) comprise of four members of the genetically distinct genera of Respirovirus (HPIV1&3) and Orthorubulavirus (HPIV2&4), causing significant upper and lower respiratory tract infections worldwide, particularly in children. However, despite frequent molecular diagnosis, they are frequently considered collectively or with HPIV4 overlooked entirely. We therefore investigated clinical and viral epidemiological distinctions of the relatively less prevalent Orthorubulaviruses HPIV2&4 at a regional UK hospital across four autumn/winter epidemic seasons. Methods A retrospective audit of clinical features of all HPIV2 or HPIV4 RT-PCR-positive patients, diagnosed between 1st September 2013 and 12th April 2017 was undertaken, alongside sequencing of viral genome fragments in a representative subset of samples. Results Infection was observed across all age groups, but predominantly in children under nine and adults over 40, with almost twice as many HPIV4 as HPIV2 cases. Fever, abnormal haematology, elevated C-reactive protein and hospital admission were more frequently seen in HPIV2 than HPIV4 infection. Each of the four seasonal peaks of either HPIV2, HPIV4 or both, closely matched that of RSV, occurring in November and December and preceding that of Influenza A. A subset of viruses were partially sequenced, indicating co-circulation of multiple subtypes of both HPIV2&4, but with little variation between each epidemic season or from limited global reference sequences. Conclusions Despite being closest known genetic relatives, our data indicates a potential difference in associated disease between HPIV2 and HPIV4, with more hospitalisation seen in HPIV2 mono-infected individuals, but a greater overall number of HPIV4 cases.

Background: In France, each year, influenza viruses are responsible for seasonal epidemics leading to 2-6 million cases. Influenza can cause severe disease that may lead to hospitalization or death. As severe disease may be due to the virus itself or to disease complications, estimating the burden of severe influenza is complex. The present study aimed at estimating the epidemiological and economic burden of severe influenza in France during eight consecutive influenza seasons (2010-2018). Methods: Influenza-related hospitalization and mortality data and patient characteristics were taken from the French hospital information database, PMSI. An ecological approach using cyclic regression models integrating the incidence of influenza syndrome from the Sentinelles Network supplemented the PMSI data analysis in estimating excess hospitalization and mortality (CépiDc – 2010-2015) and medical costs. Results: Each season, the average number of influenza-related hospitalizations was 18,979 (range: 8,627-44,024), with an average length of stay of 8 days. The average number of respiratory hospitalizations indirectly related with influenza (i.e., influenza-associated) was 31,490 (95% CI: 24,542-39,012), with an average cost of \euro141 million (range: 54-217); 70% of these hospitalizations and 77% of their costs concerned individuals ≥ 65 years of age (65+). More than 90% of excess mortality was in 65+ subjects. Conclusions: The combination of two complementary approaches allowed estimation of both influenza-related and associated hospitalizations and deaths and their burden in France, showing the substantial impact of complications. The present study highlighted the major public health burden of influenza and its severe complications, especially in 65+ subjects.

Background: While the high burden of illness caused by seasonal influenza in children and the elderly is well-recognized, less is known about the burden in adults 50-64 years of age. The lack of data for this age group is a key challenge in evaluating the cost-effectiveness of vaccination programs. We aimed to assess influenza-associated hospitalization and mortality rates, and case fatality rates for hospitalized cases among adults aged 50-64 years. Methods: This review was conducted according to the PRISMA: we searched MEDLINE, EMBASE, Cochrane, Web of Science, and grey literature for articles and reports published since 2010. Studies reporting rates of hospitalization and/or mortality associated with laboratory-confirmed influenza among adults 50-64 or 45-64 years of age for the 2010-11 through 2019-20 seasons were included. Results: Twenty studies from 13 countries were included. Reported hospitalization rates associated with laboratory-confirmed influenza 5.7 to 112.8 per 100,000. Rates tended to be higher in 2015-2019 compared to 2010-2014, and were higher in studies reporting data from high income versus low and middle-income countries. Mortality rates were reported in only one study, with rates ranging from 0.8-3.5 per 100,000 in four different seasons. The case fatality rate among those hospitalized with influenza, as reported by population-based studies, ranged from 1.3% to 5.6%. Conclusions: Seasonal influenza imposes a significant burden of morbidity in adults 50-64 years of age, but with high heterogeneity across seasons and geographic regions. Ongoing surveillance is required to improve estimates of burden to better inform influenza vaccination and other public health policy.

