Comprehensive Evaluation of the Impact of Sociodemographic Inequalities on Adverse Outcomes and Excess Mortality During the Coronavirus Disease 2019 (COVID-19) Pandemic in Mexico City.

BACKGROUND: The impact of the coronavirus disease 2019 (COVID-19) pandemic in Mexico City has been sharp, as several social inequalities at all levels coexist. Here we conducted an in-depth evaluation of the impact of individual and municipal-level social inequalities on the COVID-19 pandemic in Mexico City. METHODS: We analyzed suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases, from the Mexico City Epidemiological Surveillance System from 24 February 2020 to 31 March 2021. COVID-19 outcomes included rates of hospitalization, severe COVID-19, invasive mechanical ventilation, and mortality. We evaluated socioeconomic occupation as an individual risk, and social lag, which captures municipal-level social vulnerability, and urban population density as proxies of structural risk factors. Impact of reductions in vehicular mobility on COVID-19 rates and the influence of risk factors were also assessed. Finally, we assessed discrepancies in COVID-19 and non-COVID-19 excess mortality using death certificates from the general civil registry. RESULTS: We detected vulnerable groups who belonged to economically unfavored sectors and experienced increased risk of COVID-19 outcomes. Cases living in marginalized municipalities with high population density experienced greater risk for COVID-19 outcomes. Additionally, policies to reduce vehicular mobility had differential impacts modified by social lag and urban population density. Finally, we report an under-registry of COVID-19 deaths along with an excess mortality closely related to marginalized and densely populated communities in an ambulatory setting. This could be attributable to a negative impact of modified hospital admission criteria during the pandemic. CONCLUSIONS: Socioeconomic occupation and municipality-wide factors played a significant role in shaping the course of the COVID-19 pandemic in Mexico City.

Awake prone positioning and oxygen therapy in patients with COVID-19: the APRONOX study.

BACKGROUND: The awake prone positioning strategy for patients with acute respiratory distress syndrome is a safe, simple and cost-effective technique used to improve hypoxaemia. We aimed to evaluate intubation and mortality risk in patients with coronavirus disease 2019 (COVID-19) who underwent awake prone positioning during hospitalisation. METHODS: In this retrospective, multicentre observational study conducted between 1 May 2020 and 12 June 2020 in 27 hospitals in Mexico and Ecuador, nonintubated patients with COVID-19 managed with awake prone or awake supine positioning were included to evaluate intubation and mortality risk through logistic regression models; multivariable and centre adjustment, propensity score analyses, and E-values were calculated to limit confounding. RESULTS: 827 nonintubated patients with COVID-19 in the awake prone (n=505) and awake supine (n=322) groups were included for analysis. Fewer patients in the awake prone group required endotracheal intubation (23.6% versus 40.4%) or died (19.8% versus 37.3%). Awake prone positioning was a protective factor for intubation even after multivariable adjustment (OR 0.35, 95% CI 0.24-0.52; p<0.0001, E=2.12), which prevailed after propensity score analysis (OR 0.41, 95% CI 0.27-0.62; p<0.0001, E=1.86) and mortality (adjusted OR 0.38, 95% CI 0.26-0.55; p<0.0001, E=2.03). The main variables associated with intubation among awake prone patients were increasing age, lower baseline peripheral arterial oxygen saturation/inspiratory oxygen fraction ratio (P aO2 /F IO2 ) and management with a nonrebreather mask. CONCLUSIONS: Awake prone positioning in hospitalised nonintubated patients with COVID-19 is associated with a lower risk of intubation and mortality.

Exploring the rationale for thermotherapy in COVID-19.

