Disentangling the influence of reservoir abundance and pathogen shedding on zoonotic spillover of the Leptospira agent in urban informal settlements.

Rats are major reservoirs for pathogenic Leptospira, the bacteria causing leptospirosis, particularly in urban informal settlements. However, the impact of variation in rat abundance and pathogen shedding rates on spillover transmission to humans remains unclear. This study aimed to investigate how spatial variation in reservoir abundance and pathogen pressure affect Leptospira spillover transmission to humans in a Brazilian urban informal settlement. A longitudinal eco-epidemiological study was conducted from 2013 to 2014 to characterize the spatial distribution of rat abundance and Leptospira shedding rates in rats and determine the association with human infection risk in a cohort of 2,206 community residents. Tracking plates and live-trapping were used to measure rat abundance and quantify rat shedding status and load. In parallel, four sequential biannual serosurveys were used to identify human Leptospira infections. To evaluate the role of shedding on human risk, we built three statistical models for: (1) the relative abundance of rats, (2) the shedding rate by individual rats, and (3) human Leptospira infection, in which "total shedding", obtained by multiplying the predictions from those two models, was used as a risk factor. We found that Leptospira shedding was associated with older and sexually mature rats and varied spatially and temporally-higher at valley bottoms and with seasonal rainfall (December to March). The point estimate for "total shedding" by rat populations was positive, i.e., Leptospira infection risk increased with total shedding, but the association was not significant [odds ratio (OR) = 1.1; 95% confidence interval (CI): 0.9, 1.4]. This positive trend was mainly driven by rat abundance, rather than individual rat shedding (OR = 1.8; 95% CI: 0.6, 5.4 vs. OR = 1.0; 95% CI: 0.7, 1.4]. Infection risk was higher in areas with more vegetative land cover (OR = 2.4; 95% CI: 1.2, 4.8), and when floodwater entered the house (OR = 2.4; 95% CI: 1.6, 3.4). Our findings indicate that environmental and hydrological factors play a more significant role in Leptospira spillover than rat associated factors. Furthermore, we developed a novel approach combining several models to elucidate complex links between animal reservoir abundance, pathogen shedding and environmental factors on zoonotic spillover in humans that can be extended to other environmentally transmitted diseases.

Hematological and biochemical profiles, infection and habitat quality in an urban rat population.

Host condition is key in understanding disease dynamics. In an urban population of Rattus norvegicus, we aimed to assess whether infection of Leptospira interrogans and helminths was associated with patterns of host hematological and hormone-biochemical stress-related conditions. Rat kidney imprints and urine were used to identify and quantify L. interrogans, and feces samples for helminth eggs and corticosterone metabolites. Blood samples were taken for complete blood counts and specific biochemicals in rats' sera. Principal Component Analyses were performed to check whether rats would be grouped according to health profiles. We obtained hematological and hormone-biochemical data from 95 and 61 rats, respectively. Hematological PCA revealed distinct rat groups: typical (T), eosinophil deficient (Eos-D), eosinophil- and monocyte- deficient (EM-D) and monocyte deficient with high immature neutrophils (Mon-D). No association between L. interrogans or helminths and rat health profiles was observed, except with Trichiuridae, which mean intensity was significantly higher when all deficient groups were pooled together compared to the T-group. The poorest condition group was found in areas with fewer rat burrows than the T-group, indicating EM-D had a reduced ability to occupy "good" quality habitats. In natural populations, hematological profiles may reflect host's overall condition, instead of responses to specific infections.

Severity-dependent test-seeking behaviors and test-negative designs: impact on estimated vaccine effectiveness and utility of analytic and design choices.

