Fungal Infections in the ICU during the COVID-19 Pandemic in Mexico.

Background: Invasive Fungal Infections (IFI) are emergent complications of COVID-19. In this study, we aim to describe the prevalence, related factors, and outcomes of IFI in critical COVID-19 patients. Methods: We conducted a nested case-control study of all COVID-19 patients in the intensive care unit (ICU) who developed any IFI and matched age and sex controls for comparison (1:1) to evaluate IFI-related factors. Descriptive and comparative analyses were made, and the risk factors for IFI were compared versus controls. Results: We found an overall IFI prevalence of 9.3% in COVID-19 patients in the ICU, 5.6% in COVID-19-associated pulmonary aspergillosis (CAPA), and 2.5% in invasive candidiasis (IC). IFI patients had higher SOFA scores, increased frequency of vasopressor use, myocardial injury, and more empirical antibiotic use. CAPA was classified as possible in 68% and 32% as probable by ECMM/ISHAM consensus criteria, and 57.5% of mortality was found. Candidemia was more frequent for C. parapsilosis Fluconazole resistant outbreak early in the pandemic, with a mortality of 28%. Factors related to IFI in multivariable analysis were SOFA score > 2 (aOR 5.1, 95% CI 1.5-16.8, p = 0.007) and empiric antibiotics for COVID-19 (aOR 30, 95% CI 10.2-87.6, p = <0.01). Conclusions: We found a 9.3% prevalence of IFIs in critically ill patients with COVID-19 in a single center in Mexico; factors related to IFI were associated with higher SOFA scores and empiric antibiotic use for COVID-19. CAPA is the most frequent type of IFI. We did not find a mortality difference.

Post-COVID-19 syndrome and quality of life impairment in severe COVID-19 Mexican patients.

Introduction: Post-COVID-19 syndrome (PCS) usually occurs 3 months after the onset of COVID-19 with a symptom duration of at least 2 months without an alternative diagnosis. Objective: This study aimed to describe the prevalence, characteristics, and impact on the quality of life (QoL) of post-COVID-19 syndrome in patients with a history of hospitalization for COVID-19. Materials and methods: We conducted a cross-sectional study. Patients who required hospitalization due to COVID-19 between March 2020 and October 2021 were invited to answer a PCS questionnaire and the EQ-5D instrument. A total of 246 patients were included: 187 (76%) met the definition of PCS and 54% were men, with a median age of 50 years (IQR 41-63). Results: From 187 patients with PCS, the median time to symptom onset after hospital discharge was 1 day (IQR 1-20), and the median symptom duration was 150 days (IQR 90-225). A total of 27 different symptoms were reported; the most frequent were difficulty concentrating (81%), dyspnea (75%), arthralgia (71%), fatigue (68%), and hair loss (60%). Some symptoms, such as difficulty concentrating, arthralgia/myalgia, and hair loss, were more prevalent in women with PCS. Patients with PCS had a higher frequency of tobacco smoking (37 vs. 4%, p = 0.02) and increased severity of lung involvement in the initial chest tomography (75 vs. 58%, p = 0.01) than those without PCS. Patients with PCS were less likely to receive antivirals (15.5 vs. 27%, p = 0.04). No difference between ICU admission, mechanical ventilation, and length of hospital stay was found. Patients with PCS had a lower visual analog scale result for EQ-5D vs. those without (80 [IQR 70-90] vs. 89.5 [IQR 75-90], p = 0.05). All five QoL dimensions were affected in PCS patients, showing increased pain/discomfort (67 vs. 39%, p = < 0.001), difficulties in performing usual activities (39.2 vs. 20.3%, p = 0.03), and anxiety/depression (57.5 vs. 37%, p = 0.02). Conclusion: PCS occurred in 76% of hospitalized patients with prolonged duration and QoL impairment. Neurological symptoms such as difficulty concentrating were the most frequent symptoms. Timely diagnostic and therapeutic interventions are required.

Predictors of Poor Outcomes in Young Non-Comorbid Patients with COVID-19.

