Correction: Effectiveness of a monthly schedule of follow-up for the treatment of uncomplicated severe acute malnutrition in Sokoto, Nigeria: A cluster randomized crossover trial.

[This corrects the article DOI: 10.1371/journal.pmed.1003923.].

Confronting Health Misinformation Surrounding COVID-19 Vaccines in the State of Florida.

COVID-19 vaccination is estimated to have averted more than 2.4 million deaths globally. In the United States (U.S.) alone, more than 120,000 deaths and 700,000 hospitalizations are reportedly estimated to have been prevented during the first six months of the vaccine campaign. Despite the overwhelming evidence regarding the safety and efficacy of vaccination, COVID-19 vaccine hesitancy continues to pose a significant threat to public health. Notably, an unexpected source of vaccine misinformation has been the Surgeon General of the State of Florida, Dr. Joseph Ladapo. While both a tenured faculty member of the University of Florida, College of Medicine and the Surgeon General of Florida, Dr. Ladapo has delivered official Florida Department of Health statements regarding COVID-19 vaccines that run contrary to those of the U.S. Centers for Disease Control and Prevention (CDC). While tenure is designed to protect those with contrarian views, we believe that the University has an ethical obligation to condemn misleading statements that put public health at risk. Herein, we explore the challenges of managing misinformation disseminated by someone who is simultaneously a tenured professor at a public, state-supported university, and a politically appointed public health official.

Overestimation of Severe Acute Respiratory Syndrome Coronavirus 2 Household Transmission in Settings of High Community Transmission: Insights From an Informal Settlement Community in Salvador, Brazil.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has spread globally. However, the contribution of community versus household transmission to the overall risk of infection remains unclear. Methods: Between November 2021 and March 2022, we conducted an active case-finding study in an urban informal settlement with biweekly visits across 1174 households with 3364 residents. Individuals displaying coronavirus disease 2019 (COVID-19)-related symptoms were identified, interviewed along with household contacts, and defined as index and secondary cases based on reverse-transcription polymerase chain reaction (RT-PCR) and symptom onset. Results: In 61 households, we detected a total of 94 RT-PCR-positive cases. Of 69 sequenced samples, 67 cases (97.1%) were attributed to the Omicron BA.1* variant. Among 35 of their households, the secondary attack rate was 50.0% (95% confidence interval [CI], 37.0%-63.0%). Women (relative risk [RR], 1.6 [95% CI, .9-2.7]), older individuals (median difference, 15 [95% CI, 2-21] years), and those reporting symptoms (RR, 1.73 [95% CI, 1.0-3.0]) had a significantly increased risk for SARS-CoV-2 secondary infection. Genomic analysis revealed substantial acquisition of viruses from the community even among households with other SARS-CoV-2 infections. After excluding community acquisition, we estimated a household secondary attack rate of 24.2% (95% CI, 11.9%-40.9%). Conclusions: These findings underscore the ongoing risk of community acquisition of SARS-CoV-2 among households with current infections. The observed high attack rate necessitates swift booster vaccination, rapid testing availability, and therapeutic options to mitigate the severe outcomes of COVID-19.

Extensive transmission of SARS-CoV-2 BQ.1* variant in a population with high levels of hybrid immunity: A prevalence survey.

OBJECTIVES: The SARS-CoV-2 BQ.1* variant rapidly spread globally in late 2022, posing a challenge due to its increased immune evasion. METHODS: We conducted a prevalence survey in Brazil from November 16 to December 22, 2022, as part of a cohort study. We conducted interviews and collected nasal samples for reverse transcription-polymerase chain reaction (RT-PCR) testing and whole-genome sequencing. Cumulative incidence was estimated using RT-PCR positivity, cycle threshold values, and external data on the dynamics of RT-PCR positivity following infection. RESULTS: Among 535 participants, 54% had documented SARS-CoV-2 exposure before this outbreak and 74% had received COVID-19 vaccination. In this study, 14.8% tested positive for SARS-CoV-2, with BQ.1* identified in 90.7% of cases. Using case data and cycle threshold values, cumulative incidence was estimated at 56% (95% confidence interval, 36-88%). Of the 79 positive participants, 48.1% had a symptomatic illness, with a lower proportion fulfilling the World Health Organization COVID-19 case definition compared to prior Omicron waves. No participants required medical attention. CONCLUSIONS: Despite high population-level hybrid immunity, the BQ.1* variant attacked 56% of our population. Lower disease severity was associated with BQ.1* compared to prior Omicron variants. Hybrid immunity may provide protection against future SARS-CoV-2 variants but in this case was not able to prevent widespread transmission.

