Differences in mortality rate among patients hospitalized with severe COVID-19 according to their body mass index.

Background: Obesity has been described as a risk factor for COVID-19 severity and mortality. Previous studies report a linear association between BMI and adverse outcomes, meanwhile in other critical illness, excessive fat tissue is related to improved survival. Whether different BMI is related with the survival of patients with severe COVID-19 deserves further analysis. Objective: To determine the mortality rate among hospitalized patients with severe COVID-19 stratified according to BMI. Methods: The clinical files of all patients hospitalized from March to December 2020 with a positive PCR test for SARS-CoV-2 discharged due to improvement or death, were analyzed. A mixed effects logistic regression was carried out to determine which clinical and biochemical characteristics and comorbidities were associated with in-hospital mortality. Results: The cohort consisted of 608 patients with a median age of 59 years (interquartile ranges, IQR 46-69 years), median BMI of 28.7 kg/m2 (IQR 25.4-32.4 kg/m2), 65.5% were male. In-hospital mortality rate was 43.4%. Of the cohort 0.8% had low weight, 20.9% normal weight, 36.0% overweight, 26.5% obesity grade I, 10.2% obesity grade II and 5.6% obesity grade III. Mortality rate was highest in patients with low weight (80%), followed by patients with obesity grade III (58.8%) and grade II (50.0%). Overweight and underweight/obesity grade III were associated with higher mortality (OR of 9.75 [1.01-1.10] and OR 4.08 [1.64-10.14]), after adjusting by sex and age. Conclusions: The patients in the underweight/overweight and grade 3 obesity categories are at higher risk of COVID-19 related mortality, compared to those with grade I or II obesity.

Prone position in non-intubated patient with COVID-19 as a maneuver to avoid intubation. / Posición prono en paciente no intubado con COVID-19 como maniobra para evitar la intubación.

BACKGROUND: The COVID-19 (from Coronavirus Disease 2019) is a disease that has generated a pandemic that has affected the world, Mexico included. The spectrum of the disease ranges from asymptomatic infection to severe acute respiratory distress syndrome (ARDS). The objective of the case is to demonstrate the usefulness of the prone position in non-intubated patients. CLINICAL CASE: We present the case of a woman without comorbidities with COVID-19 and moderate ARDS, in whom intubation was avoided after improvement with the prone position, as determined by arterial oxygen saturation by pulse oximetry and by the relationship of arterial oxygen pressure and the fraction of inspired oxygen (PaO2/FiO2). CONCLUSION: There is scarce evidence of this therapeutic maneuver in awake patients. However, it can help to improve oxygenation and to avoid intubation in these patients.

INTRODUCCIÓN: la COVID-19 (del inglés Coronavirus Disease 2019) es una enfermedad que ha generado una pandemia, la cual ha afectado a todo el mundo, incluido México. Esta enfermedad puede presentarse desde una infección asintomática hasta síndrome de distrés respiratorio agudo (SDRA) grave. El objetivo del reporte de caso es mostrar la utilidad de la posición prono en pacientes no intubados. CASO CLÍNICO: presentamos el caso de una mujer sin comorbilidades con COVID-19 y SDRA moderado, en quien se evitó la intubación tras la mejoría con la posición prono, evaluada por la saturación arterial de oxígeno por pulsioximetría y por la relación de la presión arterial de oxígeno y la fracción inspirada de oxígeno (PaO2/FiO2). CONCLUSIÓN: existe poca evidencia sobre esta maniobra terapéutica en pacientes despiertos. Sin embargo, puede ser de ayuda para mejorar la oxigenación y evitar la intubación en estos pacientes.

Association of neutrophil-to-lymphocyte and lymphocyte-to-C-reactive protein ratios with COVID-19-related mortality.

