Pediatric COVID-19 in Argentina: a comprehensive analysis of disease and economic burden through official data and a systematic literature review.

Background: Limited data are available on the clinical impact and economic burden of COVID-19 in the pediatric population in Argentina. We aimed to estimate the disease and economic burden of COVID-19 on children and adolescents. Methods: We analyzed official national databases and conducted a supplemental systematic review of the published literature with meta-analysis in children aged 0-18. The period of interest was from March 2020 to August 2021, before the introduction of vaccination in this age group as a national strategic plan. In addition, we used a cost of illness analysis to estimate the direct medical costs associated with COVID-19. All costs are reported in US dollars 2023. Results: A total of 450,503 confirmed COVID-19 cases and 180 multisystem inflammatory syndrome (MIS-C) were reported in Argentina in the study period. Fourteen observational clinical studies were identified. The meta-analyses of severity level from hospital patients showed that according to different studies 15%-28% of cases were asymptomatic, 68%-88% were mild or moderate, and 3%-10% were severe or critical. About 28% of children had an underlying disease. In addition, the estimated economic burden associated with COVID-19 was 80 million dollars and 4 million dollars corresponded to MISC. Conclusion: Significant impact of COVID-19 on the healthcare system and substantial economic implications for the pediatric population in Argentina were identified. The findings should help policymakers to make informed decisions and allocate resources effectively.

Duration of SARS-CoV-2 shedding: A systematic review.

Background: Positive viral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cultures indicate shedding of infectious virus and corresponding transmission risk of coronavirus disease 2019 (COVID-19). The research question of this systematic review was: Is there a discernible pattern in the timing of SARS-CoV-2 virus isolation, and what is the proportion of positive and negative results for isolation of SARS-CoV-2 virus with viral culture relative to the onset of clinical symptoms or the day of diagnosis, as indicated by longitudinal studies? Methods: We systematically searched PubMed and Embase from inception to 16 February 2023 for English-language studies with serial viral culture testing within symptomatic or asymptomatic SARS-CoV-2 infected persons during the post-vaccination period. Outcomes of interest were the daily culture status per study and the overall daily culture positivity rate of SARS-CoV-2. We critically appraised the selected studies using the Newcastle-Ottawa quality assessment scale. Results: We included 14 viral shedding studies in this systematic review. Positive viral SARS-CoV-2 cultures were detected in samples ranging from 4 days before to 18 days after symptom onset. The daily culture SARS-CoV-2 positivity rate since symptom onset or diagnosis showed a steep decline between day 5 and 9, starting with a peak ranging from 44% to 50% on days -1 to 5, decreasing to 28% on day 7 and 11% on day 9, and finally ranging between 0% and 8% on days 10-17. Conclusions: Viral shedding peaked within 5 days since symptom onset or diagnosis and the culture positivity rate rapidly declined hereafter. This systematic review provides an overview of current evidence on the daily SARS-CoV-2 culture positivity rates during the post-vaccination period. These findings could be used to estimate the effectiveness of public health control measures, including treatment and preventive strategies, to reduce the spread of COVID-19.

Epidemiology and clinical features of SARS-CoV-2 infection in children and adolescents in the pre-Omicron era: A global systematic review and meta-analysis.