Increased transmissibility of the pandemic severe acute respiratory coronavirus 2 (SARS-CoV-2) has been noted to occur at lower ambient temperatures. This is seemingly related to a better replication of most respiratory viruses, including SARS-CoV-2, at lower-than-core body temperatures (i.e., 33 °C vs 37 °C). Also, intrinsic characteristics of SARS-CoV-2 make it a heat-susceptible pathogen. Thermotherapy has successfully been used to combat viral infections in plants which could otherwise result in great economic losses; 90% of viruses causing infections in plants are positive-sense single-stranded ribonucleic acid (+ssRNA) viruses, a characteristic shared by SARS-CoV-2. Thus, it is possible to envision the use of heat-based interventions (thermotherapy or mild-temperature hyperthermia) in patients with COVID-19 for which moderate cycles (every 8-12 h) of mild-temperature hyperthermia (1-2 h) have been proposed. However, there are potential safety and mechanistic concerns which could limit the use of thermotherapy only to patients with mild-to-moderate COVID-19 to prevent disease progression rather than to treat patients who have already progressed to severe-to-critical COVID-19. Here, we review the characteristics of SARS-CoV-2 which make it a heat-susceptible virus, potential host mechanisms which could be enhanced at higher temperatures to aid viral clearance, and how thermotherapy could be investigated as a modality of treatment in patients with COVID-19 while taking into consideration potential risks.

Statistical Considerations for the Design and Analysis of Pragmatic Trials in Aging Research.

Pragmatic trials aim to assess intervention efficacy in usual patient care settings, contrasting with explanatory trials conducted under controlled conditions. In aging research, pragmatic trials are important designs for obtaining real-world evidence in elderly populations, which are often underrepresented in trials. In this review, we discuss statistical considerations from a frequentist approach for the design and analysis of pragmatic trials. When choosing the dependent variable, it is essential to use an outcome that is highly relevant to usual medical care while also providing sufficient statistical power. Besides traditionally used binary outcomes, ordinal outcomes can provide pragmatic answers with gains in statistical power. Cluster randomization requires careful consideration of sample size calculation and analysis methods, especially regarding missing data and outcome variables. Mixed effects models and generalized estimating equations (GEEs) are recommended for analysis to account for center effects, with tools available for sample size estimation. Multi-arm studies pose challenges in sample size calculation, requiring adjustment for design effects and consideration of multiple comparison correction methods. Secondary analyses are common but require caution due to the risk of reduced statistical power and false-discovery rates. Safety data collection methods should balance pragmatism and data quality. Overall, understanding statistical considerations is crucial for designing rigorous pragmatic trials that evaluate interventions in elderly populations under real-world conditions. In conclusion, this review focuses on various statistical topics of interest to those designing a pragmatic clinical trial, with consideration of aspects of relevance in the aging research field.

Role of Renal Venous Oxygen Pressure for Renal Function Monitoring After Related Living-Donor Kidney Transplantation: Cohort Study.

BACKGROUND: Monitoring of renal function after kidney transplantation (KT) is performed by measuring serum creatinine (SCr), urine volumes (UV), and glomerular filtration rate (GFR). Other methods based on oxygen metabolism, such as the renal venous oxygen pressure (PrvO2), may be useful. The aim of this study was to explore the correlation between PrvO2 and SCr, UV, and GFR 5 days after KT (SCr5, UV5, and GFR5, respectively). METHODS: We conducted a prospective cohort study in adults scheduled for living donor KT. A venous blood sample was taken from the renal vein after declamping the renal artery, and blood gas determinations were made. Correlation analyses between PrvO2 and SCr5, UV5, and GFR5 were done by calculating Spearman's correlation coefficient with generalized linear models (GLM). A Spearman's correlation analysis was performed between the percentage decrease in SCr (%ΔSCr) and PrvO2. A GLM was also performed to determine the association of PrvO2 with slow graft function (SGF). RESULTS: The study included 42 patients, of whom 67% were men. The median age was 31 years (IQR, 27-43.5). PrvO2 was negatively correlated with SCr5 (ρ = -0.53, P = .003), and positively correlated with GFR5 (ρ = 0.49, P = .001) and %ΔSCr (ρ = 0.47, P = .002). A higher PrvO2 was associated with an increase in GFR in univariable (ß = 1.24, 95% CI, 0.56-1.93, P = .001) and multivariable (ß = 1.24, 95% CI, 0.53-1.94, P = .001) analyses. No association was found between PrvO2 and SGF. CONCLUSION: PrvO2 could be used to monitor renal function in the first 5 days after related living-donor KT, given its good correlation with SCr and GFR.