Background: Prognostic factors in previously healthy young patients with COVID-19 remained understudied. Objectives: The objective of the study was to identify factors associated with in-hospital death or need for invasive mechanical ventilation (IMV) in young (aged ≤ 65 years) and previously healthy patients with COVID-19. Methods: We conducted a prospective cohort study that included patients admitted with COVID-19. The primary outcome was in-hospital death/need for IMV. Secondary outcomes included need for IMV during follow-up, days on IMV, length of stay (LOS), hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP), and pulmonary embolism (PE). Bivariate and multivariate analyses were performed. Results: Among 92 patients, primary outcome occurred in 16 (17%), death in 12 (13%), need for IMV in 16 (17%), HAP/VAP in 7 (8%), and PE in 2 (2%). Median LOS and IMV duration were 7 and 12 days, respectively. Independent associations were found between the primary outcome and male sex (Adjusted odds ratio [aOR] 7.1, 95%CI 1.1-46.0, p < 0.05), D-dimer levels > 1000ng/mL (aOR 9.0, 95%CI 1.6-49.1, p < 0.05), and RT-PCR Ct-value ≤ 24 on initial swab samples (aOR 14.3, 95%CI 2.0-101.5, p < 0.01). Conclusions: In young and non-comorbid COVID-19 patients, male sex, higher levels of D-dimer, and low SARS-CoV-2 RT-PCR Ct-value on an initial nasopharyngeal swab were independently associated with increased in-hospital mortality or need for IMV. (Rev Invest Clin. 2022;74(5):268-75).

Probability of hospitalisation and death among COVID-19 patients with comorbidity during outbreaks occurring in Mexico City.

Background: We compared the probability of hospitalization and death caused by COVID-19 in patients with comorbidities during three periods defined for this study: first-wave (FW), interwave period (IP), and second-wave (SW) observed in Mexico City. Methods: In this registry-based study, we included individuals over 20 years of age. During the FW (symptomatic), the IP, and the SW (symptomatic and asymptomatic), participants were diagnosed using nasopharyngeal swabs. Symptomatic individuals with risk factors for serious disease or death were referred to the hospital. SARS-CoV-2 infection was defined by RT-qPCR in all hospitalized patients. All data were added to the SISVER database. Bayesian analysis and False Discovery Rate were used for further evaluation. Results: The study included 2 260 156 persons (mean age of 43.1 years). Of these, 8.6% suffered from DM, 11.6% arterial hypertension, and 9.7% obesity. Of the total, 666 694 persons tested positive (29.5%). Of the infected persons, a total of 85 587 (12.8%) were hospitalized: 24 023 in the FW; 16 935 in the IP, and 44 629 in the SW. Of the hospitalized patients, there were 42 979 deaths (50.2%), in the FW, 11 964 (49.8%), in the IP, 6794 (40.1%), and in the SW 24 221 (54.3%). The probability of death among individuals hospitalized with or without comorbidities increased consistently in all age groups. A significant increase in the Fatality Rate was observed in individuals with comorbidities (1.36E-19< = FDR< = 3.36E-2). A similar trend was also observed in individuals without comorbidities (1.03E-44< = FDR< = 5.58E-4). Conclusions: The data from this study show a considerable increase in the number of detected cases of infection between the FW and SW. In addition, 12.8% of those infected were hospitalized for severe COVID-19. A high mortality rate was observed among hospitalized patients (>50%). An age-dependent probability of death was observed with a positive trend in hospitalized patients with and without comorbidities.

Early Outpatient Treatment With Remdesivir in Patients at High Risk for Severe COVID-19: A Prospective Cohort Study.

Background: Early treatment of coronavirus disease 2019 (COVID-19) with remdesivir in high-risk patients, including those with immunosuppression of different causes, has not been evaluated. The objective of this study was to assess the clinical effectiveness of early remdesivir treatment among patients with mild to moderate COVID-19 at high risk of progression. Methods: This prospective cohort comparative study was conducted in a tertiary referral center in Mexico City. Patients with mild to moderate COVID-19 at high risk for progression were treated with an ambulatory 3-day course of remdesivir. The primary efficacy composite outcome was hospitalization or death at 28 days after symptom onset. A Cox proportional hazards regression model was used to identify associations with the primary outcome. Results: From December 1, 2021, to April 30, 2022, a total of 196 high-risk patients were diagnosed with COVID-19, of whom 126 were included in this study (43%, 54/126, received remdesivir; 57%, 72/126, did not receive remdesivir). Baseline clinical characteristics were similar between groups; autoimmune diseases (39/126), solid organ transplant (31/126), and malignant neoplasms (24/126) were the most common immunocompromising conditions. Diabetes mellitus was strongly associated with the primary outcome in both groups. Prior severe acute respiratory syndrome coronavirus 2 infection or vaccination was not independently associated with COVID-19 progression. Treatment with remdesivir significantly reduced the odds of hospitalization or death (adjusted hazard ratio, 0.16; 95% CI, 0.06-0.44; P < .01). Conclusions: Early outpatient treatment with remdesivir significantly reduces hospitalization or death by 84% in high-risk, majority immunosuppressed patients with Omicron variant COVID-19.

