Protection of hybrid immunity against SARS-CoV-2 reinfection and severe COVID-19 during periods of Omicron variant predominance in Mexico

BackgroundWith the widespread transmission of the Omicron SARS-CoV-2 variant, reinfections have become increasingly common. Here, we explored the role of immunity, primary infection severity, and variant predominance in the risk of reinfection and severe COVID-19 during Omicron predominance in Mexico.MethodsWe analyzed reinfections in Mexico in individuals with a primary infection separated by at least 90 days from reinfection using a national surveillance registry of SARS-CoV-2 cases from March 3rd, 2020, to August 13th, 2022. Immunity-generating events included primary infection, partial or complete vaccination, and booster vaccines. Reinfections were matched by age and sex with controls with primary SARS-CoV-2 infection and negative RT-PCR or antigen test at least 90 days after primary infection to explore reinfection and severe disease risk factors. We also compared the protective efficacy of heterologous and homologous vaccine boosters against reinfection.ResultsWe detected 231,202 SARS-CoV-2 reinfections in Mexico, most occurring in unvaccinated individuals (41.55%). Over 207,623 reinfections occurred during periods of Omicron (89.8%), BA.1 (36.74%), and BA.5 (33.67%) subvariant predominance and a case-fatality rate of 0.22%. Vaccination protected against reinfection, without significant influence of the order of immunity-generating events and provided >90% protection against severe reinfections. Heterologous booster schedules were associated with ~11% and ~ 54% lower risk for reinfection and reinfection-associated severe COVID-19, respectively, modified by time-elapsed since the last immunity-generating event, when compared against complete primary schedules.ConclusionSARS-CoV-2 reinfections increased during Omicron predominance. Hybrid immunity provides protection against reinfection and associated severe COVID-19, with potential benefit from heterologous booster schedules

Systemic Inflammation and the Brain: novel roles of genetic, molecular, and environmental cues as drivers of neurodegeneration.

The nervous and immune systems have evolved in parallel from the early bilaterians, in which innate immunity and a central nervous system coexisted for the first time, to jawed vertebrates and the appearance of adaptive immunity. The central nervous system (CNS) feeds from, and integrates efferent signals in response to, somatic and autonomic sensory information. The CNS receives input also from the periphery about inflammation and infection. Cytokines, chemokines, damage-associated soluble mediators of systemic inflammation can also gain access to the CNS via blood flow. In response to systemic inflammation, those soluble mediators can access directly through the circumventricular organs, as well as open the blood-brain barrier (BBB). The resulting translocation of inflammatory mediators can interfere with neuronal and glial well-being, leading to a break of balance in brain homeostasis. This in turn results in cognitive and behavioral manifestations commonly present during acute infections -including anorexia, malaise, depression, and decreased physical activity- collectively known as the sickness behavior (SB). While SB manifestations are transient and self-limited, under states of persistent systemic inflammatory response the cognitive and behavioral changes can become permanent. For example, cognitive decline is almost universal in sepsis survivors, and a common finding in patients with systemic lupus erythematosus (SLE). Here, we review recent genetic evidence suggesting an association between neurodegenerative disorders and persistent immune activation; clinical and experimental evidence indicating previously unidentified immune-mediated pathways of neurodegeneration; and novel immunomodulatory targets and their potential relevance for neurodegenerative disorders

Epidemiological and clinical characteristics of patients with human monkeypox infection in Mexico: a nationwide observational studyResearch in context

Summary: Background: Human monkeypox, a zoonosis historically endemic to West and South Africa, has led to a worldwide outbreak driven by human-to-human transmission resulting in an international public health emergency. Endemic and outbreak monkeypox cases may differ in their affected populations, clinical features, and outcomes. Thus, profiling cases of the current monkeypox outbreak worldwide is crucial. Methods: We performed a nationwide observational surveillance-based study from May 24 to September 5, 2022. Patients that met the operational clinical definition of monkeypox or symptomatic close contacts of confirmed cases were tested by real-time polymerase chain reaction. Clinical data were collected with a standardized case-report form. We report epidemiologic, sociodemographic, and clinical characteristics of confirmed cases. Findings: Five-hundred and sixty-five human monkeypox confirmed cases were analysed; 97.2% were men, of whom 59.5% identified as men who have sex with men, and 54.5% had human immunodeficiency virus infection. The median age was 34 years. All patients but one had rash (99.8%), 78.9% had fever, and 47.8% reported myalgia. The anogenital area was the most commonly affected one by rash (49.6%), and proctitis occurred in 6.2% of patients. Six patients required hospitalization, of which one died due to causes unrelated to monkeypox. Interpretation: The 2022 monkeypox outbreak in Mexico is mainly driven by middle-aged men who have sex with men, of which a large proportion are persons who live with human immunodeficiency virus infection. Clinical features such as the high proportion of anogenital lesions suggest sexual contact is a pivotal transmission mechanism in this outbreak. Funding: This research was supported by grant A1-S-18342 from Consejo Nacional de Ciencia y Tecnología (CONACyT), Mexico (to S.I.V.-F.)