Weight Gain After 12 Months of Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed HIV Patients.

Recent studies suggest that the introduction of antiretroviral agents such as integrase strand transfer inhibitors (INSTI) may lead to weight gain in people living with HIV (PLHIV). In this retrospective observational study, we report the weight changes observed in virologically suppressed HIV patients after 12 months of switching to bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF) due to a national change in public policy in Mexico. Patients on prior regimens based on TDF/FTC or ABC/3TC plus non-nucleoside retrotranscriptase inhibitor, INSTI, or protease inhibitor were included. In the 399 patients analyzed, a significant weight increase was found, as well as an increase in body mass index (BMI), total cholesterol, low-density lipoprotein cholesterol (LDL-C), glucose, creatinine, and CD4+ cells after 12 months of switching treatment (all p ≤ .001). Mean weight gain was 1.63 kg [confidence interval (95% CI): 1.14-2.11], whereas the average percentage of weight gained was 2.5% (95% CI: 1.83-3.17). After considering the confounding effect of baseline weight status, the change in weight and BMI did not present significant differences between any of the prior treatment schemes. In conclusion, PLHIV switching to BIC/F/TAF therapy experienced weight gain after the first year of switching treatment. Although this weight gain could be due to the switch in treatment regimen, it cannot be excluded that it was caused by other factors since no comparable control group could be used for comparison.

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

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.

SOFA Score Plus Impedance Ratio Predicts Mortality in Critically Ill Patients Admitted to the Emergency Department: Retrospective Observational Study.

BACKGROUND: The Sequential Organ Failure Assessment (SOFA) is a scoring system used for the evaluation of disease severity and prognosis of critically ill patients. The impedance ratio (Imp-R) is a novel mortality predictor. AIMS: This study aimed to evaluate the combination of the SOFA + Imp-R in the prediction of mortality in critically ill patients admitted to the Emergency Department (ED). METHODS: A retrospective cohort study was performed in adult patients with acute illness admitted to the ED of a tertiary-care referral center. Baseline SOFA score and bioelectrical impedance analysis to obtain the Imp-R were performed within the first 24 h after admission to the ED. A Cox regression analysis was performed to evaluate the mortality risk of the initial SOFA score plus the Imp-R. Harrell's C-statistic and decision curve analyses (DCA) were performed. RESULTS: Out of 325 patients, 240 were included for analysis. Overall mortality was 31.3%. Only 21.3% of non-surviving patients died after hospital discharge, and 78.4% died during their hospital stay. Of the latter, 40.6% died in the ED. The SOFA and Imp-R values were higher in non-survivors and were significantly associated with mortality in all models. The combination of the SOFA + Imp-R significantly predicted 30-day mortality, in-hospital mortality, and ED mortality with an area under the curve (AUC) of 0.80 (95% CI: 74-0.86), 0.79 (95% CI: 0.74-0.86) and 0.75 (95% CI: 0.66-0.84), respectively. The DCA showed that combining the SOFA + Imp-R improved the prediction of mortality through the lower risk thresholds. CONCLUSIONS: The addition of the Imp-R to the baseline SOFA score on admission to the ED improves mortality prediction in severely acutely ill patients admitted to the ED.

Anatomical and Clinical Factors Associated With Valvulopathy and Aortopathy in Mexican Patients With Bicuspid Aortic Valves.