Significant Rise in SARS-CoV-2 Reinfection Rate in Vaccinated Hospital Workers during the Omicron Wave: A Prospective Cohort Study.

Background: Relatively low SARS-CoV-2 reinfection rates have been reported in vaccinated individuals, but updates considering the Omicron variant are lacking. Objectives: The objective of the study was to provide a current estimate of the SARS-CoV-2 reinfection rate in a highly immunized population. Methods: A prospective cohort of Mexican hospital workers was followed (March 2020-February 2022). Reinfection was defined as the occurrence of two or more episodes of COVID-19 separated by a period of ≥ 90 days without symptoms. The reinfection rate was calculated as the number of reinfection episodes per 100,000 persons per day. Results: A total of 3732 medical consultations were provided to 2700 workers, of whom 1388 (51.4%) were confirmed COVID-19 cases. A total of 73 reinfection cases were identified, of whom 71 (97.3%) had completed their primary vaccination series and 22 (30.1%) had had a booster dose before the second episode. The overall reinfection rate was 23.1 per 100,000 persons per day (as compared to a rate of 1.9 per 100,000 persons per day before the Omicron wave). Conclusions: The SARS-CoV-2 reinfection rate rose significantly during the Omicron wave despite a high primary vaccination coverage rate. Almost one-third of reinfected workers had a vaccine booster ≥ 14 days before the last COVID-19 episode.

Correction: In-hospital mortality from severe COVID-19 in a tertiary care center in Mexico City; causes of death, risk factors and the impact of hospital saturation.

[This corrects the article DOI: 10.1371/journal.pone.0245772.].

Clinicopathologic characteristics of severe COVID-19 patients in Mexico City: A post-mortem analysis using a minimally invasive autopsy approach.

OBJECTIVE: Describe the histological findings of minimally ultrasound-guided invasive autopsies in deceased patients with severe SARS-CoV-2 and compare the diagnostic yield with open autopsies. DESIGN: Observational post-mortem cohort study. Minimally invasive ultrasound-guided autopsies were performed in fourteen deceased patients with a confirmed diagnosis of SARS-CoV-2 pneumonia. Histological and clinical findings of lung, kidney, and liver tissue are described and contrasted with those previously reported in the literature. SETTING: Single-center COVID-19 reference center in Mexico City. RESULTS: Fourteen minimally invasive autopsies revealed a gross correlation with open autopsies reports: 1) Lung histology was characterized mainly by early diffuse alveolar damage (12/13). Despite low lung compliances and prolonged mechanical ventilation, the fibrotic phase was rarely observed (2/13). 2) Kidney histopathology demonstrated acute tubular injury (12/13), interstitial nephritis (11/13), and glomerulitis (11/13) as the predominant features 3) Liver histology was characterized by neutrophilic inflammation in all of the cases, as well as hepatic necrosis (8/14) despite minimal alterations in liver function testing. Hepatic steatosis was observed in most cases (12/14). SARS-CoV-2 positivity was widely observed throughout the immunohistochemical analysis. However, endothelitis and micro thrombosis, two of the hallmark features of the disease, were not observed. CONCLUSION: Our data represents the largest minimally invasive, ultrasound-guided autopsy report. We demonstrate a gross histological correlation with large open autopsy cohorts. However, this approach might overlook major histologic features of the disease, such as endothelitis and micro-thrombosis. Whether this represents sampling bias is unclear.

Ruxolitinib in addition to standard of care for the treatment of patients admitted to hospital with COVID-19 (RUXCOVID): a randomised, double-blind, placebo-controlled, phase 3 trial.