Test-negative designs are increasingly used to evaluate vaccine effectiveness because of desirable properties like reduced confounding due to healthcare-seeking behaviors and lower cost compared to other study designs. An individual's decision to seek care often depends on their disease severity, with severe disease more likely to be captured than mild disease. As many vaccines likely attenuate disease severity, this phenomenon generally results in an upward-biased estimate of vaccine effectiveness against symptomatic disease. To address the resulting bias, analytic solutions like adjusting for or matching on severity have been suggested. In this paper, we examine the performance of the test-negative design under different vaccine effects on disease severity and the utility of adjusting or matching on severity. We further consider the implications of studies that focus only on milder disease by restricting recruitment to outpatient settings. Through an analytic framework and simulations accompanied by a real-world example, we demonstrate that, when vaccination attenuates disease severity, the magnitude of bias is influenced by the degree of under-ascertainment of mild disease relative to severe disease. When vaccination does not attenuate disease severity, bias is not present. We further show that analytic fixes negligibly impact bias and that outpatient-only studies frequently produce downward-biased estimates.

Two mosquito salivary antigens demonstrate promise as biomarkers of recent exposure to P. falciparum infected mosquito bites.

Background: Measuring malaria transmission intensity using the traditional entomological inoculation rate is difficult. Antibody responses to mosquito salivary proteins such as SG6 have previously been used as biomarkers of exposure to Anopheles mosquito bites. Here, we investigate four mosquito salivary proteins as potential biomarkers of human exposure to mosquitoes infected with P. falciparum: mosGILT, SAMSP1, AgSAP, and AgTRIO. Methods: We tested population-level human immune responses in longitudinal and cross-sectional plasma samples from individuals with known P. falciparum infection from low and moderate transmission areas in Senegal using a multiplexed magnetic bead-based assay. Results: AgSAP and AgTRIO were the best indicators of recent exposure to infected mosquitoes. Antibody responses to AgSAP, in a moderate endemic area, and to AgTRIO in both low and moderate endemic areas, were significantly higher than responses in a healthy non-endemic control cohort (p-values = 0.0245, 0.0064, and <0.0001 respectively). No antibody responses significantly differed between the low and moderate transmission area, or between equivalent groups during and outside the malaria transmission seasons. For AgSAP and AgTRIO, reactivity peaked 2-4 weeks after clinical P. falciparum infection and declined 3 months after infection. Discussion: Reactivity to both AgSAP and AgTRIO peaked after infection and did not differ seasonally nor between areas of low and moderate transmission, suggesting reactivity is likely reflective of exposure to infectious mosquitos or recent biting rather than general mosquito exposure. Kinetics suggest reactivity is relatively short-lived. AgSAP and AgTRIO are promising candidates to incorporate into multiplexed assays for serosurveillance of population-level changes in P. falciparum-infected mosquito exposure.

Effectiveness of the fourth dose of COVID-19 vaccines against severe COVID-19 among adults 40 years or older in Brazil: a population-based cohort study.