Effectiveness of a nationwide COVID-19 vaccination program in Mexico against symptomatic COVID-19, hospitalizations, and death: a retrospective analysis of national surveillance data

ABSTRACT: Objectives: Vaccination has been effective in ameliorating the impact of COVID-19. Here, we report vaccine effectiveness (VE) of the nationally available COVID-19 vaccines in Mexico. Methods: Retrospective analysis of a COVID-19 surveillance system to assess the VE of the BNT162b2, messenger RNA (mRNA)-12732, Gam-COVID-Vac, Ad5-nCoV, Ad26.COV2.S, ChAdOx1, and CoronaVac vaccines against SARS-CoV-2 infection, COVID-19 hospitalization, and death in Mexico. The VE was estimated using time-varying Cox proportional hazard models in vaccinated and unvaccinated adults, adjusted for age, sex, and comorbidities. VE was also estimated for adults with diabetes, aged ≥60 years, and comparing the predominance of SARS-CoV-2 variants B.1.1.519 and B.1.617.2. Results: We assessed 793,487 vaccinated and 4,792,338 unvaccinated adults between December 24, 2020 and September 27, 2021. The VE against SARS-CoV-2 infection was the highest for fully vaccinated individuals with mRNA-12732 (91.5%, 95% confidence interval [CI] 90.3-92.4) and Ad26.COV2.S (82.2%, 95% CI 81.4-82.9); for COVID-19 hospitalization, BNT162b2 (84.3%, 95% CI 83.6-84.9) and Gam-COVID-Vac (81.4% 95% CI 79.5-83.1), and for mortality, BNT162b2 (89.8%, 95% CI 89.2-90.2) and mRNA-12732 (93.5%, 95% CI 86.0-97.0). The VE decreased for all vaccines in adults aged ≥60 years, people with diabetes, and periods of Delta variant predominance. Conclusion: All the vaccines implemented in Mexico were effective against SARS-CoV-2 infection, COVID-19 hospitalization, and death. Mass vaccination with multiple vaccines is useful to maximize vaccination coverage

The Selective α7 Agonist GTS-21 Attenuates Cytokine Production in Human Whole Blood and Human Monocytes Activated by Ligands for TLR2, TLR3, TLR4, TLR9, and RAGE

The cholinergic antiinflammatory pathway modulates inflammatory cytokine production through a mechanism dependent on the vagus nerve and the α7 subunit of the nicotinic acetylcholine receptor. GTS-21 [3-(2,4-dimethoxybenzylidene) anabaseine], a selective α7 agonist, inhibits inflammatory cytokine production in murine and human macrophages and in several models of inflammatory disease in vivo, but to date its antiinflammatory efficacy in human monocytes has not been characterized. We report here our findings that GTS-21 attenuates tumor necrosis factor (TNF) and interleukin 1β levels in human whole blood activated by exposure to endotoxin. GTS-21 inhibited TNF production in endotoxin-stimulated primary human monocytes in vitro at the transcriptional level. The suppressive effect of GTS-21 was more potent than nicotine in whole blood and monocytes. Furthermore, GTS-21 attenuated TNF production in monocytes stimulated with peptidoglycan, polyinosinic-polycytidylic acid, CpG, HMGB1 (high-mobility group box 1 protein), and advanced glycation end product–modified albumin. GTS-21 decreased TNF levels in endotoxin-stimulated whole blood obtained from patients with severe sepsis. These findings establish the immunoregulatory effect of GTS-21 on human monocytes, and indicate the potential benefits of further exploration of GTS-21’s therapeutic uses in human inflammatory disease