Background: COVID-19 is associated with acute respiratory distress and cytokine release syndrome. The Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib reduces inflammatory cytokine concentrations in disorders characterised by cytokine dysregulation, including graft-versus-host disease, myelofibrosis, and secondary hemophagocytic lymphohistiocytosis. We assessed whether treatment with the JAK1/JAK2 inhibitor ruxolitinib would be beneficial in patients with COVID-19 admitted to hospital. Methods: RUXCOVID was an international, randomised, double-blind, phase 3 trial of ruxolitinib plus standard of care versus placebo plus standard of care in patients with COVID-19. Patients who were hospitalised but not on mechanical ventilation or in the intensive care unit [ICU] were randomly assigned (2:1) to oral ruxolitinib 5 mg twice per day or placebo for 14 days (14 additional days were allowed if no improvement). The primary endpoint was a composite of death, respiratory failure (invasive ventilation), or ICU care by day 29, analysed by logistic regression including region, treatment, baseline clinical status, age, and sex as covariates. This trial is registered with ClinicalTrials.gov, NCT04362137. Findings: Between May 4 and Sept 19, 2020, 432 patients were randomly assigned to ruxolitinib (n=287) or placebo (n=145) plus standard of care; the mean age was 56·5 years (SD 13·3), 197 (46%) were female, and 235 (54%) were male. The primary objective was not met: the composite endpoint occurred in 34 (12%) of 284 ruxolitinib-treated patients versus 17 (12%) of 144 placebo-treated patients (odds ratio 0·91, 95% CI 0·48-1·73; p=0·77). By day 29, nine (3%) of 286 ruxolitinib-treated patients had died compared with three (2%) of 145 placebo-treated patients; 22 (8%) of 286 ruxolitinib-treated patients had received invasive ventilation compared with ten (7%) of 145 placebo-treated patients; and 30 (11%) of 284 ruxolitinib-treated patients had received ICU care compared with 17 (12%) of 144 placebo-treated patients. In an exploratory analysis, median time to recovery was 1 day faster with ruxolitinib versus placebo (8 days vs 9 days; hazard ratio 1·10, 95% CI 0·89-1·36). Adverse events included headache (23 [8%] of 281 on ruxolitinib vs 11 [8%] of 143 on placebo) and diarrhoea (21 [7%] vs 12 [8%]). Interpretation: Ruxolitinib 5 mg twice per day showed no benefit in the overall study population. A larger sample is required to determine the clinical importance of trends for increased efficacy in patient subgroups. Funding: Novartis and Incyte.

Serum Vitamin D Levels Are Associated With Increased COVID-19 Severity and Mortality Independent of Whole-Body and Visceral Adiposity.

INTRODUCTION: Coronavirus 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. METHODS: Consecutive 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 <20 ng/ml (<50nmol/L) and deficient Vitamin D as a level ≤12 ng/ml (<30 nmol/L). RESULTS: Of 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. CONCLUSION: Vitamin D deficiency (≤12 ng/ml or <30 nmol/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.

Effect of Tocilizumab in Mortality among Patients with Severe and Critical Covid-19: Experience in a Third-Level Medical Center.

BACKGROUND: Trials evaluating safety and efficacy of tocilizumab in coronavirus disease 19 (COVID-19) show contradictory results. OBJECTIVE: The objective of the study was to evaluate the effect of tocilizumab in hospital mortality among patients with severe COVID-19 in a third-level medical center. METHODS: This prospective cohort study included patients with severe and critical COVID-19. Primary outcome was death during hospitalization. Secondary outcomes included invasive mechanical ventilation (IMV), days on IMV, ventilator-free days (VFDs), length of hospital stay (LOS), and development of hospitalacquired infections (HAIs). Bivariate, multivariate, and propensity score matching analysis were performed. RESULTS: During the study period, 99/794 (12%) patients received tocilizumab. Male patients, health care workers, and patients with increased inflammatory markers received tocilizumab more frequently. No difference in hospital mortality was observed between groups (34% vs. 34%, p = 0.98). Tocilizumab was not independently associated with mortality. No significant treatment effects were observed in propensity score analysis. IMV was more frequent (46% vs. 11%, p < 0.01) and LOS was longer (12 vs. 7 days, p < 0.01) in the tocilizumab group, reflecting increased severity. Although HAIs were more frequent in the tocilizumab group (22% vs. 10%, p < 0.01), no difference was seen after adjusting for IMV (38% vs. 40%, p = 0.86). CONCLUSIONS: In our study, tocilizumab was not associated with decreased hospital mortality among patients with severe COVID-19.

