Real-world effectiveness of original BNT162b2 mRNA COVID-19 against symptomatic Omicron infection among children 5-11 years of age in Brazil: A prospective test-negative design study.

OBJECTIVE: To estimate original wild-type BNT162b2 effectiveness against symptomatic Omicron infection among children 5-11 years of age. METHODS: This prospective test-negative, case-control study was conducted in Toledo, southern Brazil, from June 2022 to July 2023. Patients were included if they were aged 5-11 years, sought care for acute respiratory symptoms in the public health system, and were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction. In the primary analysis, we determined the effectiveness of two doses of original wild-type BNT162b2 against symptomatic COVID-19. The reference exposure group was the unvaccinated. RESULTS: A total of 757 children were enrolled; of these, 461 (25 cases; 436 controls) were included in the primary analysis. Mean age was 7.4 years, 49.7 % were female, 34.6 % were obese, and 14.1 % had chronic pulmonary disease. Omicron accounted for 100 % of all identified SARS-CoV-2 variants with BA.5, BQ.1, and XBB.1 accounting for 35.7 %, 21.4 % and 21.4 %, respectively. The adjusted estimate of two-dose vaccine effectiveness against symptomatic Omicron was 3.1 % (95 % CI, -133.7 % to 61.8 %) after a median time between the second dose and the beginning of COVID-19 symptoms of 192.5 days (interquartile range, 99 to 242 days). CONCLUSION: In this study with children 5-11 years of age, a two dose-schedule of original wild-type BNT162b2 was not associated with a significant protection against symptomatic Omicron infection after a median time between the second dose and the beginning of COVID-19 symptoms of 192 days, although the study may have been underpowered to detect a clinically important difference. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT05403307 (https://classic. CLINICALTRIALS: gov/ct2/show/NCT05403307).

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.

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.

COVID-19 in Latin America: A Snapshot in Time and the Road Ahead.

Since its initial detection in Brazil in February 2020, SARS-CoV-2 and the associated COVID-19 pandemic have continued to devastate Latin America. Specific comorbidities, as well as sociodemographic and lifestyle factors that may be more prevalent in underserved areas, have been identified as risk factors for COVID-19 infection or associated adverse outcomes. Dynamics of infections and deaths in Latin America have varied by country and temporally, as has SARS-CoV-2 variant prevalence; however, more recently, the Delta and subsequent Omicron variants have become ubiquitous. Successful pandemic responses have involved robust infection mitigation measures, testing, and smart deployment of healthcare resourcing. While in some Latin American countries up to 90% of the population is fully vaccinated (i.e., 2 doses) against COVID-19, other countries have failed to reach the World Health Organization's 70% target. Continued focus on comprehensive surveillance, strategies to maximize vaccine availability and uptake, and mitigation of collateral damage on other aspects of public health and social services are critical for managing the COVID-19 pandemic. This review summarizes the COVID-19 experience in Latin America, including epidemiology and vaccination. Key learnings and future considerations for the ongoing pandemic response are also discussed.

Psychological trauma and depression in recovered COVID-19 patients: a telecommunication based observational study.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is adversely affecting the mental health of patients infected with the virus and the psychological impact on recovered COVID-19 patients is unclear. OBJECTIVES: The study aimed to assess posttraumatic stress disorder (PTSD) and depression among COVID-19 patients after recovery from the disease. METHODS: This cross-sectional study was conducted from November 9, 2020, to December 23, 2020. The study used a telemedicine model to enroll recovered COVID-19 patients from a database of patients provided by the health authorities. The National Stressful Events Survey PTSD Short Scale (NSESSS) for adults was used to assess PTSD symptoms and the Patient Health Questionnaire (PHQ-9) was used to assess depression. RESULTS: The study enrolled 503 recovered COVID-19 patients with a mean age of 41.90 years. The majority were asymptomatic (64.6%), while 21.5% had had moderate to severe forms of the disease. Prevalence rates of PTSD symptoms and depression were 56.9 and 29% respectively. COVID-19 patients with severe forms of the disease were significantly more affected by PTSD symptoms (vs. mild, odds ratio [OR] = 18.7, 95%confidence interval [CI] 9.9-35.5) and depression (vs. mild, OR = 19.8, 95% CI 9.9-39.5). Similarly, patients who required oxygen or ventilator support reported significantly higher rates of PTSD symptoms (vs. managed at home, OR = 17.4, 95% CI 8.3-36.4) and depression (vs. managed at home, OR = 22.0, 95% CI 10.1-47.7). CONCLUSION: This study reports that recovered COVID-19 patients suffered from a significant amount of depression and experienced significant PTSD symptoms. It will help with addressing a major psychological concern among the recovered subjects.