Methods: We searched MEDLINE, Embase, Global Health, CINAHL, China National Knowledge Infrastructure, Wanfang, CQvip, and the World Health Organization (WHO) COVID-19 global literature databases for primary studies recruiting children aged ≤18 years with a diagnosis of SARS-CoV-2 infection confirmed either by molecular or antigen tests. We used the Joanna Briggs Institute critical appraisal tools to appraise the study quality and conducted meta-analyses using the random effects model for all outcomes except for race/ethnicity as risk factors of SARS-CoV-2 infection. Results: We included 237 studies, each reporting at least one of the study outcomes. Based on data from 117 studies, the pooled SARS-CoV-2 positivity rate was 9.30% (95% confidence interval (CI) = 7.15-11.73). Having a comorbidity was identified as a risk factor for SARS-CoV-2 infection (risk ratio (RR) = 1.33; 95% CI = 1.04-1.71) based on data from 49 studies. Most cases in this review presented with mild disease (n = 50; 52.47% (95% CI = 44.03-60.84)). However, 20.70% of paediatric SARS-CoV-2 infections were hospitalised (67 studies), 7.19% required oxygen support (57 studies), 4.26% required intensive care (93 studies), and 2.92% required assisted ventilation (63 studies). The case fatality ratio (n = 119) was 0.87% (95% CI = 0.54-1.28), which included in-hospital and out-of-hospital deaths. Conclusions: Our data showed that children were at risk for SARS-CoV-2 infections and severe outcomes in the pre-Omicron era. These findings underscore the need for effective vaccination strategies for the paediatric population to protect against the acute and long-term sequelae of COVID-19. Registration: PROSPERO: CRD42022327680.

Descriptive analysis to assess seasonal patterns of COVID-19 and influenza in low-income and middle-income countries in Asia, the Middle East and Latin America.

OBJECTIVES: Understanding disease seasonality can help predict the occurrence of outbreaks and inform public health planning. Respiratory diseases typically follow seasonal patterns; however, knowledge regarding the seasonality of COVID-19 and its impact on the seasonality of influenza remains limited. The objective of this study was to provide more evidence to understand the circulation of SARS-CoV-2, the virus responsible for COVID-19, in an endemic scenario to guide potential preventive strategies. DESIGN: In this study, a descriptive analysis was undertaken to describe seasonality trends and/or overlap between COVID-19 and influenza in 12 low-income and middle-income countries using Our World in Data and FluMart data sources. Plots of COVID-19 and influenza cases were analysed. SETTING: Singapore, Thailand, Malaysia, the Philippines, Argentina, Brazil, Mexico, South Africa, Morocco, Bahrain, Qatar and Saudi Arabia. OUTCOME MEASURES: COVID-19 cases and influenza cases. RESULTS: No seasonal patterns of SARS-CoV-2 or SARS-CoV-2/influenza cocirculation were observed in most countries, even when considering the avian influenza pandemic period. CONCLUSIONS: These results can inform public health strategies. The lack of observed seasonal behaviour highlights the importance of maintaining year-round vaccination rather than implementing seasonal campaigns. Further research investigating the influence of climate conditions, social behaviour and year-round preventive measures could be fundamental for shaping appropriate policies related to COVID-19 and respiratory viral disease control in low-income and middle-income countries as COVID-19 variant data and epidemiologic patterns accrue over time.

Definition and measurement of post-COVID-19 conditions in real-world practice: a global systematic literature review.

Post-COVID-19 conditions (PCC) is an umbrella term that encompasses a range of signs, symptoms and conditions present weeks after the acute phase of a SARS-CoV-2 infection. This systematic literature review summarises the heterogeneous methodology used to measure PCC across real-world studies and highlights trends by region, age group, PCC follow-up period and data source. METHODS: Medline, EMBASE and the Cochrane Library were searched and supplemented with conference and grey literature searches. Eligible studies included individuals with (1) PCC or (2) a positive SARS-CoV-2 test or COVID-19 diagnosis who were followed over time. Included studies were published in English between 1 January 2020 and 14 November 2022. FINDINGS: Of 291 publications included, 175 (60%) followed individuals with confirmed COVID-19 over time for PCC and 116 (40%) used a prespecified PCC definition. There was substantial heterogeneity in study design, geography, age group, PCC conditions/symptoms assessed and their classification and duration of follow-up. Among studies using a prespecified PCC definition, author-defined criteria (51%) were more common than criteria recommended by major public health organisations (19%). Measurement periods for PCC outcomes from date of acute COVID-19 test were primarily 3 to <6 months (39.2%), followed by 6 to <12 months (27.5%) and <3 months (22.9%). When classified by organ/system, constitutional-related PCC were the most frequently assessed in adult (86%) and paediatric (87%) populations. Within constitutional symptoms, fatigue was most frequently assessed in adult (91.6%) and paediatric (95.0%) populations, followed by fever/chills (37.9% and 55%, respectively). CONCLUSIONS: PCC definitions are heterogenous across real-world studies, which limits reliable comparisons between studies. However, some similarities were observed in terms of the most frequently measured PCC-associated symptoms/conditions, which may aid clinical management of patients with PCC.CRD42022376111.