Evidence of leaky protection following COVID-19 vaccination and SARS-CoV-2 infection in an incarcerated population.

Whether SARS-CoV-2 infection and COVID-19 vaccines confer exposure-dependent ("leaky") protection against infection remains unknown. We examined the effect of prior infection, vaccination, and hybrid immunity on infection risk among residents of Connecticut correctional facilities during periods of predominant Omicron and Delta transmission. Residents with cell, cellblock, and no documented exposure to SARS-CoV-2 infected residents were matched by facility and date. During the Omicron period, prior infection, vaccination, and hybrid immunity reduced the infection risk of residents without a documented exposure (HR: 0.36 [0.25-0.54]; 0.57 [0.42-0.78]; 0.24 [0.15-0.39]; respectively) and with cellblock exposures (0.61 [0.49-0.75]; 0.69 [0.58-0.83]; 0.41 [0.31-0.55]; respectively) but not with cell exposures (0.89 [0.58-1.35]; 0.96 [0.64-1.46]; 0.80 [0.46-1.39]; respectively). Associations were similar during the Delta period and when analyses were restricted to tested residents. Although associations may not have been thoroughly adjusted due to dataset limitations, the findings suggest that prior infection and vaccination may be leaky, highlighting the potential benefits of pairing vaccination with non-pharmaceutical interventions in crowded settings.

Previous Dengue Infection among Children in Puerto Rico and Implications for Dengue Vaccine Implementation.

Limited dengue virus (DENV) seroprevalence estimates are available for Puerto Rico, which are needed to inform the potential use and cost-effectiveness of DENV vaccines. The Communities Organized to Prevent Arboviruses (COPA) is a cohort study initiated in 2018 in Ponce, Puerto Rico, to assess arboviral disease risk and provide a platform to evaluate interventions. We recruited participants from households in 38 study clusters, who were interviewed and provided a serum specimen. Specimens from 713 children aged 1 to 16 years during the first year of COPA were tested for the four DENV serotypes and ZIKV using a focus reduction neutralization assay. We assessed the seroprevalence of DENV and ZIKV by age and developed a catalytic model from seroprevalence and dengue surveillance data to estimate the force of infection for DENV during 2003-2018. Overall, 37% (n = 267) were seropositive for DENV; seroprevalence was 9% (11/128) among children aged 1 to 8 years and 44% (256/585) among children aged 9 to 16 years, exceeding the threshold over which DENV vaccination is deemed cost-effective. A total of 33% were seropositive for ZIKV, including 15% among children aged 0 to 8 years and 37% among children aged 9 to 16 years. The highest force of infection occurred in 2007, 2010, and 2012-2013, with low levels of transmission from 2016 to 2018. A higher proportion of children had evidence of multitypic DENV infection than expected, suggesting high heterogeneity in DENV risk in this setting.

A Mixture Model for Estimating SARS-CoV-2 Seroprevalence in Chennai, India.

