The continuous emergence of SARS-CoV-2 variants requires ongoing update to research into COVID-19 severity and clinical characteristics. This systematic review aimed to explore COVID-19 disease severity across variants from the Omicron dominance period onwards (i.e., BA.2, XBB, and JN.1 sublineages; see Figure 1).Table 1.Summary of included publication study characteristicsFigure 1.Global genomic epidemiology of the SARS-CoV-2 Omicron period from 2022 to current Systematic searches of Medline and Embase databases were conducted in November 2024 and supplemented by conference searches from 2022 to 2024 (PROSPERO ID: CRD42024619193). Eligible records compared acute COVID-19 outcomes for individuals testing positive for SARS-CoV-2 between variants, with variant determined through sequencing or study author definition of dominance period. Study quality was assessed using the Joanna Briggs Institute critical appraisal tools.Figure 2.Direct comparison by variant period (all adjusted, not including subgroup analysis, estimate < 1 indicates increased severity during reference group period) of composite outcomes for disease severity (A), hospitalization (B), ICU admission (C), mortality (D)Heatmap summaries of included studies* reporting descriptive analyses without direct comparison between variants (not including subgroup analyses, outcomes reported for < 20 persons excluded) for hospitalization (A) and ICU admission (B) Most studies (31/33; 94%) reported on earlier circulating Omicron variants (BA.4/5 and XBB; Table 1). Figure 2 summarizes studies that directly compared hospitalization, ICU admission, mortality, and composite measures of disease severity by SARS-CoV-2 variant. COVID-19 severity was comparable between variants across all outcomes, although two studies (6%) reported increased severity associated with earlier variants. A similar trend is depicted in Figure 3, which summarizes studies reporting descriptive analyses without direct comparison between variants (i.e., not included in Figure 2). The heatmaps depict analogous severity between BA.2 sublineages and most BA.2 versus XBB sublineage comparisons, although multiple studies indicated reduced severity with XBB infection versus BA.2 sublineages. The observed COVID-19 morbidity and mortality were comparable throughout Omicron sub-variants dominance. Comparison with JN.1 sublineages was limited by few reporting studies. The continued evolution of SARS-CoV-2 variants highlights the importance of continued vaccination campaigns with updated COVID-19 vaccines to better match circulating strains. Deepa Malhotra, MS MBA, Pfizer Inc.: Stocks/Bonds (Public Company) Daniel Curcio, M.Sc., Pfizer Inc.: Employee of Pfizer Inc. and may hold stock or stock options Moe H. Kyaw, PhD, Pfizer: Stocks/Bonds (Public Company) Rodrigo Sini de Almeida, Doctor, Pfizer: Board Member|Pfizer: Stocks/Bonds (Private Company) Rajeev M. Nepal, PhD, Pfizer Inc.: Employee of Pfizer Inc. and may hold stock or stock options Pinelopi Nikolopoulou, PhD, Pfizer: current employee|Pfizer: Stocks/Bonds (Private Company) Stephen Wiblin, Masters, Pfizer: Stocks/Bonds (Private Company) Santiago M.C. Lopez, MD, Pfizer Inc.: Employee of Pfizer Inc. and may hold stock or stock options|Pfizer Inc.: Stocks/Bonds (Public Company) Irini Zografaki, MPH, Pfizer: Current employee|Pfizer: Stocks/Bonds (Private Company) Isabelle Whittle, MSc, Pfizer Inc.: Contracted research support Fiona Pearson, PhD, Pfizer Inc. (Contracted research support): Advisor/Consultant Sophie Pope, BSc, Pfizer Inc.: Contracted research support Fraser Williams, MSc, Pfizer Inc.: Contracted research support

We evaluated whether having early COVID-19 reduced the severity of subsequent Omicron infection, assessing activities of daily living (ADL), healthcare utilization and illness duration. Comparisons were made between persons with (1) early COVID-19-compatible illness with a negative test, (2) early lab-confirmed SARS-CoV-2 14-26 months and (3) early lab-confirmed SAR-CoV-2 > 26 months before Omicron infection. Among 261 patients with laboratory-confirmed Omicron, 177 (68%) had COVID-19 in 2020, a median of 793 days (IQR, 659-902) prior to Omicron infection. Compared to no early COVID-19, COVID-19 14-26 months, but not > 26 months, before was associated with reduced impact on ADL during first Omicron infection (OR 0.52, 95% CI 0.29-0.93).