Modelling the Potential Public Health Impact of Different COVID-19 Vaccination Strategies with an Adapted Vaccine in Singapore.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 has been a dynamically changing virus, requiring the development of adapted vaccines. This study estimated the potential public health impact alternative vaccination strategies for COVID-19 in Singapore. RESEARCH DESIGN AND METHODS: The outcomes of alternative vaccination strategies with a future adapted vaccine were estimated using a combined Markov decision tree model. The population was stratified by high- and standard-risk. Using age-specific inputs informed by local surveillance data and published sources, the model estimated health (case numbers, hospitalizations, and deaths) and economic (medical costs and productivity losses) outcomes in different age and risk subpopulations. RESULTS: Booster vaccination in only the elderly and high-risk subpopulation was estimated to avert 278,614 cases 21,558 hospitalizations, 239 deaths, Singapore dollars (SGD) 277 million in direct medical costs, and SGD 684 million in indirect medical costs. These benefits increased as vaccination was expanded to other subpopulations. Increasing the booster vaccination coverage to 75% of the standard-risk population averted more deaths (3%), hospitalizations (29%), infections (145%), direct costs (90%), and indirect costs (192%) compared to the base case. CONCLUSIONS: Broader vaccination strategies using an adapted booster vaccine could have substantial public health and economic impact in Singapore.

Incidence and outcome of SARS-CoV-2 reinfection in the pre-Omicron era: A global systematic review and meta-analysis.

Background: With the emergence of new variants and sub-lineages of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), reinfections can significantly impact herd immunity, vaccination policies, and decisions on other public health measures. We conducted a systematic review and meta-analysis to synthesise the global evidence on SARS-CoV-2 reinfections in the pre-Omicron era. Methods: We searched five global databases (MEDLINE, Embase, CINAHL Plus, Global Health, WHO COVID-19) on 12 May 2022 and 28 July 2023 and three Chinese databases (CNKI, Wanfang, CQvip) on 16 October 2022 for articles reporting incidence and outcomes of SARS-CoV-2 reinfection before the period of Omicron (B.1.1.529) predominance. We assessed risk of bias using Joanna Briggs Institute critical appraisal tools and conducted meta-analyses with random effects models to estimate the proportion of SARS-CoV-2 reinfection among initially infected cases and hospitalisation and mortality proportions among reinfected ones. Results: We identified 7593 studies and extracted data from 64 included ones representing 21 countries. The proportion of SARS-CoV-2 reinfection was 1.16% (95% confidence interval (CI) = 1.01-1.33) based on 11 639 247 initially infected cases, with ≥45 days between the two infections. Healthcare providers (2.28%; 95% CI = 1.37-3.40) had a significantly higher risk of reinfection than the general population (1.00%; 95% CI = 0.81-1.20), while young adults aged 18 to 35 years (1.01%; 95% CI = 0.8-1.25) had a higher reinfection burden than other age groups (children <18 years old: 0.57%; 95% CI = 0.39-0.79, older adults aged 36-65 years old: 0.53%; 95% CI = 0.41-0.65, elderly >65 years old: 0.37%; 95% CI = 0.15-0.66). Among the reinfected cases, 8.12% (95% CI = 5.30-11.39) were hospitalised, 1.31% (95% CI = 0.29-2.83) were admitted to the intensive care unit, and 0.71% (95% CI = 0.02-2.01) died. Conclusions: Our data suggest a relatively low risk of SARS-CoV-2 reinfection in the pre-Omicron era, but the risk of hospitalisation was relatively high among the reinfected cases. Considering the possibility of underdiagnosis, the reinfection burden may be underestimated. Registration: PROSPERO: CRD42023449712.

