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).

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.

COVID-19: WHAT'S NEXT?

Since December 2019, when severe acute respiratory syndrome coronavirus 2 emerged in Wuhan, China, this virus and the resulting disease, coronavirus disease (COVID-19), has spread worldwide. What has occurred in this year and a half goes beyond anything we have dealt with, as humankind, in the past two centuries, perhaps obscured only by war. An incredible number of articles, whether scientific or in the press, have been published, making it impossible to discern between what is biological and what is social in nature. Here, we aim to reflect on the basic structure of the virus and associate its behavior to that of determining factors of the human condition that may be modifiable soon. Needless to say, we find our effort clearly incomplete, and that both scientific and social aspects regarding COVID-19 or any other pandemic encountered in the future, will be constantly changing, from their beginning to their end.

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.

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.

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.

Isolation of Rhizopus microsporus and Lichtheimia corymbifera from tracheal aspirates of two immunocompetent critically ill patients with COVID-19.

We describe two fatal cases of COVID-19 in which Rhizopus microsporus and Lichtheimia corymbifera were cultured from endotracheal aspirate samples. Both patients had no underlying comorbidities other than obesity. Despite antifungal therapy, both cases developed septic shock and progressive refractory hypoxemia without evidence of other underlying infections. It is unclear whether isolation of these fungal organisms represents invasive disease or corresponds to an epiphenomenon of critical illness. Yet, patients suffering from COVID-19 may be at risk of superinfection from a broader range of fungal organisms than previously thought.

Surge in Ventilator-Associated Pneumonias and Bloodstream Infections in An Academic Referral Center Converted to Treat COVID-19 Patients.

BACKGROUND: Healthcare-associated infections (HAIs) are important adverse events that must be prevented. OBJECTIVE: The objective of the study was to report and study possible changes in HAI rates as well as their causes after the COVID-19 hospital surge capacity response (HSCR) in an academic referral center. METHODS: This was a before-after observational study. The Infection Prevention and Control (IPC) program (prospective surveillance, prevention bundles, antibiotic stewardship, continuing education, and feedback) was transiently disrupted after the start of HSCR (March 2020). HAI rates were compared before (January 2019-February 2020) and after (April-July 2020) HSCR, and plausible predisposing factors in affected patients were compared. RESULTS: An increase in the HAI rate from 6.2 to 11.8 cases/1000 patient-days was noted between periods due to increases in ventilator-associated pneumonia and bloodstream infection (BSI) rates. More critically ill patients were admitted during HSCR, and use of invasive devices increased. Prone positioning and infusion of muscle relaxants became commonplace. The nurse-to-patient ratio in the intensive care unit decreased, and 4 h shifts were introduced to avoid fatigue. The BSI rate decreased after the IPC program with additional measures was reintroduced in May 2020. CONCLUSIONS: The strain on the workforce and modifications to the IPC program very possibly underlay the findings. IPC programs continue to be essential during the pandemic.

Large-scale screening for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) among healthcare workers: Prevalence and risk factors for asymptomatic and pauci-symptomatic carriers, with emphasis on the use of personal protective equipment (PPE).

Healthcare workers (HCWs) not fulfilling the coronavirus disease 2019 (COVID-19) case definition underwent severe acute respiratory coronavirus virus 2 (SARS-CoV-2) screening. Risk of exposure, adherence to personal protective equipment (PPE), and symptoms were assessed. In total, 2,000 HCWs were screened: 5.5% were positive for SARS-CoV-2 by polymerase chain reaction (PCR). There were no differences in PPE use between SARS-CoV-2-positive and -negative HCWs (adherence, >90%). Nursing and kitchen staff were independently associated with positive SARS-CoV-2 results.

Factors Associated with COVID-19 and Asymptomatic Carriage in Healthcare Workers of a COVID-19 Hospital.

BACKGROUND: Risk factors for coronavirus disease (COVID-19) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) asymptomatic carriage (AC) in healthcare workers (HCWs) have been scarcely characterized. OBJECTIVE: The objective of the study was to study factors associated with COVID-19 and AC in HCWs of a COVID-19 academic medical center. METHODS: This is a case-control study. Cases were either symptomatic or asymptomatic HCWs with a positive SARS-CoV-2 polymerase chain reaction (PCR) test result between March 16 and May 21 of 2020. Adjusted odds ratios (aOR) were calculated by means of multivariable logistic regression. In addition, each subject was followed for 14 days to inform outcomes. RESULTS: One hundred thirty of 249 (52.2%) symptomatic HCWs had COVID-19; 10 were hospitalized but none died. Of 987 asymptomatic HCWs,37 (3.7%) were AC; 6 of the remaining 950 asymptomatic HCWs with a negative PCR test result were found to be presymptomatic COVID-19 cases the following 14 days. Nurses were more frequently present in the COVID-19 group (51.5% vs. 37.0%), but multivariable analysis rendered non-significant results. After adjustment for age, comorbidities, and working place, factors found to be associated with AC were: working in wards as a nurse (aOR = 9.19, 95% confidence interval [CI] = 1.05-80.22, p = 0.045), kitchen personnel (aOR = 4.09, 95% CI = 1.55-10.83, p = 0.005), and being a physician (aOR = 0.12, 95% CI = 0.03-0.54, p = 0.006). CONCLUSIONS: HCW category was the predominant factor associated with AC of SARS-CoV-2 in this study.