NAFLD determined by Dallas Steatosis Index is associated with poor outcomes in COVID-19 pneumonia: a cohort study.

Coronavirus disease 2019 is a worldwide health challenge. Liver steatosis diagnosis based on imaging studies has been implicated in poor outcomes of COVID-19 pneumonia, but results are inconsistent. The Dallas Steatosis Index (DSI) is an available calculator developed to identify patients with non-alcoholic fatty liver disease (NAFLD). We hypothesized that it would be associated with in-hospital mortality, intensive care unit admission (ICU), and invasive mechanical ventilation (IMV). We conducted a retrospective cohort study on inpatients with confirmed COVID-19 pneumonia between February 26 and April 11, 2020. We computed the DSI on admission, and patients with high DSI were considered with NAFLD. We employed logistic regression to study the association between NAFLD, mortality, ICU admission, and IMV. We studied the association between liver steatosis on computed tomography (CT) and these outcomes, and also between Metabolic Associated Fatty Liver Disease (MAFLD) based on CT findings and risk factors and the outcomes. 470 patients were included; 359 had NAFLD according to the DSI. They had a higher frequency of type 2 diabetes (31% vs 14%, p < 0.001), obesity (58% vs 14%, p < 0.001), and arterial hypertension (34% vs 22%, p = 0.02). In univariable analysis, NAFLD was associated with mortality, ICU admission, and IMV. Liver steatosis by CT and MAFLD were not associated with any of these outcomes. In multivariable logistic regression, high DSI remained significantly associated with IMV and death. High DSI, which can be easily computed on admission, was associated with IMV and death, and its use to better stratify the prognosis of these patients should be explored. On the other hand, liver steatosis by CT and MAFLD were not associated with poor outcomes.

Epicardial adipose tissue thickness is associated with increased COVID-19 severity and mortality.

BACKGROUND: Increased 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. METHODS: We 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. RESULTS: EAT 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 4 C 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. CONCLUSION: EAT 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.

Outbreak of NDM-1-Producing Escherichia coli in a Coronavirus Disease 2019 Intensive Care Unit in a Mexican Tertiary Care Center.

Emergency department areas were repurposed as intensive care units (ICUs) for patients with acute respiratory distress syndrome during the initial months of the coronavirus disease 2019 (COVID-19) pandemic. We describe an outbreak of New Delhi metallo-ß-lactamase 1 (NDM-1)-producing Escherichia coli infections in critically ill COVID-19 patients admitted to one of the repurposed units. Seven patients developed infections (6 ventilator-associated pneumonia [VAP] and 1 urinary tract infection [UTI]) due to carbapenem-resistant E. coli, and only two survived. Five of the affected patients and four additional patients had rectal carriage of carbapenem-resistant E. coli. The E. coli strain from the affected patients corresponded to a single sequence type. Rectal screening identified isolates of two other sequence types bearing blaNDM-1. Isolates of all three sequence types harbored an IncFII plasmid. The plasmid was confirmed to carry blaNDM-1 through conjugation. An outbreak of clonal NDM-1-producing E. coli isolates and subsequent dissemination of NDM-1 through mobile elements to other E. coli strains occurred after hospital conversion during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. This emphasizes the need for infection control practices in surge scenarios. IMPORTANCE The SARS-CoV-2 pandemic has resulted in a surge of critically ill patients. Hospitals have had to adapt to the demand by repurposing areas as intensive care units. This has resulted in high workload and disruption of usual hospital workflows. Surge capacity guidelines and pandemic response plans do not contemplate how to limit collateral damage from issues like hospital-acquired infections. It is vital to ensure quality of care in surge scenarios.

Territorial Strategy of Medical Units for Addressing the First Wave of the COVID-19 Pandemic in the Metropolitan Area of Mexico City: Analysis of Mobility, Accessibility and Marginalization.