Background: Human respiratory syncytial virus (HRSV) is a major cause of severe viral acute respiratory illness and contributes significantly to severe pneumonia cases in Africa. Little is known about its spatial-temporal distribution as defined by its genetic diversity. Methods: A retrospective study conducted utilizing archived nasopharyngeal specimens from patients attending outpatient clinics in hospitals located in five demographically and climatically distinct regions of Kenya; Coast, Western, Highlands, Eastern and Nairobi. The viral total RNA was extracted and tested using multiplex real time RT-PCR (reverse transcriptase polymerase chain reaction). A segment of the G-gene was amplified using one-step RT-PCR and sequenced by Sanger di-deoxy method. Bayesian analysis of phylogeny was utilized and subsequently median joining methods for haplotype network reconstruction. Results: Three genotypes of HRSVA were detected; GA5 (14.0%), GA2 (33.1%) and NA1 (52.9%). HRSVA prevalence varied by location from 33% to 13.2% in the Highlands and the Eastern regions respectively. The mean nucleotide diversity (Pi(π)) varied by genotype: highest of 0.018 for GA5 and lowest of 0.005 for NA1. A total of 58 haplotypes were identified (GA5 10; GA2 20; NA1 28). These haplotypes were introduced into the population locally by single haplotypes and additional subsidiary seeds amongst the GA2 and the NA1 haplotypes. Conclusions: HRSVA was found across all the regions throughout the study period and comprised three genotypes; GA5, GA2 and NA1 genotypes. The genotypes were disproportionately distributed across the regions with GA5 gradually increasing towards the Western zones and decreasing towards the Eastern zones of the country.

Background: Data on disease burden of respiratory syncytial virus (RSV) associated acute lower respiratory infection (ALRI) among young children are limited in China. This study aimed to estimate the hospitalization rate of RSV-associated ALRI (RSV-ALRI) among children aged 0~59 months in Suzhou, China. Methods: We retrospectively identified all hospitalized ALRI children aged 0~59 months in Suzhou University Affiliated Children’s Hospital during January 2010 to December 2014. Detailed diagnosis and treatment data were collected by individual medical chart review. Referring to WHO influenza disease burden estimation method, we estimated the hospitalization rate of RSV-ALRI among children aged 0~59 months in Suzhou, China. Results: Among 28,209 ALRI cases, 19,317 (68.5%) were tested for RSV and the RSV positive proportion was 21.3% (4,107/19,317). The average hospitalization rate of RSV-ALRI for children aged 0~59 months was 14 (95% confidence interval [CI]:14~14)/1,000 children-years, for children aged 0~5, 6~11, 12~23, and 24~59 months were 70 (95%CI: 67~73), 31 (95%CI: 29~33), 11 (95%CI: 10~12), and 3 (95%CI: 3~3) /1,000 children-years, respectively. Conclusion: There is considerable RSV-ALRI hospitalization among children aged 0~59 months, particularly among children aged <1 years. An effective monoclonal antibody or vaccine is urgently needed to address the substantial hospitalization burden owing to RSV infection. Key words: Respiratory syncytial virus, Hospitalization rate, Acute lower respiratory infection, Children, China

Background. We sought to evaluate the impact of changes in estimates of COVID-19 vaccine effectiveness on the incidence of laboratory-confirmed infection among frontline workers at high risk for SARS-CoV-2. Methods. We analyzed data from a prospective frontline worker cohort to estimate the incidence of COVID-19 by month as well as the association of COVID-19 vaccination, occupation, demographics, physical distancing and mask use with infection risk. Participants completed baseline and quarterly surveys, and each week self-collected mid-turbinate nasal swabs and reported symptoms. Results. Among 1,018 unvaccinated and 3,531 fully vaccinated workers, the monthly incidence of laboratory-confirmed SARS-CoV-2 infection in January 2021 was 13.9 (95% confidence interval [CI]: 10.4-17.4), declining to 0.5 (95% CI -0.4-1.4) per 1000 person-weeks in June. By September 2021, when the Delta variant predominated, incidence had once again risen to 13.6 (95% CI 7.8-19.4) per 1000 person-weeks. In contrast, there was no reportable incidence among fully vaccinated participants at the end of January 2021, and incidence remained low until September 2021 when it rose modestly to 4.1 (95% CI 1.9-3.8) per 1000. Below average facemask use was associated with a higher risk of infection for unvaccinated participants during exposure to persons who may have COVID-19, and vaccinated participants during hours in the community. Conclusions. COVID-19 vaccination was significantly associated with a lower risk of SARS-CoV-2 infection despite Delta variant predominance. Our data demonstrate the added protective benefit of facemask use among both unvaccinated and vaccinated frontline workers.