Modelling the potential public health impact of different vaccination strategies with an omicron-adapted bivalent vaccine in Thailand.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 has continuously evolved, requiring the development of adapted vaccines. This study estimated the impact of the introduction and increased coverage of an Omicron-adapted bivalent booster vaccine in Thailand. RESEARCH DESIGN AND METHODS: The outcomes of booster vaccination with an Omicron-adapted bivalent vaccine versus no booster vaccination were estimated using a combined cohort Markov decision tree model. The population was stratified into high- and standard-risk subpopulations. Using age-specific inputs informed by published sources, the model estimated health (case numbers, hospitalizations, and deaths) and economic (medical costs and productivity losses) outcomes in different age and risk subpopulations. RESULTS: Booster vaccination in only the elderly and high-risk subpopulation was estimated to avert 97,596 cases 36,578 hospitalizations, 903 deaths, THB 3,119 million in direct medical costs, and THB 10,589 million in indirect medical costs. These benefits increased as vaccination was expanded to other subpopulations. Increasing the booster vaccination coverage to 75% of the standard-risk population averted more deaths (95%), hospitalizations (512%), infections (782%), direct costs (550%), and indirect costs (687%) compared to the base case. CONCLUSIONS: Broader vaccination with an Omicron-adapted bivalent booster vaccine could have significant public health and economic benefits in Thailand.

Impact of vaccination and non-pharmacological interventions on COVID-19: a review of simulation modeling studies in Asia.

Introduction: Epidemiological modeling is widely used to offer insights into the COVID-19 pandemic situation in Asia. We reviewed published computational (mathematical/simulation) models conducted in Asia that assessed impacts of pharmacological and non-pharmacological interventions against COVID-19 and their implications for vaccination strategy. Methods: A search of the PubMed database for peer-reviewed, published, and accessible articles in English was performed up to November 2022 to capture studies in Asian populations based on computational modeling of outcomes in the COVID-19 pandemic. Extracted data included model type (mechanistic compartmental/agent-based, statistical, both), intervention type (pharmacological, non-pharmacological), and procedures for parameterizing age. Findings are summarized with descriptive statistics and discussed in terms of the evolving COVID-19 situation. Results: The literature search identified 378 results, of which 59 met criteria for data extraction. China, Japan, and South Korea accounted for approximately half of studies, with fewer from South and South-East Asia. Mechanistic models were most common, either compartmental (61.0%), agent-based (1.7%), or combination (18.6%) models. Statistical modeling was applied less frequently (11.9%). Pharmacological interventions were examined in 59.3% of studies, and most considered vaccination, except one study of an antiviral treatment. Non-pharmacological interventions were also considered in 84.7% of studies. Infection, hospitalization, and mortality were outcomes in 91.5%, 30.5%, and 30.5% of studies, respectively. Approximately a third of studies accounted for age, including 10 that also examined mortality. Four of these studies emphasized benefits in terms of mortality from prioritizing older adults for vaccination under conditions of a limited supply; however, one study noted potential benefits to infection rates from early vaccination of younger adults. Few studies (5.1%) considered the impact of vaccination among children. Conclusion: Early in the COVID-19 pandemic, non-pharmacological interventions helped to mitigate the health burden of COVID-19; however, modeling indicates that high population coverage of effective vaccines will complement and reduce reliance on such interventions. Thus, increasing and maintaining immunity levels in populations through regular booster shots, particularly among at-risk and vulnerable groups, including older adults, might help to protect public health. Future modeling efforts should consider new vaccines and alternative therapies alongside an evolving virus in populations with varied vaccination histories.