Psychological trauma and depression in recovered COVID-19 patients: a telecommunication based observational study

Abstract Introduction Coronavirus disease 2019 (COVID-19) is adversely affecting the mental health of patients infected with the virus and the psychological impact on recovered COVID-19 patients is unclear. Objectives The study aimed to assess posttraumatic stress disorder (PTSD) and depression among COVID-19 patients after recovery from the disease. Methods This cross-sectional study was conducted from November 9, 2020, to December 23, 2020. The study used a telemedicine model to enroll recovered COVID-19 patients from a database of patients provided by the health authorities. The National Stressful Events Survey PTSD Short Scale (NSESSS) for adults was used to assess PTSD symptoms and the Patient Health Questionnaire (PHQ-9) was used to assess depression. Results The study enrolled 503 recovered COVID-19 patients with a mean age of 41.90 years. The majority were asymptomatic (64.6%), while 21.5% had had moderate to severe forms of the disease. Prevalence rates of PTSD symptoms and depression were 56.9 and 29% respectively. COVID-19 patients with severe forms of the disease were significantly more affected by PTSD symptoms (vs. mild, odds ratio [OR] = 18.7, 95%confidence interval [CI] 9.9-35.5) and depression (vs. mild, OR = 19.8, 95% CI 9.9-39.5). Similarly, patients who required oxygen or ventilator support reported significantly higher rates of PTSD symptoms (vs. managed at home, OR = 17.4, 95% CI 8.3-36.4) and depression (vs. managed at home, OR = 22.0, 95% CI 10.1-47.7). Conclusion This study reports that recovered COVID-19 patients suffered from a significant amount of depression and experienced significant PTSD symptoms. It will help with addressing a major psychological concern among the recovered subjects.

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.

Immune Response to COVID-19 and mRNA Vaccination in Immunocompromised Individuals: A Narrative Review.

Immunocompromised individuals are at high risk of poor coronavirus disease 2019 (COVID-19) outcomes and demonstrate a lower immune response to COVID-19 vaccines, including to the novel mRNA vaccines that have been shown to elicit high neutralizing antibody levels. This review synthesized available data on the immune response to COVID-19 and critically assessed mRNA COVID-19 vaccine immunogenicity in this vulnerable subpopulation. Patients with various immunocompromising conditions exhibit diverse responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 severity and mortality, and available vaccines elicit lower immune responses, particularly in solid organ transplant recipients. Strategies to improve vaccine responses in immunocompromised individuals are being implemented in vaccine recommendations, including the use of a third and fourth vaccine dose beyond the two-dose series. Additional doses may enhance vaccine effectiveness and help provide broad coverage against emerging SARS-CoV-2 variants. Continued investigation of vaccines and dosing regimens will help refine approaches to help protect this vulnerable subpopulation from COVID-19.

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.

Catalase Expression in Azospirillum brasilense Sp7 Is Regulated by a Network Consisting of OxyR and Two RpoH Paralogs and Including an RpoE1→RpoH5 Regulatory Cascade.

The genome of Azospirillum brasilense encodes five RpoH sigma factors: two OxyR transcription regulators and three catalases. The aim of this study was to understand the role they play during oxidative stress and their regulatory interconnection. Out of the 5 paralogs of RpoH present in A. brasilense, inactivation of only rpoH1 renders A. brasilense heat sensitive. While transcript levels of rpoH1 were elevated by heat stress, those of rpoH3 and rpoH5 were upregulated by H2O2 Catalase activity was upregulated in A. brasilense and its rpoH::km mutants in response to H2O2 except in the case of the rpoH5::km mutant, suggesting a role for RpoH5 in regulating inducible catalase. Transcriptional analysis of the katN, katAI, and katAII genes revealed that the expression of katN and katAII was severely compromised in the rpoH3::km and rpoH5::km mutants, respectively. Regulation of katN and katAII by RpoH3 and RpoH5, respectively, was further confirmed in an Escherichia coli two-plasmid system. Regulation of katAII by OxyR2 was evident by a drastic reduction in growth, KatAII activity, and katAII::lacZ expression in an oxyR2::km mutant. This study reports the involvement of RpoH3 and RpoH5 sigma factors in regulating oxidative stress response in alphaproteobacteria. We also report the regulation of an inducible catalase by a cascade of alternative sigma factors and an OxyR. Out of the three catalases in A. brasilense, those corresponding to katN and katAII are regulated by RpoH3 and RpoH5, respectively. The expression of katAII is regulated by a cascade of RpoE1→RpoH5 and OxyR2.IMPORTANCEIn silico analysis of the A. brasilense genome showed the presence of multiple paralogs of genes involved in oxidative stress response, which included 2 OxyR transcription regulators and 3 catalases. So far, Deinococcus radiodurans and Vibrio cholerae are known to harbor two paralogs of OxyR, and Sinorhizobium meliloti harbors three catalases. We do not yet know how the expression of multiple catalases is regulated in any bacterium. Here we show the role of multiple RpoH sigma factors and OxyR in regulating the expression of multiple catalases in A. brasilense Sp7. Our work gives a glimpse of systems biology of A. brasilense used for responding to oxidative stress.