Background: The emergence of COVID-19 variants with immune scape and the waning of primary vaccine schemes effectiveness have prompted many countries to indicate first and second booster COVID-19 vaccine doses to prevent severe COVID-19. However, current available evidence on second booster dose effectiveness are mostly limited to high-income countries, older adults, and mRNA-based vaccination schemes scenarios. We aimed to investigate the relative vaccine effectiveness (rVE) of the fourth dose compared to three doses for severe COVID-19 outcomes in Brazil; and compare the rVE of a fourth dose with an mRNA vaccine compared to adenovirus-based product in the same settings. Methods: We performed a target emulated trial using a population-based cohort of individuals aged 40 years or older who have received a homologous primary scheme of CoronaVac, ChAdOx1, or BNT162b2, and any third dose product and were eligible for the fourth dose in Brazil. The primary outcome was COVID-19 associated hospitalization or death. We built Cohort A matching individuals vaccinated with a fourth dose to individuals who received three doses to estimate the rVE of the fourth dose. We built Cohort B, a subset of Cohort A, matching mRNA-based (mRNA) to adenovirus-based fourth dose vaccinated individuals to compare their relative hazards for severe COVID-19. Findings: 46,693,484 individuals were included in Cohort A and 6,763,016 in Cohort B. 45% of them were aged between 40 and 60 years old, and 48% between 60 and 79 years old. In Cohort A, the most common previous series was a ChAdOx1 two-dose followed by BNT162b2 (44%), and a CoronaVac two-dose followed by a BNT162b2 (36%). Among those fourth dose vaccinated, 36.9% received ChAdOx1, 32.7% Ad26.COV2.S, 25.8% BNT162b2, and 4.7% CoronaVac. In Cohort B, among those who received an adenovirus fourth dose, 53.7% received ChAdOx1 and 46.3% received Ad26.COV2.S. The estimated rVE for the primary outcome of four doses compared to three doses was 44.1% (95% CI 42.3-46.0), with some waning during follow-up (rVE 7-60 days 46.8% [95% CI 44.4-49.1], rVE after 120 days 33.8% [95% CI 18.0-46.6]). Among fourth dose vaccinated individuals, mRNA-based vaccinated individuals had lower hazards for hospitalization or death compared to adenovirus-vaccinated individuals (HR 0.81, 95% CI 0.75-0.87). After 120 days, no difference in hazards between groups was observed (HR 1.35, 95% CI 0.93-1.97). Similar findings were observed for hospitalization and death separately, except no evidence for differences between fourth dose brands for death in Cohort B. Interpretation: In a heterogeneous scenario of primary and first booster vaccination combinations, a fourth dose provided meaningful and durable protection against severe COVID-19 outcomes. Compared to adenovirus-based booster, a fourth dose wild-type mRNA vaccine was associated with immediate lower hazards of hospitalization or death unsustained after 120 days. Funding: None.

Gender differences in the perception of leptospirosis severity, behaviours, and Leptospira exposure risk in urban Brazil: a cross-sectional study.

Background: Vulnerability to climate hazards and infectious diseases are not gender-neutral, meaning that men, women, boys, girls, and other gender identities experience different health risks. Leptospirosis, a zoonotic climate sensitive infectious disease, is commonly transmitted to humans via contact with animals and the environment, particularly soil and flood water. Gender differences in leptospiral infection risk are reported globally, with men consistently found to be at higher risk than women. However, the drivers of this difference in risk are poorly understood. Previous studies suggest that the interplay of knowledge, perceptions, and behaviours may shape differential infection risk among genders. Methodology/Principal Findings: To examine gender differences in Leptospira exposure risk we conducted a cross-sectional serosurvey among adult participants (n = 761) in four urban, marginalised, informal settlements in the city of Salvador, Brazil. We found that seroprevalence was 14.6% and 9.4% across men and women respectively. We then applied causal inference methodology to a two-part sex-disaggregated analysis to investigate: 1) the association of perceptions and behaviours with Leptospira seropositivity and 2) the association of perceptions with behaviours. We found that men who perceived leptospirosis as extremely serious had lower odds of seropositivity, walking through sewage water, or walking barefoot, suggesting an important link between perceptions, behaviours, and exposure risk. These associations were not found in women, and these behaviours were not associated with seropositivity in men or women. Conclusions: Our results highlight perceived severity of disease as a potential driver of behaviour in men, and perceptions of disease may be an important target for health education programs. Furthermore, our study identifies evidence gaps in the understanding of infection risks in women. As the first sex-disaggregated study investigating Leptospira infection risks, we advocate for a gendered lens in future studies to further understand risks specific to different gender identities.

Human antibodies in Mexico and Brazil neutralizing tick-borne flaviviruses.

Flaviviruses such as dengue virus (DENV), Zika virus (ZIKV), and yellow fever virus (YFV) are spread by mosquitoes and cause human disease and mortality in tropical areas. In contrast, Powassan virus (POWV), which causes severe neurologic illness, is a flavivirus transmitted by ticks in temperate regions of the Northern hemisphere. We find serologic neutralizing activity against POWV in individuals living in Mexico and Brazil. Monoclonal antibodies P002 and P003, which were derived from a resident of Mexico (where POWV is not reported), neutralize POWV lineage I by recognizing an epitope on the virus envelope domain III (EDIII) that is shared with a broad range of tick- and mosquito-borne flaviviruses. Our findings raise the possibility that POWV, or a flavivirus closely related to it, infects humans in the tropics.