BACKGROUND: The COVID-19 pandemic has caused an exponential increase in the demand for medical care worldwide. In Mexico, the COVID Medical Units (CMUs) conversion strategy was implemented. OBJECTIVE: To evaluate the CMU coverage strategy in the Mexico City Metropolitan Area (MCMA) by territory. MATERIALS: The CMU directory was used, as were COVID-19 infection and mobility statistics and Mexican 2020 census information at the urban geographic area scale. The degree of urban marginalization by geographic area was also considered. METHOD: Using descriptive statistics and the calculation of a CMU accessibility index, population aggregates were counted based on coverage radii. In addition, two regression models are proposed to explain (1) the territorial and temporal trend of COVID-19 infections in the MCMA and (2) the mobility of the COVID-infected population visiting medical units. RESULTS: The findings of the evaluation of the CMU strategy were (1) in the MCMA, COVID-19 followed a pattern of contagion from the urban center to the periphery; (2) given the growth in the number of cases and the overload of medical units, the population traveled greater distances to seek medical care; (3) after the CMU strategy was evaluated at the territory level, it was found that 9 out of 10 inhabitants had a CMU located approximately 7 km away; and (4) at the metropolitan level, the lowest level of accessibility to the CMU was recorded for the population with the highest levels of marginalization, i.e., those residing in the urban periphery.

Colchicine Is Safe Though Ineffective in the Treatment of Severe COVID-19: a Randomized Clinical Trial (COLCHIVID).

BACKGROUND: Colchicine is an available, safe, and effective anti-inflammatory drug and has been suggested as a COVID-19 treatment, but its usefulness in hospitalized severe COVID-19 patients has not been thoroughly demonstrated. OBJECTIVE: To address the safety and efficacy of colchicine in hospitalized patients with severe COVID-19. DESIGN: We conducted a triple-blind parallel non-stratified placebo-controlled clinical trial. PARTICIPANTS: We recruited 116 hospitalized patients with severe COVID-19 in Mexico. INTERVENTIONS: Patients were randomized to receive 1.5 mg of colchicine or placebo at the time of the recruitment in the study (baseline) and 0.5 mg BID PO to complete 10 days of treatment. MAIN MEASURES: The primary composite outcome was the progression to critical disease or death. Besides, we evaluated immunological features at baseline and after recovery or disease progression in 20 patients. KEY RESULTS: Fifty-six patients were allocated to colchicine and 60 patients received placebo. The study was suspended after the second interim analysis demonstrated colchicine had no effect on the primary outcome (OR 0.83, 95%CI 0.35-1.93, P = 0.67), nor in the days of ICU and hospital stays. Adverse events were similar between groups (OR 1.63, 95% CI 0.66-3.88, P = 0.37). After colchicine treatment, patients had higher BUN and lower serum levels of IL-8, IL-12p70, and IL-17A. CONCLUSIONS: Colchicine is safe but not effective in the treatment of severe COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04367168.

Outcomes of patients with severe and critical COVID-19 treated with dexamethasone: a prospective cohort study.

Dexamethasone implementation for COVID-19 management represented a milestone but data regarding its impact and safety have not been consistently reproduced. We aimed to evaluate in-hospital mortality before and after the implementation of corticosteroid treatment (CS-T) for severe and critical COVID-19. We conducted a cohort study that included patients admitted with severe and critical COVID-19. The primary outcome was death during hospitalization. Secondary outcomes included the length of stay (LOS), need for invasive mechanical ventilation (IMV), time to IMV initiation, IMV duration, and development of hospital-acquired infections (HAIs). Bivariate, multivariate, and propensity-score matching analysis were performed. Among 1540 patients, 688 (45%) received CS-T. Death was less frequent in the CS-T group (18 vs 31%, p < .01). Among patients on IMV, death was also less frequent in the CS-T group (25 vs 55%, p < .01). The median time to IMV was longer in the CS-T group (5 vs 3 days, p < .01). HAIs occurred more frequently in the CS-T group (20 vs 10%, p < .01). LOS, IMV, and IMV duration were similar between groups. Multivariate analysis revealed an independent association between CS-T and lower mortality (aOR 0.26, 95% CI 0.19-0.36, p < .001). Propensity-score matching analysis revealed that CS-T was independently associated with lower mortality (aOR 0.33, 95% CI 0.22-0.50, p < .01). Treatment with corticosteroids was associated with reduced in-hospital mortality among patients with severe and critical COVID-19, including those on IMV.

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 reported the emergence of SARS-CoV-2 variant B.1.1.519 in Mexico City. We reported the effective reproduction number (Rt) of B.1.1.519 and presented 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. The B.1.1.519 variant was predominant between November 2020 and May 2021, reaching 90% of all cases sequenced in February 2021. It is characterized by three amino acid changes in the spike protein: T478K, P681H, and T732A. Its Rt varies between 0.5 and 2.9. Its geographical origin remain to be investigated. 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.