Real-world evidence for the use of nirmatrelvir/ritonavir in routine clinical practice remains limited in the Kingdom of Saudi Arabia (KSA). This study aimed to describe the demographic and clinical characteristics, treatment patterns, and healthcare resource utilization (HCRU) of adult patients with coronavirus disease 2019 (COVID-19) prescribed nirmatrelvir/ritonavir in the KSA. This was a multicenter, retrospective observational cohort study, including adult patients with COVID-19 who were prescribed nirmatrelvir/ritonavir between April 2022 and June 2024. Data were collected through an electronic case report form from patients’ electronic medical records and included patient demographics, clinical characteristics, vaccination history, prescribing characteristics, and HCRU. Data were collected from the index date, defined as the date of nirmatrelvir/ritonavir prescription, up to 30 days post-index. Descriptive analyses were conducted to summarize patient and clinical characteristics, treatment patterns, and HCRU. Logistic regression models were used to assess associations between patient characteristics and COVID-19-related hospitalization at the index date. A total of 248 patients were included. The mean age was 49.9 years, 59.7

The continual emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants drives the need to update evidence on coronavirus disease 2019 (COVID-19) severity and disease burden, and better understand the impact on prevention, treatment, and healthcare systems. This systematic review aimed to determine relative disease severity, through comparative measures of hospitalization, intensive care unit admission and mortality, between SARS-CoV-2 variants of concern emerging since Omicron was first identified. A protocol was registered a priori (PROSPERO ID: CRD42024619193). Systematic searches of MEDLINE and EMBASE databases were conducted in November 2024 and supplemented by conference searches from 2022–2024. Population, Exposure, Comparisons, Outcomes (PECO) criteria were used to screen publications for inclusion. Critical appraisal tools published in the Joanna Briggs Institute (JBI) Handbook for Evidence Synthesis were used to assess the risk of bias of the primary studies included. The outcomes associated with Omicron variants, identified by sequencing or predominance periods, included hospitalization, admission to intensive care, death, and various composite endpoints. Thirty-two studies fulfilled the eligibility criteria, most reported on relative disease severity for early Omicron BA.5 (n = 23) and XBB (n = 24) variants. Overall, COVID-19 severity appeared largely comparable across the various Omicron subvariants. Among the subset of studies that directly compared various severity outcomes to earlier SARS-CoV-2 variants (n = 7), some reported modest increases or decreases in severity. However, these differences were generally not statistically significant. Five studies stratifying outcomes by the presence of comorbid conditions noted that comorbidities were predictors of significantly worse COVID-19 disease outcomes (p = 0.000–0.027). Overall, this systematic review found the severity of COVID-19 disease to be comparable among Omicron subvariants. As SARS-CoV-2 subvariants continue to emerge, these results highlight the continuing need for vaccination against SARS-CoV-2 infection alongside early antiviral intervention to support short-term management and long-term reduction of COVID-19-associated morbidity and mortality.

This study evaluates the anticipated health and economic effects of multiple COVID-19 vaccination strategies using an updated vaccine in Thailand. A previously published hybrid decision tree and Markov model, originally developed for the USA, was calibrated using Thailand-specific epidemiological, demographic, and economic data from 2024. The model assessed several age- and risk-based vaccination strategies assuming vaccine uptake ranging from 20