Serological assays used to estimate the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) often rely on manufacturers' cutoffs established on the basis of severe cases. We conducted a household-based serosurvey of 4,677 individuals in Chennai, India, from January to May 2021. Samples were tested for SARS-CoV-2 immunoglobulin G (IgG) antibodies to the spike (S) and nucleocapsid (N) proteins. We calculated seroprevalence, defining seropositivity using manufacturer cutoffs and using a mixture model based on measured IgG level. Using manufacturer cutoffs, there was a 5-fold difference in seroprevalence estimated by each assay. This difference was largely reconciled using the mixture model, with estimated anti-S and anti-N IgG seroprevalence of 64.9% (95% credible interval (CrI): 63.8, 66.0) and 51.5% (95% CrI: 50.2, 52.9), respectively. Age and socioeconomic factors showed inconsistent relationships with anti-S and anti-N IgG seropositivity using manufacturer cutoffs. In the mixture model, age was not associated with seropositivity, and improved household ventilation was associated with lower seropositivity odds. With global vaccine scale-up, the utility of the more stable anti-S IgG assay may be limited due to the inclusion of the S protein in several vaccines. Estimates of SARS-CoV-2 seroprevalence using alternative targets must consider heterogeneity in seroresponse to ensure that seroprevalence is not underestimated and correlates are not misinterpreted.

Accounting for assay performance when estimating the temporal dynamics in SARS-CoV-2 seroprevalence in the U.S.

Reconstructing the incidence of SARS-CoV-2 infection is central to understanding the state of the pandemic. Seroprevalence studies are often used to assess cumulative infections as they can identify asymptomatic infection. Since July 2020, commercial laboratories have conducted nationwide serosurveys for the U.S. CDC. They employed three assays, with different sensitivities and specificities, potentially introducing biases in seroprevalence estimates. Using models, we show that accounting for assays explains some of the observed state-to-state variation in seroprevalence, and when integrating case and death surveillance data, we show that when using the Abbott assay, estimates of proportions infected can differ substantially from seroprevalence estimates. We also found that states with higher proportions infected (before or after vaccination) had lower vaccination coverages, a pattern corroborated using a separate dataset. Finally, to understand vaccination rates relative to the increase in cases, we estimated the proportions of the population that received a vaccine prior to infection.

Dynamics of Anti-influenza Mucosal IgA Over a Season in a Cohort of Individuals Living or Working in a Long-term Care Facility.

BACKGROUND: Serological surveys are used to ascertain influenza infection and immunity, but evidence for the utility of mucosal immunoglobulin A (IgA) as a correlate of infection or protection is limited. METHODS: We performed influenza-like illness (ILI) surveillance on 220 individuals living or working in a retirement community in Gainesville, Florida from January to May 2018, and took pre- and postseason nasal samples of 11 individuals with polymerase chain reaction (PCR)-confirmed influenza infection and 60 randomly selected controls. Mucosal IgA against 10 strains of influenza was measured from nasal samples. RESULTS: Overall, 28.2% and 11.3% of individuals experienced a 2-fold and 4-fold rise, respectively, in mucosal IgA to at least 1 influenza strain. Individuals with PCR-confirmed influenza A had significantly lower levels of preseason IgA to influenza A. Influenza-associated respiratory illness was associated with a higher rise in mucosal IgA to influenza strains of the same subtype, and H3N2-associated respiratory illness was associated with a higher rise in mucosal IgA to other influenza A strains. CONCLUSIONS: By comparing individuals with and without influenza illness, we demonstrated that mucosal IgA is a correlate of influenza infection. There was evidence for cross-reactivity in mucosal IgA across influenza A subtypes.

Use of Whole-Genome Sequencing to Estimate the Contribution of Immune Evasion and Waning Immunity on Decreasing COVID-19 Vaccine Effectiveness.

BACKGROUND: The impact variant-specific immune evasion and waning protection have on declining coronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) remains unclear. Using whole-genome sequencing (WGS), we examined the contribution these factors had on the decline that followed the introduction of the Delta variant. Furthermore, we evaluated calendar-period-based classification as a WGS alternative. METHODS: We conducted a test-negative case-control study among people tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 1 April and 24 August 2021. Variants were classified using WGS and calendar period. RESULTS: We included 2029 cases (positive, sequenced samples) and 343 727 controls (negative tests). VE 14-89 days after second dose was significantly higher against Alpha (84.4%; 95% confidence interval [CI], 75.6%-90.0%) than Delta infection (68.9%; 95% CI, 58.0%-77.1%). The odds of Delta infection were significantly higher 90-149 than 14-89 days after second dose (P value = .003). Calendar-period-classified VE estimates approximated WGS-classified estimates; however, calendar-period-based classification was subject to misclassification (35% Alpha, 4% Delta). CONCLUSIONS: Both waning protection and variant-specific immune evasion contributed to the lower effectiveness. While calendar-period-classified VE estimates mirrored WGS-classified estimates, our analysis highlights the need for WGS when variants are cocirculating and misclassification is likely.

