Chronic Comorbidities in Middle Aged Patients Contribute to Ineffective Emergency Hematopoiesis in Covid-19 Fatal Outcomes

Background and Aims . Mexico is among the countries with the highest estimated excess mortality rates due to the COVID–19 pandemic, with more than half of reported deaths occurring in adults younger than 65 years old. Although this behavior is presumably influenced by the young demographics and the high prevalence of metabolic diseases, the underlying mechanisms have not been determined. Methods . The age–stratified case fatality rate (CFR) was estimated in a prospective cohort with 245 hospitalized COVID–19 cases, followed through time, for the period October 2020–September 2021. Cellular and inflammatory parameters were exhaustively investigated in blood samples by laboratory test, multiparametric flow cytometry and multiplex immunoassays. Results . The CFR was 35.51%, with 55.2% of deaths recorded in middle–aged adults. On admission, hematological cell differentiation, physiological stress and inflammation parameters, showed distinctive profiles of potential prognostic value in patients under 65 at 7 d follow–up. Pre–existing metabolic conditions were identified as risk factors of poor outcomes. Chronic kidney disease (CKD), as single comorbidity or in combination with diabetes, had the highest risk for COVID–19 fatality. Of note, fatal outcomes in middle–aged patients were marked from admission by an inflammatory landscape and emergency myeloid hematopoiesis at the expense of functional lymphoid innate cells for antiviral immunosurveillance, including NK and dendritic cell subsets. Conclusions . Comorbidities increased the development of imbalanced myeloid phenotype, rendering middle–aged individuals unable to effectively control SARS–CoV–2. A predictive signature of high–risk outcomes at day 7 of disease evolution as a tool for their early stratification in vulnerable populations is proposed. Graphical abstract Image, graphical abstract

Chronic Comorbidities in Middle Aged Patients Contribute to Ineffective Emergency Hematopoiesis in Covid-19 Fatal Outcomes.

BACKGROUND AND AIMS: Mexico is among the countries with the highest estimated excess mortality rates due to the COVID-19 pandemic, with more than half of reported deaths occurring in adults younger than 65 years old. Although this behavior is presumably influenced by the young demographics and the high prevalence of metabolic diseases, the underlying mechanisms have not been determined. METHODS: The age-stratified case fatality rate (CFR) was estimated in a prospective cohort with 245 hospitalized COVID-19 cases, followed through time, for the period October 2020-September 2021. Cellular and inflammatory parameters were exhaustively investigated in blood samples by laboratory test, multiparametric flow cytometry and multiplex immunoassays. RESULTS: The CFR was 35.51%, with 55.2% of deaths recorded in middle-aged adults. On admission, hematological cell differentiation, physiological stress and inflammation parameters, showed distinctive profiles of potential prognostic value in patients under 65 at 7 days follow-up. Pre-existing metabolic conditions were identified as risk factors of poor outcomes. Chronic kidney disease (CKD), as single comorbidity or in combination with diabetes, had the highest risk for COVID-19 fatality. Of note, fatal outcomes in middle-aged patients were marked from admission by an inflammatory landscape and emergency myeloid hematopoiesis at the expense of functional lymphoid innate cells for antiviral immunosurveillance, including NK and dendritic cell subsets. CONCLUSIONS: Comorbidities increased the development of imbalanced myeloid phenotype, rendering middle-aged individuals unable to effectively control SARS-CoV-2. A predictive signature of high-risk outcomes at day 7 of disease evolution as a tool for their early stratification in vulnerable populations is proposed.

Emergency Hematopoiesis in the Pathobiology of COVID-19: The Dark Side of an Early Innate Protective Mechanism.