BACKGROUND:Using adapted COVID-19 vaccines targeting current variants in circulation is necessary for addressing the dynamic evolution of the SARS-CoV-2 virus and protecting against emerging variants. RESEARCH DESIGN AND METHODS:Using a previously published combined Markov-decision tree model adapted for the Dominican Republic, this study estimated the outcomes of different vaccination strategies targeting various age and risk groups. The model used age-specific epidemiology, clinical, cost, and quality-of-life inputs derived from the published literature and national surveillance data. Scenario analyses that included variations in the incidence of COVID-19 and sensitivity analyses were conducted to assess uncertainty. RESULTS:Compared to no vaccination, the vaccination strategy targeting adults aged ≥65 years and the high-risk population was estimated to prevent 9,272 symptomatic cases, 9,184 outpatient cases, 88 hospitalizations, 239 lost quality-adjusted life-years (QALYs), and three deaths, translating to total direct and societal cost savings of US$11,064,184 and US$12,662,370, respectively. Expanding vaccination to adults aged ≥60 years and high-risk individuals aged 18-59 years further increased public health and economic benefits. CONCLUSIONS:Implementing an adapted COVID-19 vaccine strategy for high-risk and adults aged ≥65 in the Dominican Republic is expected to be cost-saving, with broader age group coverage yielding even greater benefits.

The burden of COVID-19 in the paediatric population in low- and middle-income countries is not well characterized. Understanding COVID-19 burden in Latin American (LATAM) countries is essential for implementing effective vaccination policies and strategies for children and adolescents. We aimed to describe the characteristics of COVID-19-confirmed cases, addressing the risk of disease, severity and outcomes of the disease in children and adolescents in four LATAM countries between 2021 and 2022. We conducted a retrospective observational study utilizing national surveillance data from the four most populated countries in LATAM, Argentina, Brazil, Colombia, and Mexico, focusing on laboratory-confirmed COVID-19 cases among children and adolescents under 18 years of age between January 2021 and December 2022. We described sociodemographic characteristics of cases by age. Incidence rates per 100,000 inhabitants for confirmed COVID-19 cases were calculated. We estimated hospitalisation and mortality rates (per 100,000 inhabitants) as well as ICU admission and ventilatory support rates (per 100,000 hospitalised cases) per quartile each year, considering the predominant SARS-CoV-2 variant in each country during the specified period. In total 2,863,244 confirmed paediatric COVID-19 cases were included in the analysis: 1,553,234 (54

This study estimated the potential public health impact of alternative COVID-19 vaccination strategies in Singapore. The outcomes of alternative vaccination strategies using a Pfizer-BioNTech COVID-19 vaccine updated to the latest circulating strain were estimated using a combined decision tree-Markov cohort model. The model was previously used to estimate the impact of vaccination based on epidemiological data from 2021/22 and vaccine coverage data from 2022/23. It has now been updated with epidemiology data from 2023/24 and an assumed vaccine coverage of 20

IntroductionThe COVID-19 pandemic has significantly impacted the pediatric population worldwide, particularly those with comorbidities who often experience more severe outcomes. However, the impact of COVID-19 on pediatric oncology patients remain poorly understood.MethodsThis retrospective observational study examined data from 85 pediatric oncology patients aged <18 years who tested positive for COVID-19 at five study sites across Lebanon from March 2020 to May 2023. Detailed demographic, clinical, treatment, healthcare resource utilization (HCRU), and disease outcomes were collected. Outcomes was summarized descriptively and two-sided 95% confidence intervals (CI) were calculated using the Clopper-Pearson method.ResultsThere was 85 pediatric oncology patients diagnosed with COVID-19, with a mean age of 11.57 years. Of these, 72 patients (84.6%) had hematological malignancies and 13 (15.4%) had solid tumors. Thirteen patients (15.3%) had comorbidities. Treatment delays on oncology care occurred in 61 patients (71.8%). Twelve patients (14.1%) required hospitalization, four of whom needed intensive care unit (ICU) admission, with ICU stays ranging from 1 day to 2 months. COVID-19 related mortality was 4.7%.DiscussionCOVID-19 was associated with changes or delay in oncological treatment. In addition, the burden of COVID related hospitalization, intensive care utilization and death were substantial among pediatric cancer patients. Our findings highlight the importance of vaccination in pediatric oncology patients.