Burden of COVID-19 during the omicron predominance in Brazil: a nationwide retrospective database study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has imposed significant burden on Brazil's health system. This study aimed to examine clinical characteristics, overall vaccine uptake, and to assess healthcare resource utilization (HCRU) and costs associated with acute COVID-19 in Brazil during the Omicron predominant period. METHODS: A nationwide retrospective study was conducted using various Brazilian databases including, COVID-19 related databases, public health systems, and other surveillance/demographic datasets. Individuals with positive COVID-19 test results between January 1 2022 and April 30 2022, during Omicron BA.1/BA.2 wave, were identified. Patients' demographics, vaccine uptake, HCRU and corresponding costs were described by age groups. RESULTS: A total of 8,160,715 (3.80%) COVID-19 cases were identified in the study cohort, ranging from 2.43% in <5 years to 62.05% in 19-49 years. The uptake of partial (Dose 1) or full immunization (Dose 2) was less than 0.1% in children aged <5 years, whereas in individuals ≥ 19 years, it exceeded 89.78% for Dose 1 and 84.07% for Dose 2. Overall booster vaccine uptake was 38.06%, which was significantly higher among individuals aged ≥ 65 years, surpassing 74.79%. Regardless of vaccination status, 87.2% cases were symptomatic, and 1.48% were hospitalized due to acute COVID-19 (<5 years: 2.33%, 5-11 years: 0.99%, 12-18 years: 0.32%, 19-49 years: 0.40%; 50-64 years: 1.50%, 65-74 years: 5.43%, and ≥ 75 years: 17.89%). Among the hospitalized patients (n = 120,450), 32.57% were admitted to ICU, of whom 31,283 (79.75%) individuals required mechanical ventilation (MV) support. The average cost per day in normal ward and ICU without MV in public/general hospital settings was $104.36 and $302.81, respectively. While average cost per day in normal ward and ICU with MV was $75.91 and $301.22 respectively. CONCLUSIONS: This study quantified the burden of COVID-19 in Brazil, suggesting substantial healthcare resources required to manage the COVID-19 pandemic.

Modeling the potential public health impact of different vaccination strategies with an omicron-adapted bivalent vaccine in Malaysia.

BACKGROUND: Coronavirus disease 2019 (COVID-19) case numbers have increased following the emergence of the Omicron variant. This study estimated the impact of introducing and increasing the coverage of an Omicron-adapted bivalent booster vaccine in Malaysia. RESEARCH DESIGN AND METHODS: A combined cohort Markov decision tree model was used to compare booster vaccination with an Omicron-adapted bivalent COVID-19 vaccine versus no booster vaccination in Malaysia. The model utilized age-specific data from January 2021 to March 2022 derived from published sources. The outcomes of interest included case numbers, hospitalizations, deaths, medical costs, and productivity losses. The population was stratified into high-risk and standard-risk subpopulations, and the study evaluated the benefits of increased coverage in different age and risk groups. RESULTS: Vaccinating only high-risk individuals and those aged ≥ 65 years was estimated to avert 274,313 cases, 33229 hospitalizations, 2,434 deaths, Malaysian ringgit (MYR) 576 million in direct medical costs, and MYR 579 million in indirect costs. Expanding vaccination coverage in the standard-risk population to 75% was estimated to avert more deaths (31%), hospitalizations (155%), infections (206%), direct costs (206%), and indirect costs (281%). CONCLUSIONS: These findings support broader population Omicron-adapted bivalent booster vaccination in Malaysia with potential for significant health and economic gains.

BNT162b2 mRNA COVID-19 against symptomatic Omicron infection following a mass vaccination campaign in southern Brazil: A prospective test-negative design study.