Background Estimates of the disease burden associated with different respiratory viruses are severely limited in low- and middle-income countries, especially in Africa. Methods We estimated age-specific numbers and rates of medically and non-medically attended influenza-like illness (ILI) and severe respiratory illness (SRI) that were associated with influenza, respiratory syncytial virus (RSV), rhinovirus, human metapneumovirus, adenovirus, enterovirus and parainfluenza virus types 1-3 after adjusting for the attributable fraction (AF) of virus detection to illness in South Africa during 2013-2015. Rates were reported per 100,000 population. Results The mean annual rates were 51,383 and 4,196 for ILI and SRI, respectively. Of these, 26% (for ILI) and 46% (for SRI) were medically attended. Among outpatients with ILI, rhinovirus had the highest AF-adjusted rate (7,221), followed by influenza (6,443) and adenovirus (1,364); whereas, among inpatients with SRI, rhinovirus had the highest AF-adjusted rate (400), followed by RSV (247) and influenza (130). Rhinovirus (9,424) and RSV (2,026) had the highest AF-adjusted rates among children aged <5 years with ILI or SRI, respectively; whereas rhinovirus (757) and influenza (306) had the highest AF-adjusted rates among individuals aged ≥65 years with ILI or SRI, respectively Conclusions There was a substantial burden of ILI and SRI in South Africa during 2013-2015. Rhinovirus and influenza had a prominent disease burden among patients with ILI. Rhinovirus had the highest burden of illness among patients of any age with SRI, followed by RSV. RSV and influenza were the most prominent causes of SRI in children and the elderly, respectively.

INTRODUCTION. Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract illness in young children and can also cause influenza-like illness (ILI). Here we investigated the epidemiological features of RSV infection in pediatric ILI cases in Lombardy (a region in Northern Italy accounting nearly 10-million inhabitants) from 2014-2015 to 2020-2021 winter seasons. MATERIAL AND METHODS. Data for this study were retrieved and statistically analyzed from the database of virological influenza surveillance of the regional reference laboratory for Lombardy within the Italian influenza surveillance network (InfluNet). RESULTS. RSV accounting for nearly 19% of pediatric ILI with a risk of infection nearly 2-fold greater than that of individuals ≥15 years. The RSV positivity rate increased to 28% considering 0-5 years old children. Although in children ≤5 years the risk of infection from influenza viruses resulted nearly 2-fold higher than the risk of RSV infection, the age group 4-6 months and 7-12 months showed 5-fold greater risk of infection from RSV than from influenza. Children ≤5 years of age with presence of one or more comorbidities had a nearly 5-fold greater risk of getting RSV infection than otherwise healthy 0-5 years old children. DISCUSSION. The use of the ILI sentinel surveillance allowed us to identify groups at higher risk of RSV and influenza infection and to define the start, duration, timing and intensity of the RSV and influenza community circulation, determining thresholds based on historical data. This surveillance approach can be implemented to assess the nearly real-time RSV circulation and impact.

In March 2021, Lao People’s Democratic Republic (Laos) reported an avian influenza A(H5N6) virus infection in a 5-year-old child identified through sentinel surveillance. This was the first human A(H5N6) infection reported outside of China. A multidisciplinary investigation undertook contact tracing and enhanced human and animal surveillance in surrounding villages and live bird markets. Seven Muscovy ducks tested positive for highly pathogenic avian influenza A(H5N6) viruses. Sequenced viruses belonged to clade 2.3.4.4h and were closely related to viruses detected in poultry in Vietnam, and to previous viruses detected in Laos. Surveillance and coordinated outbreak response remain essential to global health security.

Background: reliable country-specific data on influenza burden play a crucial role in informing prevention and control measures. Our purpose was to provide a comprehensive summary of the available evidence on the burden of seasonal influenza in Italy. Methods: we performed a sys-tematic literature review of articles published until 31 July 2020. PubMed, Embase and Web of Science were searched using terms related to burden, influenza, and Italian population. We in-cluded studies investigating seasonal influenza-related complications, hospitalizations and/or mortality. Results: sixteen studies were included: eight (50%) analyzed influenza-related compli-cations, eight (50%) hospitalizations, while seven (43.8%) influenza-related deaths. Only three studies (19.7%) concerned pediatric age. The synthesis of results showed that patients with chron-ic conditions have an increased risk for complications up to almost three times as compared to healthy people. Hospitalizations due to influenza can occur in as much as 5% of infected people depending on the study setting. Excess deaths rates were over six-fold higher in the elderly as compared to the rest of population. Conclusions: although there are still gaps in existing data, there is evidence of the significant burden that influenza places each year especially on high-risk groups. These data should be used to inform public health decision-making.