Abstract Objectives Predictions regarding the on-going burden of SARS-CoV-2, and vaccine recommendations, require an understanding of infection-associated immune protection. We assessed whether early COVID-19 provided protection against Omicron infection. Methods We enrolled a cohort of adults in Ontario, Canada, with COVID-19 prior to October 2020 (early infection, EI), and a matched cohort with COVID-19 testing and a negative PCR (non-EI). Participants completed baseline surveys then surveys every two weeks until January 2023. Multivariable Cox regression was used to assess factors associated with COVID-19 infection during the first 14 months of Omicron. Results Overall, 624 EI (70%) and 175 (77%) non-EI participants met criteria for analysis; 590 (95%) EI and 164 (94%) non-EI had received at least 2 COVID-19 vaccine doses prior to Omicron. Of 624 EI, 175 (28%) had one SARS-CoV-2 re-infection and 8 (1.3%) had two, compared to 84 (48%) non-EI participants with one, 5 (2.9%) with two and 1 (0.6%) with 3 infections (P < 0.0001). In multivariable analysis of risk factors for Omicron infection, the overall hazard ratio (HR, 95%CI) associated with EI was 0.56 (0.43–0.74); HRs for BA.1/2, BA.4/5 and mixed BA.5/BQ.1/XBB periods were 0.66 (0.45–0.97), 0.44 (0.28–0.68) and 0.71 (0.32–1.56). EI and BA.1/2 infection combined reduced later Omicron infection (HR 0.07 (0.03–0.21) compared to no prior infection. Older age, non-White ethnicity, no children in household, and lower neighbourhood income were associated with reduced risk of infection. Conclusions In our highly vaccinated population, early SARS-CoV-2 infection was associated with a 44% reduction in symptomatic COVID-19 during the first 14 months of Omicron, providing significant protection against re-infection for more than 2 years.

The COVID-19 pandemic imposed a substantial burden on healthcare systems worldwide, yet reliable data on COVID-19 morbidity, mortality, and healthcare costs in Latin America remain limited. This study explored the disease and economic burden of COVID-19 in Argentina, Brazil, Chile, Colombia, Mexico, and Peru during the pre-vaccination period. Using national databases and a systematic review of the literature, we analyzed data on adults aged 18 and older, reporting cases, death rates, years of life lost, excess mortality, and direct medical costs. Before vaccination programs began, the average COVID-19 incidence rate was 6741 per 100,000 adults. Of these, 91% were mild cases, 7% moderate/severe, and 2% critical. Among 2,201,816 hospitalizations, 27.8% required intensive care, and 17.5% required mechanical ventilation. Excess mortality ranged from 76 to 557 per 100,000, and years of life lost spanned 241,089 to 3,312,346. Direct medical costs ranged from USD 258 million to USD 10,437 million, representing 2–5% of national health expenditures. The findings highlight significant variability across countries and provide crucial insights to help policymakers to make informed decisions and allocate resources effectively to improve national strategies around surveillance, preventive and treatment strategies to control the spread of COVID-19 disease in the future.

BackgroundThe dynamic evolution of the virus causing COVID-19 necessitates the development of adapted vaccines to protect against emerging variants.Research design and methodsA combined Markov-decision tree model estimated the outcomes of alternative vaccination strategies. The Saudi Arabian population was stratified into standard-risk and high-risk subpopulations, defined as either the population comprising individuals aged >= 65 years and individuals with at least one comorbidity. The model estimated the health and economic outcomes of vaccination based on age-specific inputs taken from published sources and national surveillance data.ResultsThe vaccination strategy targeting the elderly and high-risk subpopulation (was estimated to prevent 156,694 cases 12,800 hospitalizations, and 2,919 deaths and result in cost savings of SAR 1,239 million in direct costs and SAR 4,145 million in indirect costs. These gains increased with the vaccination strategies additionally targeting other subpopulations. Compared to the base case (aged >= 65 and those at high-risk), expanding vaccination coverage to 75% of the standard-risk population prevented more cases (323%), hospitalizations (154%), and deaths (60%) and increased the direct (232%) and indirect (270%) cost savings.ConclusionsThe adoption of broad vaccination strategies using a vaccine adapted to the dominant variant in circulation would yield substantial benefits in Saudi Arabia.