Household Transmission Dynamics of Seasonal Human Coronaviruses.

BACKGROUND: Household transmission studies inform how viruses spread among close contacts, but few characterize household transmission of endemic coronaviruses. METHODS: We used data collected from 223 households with school-age children participating in weekly disease surveillance over 2 respiratory virus seasons (December 2015 to May 2017), to describe clinical characteristics of endemic human coronaviruses (HCoV-229E, HcoV-HKU1, HcoV-NL63, HcoV-OC43) infections, and community and household transmission probabilities using a chain-binomial model correcting for missing data from untested households. RESULTS: Among 947 participants in 223 households, we observed 121 infections during the study, most commonly subtype HCoV-OC43. Higher proportions of infected children (<19 years) displayed influenza-like illness symptoms than infected adults (relative risk, 3.0; 95% credible interval [CrI], 1.5-6.9). The estimated weekly household transmission probability was 9% (95% CrI, 6-13) and weekly community acquisition probability was 7% (95% CrI, 5-10). We found no evidence for differences in community or household transmission probabilities by age or symptom status. Simulations suggest that our study was underpowered to detect such differences. CONCLUSIONS: Our study highlights the need for large household studies to inform household transmission, the challenges in estimating household transmission probabilities from asymptomatic individuals, and implications for controlling endemic CoVs.

Association between primary or booster COVID-19 mRNA vaccination and Omicron lineage BA.1 SARS-CoV-2 infection in people with a prior SARS-CoV-2 infection: A test-negative case-control analysis.

BACKGROUND: The benefit of primary and booster vaccination in people who experienced a prior Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remains unclear. The objective of this study was to estimate the effectiveness of primary (two-dose series) and booster (third dose) mRNA vaccination against Omicron (lineage BA.1) infection among people with a prior documented infection. METHODS AND FINDINGS: We conducted a test-negative case-control study of reverse transcription PCRs (RT-PCRs) analyzed with the TaqPath (Thermo Fisher Scientific) assay and recorded in the Yale New Haven Health system from November 1, 2021, to April 30, 2022. Overall, 11,307 cases (positive TaqPath analyzed RT-PCRs with S-gene target failure [SGTF]) and 130,041 controls (negative TaqPath analyzed RT-PCRs) were included (median age: cases: 35 years, controls: 39 years). Among cases and controls, 5.9% and 8.1% had a documented prior infection (positive SARS-CoV-2 test record ≥90 days prior to the included test), respectively. We estimated the effectiveness of primary and booster vaccination relative to SGTF-defined Omicron (lineage BA.1) variant infection using a logistic regression adjusted for date of test, age, sex, race/ethnicity, insurance, comorbidities, social venerability index, municipality, and healthcare utilization. The effectiveness of primary vaccination 14 to 149 days after the second dose was 41.0% (95% confidence interval (CI): 14.1% to 59.4%, p 0.006) and 27.1% (95% CI: 18.7% to 34.6%, p < 0.001) for people with and without a documented prior infection, respectively. The effectiveness of booster vaccination (≥14 days after booster dose) was 47.1% (95% CI: 22.4% to 63.9%, p 0.001) and 54.1% (95% CI: 49.2% to 58.4%, p < 0.001) in people with and without a documented prior infection, respectively. To test whether booster vaccination reduced the risk of infection beyond that of the primary series, we compared the odds of infection among boosted (≥14 days after booster dose) and booster-eligible people (≥150 days after second dose). The odds ratio (OR) comparing boosted and booster-eligible people with a documented prior infection was 0.79 (95% CI: 0.54 to 1.16, p 0.222), whereas the OR comparing boosted and booster-eligible people without a documented prior infection was 0.54 (95% CI: 0.49 to 0.59, p < 0.001). This study's limitations include the risk of residual confounding, the use of data from a single system, and the reliance on TaqPath analyzed RT-PCR results. CONCLUSIONS: In this study, we observed that primary vaccination provided significant but limited protection against Omicron (lineage BA.1) infection among people with and without a documented prior infection. While booster vaccination was associated with additional protection against Omicron BA.1 infection in people without a documented prior infection, it was not found to be associated with additional protection among people with a documented prior infection. These findings support primary vaccination in people regardless of documented prior infection status but suggest that infection history may impact the relative benefit of booster doses.