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.

Eco-epidemiological study of seropositivity against Rickettsia and Leptospira agents in rural areas of Urabá, Colombia.

Rickettsioses and leptospirosis are infectious diseases that are often underdiagnosed due to a lack of knowledge about their epidemiology, pathophysiology, diagnosis, management, among others. Objetive: to characterize the seroprevalence and seroincidence of both Rickettsia and Leptospira agents and determine the risk factors for these outcomes in rural areas of Urabá, Antioquia. Methods: a secondary data analysis using information on Rickettsia and Leptospira exposure from a prior prospective study that explored sociocultural and ecological aspects of Rickettsia infection in rural Urabá, Colombia. A multinomial mixed logistic regression model was employed to analyze factors linked to seroprevalent cases of Rickettsia, Leptospira and both, along with descriptive analyses of seroincident cases. Results: the concomitant seroprevalence against Rickettsiaand Leptospira was 9.38% [95%CI 6.08%-13.37%] (56/597). The factors associated with this seroprevalence were age (ORa= 1.02 [95%CI 1.007-1.03]), male gender (ORa= 3.06 [95%CI 1.75-5.37]), fever history (ORa= 1.71 [95%CI 1.06-2.77]) the presence of breeding pigs (ORa= 2.29 [95%CI 1.36-3.88]), peridomicile yucca crops(ORa= 2.5 [95%CI 1.1-5.62]), and deforestation practices(ORa= 1.74 [95%CI 1.06-2.87]). The concomitant seroincidence against Rickettsia and Leptospira was 1.09% (3/274) [95%CI 0.29%-4.05%], three cases were female, with a median age of 31.83 years-old (IQR 8.69-56.99). At the household level, all the seroincident cases had households built partially or totally with soil floors, wooden walls, and zinc roofs. Two seroincident cases described the presence of equines, canines, and domestic chickens in intra or peri-domicile. Finally, two cases were exposed to synanthropic rodents, and one case to tick infestation. Conclusion: there is evidence of seroprevalent and seroincident cases of seropositivity against both Rickettsia and Leptospira in rural areas of Urabá, Colombia. These findings can help improve public health surveillance systems in preventing, detecting, and attending to the different clinical cases caused by these pathogens.

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.

Social determinants of adult COVID-19 vaccine acceptance and uptake in a Brazilian urban informal community: a longitudinal time-to-event study.

Residents of informal urban settlements have a high risk of COVID-19 exposure and have less access to medical care, making vaccine-driven prevention critical in this vulnerable population. Despite robust vaccination campaigns in Brazil, vaccine uptake and timing continue to be influenced by social factors and contribute to health disparities. To address this, we conducted a sequential survey in a cohort of 717 adults in an urban favela in Salvador, Brazil where participants were interviewed in 2020, before vaccines were rolled out, and in 2022, after primary and booster dose distribution. We collected data on demographics, social characteristics, and COVID-19 vaccination status and intent. Primary series uptake was high (91.10% for 1 st dose and 94.74% for 2 nd dose among eligible); however, booster uptake was lower (63.51% of eligible population) at the time of the second interview, suggesting a decreasing interest in vaccination. To account for both vaccine refusal and delays, we conducted a Cox time-to-event analysis of dose uptake using sequential independent outcomes. Exposure times were determined by dose eligibility date to account for age and comorbidities. Intent to vaccinate in 2020 (hazard ratio [HR]: 1.54, CI: [1.05, 1.98]) and age (HR: 1.27, CI: [1.01, 2.08]) were associated with higher vaccination rates for the 1 st dose. Males were less likely to receive the 1 st dose (HR: 0.61, CI: [0.35, 0.83]), and, compared to catholics, 2 nd dose uptake was lower for those identifying with Pentecostalism (HR: 0.49, CI: [0.37, 0.66]) and without a religion (HR: 0.49, CI: [0.37, 0.66]), with the latter association disappearing after controlling by age. Risk perception was associated with 2 nd dose uptake (HR: 1.15, CI: [1.08, 1.26]). The role of sex and religion in vaccination behavior highlights the need for targeted outreach and interfacing with local organizations. The data offers lessons to build a long-term COVID-19 vaccination strategy beyond availability.