This study was undertaken in COVID-19 patients treated with and without Paxlovid™ (Paxlovid) in an outpatient setting to determine hospitalization from the community. This retrospective secondary data observational cohort study was conducted between February and November 2022. All patients diagnosed by polymerase chain reaction for COVID-19 and at risk of COVID-19 disease progression were offered Paxlovid in the outpatient setting. Potential associations between Paxlovid use and likelihood of hospitalization, antibiotic use, and other clinical outcomes were explored using regression models as appropriate (i.e., logistic, multinomial, ordinal), adjusted for World Health Organization risk classification. Of 3011 COVID-19 patients offered Paxlovid, 2005 (67

OBJECTIVES:The impact of COVID-19 in Argentina's health and economic outcomes before the implementation of the national vaccination plan has not been fully characterized. This study aimed to estimate the health and economic burden of COVID-19 in the adult population in Argentina. METHODS:We conducted a retrospective observational study using a national COVID-19 surveillance data set to assess (1) clinical burden, including incidence rates, mortality rates, and patterns of hospitalization categorized by severity based on the World Health Organization criteria; (2) economic burden; and (3) years of life lost. The cost of illness analysis was used to estimate the cost per patient with COVID-19, expressed in 2023 US dollars ($). The analyzed period was from March 2020 to June 2021, before the introduction of the vaccination as a national strategic plan for COVID-19. RESULTS:During the study period, the incidence rate of COVID-19 among the adult population in Argentina was 11 490.2 cases per 100 000 persons. As in many other countries in the region, most cases were classified as mild (95%), followed by 4% severe cases (requiring hospitalization) and 1% critical cases (intensive care unit [ICU] admission). The age-standardized years of life lost per 100 000 persons increased steeply from 58.6 in the 20 to 29 age group to 576.1 in the 60 to 69 age group. The total cost associated with COVID-19 was $1370 million, ranging from $244 in mild cases to $791 in critical cases. Concerning the health sectors, a higher total cost is observed in the social security sector, accounting for nearly 51% of the total costs, mainly because it has the highest rate of health coverage. CONCLUSIONS:Before the vaccines were widely used, COVID-19 significantly strained Argentina's public health and economy. These discoveries can aid policy makers in making well-informed choices and distributing resources efficiently to enhance future national strategies concerning surveillance, prevention, treatment, and potential long-term impacts on community health.

BACKGROUND:This study evaluated the impact of various vaccination strategies using an adapted vaccine in Peru. RESEARCH DESIGN AND METHODS:Using a previously published combined Markov-decision-tree model adapted for Peru, this study estimated the outcomes of different vaccination strategies targeting various age and risk groups. The model used age-specific epidemiology, clinical, cost, and quality-of-life inputs derived from the published literature and national surveillance data. Sensitivity analyses were conducted to assess uncertainty. RESULTS:The vaccination strategy targeting older adults aged ≥ 60 years and the high-risk population between 12 and 59 years old with a 24% vaccine uptake was estimated to prevent 78,483 symptomatic cases, 2,962 hospitalizations, 103 deaths, and 2,913 lost QALYs compared with no vaccination, translating to an incremental decrease of $12,856,654 in total direct costs and an incremental decrease of $35,090,748 in total societal costs. These gains were further increased by expanding vaccination to additional age groups and increasing vaccine uptake. CONCLUSIONS:Vaccination in the population aged ≥ 60 years and the high-risk population between 12 and 59 years old in Peru was projected to yield substantial health and economic benefits. The impact could be substantially increased by expanding eligibility to younger age groups and increasing vaccine uptake.

This systematic literature review summarizes the evidence across 56 publications and pre-prints (January 2020-July 2023) with low-risk of bias based on JBI critical appraisal, that report adjusted estimates for the relationship between COVID-19 vaccination and Post-COVID-19 Condition (PCC) by timing of vaccination relative to infection or PCC-onset. Comparisons of adjusted vaccine effectiveness (aVE) against ≥1 PCC (vs. unvaccinated) across study characteristics known to impact PCC burden or VE against other COVID-19 endpoints were possible for 31 studies where vaccination preceded infection. Seventy-seven percent of pre-infection aVE estimates were statistically significant (range: 7%-95%). Statistically significant pre-infection aVE estimates were slightly higher for mRNA (range: 14%-84%) than non-mRNA vaccines (range: 16%-38%) and aVE ranges before and during Omicron overlapped. Our findings suggest that COVID-19 vaccination before SARS-CoV-2 infection reduces the risk of PCC regardless of vaccine type, number of doses received, PCC definition, predominant variant, and severity of acute infections included.