The bicuspid aortic valve (BAV) is associated with significant aortic valve dysfunction. We aimed to study Mexican patients with BAV to assess phenotypic expressions of BAV, and associations of valvulopathy and aortopathy and their predictors. A cross-sectional, retrospective study was designed. The patients were divided according to (1) normally or minimally dysfunctional BAV, (2) predominant aortic regurgitation (AR), and (3) predominant aortic stenosis (AS). A total of 189 patients were included with a high prevalence of males (68%). The overall median age was 42 (23 to 52) years. The distribution of fused BAV phenotypes was right-left fusion (77%), right noncoronary fusion (17%) and left noncoronary fusion (6%). AS-predominant group was the oldest with a high prevalence of hypertension, type 2 diabetes mellitus (T2DM), and raphe. In multivariable analysis T2DM (odds ratio [OR] 10.5 [95% confidence interval (CI) 2.1 to 52], p <0.01) and presence of raphe (OR 2.58 [95% CI 1.02 to 6.52], p = 0.04) were independently associated with AS. The AR-predominant group was composed mostly of males with significantly fewer cardiovascular risk factors. Male gender (OR 2.84 [95%CI 121 to 6.68], p = 0.01) and aortic dilatation (OR 3.58 [95% CI 1.73 to 7.39], p <0.01) were associated with AR-predominance in multivariable analysis. Aortic dilatation was associated with age (OR 1.03 [95% CI 1.008 to 1.05], p <0.01) and AR (OR 4.31 [95% CI 2.05 to 9.06], p <0.01). Independent factors associated with the root phenotype were male gender (OR 12.4 [95% CI 1.6 to 95], p <0.01) and AR (OR 5.25 [95% CI 2.18 to 12.6], p <0.01).In conclusion, in a mestizo population, the distribution of BAV-fused phenotypes was similar to European and North American populations, the presence of raphe and T2DM were independently associated with AS-predominance, and male gender and aortic dilatation were independently associated with AR-predominance.

[Stress, anxiety, and depression in health workers during the COVID-19 pandemic]. / Estrés, ansiedad y depresión en trabajadores de salud durante la pandemia por COVID-19.

Background: Mental health is an integral part of health. Having some psychiatric condition without treatment predisposes to a poor quality of life. These alterations have been found with an incidence of up to 50% in the general population. There are very few studies in Mexico on these conditions in health workers during the COVID-19 pandemic. Objective: To determine the prevalence of stress, anxiety, and depression during the COVID-19 pandemic in health workers. Material and methods: A descriptive, cross-sectional observational study was conducted on health workers in a tertiary hospital, through the application of randomized and self-completed surveys, in search of levels of stress, anxiety, and depression during the COVID-19 pandemic. Results: 44.7% of those surveyed showed depression, 83.1% anxiety, and 66.3% stress. The main groups affected were female staff, singles, and medical residents. Those with type 2 diabetes mellitus had higher anxiety and depression. Conclusion: The prevalence of stress, anxiety, and depression in health workers is similar to that of the general population in our study. Depression was the alteration most found. The scrutiny of alterations in mental health in health workers is of the utmost importance, with greater emphasis in the context of the aforementioned pandemic.

Introducción: la salud mental es parte integral de la salud. Tener algún padecimiento psiquiátrico sin tratamiento predispone a una mala calidad de vida. Estas alteraciones se han encontrado con una prevalencia de hasta 50% en la población general. En México hay muy pocos estudios acerca de la incidencia de dichos padecimientos en los trabajadores de la salud durante la pandemia por COVID-19. Objetivo: determinar la presencia de estrés, ansiedad y depresión durante la pandemia de COVID-19 en los trabajadores de la salud de un hospital de tercer nivel. Material y métodos: se realizó un estudio observacional transversal, descriptivo en los trabajadores de la salud de un hospital de tercer nivel, mediante la aplicación de encuestas aleatorizadas y autocomplementadas, en búsqueda de grado de estrés, ansiedad y depresión, durante la pandemia por COVID-19. Resultados: el 44.7% de los encuestados presentó depresión, 83.1% ansiedad y 66.3% estrés. Los principales grupos afectados fueron el personal femenino, solteros y médicos residentes. Aquellos con diabetes mellitus tipo 2 tuvieron mayor incidencia de ansiedad y depresión. Conclusión: la presencia de estrés, ansiedad y depresión en los trabajadores de la salud es similar a la de la población general en nuestro estudio. La depresión fue la alteración más encontrada. Es de suma importancia el escrutinio de alteraciones en la salud mental en los trabajadores de la salud, con mayor énfasis en el contexto de la pandemia mencionada.