Effectiveness of an inactivated Covid-19 vaccine with homologous and heterologous boosters against Omicron in Brazil.

The effectiveness of inactivated vaccines (VE) against symptomatic and severe COVID-19 caused by omicron is unknown. We conducted a nationwide, test-negative, case-control study to estimate VE for homologous and heterologous (BNT162b2) booster doses in adults who received two doses of CoronaVac in Brazil in the Omicron context. Analyzing 1,386,544 matched-pairs, VE against symptomatic disease was 8.6% (95% CI, 5.6-11.5) and 56.8% (95% CI, 56.3-57.3) in the period 8-59 days after receiving a homologous and heterologous booster, respectively. During the same interval, VE against severe Covid-19 was 73.6% (95% CI, 63.9-80.7) and 86.0% (95% CI, 84.5-87.4) after receiving a homologous and heterologous booster, respectively. Waning against severe Covid-19 after 120 days was only observed after a homologous booster. Heterologous booster might be preferable to individuals with completed primary series inactivated vaccine.

Structural factors associated with SARS-CoV-2 infection risk in an urban slum setting in Salvador, Brazil: A cross-sectional survey.

BACKGROUND: The structural environment of urban slums, including physical, demographic, and socioeconomic attributes, renders inhabitants more vulnerable to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Yet, little is known about the specific determinants that contribute to high transmission within these communities. We therefore aimed to investigate SARS-CoV-2 seroprevalence in an urban slum in Brazil. METHODS AND FINDINGS: We performed a cross-sectional serosurvey of an established cohort of 2,041 urban slum residents from the city of Salvador, Brazil between November 2020 and February 2021, following the first Coronavirus Disease 2019 (COVID-19) pandemic wave in the country and during the onset of the second wave. The median age in this population was 29 years (interquartile range [IQR] 16 to 44); most participants reported their ethnicity as Black (51.5%) or Brown (41.7%), and 58.5% were female. The median size of participating households was 3 (IQR 2 to 4), with a median daily per capita income of 2.32 (IQR 0.33-5.15) US Dollars. The main outcome measure was presence of IgG against the SARS-CoV-2 spike protein. We implemented multilevel models with random intercepts for each household to estimate seroprevalence and associated risk factors, adjusting for the sensitivity and specificity of the assay, and the age and gender distribution of our study population. We identified high seroprevalence (47.9%, 95% confidence interval [CI] 44.2% to 52.1%), particularly among female residents (50.3% [95% CI 46.3% to 54.8%] versus 44.6% [95% CI 40.1% to 49.4%] among male residents, p < 0.01) and among children (54.4% [95% CI 49.6% to 59.3%] versus 45.4% [95% CI 41.5% to 49.7%] among adults, p < 0.01). Adults residing in households with children were more likely to be seropositive (48.6% [95% CI 44.8% to 52.3%] versus 40.7% [95% CI 37.2% to 44.3%], p < 0.01). Women who were unemployed and living below the poverty threshold (daily per capita household income <$1.25) were more likely to be seropositive compared to men with the same employment and income status (53.9% [95% CI 47.0% to 60.6%] versus 32.9% [95% CI 23.2% to 44.3%], p < 0.01). Participation in the study was voluntary, which may limit the generalizability of our findings. CONCLUSIONS: Prior to the peak of the second wave of the COVID-19 pandemic, cumulative incidence as assessed by serology approached 50% in a Brazilian urban slum population. In contrast to observations from industrialized countries, SARS-CoV-2 incidence was highest among children, as well as women living in extreme poverty. These findings emphasize the need for targeted interventions that provide safe environments for children and mitigate the structural risks posed by crowding and poverty for the most vulnerable residents of urban slum communities.