Background:Identifying cases at higher risk for severe COVID-19 outcomes is essential for tailoring interventions for prevention and treatment. We aimed to determine the factors related to hospitalisation, intensive care unit (ICU) admission, use of ventilatory support, and mortality in four Latin American countries. Methods:We conducted a retrospective study using national COVID-19 surveillance databases from Argentina, Brazil, Colombia, and Mexico, covering the period from January 2021 to December 2022. We used multivariate logistic regression models to identify factors associated with hospitalisation, ICU admission, ventilatory support, and death, adjusting for confounding variables. Results:We included 34 955 384 confirmed cases in the analysis. Age and sex were significantly associated with increased odds of all outcomes. For hospitalisation, in cases aged >85 years, the odds ratio (OR) for hospitalisation ranged from 26.46 (95% confidence interval (CI) = 25.67-27.28) in Mexico to 2763.87 (95% CI = 2644.40-2888.73) in Brazil, and for males, it ranged from 1.42 (95% CI = 1.41-1.43) in Colombia to 1.77 (95% CI = 1.76-1.78) in Brazil. Indigenous race was significantly associated with higher odds of hospitalisation (ORs ranging from 1.26 to 1.98) and death (ORs ranging from 1.05 to 1.84). The number of comorbidities reported was related to increased odds of severe outcomes and varied across countries. The odds of death for cases with zero vaccine doses were significantly higher (ORs ranging from 1.72 to 31.73) compared to cases with two doses. Similarly, the odds of death for cases with one dose were significantly higher (ORs ranging from 1.73 to 7.00) compared to cases with two doses. Conclusions:Even in a post-vaccine implementation scenario, individual factors such as age, gender, comorbidities, and race still pose a risk to severe COVID-19, which demands tailoring public health strategies for prevention and treatment.

BACKGROUND:This study evaluated the impact of vaccination strategies using an adapted COVID-19 vaccine in Mexico. RESEARCH DESIGN AND METHODS:This study used a previously published combined Markov-decision tree model adapted for the Mexican context. The base case examined the population aged ≥ 65 years and the high-risk population (defined as those with one or more comorbidities associated with high risk of severe disease) aged 12-64 years. Scenario analyses examined lower age cutoffs for eligibility in the standard risk population (≥50 years, ≥18 years, and ≥12 years). Sensitivity analyses varying the parameters by ± 20% was conducted to assess uncertainty. RESULTS:Compared to no vaccination, the base case was estimated to prevent 1,509,194 cases, 132,166 hospitalizations 24,575 deaths, and 276,223 lost quality-adjusted life-years (QALYs), increasing direct costs by $602,446,820 and decreasing societal cost by $2,264,266,271. The ICER was dominant from the societal perspective and $2,181 from the payer perspective, which was cost-effective at a willingness-to-pay threshold of 1× GDP per capita ($11,812). The benefits were further increased in scenarios expanding vaccination to additional age groups. CONCLUSIONS:Vaccination strategies targeting a broader age range with an adapted vaccine would result in considerable health and economic benefits and be cost-effective in Mexico.