Simplified acute physiology score II and Mannheim peritonitis index are associated with in-hospital mortality in patients with abdominal sepsis admitted to ICU.

OBJECTIVE: The objective of this study was to assess the association and interaction of laboratory parameters, Simplified Acute Physiology Score II (SAPSII), Modified Shock Index (MSI), and Mannheim Peritonitis Index (MPI) with in-hospital mortality. MATERIAL AND METHODS: We conducted a single-center case-control study. Adult patients with abdominal sepsis were included from May 2015 to May 2020. Baseline characteristics, laboratory parameters, SAPSII, MSI, and MPI scores at admission were collected. A principal component (PC) analysis was applied to evaluate variable interactions. In-hospital mortality risk was determined through logistic regression models. RESULTS: One hundred and twenty-seven patients were identified, 60 of which were included for analyses. Non-survivors (48.4%) had a higher frequency of hypertension, lactate and MPI, and lower BE and alactic BE levels. Eight PCs were obtained, PC1 being a linear combination of pH, AG, cAG, alactic BE, bicarbonate, and BE. MPI (OR = 9.87, 95% CI: 3.07-36.61, p = 0.0002), SAPSII (OR = 1.07, 95% CI: 1.01-1.14, p = 0.01), and PC1 (OR = 2.13, 95% CI: 1.12-4.76, p = 0.04) were significantly associated with mortality in univariate analysis, while MPI (OR = 10.1, 95% CI: 3.03-40.06, p = 0.0003) and SAPSII (OR = 1.07, CI95%: 1.01-1.14, p = 0.02) remained significant after adjusting for age and sex. CONCLUSION: MPI and SAPSII were associated with mortality, although the interaction of laboratory parameters was not.

OBJETIVO: Evaluar la asociación e interacción de los parámetros de laboratorio, SAPSII, MSI y MPI con la mortalidad intrahospitalaria. MATERIALES Y MÉTODOS: Nosotros realizamos un estudio de casos y controles de pacientes adultos con sepsis abdominal desde mayo 2015 a mayo 2020. Recolectamos las características basales, parámetros de laboratorio, SAPSII, MSI y MPI al ingreso. Se aplicó un Análisis de Componentes Principales. El riesgo de mortalidad intrahospitalaria se determinó mediante modelos de regresión logística. RESULTADOS: Identificamos 127 pacientes, 60 de los cuales se incluyeron. Los no supervivientes (48,4%) tuvieron mayor frecuencia de HAS, lactato y MPI, y menores niveles de EB y EB aláctico. Se obtuvieron ocho Componentes Principales (PC), siendo PC1 una combinación lineal de pH, AG, cAG, EB aláctico, bicarbonato y EB. MPI (OR = 9.87, IC95%: 3.07-36.61, p = 0.0002), SAPSII (OR = 1.07, IC95%: 1.01-1.14, p = 0.01) y PC1 (OR = 2.13, IC95%: 1.12-4.76, p = 0.04) se asociaron significativamente con la mortalidad en el análisis univariado, mientras que MPI (OR = 10.1, IC95%: 3.03-40.06, p = 0.0003) y SAPSII (OR = 1.07, IC 95%: 1.01-1.14, p = 0.02) permanecieron significativos después del ajuste por edad y sexo. CONCLUSIONES: MPI y SAPSII se asociaron con mortalidad, aunque la interacción de los parámetros de laboratorio no lo hizo.

Association of Differences in Dietary Behaviours and Lifestyle with Self-Reported Weight Gain during the COVID-19 Lockdown in a University Community from Chile: A Cross-Sectional Study.