Change in covid-19 risk over time following vaccination with CoronaVac: test negative case-control study.

OBJECTIVE: To estimate the change in odds of covid-19 over time following primary series completion of the inactivated whole virus vaccine CoronaVac (Sinovac Biotech) in São Paulo State, Brazil. DESIGN: Test negative case-control study. SETTING: Community testing for covid-19 in São Paulo State, Brazil. PARTICIPANTS: Adults aged ≥18 years who were residents of São Paulo state, had received two doses of CoronaVac, did not have a laboratory confirmed SARS-CoV-2 infection before vaccination, and underwent reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 from 17 January to 14 December 2021. Cases were matched to test negative controls by age (in 5 year bands), municipality of residence, healthcare worker status, and epidemiological week of RT-PCR test. MAIN OUTCOME MEASURES: RT-PCR confirmed symptomatic covid-19 and associated hospital admissions and deaths. Conditional logistic regression was adjusted for sex, number of covid-19 associated comorbidities, race, and previous acute respiratory illness. RESULTS: From 202 741 eligible people, 52 170 cases with symptomatic covid-19 and 69 115 test negative controls with covid-19 symptoms were formed into 43 257 matched sets. Adjusted odds ratios of symptomatic covid-19 increased with time since completion of the vaccination series. The increase in odds was greater in younger people and among healthcare workers, although sensitivity analyses suggested that this was in part due to bias. In addition, the adjusted odds ratios of covid-19 related hospital admission or death significantly increased with time compared with the odds 14-41 days after series completion: from 1.25 (95% confidence interval 1.04 to 1.51) at 70-97 days up to 1.94 (1.41 to 2.67) from 182 days onwards. CONCLUSIONS: Significant increases in the risk of moderate and severe covid-19 outcomes occurred three months after primary vaccination with CoronaVac among people aged 65 and older. These findings provide supportive evidence for the implementation of vaccine boosters in these populations who received this inactivated vaccine. Studies of waning should include analyses designed to uncover common biases.

Effectiveness of CoronaVac, ChAdOx1 nCoV-19, BNT162b2, and Ad26.COV2.S among individuals with previous SARS-CoV-2 infection in Brazil: a test-negative, case-control study.