Abstract Background As SARS-CoV-2 evolves, assessing changes in COVID-19 severity over time, and the impact of prior infection on repeat infection, is important. We determined whether developing COVID-19 early in the pandemic was associated with reduced severity of subsequent infection with Omicron sub-lineages. Methods We evaluated COVID-19 severity among patients infected during the Omicron wave. Severity was measured in 3 ways:(1) an ordinal measure combining activities of daily living (ADL) and presence of fever,(2) healthcare required (yes/no),(3) an ordinal measure of illness duration. We compared these outcomes in a study of age and time-period matched cohorts in Toronto, Canada: one with symptomatic COVID-19 between Mar 1 & Sep 30/2020 ('early COVID-19') and another who did not test positive for SARS-CoV-2 during the same period. Participants completed baseline, then biweekly surveys to identify SARS-CoV-2 infection episodes from Jan 2020 to Jan 2023. Multivariable binary and ordinal logistic regression models were used to construct ORs and 95% CI for impact of early COVID-19 on severity, adjusted for social/demographic characteristics, comorbidities, COVID-19 vaccination status, and time from early COVID-19 to first Omicron infection. Results Of 261 participants with COVID-19 due to Omicron (Table 1), 177 had early COVID-19 at a median of 26 months prior. In adjusted analyses, those with early COVID-19 occurring < 24 months prior to their Omicron infection had lower odds of having severe Omicron-related illness; OR 0.35 (95%CI 0.15-0.80); with non-significant lower odds of requirement for healthcare (OR 0.49,95%CI 0.14-1.8) and illness duration (OR 0.80, 95%CI 0.32-2.0) (Table 2). Immunocompromise was associated with more severe illness based on all 3 outcomes; other non-immunocompromising comorbidities were associated with requiring healthcare and longer illness duration, and females reported longer illness duration (Table 2). Conclusion Developing COVID-19 early in the pandemic was associated with reduced severity of first Omicron infection if it occurred < 24 months later. Immunocompromise and the presence of other underlying comorbidities were associated with increased severity, and women reported longer duration of illness. Disclosures Moe H. Kyaw, PhD, Pfizer: Employee Catherine Martin, PhD, Pfizer: employee|Pfizer: Stocks/Bonds (Private Company) Maria Major, B.Sc., M.P.H., Pfizer: Employee Samira Mubareka, MD, Pfizer: Grant/Research Support Srinivas Valluri, PhD, Pfizer: Employee John M. McLaughlin, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Allison McGeer, MD, AstraZeneca: Honoraria|GSK: Honoraria|Merck: Honoraria|Moderna: Honoraria|Novavax: Honoraria|Pfizer: Grant/Research Support|Pfizer: Honoraria|Roche: Honoraria|Seqirus: Grant/Research Support|Seqirus: Honoraria

Background:Our previous systematic review estimated the cumulative incidence of SARS-CoV-2 reinfections as 1.16% (95% CI = 1.01-1.33%) during the pre-Omicron period. The Omicron variant that emerged in November 2021 was significantly genetically distinct from the previous SARS-CoV-2 variants and thus, more transmissible and posed an increased risk of SARS-CoV-2 reinfections in the population. We, therefore, conducted a fresh systematic review and meta-analysis to estimate the SARS-CoV-2 reinfection burden during the Omicron period. Methods:We searched CINAHL, Medline, Global Health, Embase, and WHO COVID-19 in October 2023 for studies reporting the SARS-CoV-2 reinfection incidence during the Omicron period. The quality of the included studies was assessed using the Joanna Briggs Institute checklists. Random effects meta-analyses were conducted to estimate the incidence, and requirement of hospitalisation of SARS-CoV-2 reinfections. Symptomatic severity of reinfections and case fatality rates were analysed narratively. Results:Thirty-six studies were included. The reinfection cumulative incidence during the Omicron period was 3.35% (95% CI = 1.95-5.72%) based on data from 28 studies. The cumulative incidence was higher in 18-59-year-old adults (6.62% (95% CI = 3.22-13.12%)) compared to other age groups and in health care workers (9.88% (95% CI = 5.18-18.03%)) compared to the general population (2.48% (95% CI = 1.34-4.54%)). We estimated about 1.81% (95% CI = 0.18-15.87%) of the reinfected cases required hospitalisation based on limited and highly variable data. Conclusions:There was an increased risk of reinfections during the Omicron period compared to the pre-Omicron period. The incidence was higher in 18-59-year-old adults and health care workers and generally less severe during the Omicron period. However, data were limited on disease severity and long-term outcomes. Registration:PROSPERO: CRD42023482598.