INTRODUCTION: Neutrophil-to-lymphocyte (NLR) and lymphocyte-to-C-reactive protein (LCR) ratios are used to predict severity and mortality in various infections. OBJECTIVE: To establish the best NLR and LCR cutoff point to predict mortality in patients hospitalized for COVID-19 in Mexico. METHOD: Analytical cross-sectional study of patients hospitalized for severe COVID-19 in a specialty hospital. RESULTS: Out of 242 analyzed patients, 34 % died. The deceased subjects were older (62 vs. 51 years; p < 0.001), had a higher prevalence of > 10 years with systemic arterial hypertension (59.4 vs. 45.1 %, p = 0.022), as well as a higher NLR (17.66 vs. 8.31, p < 0.001) and lower LCR (0.03 vs. 0.06, p < 0.002) with regard to those who survived. The cutoff points to predict mortality were NLR > 12 and LCR < 0.03. The combination of NLR/LCR had a sensitivity of 80 %, specificity of 74 %, positive predictive value of 46.15 %, negative predictive value of 93.02 % and an odds ratio of 11.429 to predict mortality. CONCLUSION: NLR > 12 and LCR < 0.03 are useful biomarkers to evaluate the risk of mortality in Mexican patients with severe COVID- 19. INTRODUCCIÓN: Los índices neutrófilo/linfocito (INL) y linfocito/proteína C reactiva (ILR) se usan para predecir severidad y mortalidad en diversas infecciones. OBJETIVO: Establecer en México el mejor punto de corte de INL e ILR para predecir la mortalidad en pacientes hospitalizados por COVID-19. MÉTODO: Estudio transversal analítico de pacientes hospitalizados por COVID-19 grave en un hospital de especialidades. RESULTADOS: Falleció 34 % de 242 pacientes analizados. Los sujetos fallecidos tenían mayor edad (62 versus 51 años, p < 0.001), mayor prevalencia de hipertensión arterial sistémica > 10 años (59.4 versus 45.1 %, p = 0.022), así como INL más alto (17.66 versus 8.31, p < 0.001) e ILR más bajo (0.03 versus 0.06, p < 0.002) respecto a quienes sobrevivieron. Los puntos de corte para predecir mortalidad fueron INL > 12 e ILR < 0.03. La combinación de INL e ILR tuvo sensibilidad de 80 %, especificidad de 74 %, valor predictivo positivo de 46.15 %, valor predictivo negativo de 93.02 % y razón de momios de 11.429 para predecir la mortalidad. CONCLUSIÓN: INL > 12 e ILR < 0.03 son biomarcadores útiles para evaluar el riesgo de mortalidad en pacientes mexicanos con COVID-19 grave.

The tale of two pandemics: High prevalence of severe obesity among patients with suspected COVID-19

Background: Obesity is frequent in Mexico, but its importance for COVID-19 is still under debate. We aimed to describe its frequency in patients with severe COVID-19 in a referral hospital. Materials and methods: 167 patients hospitalized for suspicious or confirmed COVID-19, 66.7% male with a median age of 54 (interquartile range 43-63) were classified according to BMI and evaluated for comorbidities, coronavirus-2 polymerase chain reaction test results, and reason for discharge. Results: 75.3% of the patients were overweight or obese and 7.8% had grade III obesity. Increasing BMI related to higher probabilities of hyperglycemia (fasting glucose > 100 mg/dL, p = 0.044), but other comorbidities were similar among groups. The mortality rate among patients with Grade I obesity was 11%, whereas 33% of patients with either underweight or Grade III obesity died, depicting a U-shaped mortality curve. Conclusions: Obesity and its comorbidities are common in hospitalized patients in Mexico. Special efforts must be made to detect them, and further interventions to control the obesity pandemic will also be necessary to improve long-term results. Antecedentes: la obesidad severa es frecuente en México, pero su impacto en el COVID-19 es debatida. Buscamos describir su frecuencia en pacientes con COVID-19 severo en un hospital de referencia. Material y métodos: 167 pacientes hospitalizados con COVID-19 (sospechoso o confirmado), 66.7% hombres con una mediana de edad de 54 años (rangos intercuartílicos 43-63) se clasificaron de acuerdo al IMC, sus comorbilidades, la prueba de reacción de polimerasa para coronavirus-2 y causa de egreso. Resultados: 75.3% tenían sobrepeso u obesidad y 7.8% estaban en obesidad grado III. El aumento de IMC se relacionó con mayor probabilidad de hiperglucemia (glucosa en ayuno > 100 mg/dL, p=0.044), otras comorbilidades fueron similares entre grupos. La portalidad en pacientes con obesidad grado I fue 11% y 33% en peso bajo u obesidad grado III, mostrando una curva con forma de U. Conclusiones: La obesidad y sus comorbilidades son comunes en pacientes hospitalizados en México. Se deben hacer esfuerzos especiales por detectarlas y se necesitarán intervenciones sobre la pandemia de obesidad para mejorar resultados a largo plazo.

Association of neutrophil-to-lymphocyte and lymphocyte-to-C-reactive protein ratios with COVID-19-related mortality / Asociación de los índices neutrófilo/linfocito y linfocito/proteína C reactiva con mortalidad por COVID-19

Resumen Introducción: Los índices neutrófilo/linfocito (INL) y linfocito/proteína C reactiva (ILR) se usan para predecir severidad y mortalidad en diversas infecciones. Objetivo: Establecer en México el mejor punto de corte de INL e ILR para predecir la mortalidad en pacientes hospitalizados por COVID-19. Método: Estudio transversal analítico de pacientes hospitalizados por COVID-19 grave en un hospital de especialidades. Resultados: Falleció 34 % de 242 pacientes analizados. Los sujetos fallecidos tenían mayor edad (62 versus 51 años, p < 0.001), mayor prevalencia de hipertensión arterial sistémica > 10 años (59.4 versus 45.1 %, p = 0.022), así como INL más alto (17.66 versus 8.31, p < 0.001) e ILR más bajo (0.03 versus 0.06, p < 0.002) respecto a quienes sobrevivieron. Los puntos de corte para predecir mortalidad fueron INL > 12 e ILR < 0.03. La combinación de INL e ILR tuvo sensibilidad de 80 %, especificidad de 74 %, valor predictivo positivo de 46.15 %, valor predictivo negativo de 93.02 % y razón de momios de 11.429 para predecir la mortalidad. Conclusión: INL > 12 e ILR < 0.03 son biomarcadores útiles para evaluar el riesgo de mortalidad en pacientes mexicanos con COVID-19 grave.