Predictors of Neurodevelopment in Microcephaly Associated with Congenital Zika Syndrome: A Prospective Study.

The municipality of Salvador, situated in Brazil, distinguished itself as the epicenter of the emergence of microcephaly related to congenital manifestations of Zika syndrome. Despite the anticipated significant developmental setbacks in these children, research has indicated a varied range of outcomes, with certain instances even reflecting minimal developmental delay. Our objective was to pinpoint determinants that could forecast developmental anomalies in children diagnosed with microcephaly associated with congenital Zika syndrome (CZS). METHODOLOGY: A forward-looking clinical and neurodevelopmental examination was conducted focusing on neonates diagnosed with microcephaly with CZS, birthed between September 2015 and April 2016 at the Hospital Geral Roberto Santos, in Salvador city. That infants were monitored up to their third year by a multiprofessional team. Child development was assessed using the composite Bayley III score. Undertaken by two blinded experts, cranial CT scan analysis was performed during the neonate period for the detection of brain abnormalities and to quantify ventricle enlargement, measured by Evans' index (EI). RESULTS: Fifty newborns were evaluated with a median head circumference of 28 cm (interquartile range 27-31 cm). EI was associated with neurodevelopmental delay at three years and remained significant after adjustment for head circumference. A 0.1-point increase in EI was associated with a delay of 3.2 months in the receptive language (p = 0.016), 3.4 months in the expressive language (p = 0.016), 3.4 months in the cognitive (p = 0.016), 2.37 months in the gross motor (p = 0.026), and 3.1 months in the fine motor (p = 0.021) domains. CONCLUSIONS: EI predicted neurodevelopmental delay in all Bayley domains in children with microcephaly associated with CZS.

Dynamics of chikungunya virus transmission in the first year after its introduction in Brazil: A cohort study in an urban community.

BACKGROUND: The first chikungunya virus (CHIKV) outbreaks during the modern scientific era were identified in the Americas in 2013, reaching high attack rates in Caribbean countries. However, few cohort studies have been performed to characterize the initial dynamics of CHIKV transmission in the New World. METHODOLOGY/PRINCIPAL FINDINGS: To describe the dynamics of CHIKV transmission shortly after its introduction in Brazil, we performed semi-annual serosurveys in a long-term community-based cohort of 652 participants aged ≥5 years in Salvador, Brazil, between Feb-Apr/2014 and Nov/2016-Feb/2017. CHIKV infections were detected using an IgG ELISA. Cumulative seroprevalence and seroincidence were estimated and spatial aggregation of cases was investigated. The first CHIKV infections were identified between Feb-Apr/2015 and Aug-Nov/2015 (incidence: 10.7%) and continued to be detected at low incidence in subsequent surveys (1.7% from Aug-Nov/2015 to Mar-May/2016 and 1.2% from Mar-May/2016 to Nov/206-Feb/2017). The cumulative seroprevalence in the last survey reached 13.3%. It was higher among those aged 30-44 and 45-59 years (16.1% and 15.6%, respectively), compared to younger (12.4% and 11.7% in <15 and 15-29 years, respectively) or older (10.3% in ≥60 years) age groups, but the differences were not statistically significant. The cumulative seroprevalence was similar between men (14.7%) and women (12.5%). Yet, among those aged 15-29 years, men were more often infected than women (18.1% vs. 7.4%, respectively, P = 0.01), while for those aged 30-44, a non-significant opposite trend was observed (9.3% vs. 19.0%, respectively, P = 0.12). Three spatial clusters of cases were detected in the study site and an increased likelihood of CHIKV infection was detected among participants who resided with someone with CHIKV IgG antibodies. CONCLUSIONS/SIGNIFICANCE: Unlike observations in other settings, the initial spread of CHIKV in this large urban center was limited and focal in certain areas, leaving a high proportion of the population susceptible to further outbreaks. Additional investigations are needed to elucidate the factors driving CHIKV spread dynamics, including understanding differences with respect to dengue and Zika viruses, in order to guide prevention and control strategies for coping with future outbreaks.