BACKGROUND: COVID-19 vaccines have proven highly effective among individuals without a previous SARS-CoV-2 infection, but their effectiveness in preventing symptomatic infection and severe outcomes among individuals with previous infection is less clear. We aimed to estimate the effectiveness of four COVID-19 vaccines against symptomatic infection, hospitalisation, and death for individuals with laboratory-confirmed previous SARS-CoV-2 infection. METHODS: Using national COVID-19 notification, hospitalisation, and vaccination datasets from Brazil, we did a test-negative, case-control study to assess the effectiveness of four vaccines (CoronaVac [Sinovac], ChAdOx1 nCoV-19 [AstraZeneca], Ad26.COV2.S [Janssen], and BNT162b2 [Pfizer-BioNtech]) for individuals with laboratory-confirmed previous SARS-CoV-2 infection. We matched cases with RT-PCR positive, symptomatic COVID-19 with up to ten controls with negative RT-PCR tests who presented with symptomatic illnesses, restricting both groups to tests done at least 90 days after an initial infection. We used multivariable conditional logistic regression to compare the odds of test positivity and the odds of hospitalisation or death due to COVID-19, according to vaccination status and time since first or second dose of vaccines. FINDINGS: Between Feb 24, 2020, and Nov 11, 2021, we identified 213 457 individuals who had a subsequent, symptomatic illness with RT-PCR testing done at least 90 days after their initial SARS-CoV-2 infection and after the vaccination programme started. Among these, 30 910 (14·5%) had a positive RT-PCR test consistent with reinfection, and we matched 22 566 of these cases with 145 055 negative RT-PCR tests from 68 426 individuals as controls. Among individuals with previous SARS-CoV-2 infection, vaccine effectiveness against symptomatic infection 14 or more days from vaccine series completion was 39·4% (95% CI 36·1-42·6) for CoronaVac, 56·0% (51·4-60·2) for ChAdOx1 nCoV-19, 44·0% (31·5-54·2) for Ad26.COV2.S, and 64·8% (54·9-72·4) for BNT162b2. For the two-dose vaccine series (CoronaVac, ChAdOx1 nCoV-19, and BNT162b2), effectiveness against symptomatic infection was significantly greater after the second dose than after the first dose. Effectiveness against hospitalisation or death 14 or more days from vaccine series completion was 81·3% (75·3-85·8) for CoronaVac, 89·9% (83·5-93·8) for ChAdOx1 nCoV-19, 57·7% (-2·6 to 82·5) for Ad26.COV2.S, and 89·7% (54·3-97·7) for BNT162b2. INTERPRETATION: All four vaccines conferred additional protection against symptomatic infections and severe outcomes among individuals with previous SARS-CoV-2 infection. The provision of a full vaccine series to individuals after recovery from COVID-19 might reduce morbidity and mortality. FUNDING: Brazilian National Research Council, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Oswaldo Cruz Foundation, JBS, Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Generalitat de Catalunya.

Use of Recently Vaccinated Individuals to Detect Bias in Test-Negative Case-Control Studies of COVID-19 Vaccine Effectiveness.

Postauthorization observational studies play a key role in understanding COVID-19 vaccine effectiveness following the demonstration of efficacy in clinical trials. Although bias due to confounding, selection bias, and misclassification can be mitigated through careful study design, unmeasured confounding is likely to remain in these observational studies. Phase III trials of COVID-19 vaccines have shown that protection from vaccination does not occur immediately, meaning that COVID-19 risk should be similar in recently vaccinated and unvaccinated individuals, in the absence of confounding or other bias. Several studies have used the estimated effectiveness among recently vaccinated individuals as a negative control exposure to detect bias in vaccine effectiveness estimates. In this paper, we introduce a theoretical framework to describe the interpretation of such a bias indicator in test-negative studies, and outline strong assumptions that would allow vaccine effectiveness among recently vaccinated individuals to serve as a negative control exposure.

EVITA Dengue: a cluster-randomized controlled trial to EValuate the efficacy of Wolbachia-InfecTed Aedes aegypti mosquitoes in reducing the incidence of Arboviral infection in Brazil.

BACKGROUND: Arboviruses transmitted by Aedes aegypti including dengue, Zika, and chikungunya are a major global health problem, with over 2.5 billion at risk for dengue alone. There are no licensed antivirals for these infections, and safe and effective vaccines are not yet widely available. Thus, prevention of arbovirus transmission by vector modification is a novel approach being pursued by multiple researchers. However, the field needs high-quality evidence derived from randomized, controlled trials upon which to base the implementation and maintenance of vector control programs. Here, we report the EVITA Dengue trial design (DMID 17-0111), which assesses the efficacy in decreasing arbovirus transmission of an innovative approach developed by the World Mosquito Program for vector modification of Aedes mosquitoes by Wolbachia pipientis. METHODS: DMID 17-0111 is a cluster-randomized trial in Belo Horizonte, Brazil, with clusters defined by primary school catchment areas. Clusters (n = 58) will be randomized 1:1 to intervention (release of Wolbachia-infected Aedes aegypti mosquitoes) vs. control (no release). Standard vector control activities (i.e., insecticides and education campaigns for reduction of mosquito breeding sites) will continue as per current practice in the municipality. Participants (n = 3480, 60 per cluster) are children aged 6-11 years enrolled in the cluster-defining school and living within the cluster boundaries who will undergo annual serologic surveillance for arboviral infection. The primary objective is to compare sero-incidence of arboviral infection between arms. DISCUSSION: DMID 17-0111 aims to determine the efficacy of Wolbachia-infected mosquito releases in reducing human infections by arboviruses transmitted by Aedes aegypti and will complement the mounting evidence for this method from large-scale field releases and ongoing trials. The trial also represents a critical step towards robustness and rigor for how vector control methods are assessed, including the simultaneous measurement and correlation of entomologic and epidemiologic outcomes. Data from this trial will inform further the development of novel vector control methods. TRIAL REGISTRATION: ClinicalTrials.gov NCT04514107 . Registered on 17 August 2020 Primary sponsor: National Institute of Health, National Institute of Allergy and Infectious Diseases.