Abstract Introduction: Neutrophil-to-lymphocyte (NLR) and lymphocyte-to-C-reactive protein (LCR) ratios are used to predict severity and mortality in various infections. Objective: To establish the best NLR and LCR cutoff point to predict mortality in patients hospitalized for COVID-19 in Mexico. Method: Analytical cross-sectional study of patients hospitalized for severe COVID-19 in a specialty hospital. Results: Out of 242 analyzed patients, 34 % died. The deceased subjects were older (62 vs. 51 years; p < 0.001), had a higher prevalence of > 10 years with systemic arterial hypertension (59.4 vs. 45.1 %, p = 0.022), as well as a higher NLR (17.66 vs. 8.31, p < 0.001) and lower LCR (0.03 vs. 0.06, p < 0.002] with regard to those who survived. The cutoff points to predict mortality were NLR > 12 and LCR < 0.03. The combination of NLR/LCR had a sensitivity of 80 %, specificity of 74 %, positive predictive value of 46.15 %, negative predictive value of 93.02 % and an odds ratio of 11.429 to predict mortality. Conclusion: NLR > 12 and LCR < 0.03 are useful biomarkers to evaluate the risk of mortality in Mexican patients with severe COVID- 19.

Increased expression of hypoxia-induced factor 1α mRNA and its related genes in myeloid blood cells from critically ill COVID-19 patients.

BACKGROUND: COVID-19 counts 46 million people infected and killed more than 1.2 million. Hypoxaemia is one of the main clinical manifestations, especially in severe cases. HIF1α is a master transcription factor involved in the cellular response to oxygen levels. The immunopathogenesis of this severe form of COVID-19 is poorly understood. METHODS: We performed scRNAseq from leukocytes from five critically ill COVID-19 patients and characterized the expression of hypoxia-inducible factor1α and its transcriptionally regulated genes. Also performed metanalysis from the publicly available RNAseq data from COVID-19 bronchoalveolar cells. RESULTS: Critically-ill COVID-19 patients show a shift towards an immature myeloid profile in peripheral blood cells, including band neutrophils, immature monocytes, metamyelocytes, monocyte-macrophages, monocytoid precursors, and promyelocytes-myelocytes, together with mature monocytes and segmented neutrophils. May be the result of a physiological response known as emergency myelopoiesis. These cellular subsets and bronchoalveolar cells express HIF1α and their transcriptional targets related to inflammation (CXCL8, CXCR1, CXCR2, and CXCR4); virus sensing, (TLR2 and TLR4); and metabolism (SLC2A3, PFKFB3, PGK1, GAPDH and SOD2). CONCLUSIONS: The up-regulation and participation of HIF1α in events such as inflammation, immunometabolism, and TLR make it a potential molecular marker for COVID-19 severity and, interestingly, could represent a potential target for molecular therapy. Key messages Critically ill COVID-19 patients show emergency myelopoiesis. HIF1α and its transcriptionally regulated genes are expressed in immature myeloid cells which could serve as molecular targets. HIF1α and its transcriptionally regulated genes is also expressed in lung cells from critically ill COVID-19 patients which may partially explain the hypoxia related events.

A Shift Towards an Immature Myeloid Profile in Peripheral Blood of Critically Ill COVID-19 Patients.

BACKGROUND: SARS-CoV-2, the etiological agent causing COVID-19, has infected more than 27 million people with over 894000 deaths worldwide since its emergence in December 2019. Factors for severe diseases, such as diabetes, hypertension, and obesity have been identified however, the precise pathogenesis is poorly understood. To understand its pathophysiology and to develop effective therapeutic strategies, it is essential to define the prevailing immune cellular subsets. METHODS: We performed whole circulating immune cells scRNAseq from five critically ill COVID-19 patients, trajectory and gene ontology analysis. RESULTS: Immature myeloid populations, such as promyelocytes-myelocytes, metamyelocytes, band neutrophils, monocytoid precursors, and activated monocytes predominated. The trajectory with pseudotime analysis supported the finding of immature cell states. While the gene ontology showed myeloid cell activation in immune response, DNA and RNA processing, defense response to the virus, and response to type 1 interferon. Lymphoid lineage was scarce. Expression of genes such as C/EBPß, IRF1and FOSL2 potentially suggests the induction of trained immunity. CONCLUSIONS: Our results uncover transcriptomic profiles related to immature myeloid lineages and suggest the potential induction of trained immunity.