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BACKGROUNDWith widespread transmission of the Omicron SARS-CoV-2 variant, reinfections have become increasingly common. Here, we explored the role hybrid immunity, primary infection severity, and variant predominance on the risk of reinfection and severe COVID-19 during periods of Omicron predominance in Mexico. METHODSWe analyzed reinfections in Mexico in individuals with [≥]90 days from a previous primary infection using a national surveillance registry of SARS-CoV-2 cases from March 3rd, 2020, until August 13th, 2022. Immunity-generating events included primary infection, partial or full vaccination and vaccine boosting. Reinfections were matched by age and sex with controls with primary SARS-CoV-2 infection and negative RT-PCR or antigen test [≥]90 days after infection to explore risk factors for reinfection and reinfection-associated severe COVID-19. We also explored the protective role of heterologous vs. homologous vaccine boosters against reinfection or severe COVID-19 in fully vaccinated individuals. RESULTSWe detected 231,202 SARS-CoV-2 reinfections in Mexico, with 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. CONCLUSIONSSARS-CoV-2 reinfections have increased during periods of Omicron predominance. Hybrid immunity provides protection against reinfection and reinfection-associated severe COVID-19, with potential benefit from heterologous booster schemes. RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for the terms "SARS-CoV-2" AND "reinfection" AND "hybrid immunity" until November 20th, 2022, and identified a few population studies previously conducted in Israel, Sweden, Qatar, United States and Canada which explored risk of reinfection and the protective role of hybrid immunity in individuals with one, two or three doses of COVID-19 vaccines, predominantly during periods of predominance of Omicron BA.1 and BA.2 subvariants. Notably, no studies were conducted in any Latin American country or reported on the benefit of heterologous booster schemes or the order of immunity-generating events. Added value of this studyWe report the results of nation-wide study in Mexico of over 230,000 SARS-CoV-2 reinfections, with [~]90% occurring during periods of Omicron predominance. We identified that vaccination provided additional benefit on reducing the risk of SARS-CoV-2 reinfection, with the highest benefit observed in individuals with complete vaccination and booster protocols prior to primary infection or with primary infection during periods of BA.1 and BA.2 subvariant predominance. Hybrid immunity also provides a substantial reduction in the risk of reinfection-associated severe COVID-19, with >90% reduction in risk compared to unvaccinated individuals with previous SARS-CoV-2 infection, regardless of the order of immunity-generating events. Finally, heterologous COVID-19 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. Implications of all the available evidenceOur results support that COVID-19 vaccination and boosters provide additional benefit to protect against SARS-CoV-2 reinfection and reinfection-associated severe COVID-19. The use of heterologous boosters appears to provide additional protection in previously infected individuals and such schemes may prove beneficial to increase vaccination coverage as newer, more transmissible variants emerge.
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BACKGROUNDIn 2020, Mexico experienced one of the highest rates of excess mortality globally. However, the extent to which non-COVID deaths contributed to excess mortality, its regional characterization, and the association between municipal-and individual-level sociodemographic inequality has not been characterized. METHODSWe conducted a retrospective municipal an individual-level study using death certificate data in Mexico from 2016-2020. We analyzed mortality related to COVID-19 and to non-COVID-19 causes using ICD-10 codes to identify cause-specific mortality. Excess mortality was estimated as the increase in deaths in 2020 compared to the average of 2016-2019, disaggregated by primary cause of death, death setting (in-hospital and out-of-hospital) and geographical location. We evaluated correlates of non-COVID-19 mortality at the individual level using mixed effects logistic regression and correlates of non-COVID-19 excess mortality in 2020 at the municipal level using negative binomial regression. RESULTSWe identified 1,069,174 deaths in 2020 (833.5 per 100,000 inhabitants), which was 49% higher compared to the 2016-2019 average (557.38 per 100,000 inhabitants). Overall excess mortality (276.11 deaths per 100,000 inhabitants) was attributable in 76.1% to COVID-19; however, non-COVID-19 causes comprised one-fifth of excess deaths. COVID-19 deaths occurred primarily in-hospital, while excess non-COVID-19 deaths decreased in this setting and increased out-of-hospital. Excess non-COVID-19 mortality displayed geographical heterogeneity linked to sociodemographic inequalities with clustering in states in southern Mexico. Municipal-level predictors of non-COVID-19 excess mortality included levels of social security coverage, higher rates of COVID-19 hospitalization, and social marginalization. At the individual level, lower educational attainment, blue collar workers, and lack of medical care assistance were associated with non-COVID-19 mortality during 2020. CONCLUSIONNon-COVID-19 causes of death, largely chronic cardiometabolic conditions, comprised up to one-fifth of excess deaths in Mexico during 2020. Non-COVID-19 excess deaths occurred disproportionately out-of-hospital and were associated with both individual-and municipal-level sociodemographic inequalities. These findings should prompt an urgent call to action to improve healthcare coverage and access to reduce health and sociodemographic inequalities in Mexico to reduce preventable mortality in situations which increase the stress of healthcare systems, including the ongoing COVID-19 pandemic.
