PROBABILITY OF HOSPITALIZATION AND DEATH AMONG COVID-19 PATIENTS WITH COMORBIDITY DURING OUTBREAKS OCCURRING IN MEXICO CITY.

BackgroundWorldwide, it has been observed that there is a strong association between the severity of COVID-19 and with being over 40 years of age, having diabetes mellitus (DM), hypertension and/or obesity. ObjectiveTo compare the probability of death caused by COVID-19 in patients with comorbidities during three periods defined for this study as follows: first wave (March 23 to July 12, 2020), interwave period (July 13 to October 25, 2020), and the second wave (October 26, 2020, to March 29, 2021) using the different fatality rates observed in Mexico City. MethodsThe cohort studied included individuals over 20 years of age. During the first wave (symptomatic), the interwave period, and the second wave (symptomatic and asymptomatic), participants were diagnosed using nasopharyngeal swabs taken in kiosks. Symptomatic individuals with risk factors for serious disease or death were referred to hospital. SARS-CoV-2 infection was defined by real time polymerase chain reaction in all hospitalized patients. All data from hospitalized patients and outpatients were added to the SISVER database. ResultsThe total cohort size for this study was 2,260,156 persons (having a mean age of 43.1 years). Of these, 8.6% suffered from DM, 11.6% from hypertension, and 9.7% from obesity. Of the total of 2,260,156 persons, 666,694 tested positive (29.5%) to SARS CoV-2, (with a mean age of 45). During the first wave, 82,489 tested positive; in the interwave period, 112,115; and during the second wave, 472,090. That is, a considerable increase in the number of cases of infection was observed in all age groups between the first and second waves (an increase of +472% on the first wave). Of the infected persons, a total of 85,587 (12.8%) were hospitalized: 24,023 in the first wave (29.1% of those who tested positive in this period); 16,935 (15.1%) during the interwave period, and 44,629 (9.5%) in the second wave, which represents an increase of 85.77% on the first wave. Of the hospitalized patients, there were 42,979 deaths (50.2% of those hospitalized), in the first wave, 11,964 (49.8% of those hospitalized in this period), during the interwave period, 6,794 (40.1%), and in the second wave 24,221 (54.3%), an increase of +102.4% between the first wave and the second. While within the general population, the probability of a patient dying having both COVID-19 and one of the specified comorbidities (DM, obesity, or arterial hypertension) showed a systematic reduction across all age groups, the probability of death for a hospitalized patient with comorbidities increased across all age groups during the second wave. When comparing the fatality rate of hospitalized COVID-19 patients in the second wave with those of the first wave and the interwave period, a significant increase was observed across all age groups, even in individuals without comorbidities. ConclusionThe data from this study show a considerable increase in the number of detected cases of infection in all age groups between the first and second waves. In addition, 12.8% of those infected were hospitalized for severe COVID-19, representing an increase of +85.9% from the first wave to the second. A high mortality rate was observed among hospitalized patients (>50%), as was a higher probability of death in hospitalized COVID-19 patients with comorbidities for all age groups during the second wave, although there had been a slight decrease during the interwave period. SUMMARY BOXO_ST_ABSWhat is already known?C_ST_ABSWorldwide the resurging of COVID-19 cases in waves has been observed. In Mexico, like in the rest of the world, we have observed surges of SARS CoV-2 infections, COVID-19 hospitalizations and fatal outcomes followed by decreases leading to local minima. Pre-existing health conditions such as being older, having diabetes mellitus (DM), hypertension and/or obesity has been observed to be associated with an increase in the severity of COVID-19. What are the new findings?O_LIBetween the first and second waves, considerable increases were observed in the number of detected cases of infection (+472%), in the number of hospitalized subjects (+85.9%), and the number of hospitalized subjects and deaths (+102.4%) in all age groups. C_LIO_LIWhen analysing only hospitalized individuals, with or without comorbidities, the Case Fatality Rate was high (50.2%), the probability of death increased considerably in all age groups between the first and second waves. This increase was more noticeable in those individuals with previously identified comorbidities (DM, hypertension, or obesity). C_LIO_LIAn increased probability of death among individuals without comorbidities was observed between the first and second waves. C_LI What do the new findings imply?During the second wave, demand for hospitalization increased, magnifying the impact of age and comorbidities as risk factors. This situation highlights the importance of decreasing the prevalence of comorbidities among the population.

The evolutionary landscape of SARS-CoV-2 variant B.1.1.519 and its clinical impact in Mexico City

The SARS-CoV-2 pandemic is one of the most concerning health problems around the globe. We report the emergence of SARS-CoV-2 variant B.1.1.519 in Mexico City. This variant represented up to 90% of sequenced cases in February 2021. It is characterized by three amino acid changes in the spike protein: T478K, P681H, and T732A. We report the effective reproduction number of B.1.1.519 and present evidence of its geographical origin based on phylogenetic analysis. We also studied its evolution via haplotype analysis and identified the most recurrent haplotypes. Finally, we studied the clinical impact of B.1.1.519: patients infected with variant B.1.1.519 showed a highly significant adjusted odds ratio (aOR) increase of 1.85 over non-B.1.1.519 patients for developing a severe/critical outcome (P = 0.000296, 1.33-2.6 95% CI) and a 2.35-fold increase for hospitalization (P = 0.005, 1.32-4.34 95% CI). The continuous monitoring of this and other variants will be required to control the ongoing pandemic as it evolves.