BACKGROUND: Evidence regarding effectiveness of BNT162b2 mRNA COVID-19 vaccine against Omicron in Latin America is limited. We estimated BNT162b2 effectiveness against symptomatic COVID-19 in Brazil when Omicron was predominant. METHODS: This prospective test-negative, case-control study was conducted in Toledo, Brazil, following a mass COVID-19 vaccination with BNT162b2. Patients were included if they were aged ≥12 years, sought care for acute respiratory symptoms in the public health system between November 3, 2021 and June 20, 2022, and were tested for SARS-CoV-2 using RT-PCR. In the primary analysis, we determined the effectiveness of two doses of BNT162b2 against symptomatic COVID-19. RESULTS: A total of 4,574 were enrolled; of these, 1,758 patients (586 cases and 1,172 controls) were included in the primary analysis. Mean age was 27.7 years, 53.8 % were women, and 90.1 % had a Charlson comorbidity index of zero. Omicron accounted for >97 % of all identified SARS-CoV-2 variants, with BA.1 and BA.2 accounting for 84.3 % and 12.6 %, respectively. Overall adjusted estimate of two-dose vaccine effectiveness against symptomatic COVID-19 was 46.7 % (95 %CI, 19.9 %-64.6 %) after a median time between the second dose and the beginning of COVID-19 symptoms of 94 days (IQR, 60-139 days). Effectiveness waned from 77.7 % at 7-29 days after receipt of a second dose to <30 % (non-significant) after ≥120 days. CONCLUSION: In a relatively young and healthy Brazilian population, two doses of BNT162b2 provided protection against symptomatic Omicron infection. However, this protection waned significantly over time, underscoring the need for boosting with variant-adapted vaccines in this population prior to waves of disease activity. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT05052307 (https://clinicaltrials.gov/ct2/show/NCT05052307).

Narrative Review of the Evolution of COVID-19 Vaccination Recommendations in Countries in Latin America, Africa and the Middle East, and Asia.

The rapid rollout of vaccines to combat the coronavirus disease 2019 (COVID-19) pandemic over the past 2 years has resulted in the use of various vaccine platforms and regional differences in COVID-19 vaccine implementation strategies. The aim of this narrative review was to summarize evolving COVID-19 vaccine recommendations in countries in Latin America, Asia, and Africa and the Middle East across various vaccine platforms, age groups, and specific subpopulations. Nuances in primary and booster vaccination schedules were evaluated, and the preliminary impact of such diverse vaccination strategies are discussed, including key vaccine effectiveness data in the era of Omicron-lineage variants. Primary vaccination rates for included Latin American countries were 71-94% for adults and between 41% and 98% for adolescents and children; rates for first booster in adults were 36-85%. Primary vaccination rates for adults in the included Asian countries ranged from 64% in the Philippines to 98% in Malaysia, with corresponding booster rates varying from 9% in India to 78% in Singapore; for adolescents and children, primary vaccination rates ranged from 29% in the Philippines to 93% in Malaysia. Across included African and Middle Eastern countries, primary vaccination rates in adults varied widely from 32% in South Africa to 99% in the United Arab Emirates; booster rates ranged from 5% in South Africa to 60% in Bahrain. Evidence from the regions studied indicates preference of using an mRNA vaccine as a booster on the basis of safety and effectiveness of observed real-world data, especially during circulation of Omicron lineages. Vaccination against COVID-19 remains of paramount importance to reduce the burden of disease; strategies to overcome vaccine inequity, fatigue, hesitancy, and misinformation and to ensure adequate access and supply are also important.

Evidence synthesis and pooled analysis of vaccine effectiveness for COVID-19 mRNA vaccine BNT162b2 as a heterologous booster after inactivated SARS-CoV-2 virus vaccines.