Domiciliary confinement of people is one of the main strategies to limit the impact of COVID-19. Lockdowns have led to changes in lifestyle, emotional health, and eating habits. We aimed to evaluate the association of differences in dietary behaviours and lifestyle with self-reported weight gain during the COVID-19 lockdown in Chile. In this cross-sectional analytical study, five previously validated surveys were condensed into a single 86-item online questionnaire. The survey was sent to 1000 potential participants of the university community; it was kept online for 28 days to be answered. Of the 639 respondents, the mean self-reported weight gain during confinement was 1.99 kg (standard deviation [SE]: 0.17) and 0.7 (SE: 0.06) units of body mass index (BMI) (both p < 0.001) and the median difference in body weight during lockdown was 3.3% (interquartile range [IQR]: 0.0-6.7). The differences of intake of most food groups before and during lockdown were associated with greater self-reported weight, BMI and percentage weight gain. Differences in lifestyle (odds ratio [OR] = 14.21, 95% confidence interval [95%CI]: 2.35-85.82) worsening eating habits (OR = 3.43, 95%CI: 2.31-5.09), and more consumption of sweet or filled cookies and cakes during lockdown (OR = 2.11, 95%CI: 1.42-3.13) were associated with self-reported weight gain. In conclusion, different dietary behaviours (mainly consumption of industrialized foods) during lockdown, as well as quality of life deterioration were the main factors associated with self-reported weight gain during lockdown.

Food Insecurity Is Associated with the Quality of Diet of Non-Institutionalized Older Adults from a Southern Chilean Commune: A Cross-Sectional Study.

As the population ages, greater attention to age-related health problems related to diet and lifestyles is needed. Here, we sought to evaluate the associations between demographic and clinical characteristics and food insecurity with the quality of diet of non-institutionalized elderly from a southern Chilean commune. We performed an analytical cross-sectional study in a sample of 376 older adults. Nutritional status was evaluated through anthropometric measurements. Quality of diet was determined by the healthy eating index (HEI), obtained through the frequency of consumption questionnaire. Socioeconomic, demographic, and lifestyle variables were also collected. Ordinal logistic and Poisson regression models were applied to study associations with quality of diet. The sample consisted of more women (81.6%) than men (18.4%). Most older adults were found to live in a situation of vulnerability or poverty (82.4%), with most having food security (65.7%). According to the HEI, only 14.1% had a good quality of diet, 83.8% had diet in need of improvement, and 2.1% had an unhealthy diet. There was an association of food insecurity and cardiovascular risk (according to waist circumference) with lower quality of diet categories. However, an association with the unhealthy quality of diet category was not confirmed with Poisson regression analysis, which was possibly due to the low number of subjects in that category (n = 8, 2.1%). Other modifiable factors like physical activity, hours of sleep, and polypharmacy were not associated with lower quality of diet categories. Socioeconomic status, which is a structural health determinant, was not associated with decreased quality of diet. Since this was a cross-sectional study performed on a small sample from a Chilean commune, directionality of associations cannot be discerned, and future longitudinal studies could aim to better characterize these associations in larger samples of elderly patients.

All-cause mortality among patients treated with repurposed antivirals and antibiotics for COVID-19 in Mexico City: A real-world observational study.