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BACKGROUNDVaccination has been effective in ameliorating the impact of COVID-19. However, estimation of vaccine effectiveness (VE) is still unavailable for some widely used vaccines and underrepresented groups. Here, we report on the effectiveness of a nation-wide COVID-19 vaccination program in Mexico. METHODSWe used a test-negative design within a national COVID-19 surveillance system to assess VE of the BNT162b2, mRNA-12732, Gam-COVID-Vac, Ad5-nCoV, Ad26.COV2.S, ChAdOx1 and CoronaVac vaccines, against SARS-CoV-2 infection, COVID-19 related hospitalization and death for adults [≥]18 years in Mexico. VE was estimated using Cox proportional hazard models considering time-varying vaccination status in partial and fully vaccinated individuals compared to unvaccinated adults, adjusted by age, sex, comorbidities and municipality. We also estimated VE for adults [≥]60 years, for cases with diabetes and comparing periods with predominance of variants B.1.1.519 and B.1.617.2. RESULTSWe assessed 793,487 vaccinated compared to 4,792,338 unvaccinated adults between December 24th, 2020, and September 27th, 2021. VE against SARS-CoV-2 infection was highest for fully vaccinated individuals with mRNA-12732 (91.5%, 95%CI 90.3-92.4) and Ad26.COV2.S (82.2%, 95%CI 81.4-82.9), whereas for COVID-19 related hospitalization were 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). VE for all evaluated vaccines was reduced for adults [≥]60 years, people with diabetes, and in periods of Delta variant predominance. CONCLUSIONSAll evaluated vaccines were effective against SARS-CoV-2 infection and COVID-19 related hospitalization and death. Mass vaccination campaigns with multiple vaccine products are feasible and effective to maximize vaccination coverage.
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BACKGROUNDExcess all-cause mortality rates in Mexico in 2020 during the COVID-19 pandemic were among the highest globally. Recent reports suggest that diabetes-related deaths were also higher, but the contribution of diabetes as a cause of excess mortality in Mexico during 2020 compared to prior years has not yet been characterized. METHODSWe conducted a retrospective, state-level study using national death registries from Mexican adults [≥]20 years for the 2017-2020 period. Diabetes-related deaths were classified using ICD-10 codes that listed diabetes as the primary cause of death, excluding certificates which listed COVID-19 as a cause of death. Excess mortality was estimated as the increase in diabetes-related mortality in 2020 compared to average rates in 2017-2019. Analyses were stratified by diabetes type, diabetes-related complication, and in-hospital vs. out-of-hospital death. We evaluated the geographic distribution of diabetes-related excess mortality and its socio-demographic and epidemiologic correlates using spatial analyses and negative binomial regression models. RESULTSWe identified 148,437 diabetes-related deaths in 2020 (177/100,000 inhabitants), 41.6% higher than the average for 2017-2019, with the excess occurring after the onset of the COVID-19 pandemic. In-hospital diabetes-related deaths decreased by 17.8% in 2020 compared to 2017-2019, whereas out-of-hospital deaths increased by 89.4%. Most deaths were attributable to type 2 diabetes and type 1 diabetes (129.7 and 4.0/100,000 population). Diabetes-related emergencies as contributing causes of death also increased in 2020 compared to 2017-2019 for hyperglycemic hyperosmolar state (128%), and ketoacidosis (116%). Diabetes-related excess mortality clustered in southern Mexico and was highest in states with higher social lag, higher rates of COVID-19 hospitalization, and higher prevalence of HbA1c [≥]7.5%. INTERPRETATIONDiabetes-related mortality increased among Mexican adults by 41.6% in 2020 after the onset of the pandemic compared to 2017-2019, largely attributable to type 2 diabetes. Excess diabetes-related deaths occurred disproportionately out-of-hospital, clustered in southern Mexico, and were associated with higher state-level marginalization, rates of COVID-19 hospitalizations, and higher prevalence of suboptimal glycemic control. Urgent policies to mitigate mortality due to diabetes in Mexico are needed, particularly given the ongoing challenges in caring for people with diabetes posed by the COVID-19 pandemic. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed and Google Scholar for research articles published up to February 15, 2022, using the terms [("diabetes-related mortality" OR ("excess mortality" AND "diabetes"))]. No language restriction was applied. This search revealed few international studies evaluating nationwide diabetes-related mortality in general. In Mexico, only one unpublished study evaluated diabetes-related mortality up to 2019. We identified no studies which evaluated diabetes-related excess mortality in Mexico or elsewhere during 2020 or which explored correlates of diabetes-related excess mortality in 2020. Added value of this studyThis is the first report and characterization of an excess in diabetes-related mortality in Mexico during 2020 compared to recent years. Diabetes as a primary cause of death in Mexico was higher in 2020 compared to 2017-2019, particularly for people living with type 2 diabetes, starting in March 2020 with the onset of the COVID-19 pandemic. Compared to the 2017-2019 period, most of these excess deaths occurred out of hospital, with a concurrent decrease in in-hospital diabetes-related mortality. Hyperosmolar hyperglycemic state and ketoacidosis as primary causes of diabetes-related deaths also increased in 2020 compared to prior years. Our study also identified substantial geographic variation in diabetes-related excess mortality in Mexico, with southern, poorer States bearing a disproportionate burden. Finally, we report that diabetes-related excess mortality was associated with higher marginalization, suboptimal glycemic control, and higher rates of COVID-19 hospitalization, which were clustered in southern Mexico. Implications of the available evidenceReadily treatable, high morbidity diabetes-related conditions were likely untreated due to the constraints of the health care system during the COVID-19 pandemic, leading to diabetes-related excess mortality. This is a problem for Mexico, but it is likely to be generalizable to other countries and other conditions, as seen even in high-income countries. Given the ongoing challenges posed by the COVID-19 pandemic on healthcare systems, policies that can strengthen care for diabetes and other chronic conditions are urgently needed to mitigate the dramatic rise in diabetes-related mortality occurring in the out-of-hospital setting and its disproportionate burden on populations with high levels of marginalization.