Introduction of primary COVID-19 vaccination has helped reduce severe disease and death caused by SARS-CoV-2 infection. Understanding the protection conferred by heterologous booster regimens informs alternative vaccination strategies that enable programmatic resilience and can catalyze vaccine confidence and coverage. Inactivated SARS-CoV-2 vaccines are among the most widely used vaccines worldwide. This review synthesizes the available evidence identified as of May 26, 2022, on the safety, immunogenicity, and effectiveness of a heterologous BNT162b2 (Pfizer-BioNTech) mRNA vaccine booster dose after an inactivated SARS-CoV-2 vaccine primary series, to help protect against COVID-19. Evidence showed that the heterologous BNT16b2 mRNA vaccine booster enhances immunogenicity and improves vaccine effectiveness against COVID-19, and no new safety concerns were identified with heterologous inactivated primary series with mRNA booster combinations.

Hybrid Immunity to SARS-CoV-2 from Infection and Vaccination-Evidence Synthesis and Implications for New COVID-19 Vaccines.

COVID-19 has taken a severe toll on the global population through infections, hospitalizations, and deaths. Elucidating SARS-CoV-2 infection-derived immunity has led to the development of multiple effective COVID-19 vaccines and their implementation into mass-vaccination programs worldwide. After ~3 years, a substantial proportion of the human population possesses immunity from infection and/or vaccination. With waning immune protection over time against emerging SARS-CoV-2 variants, it is essential to understand the duration of protection, breadth of coverage, and effects on reinfection. This targeted review summarizes available research literature on SARS-CoV-2 infection-derived, vaccination-elicited, and hybrid immunity. Infection-derived immunity has shown 93-100% protection against severe COVID-19 outcomes for up to 8 months, but reinfection is observed with some virus variants. Vaccination elicits high levels of neutralizing antibodies and a breadth of CD4+ and CD8+ T-cell responses. Hybrid immunity enables strong, broad responses, with high-quality memory B cells generated at 5- to 10-fold higher levels, versus infection or vaccination alone and protection against symptomatic disease lasting for 6-8 months. SARS-CoV-2 evolution into more transmissible and immunologically divergent variants has necessitated the updating of COVID-19 vaccines. To ensure continued protection against SARS-CoV-2 variants, regulators and vaccine technical committees recommend variant-specific or bivalent vaccines.

BNT162b2 against COVID-19 in Brazil using a test-negative design: Study protocol and statistical analysis plan.

INTRODUCTION: Real-world data on COVID-19 vaccine effectiveness are needed to validate evidence from randomized clinical trials. Accordingly, this study aims to evaluate, in a real-world setting in Brazil, the effectiveness of Pfizer-BioNTech BNT162b2 against symptomatic COVID-19 and COVID-19-related complications across diverse populations. MATERIALS AND METHODS: A test-negative case-control study with follow-up of cases is currently being conducted in Toledo, a city in southern Brazil, following a mass COVID-19 vaccination campaign with BNT162b2. The study is being conducted among patients aged 12 years or older seeking care in the public health system with acute respiratory symptoms and tested for SARS-CoV-2 on reverse transcription polymerase chain reaction (RT-PCR). Cases are RT-PCR positive and controls RT-PCR negative. Test-positive cases are prospectively followed through structured telephone interviews performed at 15 days post-enrollment, and at 1, 3, 6, 9 and 12 months. Baseline demographic, clinical, and vaccination data are being collected by means of structured interviews and medical registry records reviews at the time of enrollment. All RT-PCR-positive samples are screened for mutations to identify SARS-CoV-2 variants. ETHICS AND DISSEMINATION: The study protocol has been approved by the research ethics committee of all participant sites. Study findings will be disseminated through peer-reviewed publications and conference presentations. TRAIL REGISTRATION: Clinicatrials.gov: NCT05052307.

COVID-19 disease and vaccination in pregnant and lactating women.