Epicardial adipose tissue thickness is associated with increased severity and mortality related to SARS-CoV-2 infection

BACKGROUNDIncreased adiposity and visceral obesity have been linked to adverse COVID-19 outcomes. The amount of epicardial adipose tissue (EAT) may have relevant implications given its proximity to the heart and lungs. Here, we explored the role of EAT in increasing the risk for COVID-19 adverse outcomes. METHODSWe included 748 patients with COVID-19 attending a reference center in Mexico City. EAT thickness, sub-thoracic and extra-pericardial fat were measured using thoracic CT scans. We explored the association of each thoracic adipose tissue compartment with COVID-19 mortality and severe COVID-19 (defined as mortality and need for invasive mechanical ventilation), according to the presence or absence of obesity. Mediation analyses evaluated the role of EAT in facilitating the effect of age, body mass index and cardiac troponin levels with COVID-19 outcomes. RESULTSEAT thickness was associated with increased risk of COVID-19 mortality (HR 1.18, 95%CI 1.01-1.39) independent of age, gender, comorbid conditions and BMI. Increased EAT was associated with lower SpO2 and PaFi index and higher levels of cardiac troponins, D-dimer, fibrinogen, C-reactive protein, and 4C severity score, independent of obesity. EAT mediated 13.1% (95%CI 3.67-28.0%) and 5.1% (95%CI 0.19-14.0%) of the effect of age and 19.4% (95%CI 4.67-63.0%) and 12.8% (95%CI 0.03-46.0%) of the effect of BMI on requirement for intubation and mortality, respectively. EAT also mediated the effect of increased cardiac troponins on myocardial infarction during COVID-19. CONCLUSIONEAT is an independent risk factor for severe COVID-19 and mortality independent of obesity. EAT partly mediates the effect of age and BMI and increased cardiac troponins on adverse COVID-19 outcomes.

Serum Vitamin D levels are associated with increased COVID-19 severity markers and mortality independent of visceral adiposity

INTRODUCTIONCoronavirus disease (COVID-19) is a global pandemic. Vitamin D deficiency has been associated with susceptibility to infectious disease. In this study, the association between COVID-19 outcomes and vitamin D levels in patients attending a COVID-19 reference center in Mexico City are examined. METHODSConsecutive patients with confirmed COVID-19 were evaluated. All patients underwent clinical evaluation and follow-up, laboratory measurements and a thoracic computerized tomography, including the measurement of epicardial fat thickness. Low vitamin D was defined as levels <20ng/mL (<50nmol/L) and deficient Vitamin D as a level [≤]12ng/mL (<30nmol/L) RESULTSOf the 551 patients included, low vitamin D levels were present in 45.6% and deficient levels in 10.9%. Deficient Vitamin D levels were associated with mortality (HR 2.11, 95%CI 1.24-3.58, p=0.006) but not with critical COVID-19, adjusted for age, sex, body-mass index and epicardial fat. Using model-based causal mediation analyses the increased risk of COVID-19 mortality conferred by low vitamin D levels was partly mediated by its effect on D-dimer and cardiac ultrasensitive troponins. Notably, increased risk of COVID-19 mortality conferred by low vitamin D levels was independent of BMI and epicardial fat. CONCLUSIONVitamin D deficiency ([≤]12ng/mL or <30nmol/L), is independently associated with COVID-19 mortality after adjustment for visceral fat (epicardial fat thickness). Low vitamin D may contribute to a pro-inflammatory and pro-thrombotic state, increasing the risk for adverse COVID-19 outcomes.

Adaptive responses to SARS-CoV-2 infection linked to accelerated aging measures predict adverse outcomes in patients with severe COVID-19

INTRODUCTIONChronological age (CA) is a predictor of adverse COVID-19 outcomes; however, CA alone does not capture individual responses to SARS-CoV-2 infection. Here, we evaluated the influence of aging metrics PhenoAge and PhenoAgeAccel to predict adverse COVID-19 outcomes. Furthermore, we sought to model adaptive metabolic and inflammatory responses to severe SARS-CoV-2 infection using individual PhenoAge components. METHODSIn this retrospective cohort study, we assessed cases admitted to a COVID-19 reference center in Mexico City. PhenoAge and PhenoAgeAccel were estimated using laboratory values at admission. Cox proportional hazards models were fitted to estimate risk for COVID-19 lethality and adverse outcomes (ICU admission, intubation, or death). To explore reproducible patterns which model adaptive responses to SARS-CoV-2 infection, we used k-means clustering using PhenoAge/PhenoAccelAge components. RESULTSWe included 1068 subjects of whom 401 presented critical illness and 204 died. PhenoAge was a better predictor of adverse outcomes and lethality compared to CA and SpO2 and its predictive capacity was sustained for all age groups. Patients with responses associated to PhenoAgeAccel>0 had higher risk of death and critical illness compared to those with lower values (log-rank p<0.001). Using unsupervised clustering we identified four adaptive responses to SARS-CoV-2 infection: 1) Inflammaging associated with CA, 2) metabolic dysfunction associated with cardio-metabolic comorbidities, 3) unfavorable hematological response, and 4) response associated with favorable outcomes. CONCLUSIONSAdaptive responses related to accelerated aging metrics are linked to adverse COVID-19 outcomes and have unique and distinguishable features. PhenoAge is a better predictor of adverse outcomes compared to CA.