Effectiveness of a monthly schedule of follow-up for the treatment of uncomplicated severe acute malnutrition in Sokoto, Nigeria: A cluster randomized crossover trial.

BACKGROUND: Community-based management of severe acute malnutrition (SAM) involves weekly or biweekly outpatient clinic visits for clinical surveillance and distribution of therapeutic foods. Distance to outpatient clinics and high opportunity costs for caregivers can represent major barriers to access. Reducing the frequency of outpatient visits while providing training to caregivers to recognize clinical danger signs at home between outpatient visits may increase acceptability, coverage, and public health impact of SAM treatment. We investigated the effectiveness of monthly clinic visits compared to the standard weekly follow-up in the outpatient treatment of uncomplicated SAM in northwestern Nigeria. METHODS AND FINDINGS: We conducted a cluster randomized crossover trial to test the noninferiority of nutritional recovery in children with uncomplicated SAM receiving monthly follow-up compared to the standard weekly schedule. From January 2018 to November 2019, 3,945 children aged 6 to 59 months were enrolled at 10 health centers (5 assigned to monthly follow-up and 5 assigned to weekly follow-up) in Sokoto, Nigeria. In total, 96% of children (n = 1,976 in the monthly follow-up group and 1,802 in the weekly follow-up group) were followed until program discharge, and 91% (n = 1,873 in the monthly follow-up group and 1,721 in the weekly follow-up group) were followed to 3 months postdischarge. The mean age at admission was 15.8 months (standard deviation [SD] 7.1), 2,097/3,945 (53.2%) were girls, and the mean midupper arm circumference (MUAC) at admission was 105.8 mm (SD 6.0). In a modified intention-to-treat analysis, the primary outcome of nutritional recovery, defined as having MUAC ≥125 mm on 2 consecutive visits, was analyzed using generalized linear models, with generalized estimating equations to account for clustering. Nutritional recovery was lower in the monthly follow-up group compared to the weekly group (1,036/1,976, 52.4% versus 1,059/1,802, 58.8%; risk difference: -6.8%), and noninferiority was not demonstrated (lower bound of the confidence interval [CI] was -11.5%, lower than the noninferiority margin of 10%). The proportion of children defaulting was lower in the monthly group than in the weekly group (109/1,976, 5.5% versus 151/1,802, 8.4%, p = 0.03). Three months postdischarge, children in the monthly group were less likely to relapse compared to those in the weekly group (58/976, 5.9% versus 78/1,005, 7.8%, p = 0.03), but cumulative mortality at 3 months postdischarge was higher in the monthly group (159/1,873, 8.5% versus 106/1,721, 6.2%, p < 0.001). Study results may depend on context-specific factors including baseline level of care and the clinical status of children presenting to health centers, and, thus, generalizability of these results may be limited. CONCLUSIONS: Where feasible, a weekly schedule of clinic visits should be preferred to maintain effectiveness of SAM treatment. Where geographic coverage of programs is low or frequent travel to outpatient clinics is difficult or impossible, a monthly schedule of visits may provide an alternative model to deliver treatment to those in need. Modifications to the outpatient follow-up schedule, for example, weekly clinic visits until initial weight gain has been achieved followed by monthly visits, could increase the effectiveness of the model and add flexibility for program delivery. TRIAL REGISTRATION: ClinicalTrials.gov NCT03140904.