BACKGROUND: More than 325,000 cases of coronavirus disease 2019 (COVID-19) have been reported among pregnant women in the Americas. AIMS: This review examines the impact of COVID-19 in pregnant women and describes available evidence on the safety, effectiveness, and immune response(s) to vaccination among pregnant and lactating women. CONTENT: Multiple studies indicate that pregnant women are more susceptible to adverse COVID-19 outcomes, including hospitalization, intensive care unit admission, and invasive ventilation than non-pregnant women with COVID-19. Furthermore, COVID-19 in pregnancy is associated with adverse maternal and neonatal outcomes. Adverse COVID-19 outcomes appear to disproportionately affect pregnant women from low- and middle-income countries, likely reflecting inequities in access to quality healthcare. Despite the absence of safety and efficacy data from randomized clinical trials in this subpopulation, observational studies and data from pregnancy registries thus far have demonstrated that vaccination of pregnant or lactating women against COVID-19 is safe, effective, and results in robust immune responses including transfer of antibodies to the newborn via the placenta and breast milk, respectively. IMPLICATIONS: These data support vaccination recommendations intending to help protect these vulnerable individuals against COVID-19 and its sequelae. Randomized clinical studies will further evaluate the safety and immunogenicity of COVID-19 vaccines in these populations. This review examines the impact of COVID-19 in pregnant women and describes available evidence on the safety, effectiveness, and immune response(s) to vaccination among pregnant and lactating women.

Incidence, aetiology and serotype coverage for pneumococcal vaccines of community-acquired pneumonia in adults: a population-based prospective active surveillance study in Brazil.

OBJECTIVES: To determine the incidence, aetiology and pneumococcal serotype distribution of community-acquired pneumonia (CAP) in Brazilian adults during a 2-year period. DESIGN: Prospective population-based surveillance study. SETTING: Patients from two emergency hospitals in Brazil were consecutively included in this study. PARTICIPANTS: A total of 111 adults aged 50 years and older with radiographically-confirmed CAP requiring an emergency department visit were prospectively enrolled between January 2018 and January 2020. MAIN OUTCOME MEASURES: Incidence rates of CAP were calculated according to age and pathogen. Pathogens were identified by conventional microbiological methods. Additionally, a novel, Luminex-based serotype specific urinary antigen detection assay was used to detect serotypes included in pneumococcal vaccines. RESULTS: Mean age of participants was 64 years and 31% were aged ≥70 years. Aetiology was established in 61 (57%) patients; among identified cases, the most common pathogens were Streptococcus pneumoniae (42/61, 69%) and influenza (4/61, 7%). Among serotypes identified from the 42 cases of pneumococcal CAP, estimated coverage ranged by pneumococcal vaccine formulations from 47.6% (13-valent), 59.5% (20-valent, licenced in the USA only) and 71.4% (23-valent). In patients with CAP, 20-valent pneumococcal vaccine serotypes were identified 2.5 times more frequently than 10-valent pneumococcal vaccine serotypes (22.5% vs 9.0%). The incidence rate for CAP in adults aged ≥50 years was 20.1 per 10 000 person-years. In general, the incidence of CAP increased consistently with age, reaching 54.4 (95% CI 36.8 to -76.6) per 10 000 in adults 80 years or older. CONCLUSIONS: We observed a high burden of pneumococcal CAP among adults in Brazil. Despite the routine immunisation of children and high-risk adults against pneumococcal disease in the Brazilian national vaccination programme, a persistent burden of pneumococcal CAP caused by vaccine serotypes remains in this population.

Reply letter to "response to article by Johnna Perdrizet et al." by Gomez and colleagues.

This communication seeks to address the questions and criticisms issued by Gomez and colleagues in their letter on our original study "Cost-effectiveness analysis of replacing the 10-valent pneumococcal conjugate vaccine (PCV10) with the 13-valent pneumococcal conjugate vaccine (PCV13) in Brazil infants." Gomez and colleagues are concerned that the assumptions used in our model may have unintended negative impacts for Brazil decision-making and we intend to clarify any potential misinterpretation of our assessment.