The recognition of pathogens to which we are constantly exposed induces the immediate replenishment of innate immune cells from the most primitive stages of their development through emergency hematopoiesis, a central mechanism contributing to early infection control. However, as with other protective mechanisms, its functional success is at risk when the excess of inducing signals accelerates immunological catastrophes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exhibits a clinical spectrum that ranges from completely asymptomatic states to fatal outcomes, with the amplification of inflammatory components being the critical point that determine the progress, complication, and severity of the disease. This review focuses on the most relevant findings that entail emergency hematopoiesis to SARS-CoV-2 infection response and revolutionize our understanding of the mechanisms governing the clinical prognosis of COVID-19. Of special interest are the metabolic or hyperinflammatory conditions in aging that exacerbate the phenomenon and favor the uncontrolled emergency myelopoiesis leading to the evolution of severe disease.

Decrease in COVID-19 adverse outcomes in adults during the Delta and Omicron SARS-CoV-2 waves, after vaccination in Mexico

Mexico, one of the countries severely affected by COVID-19, accumulated more than 5. 1 all-cause excess deaths/1,000 inhabitants and 2.5 COVID-19 confirmed deaths/1,000 inhabitants, in 2 years. In this scenario of high SARS-CoV-2 circulation, we analyzed the effectiveness of the country's vaccination strategy that used 7 different vaccines from around the world, and focused on vaccinating the oldest population first. We analyzed the national dataset published by Mexican health authorities, as a retrospective cohort, separating cases, hospitalizations, deaths and excess deaths by wave and age group. We explored if the vaccination strategy was effective to limit severe COVID-19 during the active outbreaks caused by Delta and Omicron variants. Vaccination of the eldest third of the population reduced COVID-19 hospitalizations, deaths and excess deaths by 46–55% in the third wave driven by Delta SARS-CoV-2. These adverse outcomes dropped 74–85% by the fourth wave driven by Omicron, when all adults had access to vaccines. Vaccine access for the pregnant resulted in 85–90% decrease in COVID-19 fatalities in pregnant individuals and 80% decrease in infants 0 years old by the Omicron wave. In contrast, in the rest of the pediatric population that did not access vaccination before the period analyzed, COVID-19 hospitalizations increased >40% during the Delta and Omicron waves. Our analysis suggests that the vaccination strategy in Mexico has been successful to limit population mortality and decrease severe COVID-19, but children in Mexico still need access to SARS-CoV-2 vaccines to limit severe COVID-19, in particular those 1–4 years old.

Clinical monitored in subjects metabolically healthy and unhealthy before and during a SARS-CoV-2 infection- A cross-sectional study in Mexican population.

The COVID-19 disease has forced us to consider the physiologic role of obesity and metabolically healthy and unhealthy status in response to SARS-CoV-2 infection. Hematological, coagulation, biochemical, and immunoinflammatory changes have been informed with a disparity in morbidity and mortality. Therefore, we aimed to investigate the influence of metabolic health on clinical features in a cross-sectional study in Mexican subjects with and without SARS-CoV-2 infection in non-severe stages after a rigorous classification of obese and non-obese subjects who were metabolically healthy and unhealthy. Four groups were formed: 1) metabolically healthy with normal BMI (MHN); 2) metabolically unhealthy with normal BMI (MUN); 3) metabolically healthy obese (MHO); 4) metabolically unhealthy obese (MUO). Serum proinflammatory (TNF-α, MCP-1, IL-1ß, and IL-6) and anti-inflammatory (TGF-ß, IL-1Ra, IL-4, and IL-10) cytokines, hematological parameters, coagulation, and acute phase components were evaluated. Our results showed that MHO people live with inflammaging. Meanwhile, MUN and MUO subjects develop metaflammation. Both inflammaging and metaflammation cause imperceptible modifications on hematological parameters, mainly in leukocyte populations and platelets, as well as acute phase and coagulation components. The statistical analysis revealed that many clinical features are dependent on metabolic health. In conclusion, MHO subjects seem to be transitioning from metabolically healthy to unhealthy, which is accelerated in acute processes, such as SARS-CoV-2 infection. Meanwhile, metabolically unhealthy subjects independently of BMI have a deteriorating immunometabolic status associated with a hyperinflammatory state leading to multi-organ dysfunction, treatment complications, and severe COVID-19 disease.