Bartonella in Norway rats (Rattus norvegicus) from the urban slum environment in Brazil.

Bartonella are rodent-borne bacteria that cause varied human etiologies. Studies on synanthropic rodents are rare, causing gaps in epidemiological knowledge. We tested bloodclot samples from 79 rats from an urban slum in Salvador, Brazil through PCR targeting gltA gene. Nine samples (11.4%) were positive: six had 100% identity with Bartonella sp. isolate JF429580 and 99.5% with B. queenslandensis strain AUST/NH8; three were 100% identical to isolate JF429532 and 99.7% to B. tribocorum. This is the second report on urban rat Bartonella indicating bacterial circulation at detectable rates. Its presence in rats from vulnerable human settlements demands public health attention.

An AI-powered patient triage platform for future viral outbreaks using COVID-19 as a disease model.

Over the last century, outbreaks and pandemics have occurred with disturbing regularity, necessitating advance preparation and large-scale, coordinated response. Here, we developed a machine learning predictive model of disease severity and length of hospitalization for COVID-19, which can be utilized as a platform for future unknown viral outbreaks. We combined untargeted metabolomics on plasma data obtained from COVID-19 patients (n = 111) during hospitalization and healthy controls (n = 342), clinical and comorbidity data (n = 508) to build this patient triage platform, which consists of three parts: (i) the clinical decision tree, which amongst other biomarkers showed that patients with increased eosinophils have worse disease prognosis and can serve as a new potential biomarker with high accuracy (AUC = 0.974), (ii) the estimation of patient hospitalization length with ± 5 days error (R2 = 0.9765) and (iii) the prediction of the disease severity and the need of patient transfer to the intensive care unit. We report a significant decrease in serotonin levels in patients who needed positive airway pressure oxygen and/or were intubated. Furthermore, 5-hydroxy tryptophan, allantoin, and glucuronic acid metabolites were increased in COVID-19 patients and collectively they can serve as biomarkers to predict disease progression. The ability to quickly identify which patients will develop life-threatening illness would allow the efficient allocation of medical resources and implementation of the most effective medical interventions. We would advocate that the same approach could be utilized in future viral outbreaks to help hospitals triage patients more effectively and improve patient outcomes while optimizing healthcare resources.

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.

COVID-19 annual update: a narrative review.

Three and a half years after the pandemic outbreak, now that WHO has formally declared that the emergency is over, COVID-19 is still a significant global issue. Here, we focus on recent developments in genetic and genomic research on COVID-19, and we give an outlook on state-of-the-art therapeutical approaches, as the pandemic is gradually transitioning to an endemic situation. The sequencing and characterization of rare alleles in different populations has made it possible to identify numerous genes that affect either susceptibility to COVID-19 or the severity of the disease. These findings provide a beginning to new avenues and pan-ethnic therapeutic approaches, as well as to potential genetic screening protocols. The causative virus, SARS-CoV-2, is still in the spotlight, but novel threatening virus could appear anywhere at any time. Therefore, continued vigilance and further research is warranted. We also note emphatically that to prevent future pandemics and other world-wide health crises, it is imperative to capitalize on what we have learnt from COVID-19: specifically, regarding its origins, the world's response, and insufficient preparedness. This requires unprecedented international collaboration and timely data sharing for the coordination of effective response and the rapid implementation of containment measures.