Background: The COVID-19 pandemic has highlighted the need for targeted local interventions given substantial heterogeneity within cities and counties. Publicly available case data are typically aggregated to the city or county level to protect patient privacy, but more granular data are necessary to identify and act upon community-level risk factors that can change over time. Methods: Individual COVID-19 case and mortality data from Massachusetts were geocoded to residential addresses and aggregated into two time periods: “Phase 1” (March–June 2020) and “Phase 2” (September 2020–February 2021). Institutional cases associated with long-term care facilities, prisons, or homeless shelters were identified using address data and modeled separately. Census tract sociodemographic and occupational predictors were drawn from the 2015-2019 American Community Survey. We used mixed-effects negative binomial regression to estimate incidence rate ratios (IRRs), accounting for town-level spatial autocorrelation. Results: Case incidence was elevated in census tracts with higher proportions of Black and Latinx residents, with larger associations in Phase 1 than Phase 2. Case incidence associated with proportion of essential workers was similarly elevated in both Phases. Mortality IRRs had differing patterns from case IRRs, decreasing less substantially between Phases for Black and Latinx populations and increasing between Phases for proportion of essential workers. Mortality models excluding institutional cases yielded stronger associations for age, race/ethnicity, and essential worker status. Conclusions: Geocoded home address data can allow for nuanced analyses of community disease patterns, identification of high-risk subgroups, and exclusion of institutional cases to comprehensively reflect community risk.

Introduction: We describe epidemiology and outcomes of confirmed SARS-CoV-2 infection and admissions among children <18 years in South Africa, an upper-middle income setting with high inequality. Methods: Laboratory and hospital COVID-19 surveillance data, 28 January - 19 September 2020 was used. Testing rates were calculated as number of tested for SARS-CoV-2 divided by population at risk; test positivity rates were calculated as positive tests divided by total number of tests. In-hospital case fatality ratio (CFR) was calculated based on hospitalized positive admissions with outcome data who died in-hospital and death was judged SARS-CoV-2 related by attending physician. Findings: 315,570 children aged <18 years were tested for SARS-CoV-2; representing 8.9% of all 3,548,738 tests and 1.6% of all children in the country. Of children tested, 46,137 (14.6%) were positive. Children made up 2.9% (n=2,007) of all SARS-CoV-2 positive admissions to sentinel hospitals. Among children, 47 died (2.6% case-fatality). In-hospital deaths were associated with male sex [adjusted odds ratio (aOR) 2.18 (95% confidence intervals (CI) 1.08 - 4.40)] vs female; age <1 year [aOR 4.11 (95% CI 1.08-15.54)], age 10-14 years [aOR 4.20 (95% CI1.07-16.44)], age 15-17 years [aOR 4.86 (95% 1.28 -18.51)] vs age 1-4 years; admission to a public hospital [aOR 5.07(95% 2.01 -12.76)] vs private hospital and ≥1 underlying conditions [aOR 12.09 (95% CI 4.19-34.89)] vs none Conclusions: Children with underlying conditions were at greater risk of severe SARS-CoV-2 outcomes. Children > 10 years and those with underlying conditions should be considered for increased testing and vaccination.

Background Zanamivir is a neuraminidase inhibitor effective against influenza A and B viruses. In 2009, GlaxoSmithKline (GSK) began clinical development of intravenous (IV) zanamivir, and initiated a global Compassionate Use Program (CUP) in response to the evolving H1N1 global pandemic. The goal of the CUP was to provide zanamivir to critically ill patients with limited treatment options. Methods Zanamivir was administered to patients with suspected or confirmed influenza infection, who were not suitable for other approved antiviral treatments. Reporting of serious adverse events (SAEs) was mandatory and recorded in the GSK safety database. A master summary tracking sheet captured requests and patient characteristics. A case report form was available for detailing medical conditions, dosing, treatment duration, and clinical outcomes. Results In total, 4033 requests were made for zanamivir treatment of hospitalized patients from 38 countries between 2009 and 2019. Europe had the highest number of requests (n=3051) followed by North America (n=713). At least 20 patients were aged ≤6 months, of whom 12 were born prematurely. The GSK safety database included 466 patients with ≥1 SAE, of whom 374 (80%) had a fatal outcome. Drug-related SAEs were reported in 41 (11%) patients, including hepatic failure (n=6 [2%]) and acute kidney injury (n=5 [1%)]. Conclusions The CUP fulfilled the need to provide global access to zanamivir prior to product approval. No new safety concerns were identified in the CUP compared with IV zanamivir clinical studies.