The aim of our study was to evaluate all-cause mortality risk in patients with laboratory-confirmed COVID-19 in Mexico City treated with repurposed antivirals and antibiotics. This real-world retrospective cohort study contemplated 395,343 patients evaluated for suspected COVID-19 between February 24 and September 14, 2020 in 688 primary-to-tertiary medical units in Mexico City. Patients were included with a positive RT-PCR for SARS-CoV-2; those receiving unspecified antivirals, excluded; and groups of antivirals prescribed in < 30 patients, eliminated. Survival and mortality risks were determined for patients receiving antivirals, antibiotics, both, or none. We assessed the effect of early (<2 days) versus late (>2 days) use of antivirals on mortality in a sub-cohort of patients. Multivariable adjustment, propensity score matching, generalized estimating equations, and calculation of E-values were performed to limit confounding. 136,855 patients were analyzed; mean age 44.2 (SD:16.8) years; 51.3 % were men. 16.6 % received antivirals (3 %), antibiotics (10 %), or both (3.6 %). Antivirals studied were Oseltamivir (n=8414), Amantadine (n=319), Lopinavir-Ritonavir (n=100), Rimantadine (n=61), Zanamivir (n=39), and Acyclovir (n=36). Survival with antivirals (73.7 %, p<0.0001) and antibiotics (85.8 %, p<0.0001) was lower than no antiviral/antibiotic (93.6 %). After multivariable adjustment, increased risk of death occurred with antivirals (HR=1.72, 95 % CI: 1.61-1.84) in ambulatory (HR=4.7, 95 % CI: 3.94-5.62) and non-critical (HR=2.03, 95 % CI: 1.86-2.21) patients. Oseltamivir increased mortality risk in the general population (HR=1.72, 95 % CI: 1.61-1.84), ambulatory (HR=4.79, 95 % CI: 4.01-5.75), non-critical (HR=2.05, 95 % CI: 1.88-2.23), and pregnancy (HR=8.35, 95 % CI: 1.77-39.30); as well as hospitalized (HR=1.13, 95 % CI: 1.01-1.26) and critical patients (HR=1.22, 95 % CI: 1.05-1.43) after propensity score-matching. Early versus late oseltamivir did not modify the risk. Antibiotics were a risk factor in general population (HR=1.13, 95 % CI: 1.08-1.19) and pediatrics (HR=4.22, 95 % CI: 2.01-8.86), but a protective factor in hospitalized (HR=0.81, 95 % CI: 0.77-0.86) and critical patients (HR=0.67, 95 % CI: 0.63-0.72). No significant benefit for repurposed antivirals was observed; oseltamivir was associated with increased mortality. Antibiotics increased mortality risk in the general population but may increase survival in hospitalized and critical patients.

Regional moderate hyperthermia for mild-to-moderate COVID-19 (TherMoCoV study): a randomized controlled trial.

Background: To prevent COVID-19 progression, low-cost alternatives that are available to all patients are needed. Diverse forms of thermotherapy have been proposed to prevent progression to severe/critical COVID-19. Objective: The aim of this study is to evaluate the efficacy and safety of local thermotherapy to prevent disease progression in hospitalized adult patients with mild-to-moderate COVID-19. Methods: A multicenter, open-label, parallel-group, randomized, adaptive trial is used to evaluate the efficacy and safety of local thermotherapy to prevent disease progression in hospitalized adult patients with mild-to-moderate COVID-19. Eligible hospitalized adult patients with symptoms of COVID-19 with ≤5 days from symptom onset, meeting criteria for mild or moderate COVID-19, were randomly assigned to the intervention consisting of local thermotherapy via an electric heat pad in the thorax (target temperature range 39.5­42°C) continuously for 90 min, twice daily, for 5 days, or standard care. The main outcome was the proportion of patients who progressed to severe-to-critical COVID-19 or death. Patients were randomized in a 1:1 ratio through a centralized computer-generated sequence of minimization with a random component of 20%. Participants and medical staff were not blinded to the intervention. Results: One-hundred and five participants (thermotherapy n = 54, control n = 51) with a median age of 53 (IQR: 41­64) years were included for analysis after the early cessation of recruitment due to the closure of all temporal COVID-19 units (target sample size = 274). The primary outcome of disease progression occurred in 31.4% (16/51) of patients in the control group vs. 25.9% (14/54) of those receiving thermotherapy (risk difference = 5.5%; 95%CI: −11.8­22.7, p = 0.54). Thermotherapy was well tolerated with a median total duration of thermotherapy of 900 (IQR: 877.5­900) min. Seven (13.7%) patients in the control group and seven (12.9%) in the thermotherapy group had at least one AE (p = 0.9), none of which were causally attributed to the intervention. No statistically significant differences in serum cytokines (IL-1ß, IL-6, IL-8, IL-10, IL-17, and IFN-γ) were observed between day 5 and baseline among groups. Conclusion: Local thermotherapy was safe and well-tolerated. A non-statistically significant lower proportion of patients who experienced disease progression was found in the thermotherapy group compared to standard care. Local thermotherapy could be further studied as a strategy to prevent disease progression in ambulatory settings.Clinical Trial registration: www.clinicaltrials.gov, identifier: NCT04363541.