Antimicrobial Resistance Patterns and Antibiotic Use during Hospital Conversion in the COVID-19 Pandemic.

OBJECTIVE: To describe empirical antimicrobial prescription on admission in patients with severe COVID-19, the prevalence of Hospital-Acquired Infections, and the susceptibility patterns of the causing organisms. METHODS: In this prospective cohort study in a tertiary care center in Mexico City, we included consecutive patients admitted with severe COVID-19 between March 20th and June 10th and evaluated empirical antimicrobial prescription and the occurrence of HAI. RESULTS: 794 patients with severe COVID-19 were admitted during the study period. Empiric antibiotic treatment was started in 92% of patients (731/794); the most frequent regimes were amoxicillin-clavulanate plus atypical coverage in 341 (46.6%) and ceftriaxone plus atypical coverage in 213 (29.1%). We identified 110 HAI episodes in 74/656 patients (11.3%). Ventilator-associated pneumonia (VAP) was the most frequent HAI, in 56/110 (50.9%), followed by bloodstream infections (BSI), in 32/110 (29.1%). The most frequent cause of VAP were Enterobacteriaceae in 48/69 (69.6%), followed by non-fermenter gram-negative bacilli in 18/69 (26.1%). The most frequent cause of BSI was coagulase negative staphylococci, in 14/35 (40.0%), followed by Enterobacter complex in 7/35 (20%). Death occurred in 30/74 (40.5%) patients with one or more HAI episodes and in 193/584 (33.0%) patients without any HAI episode (p < 0.05). CONCLUSION: A high frequency of empiric antibiotic treatment in patients admitted with COVID-19 was seen. VAP and BSI were the most frequent hospital-acquired infections, due to Enterobacteriaceae and coagulase negative staphylococci, respectively.

Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia.

BACKGROUND: Coronavirus disease 2019 (Covid-19) pneumonia is often associated with hyperinflammation. Despite the disproportionate incidence of Covid-19 among underserved and racial and ethnic minority populations, the safety and efficacy of the anti-interleukin-6 receptor antibody tocilizumab in patients from these populations who are hospitalized with Covid-19 pneumonia are unclear. METHODS: We randomly assigned (in a 2:1 ratio) patients hospitalized with Covid-19 pneumonia who were not receiving mechanical ventilation to receive standard care plus one or two doses of either tocilizumab (8 mg per kilogram of body weight intravenously) or placebo. Site selection was focused on the inclusion of sites enrolling high-risk and minority populations. The primary outcome was mechanical ventilation or death by day 28. RESULTS: A total of 389 patients underwent randomization, and the modified intention-to-treat population included 249 patients in the tocilizumab group and 128 patients in the placebo group; 56.0% were Hispanic or Latino, 14.9% were Black, 12.7% were American Indian or Alaska Native, 12.7% were non-Hispanic White, and 3.7% were of other or unknown race or ethnic group. The cumulative percentage of patients who had received mechanical ventilation or who had died by day 28 was 12.0% (95% confidence interval [CI], 8.5 to 16.9) in the tocilizumab group and 19.3% (95% CI, 13.3 to 27.4) in the placebo group (hazard ratio for mechanical ventilation or death, 0.56; 95% CI, 0.33 to 0.97; P = 0.04 by the log-rank test). Clinical failure as assessed in a time-to-event analysis favored tocilizumab over placebo (hazard ratio, 0.55; 95% CI, 0.33 to 0.93). Death from any cause by day 28 occurred in 10.4% of the patients in the tocilizumab group and 8.6% of those in the placebo group (weighted difference, 2.0 percentage points; 95% CI, -5.2 to 7.8). In the safety population, serious adverse events occurred in 38 of 250 patients (15.2%) in the tocilizumab group and 25 of 127 patients (19.7%) in the placebo group. CONCLUSIONS: In hospitalized patients with Covid-19 pneumonia who were not receiving mechanical ventilation, tocilizumab reduced the likelihood of progression to the composite outcome of mechanical ventilation or death, but it did not improve survival. No new safety signals were identified. (Funded by Genentech; EMPACTA ClinicalTrials.gov number, NCT04372186.).

Accuracy of galactomannan testing on tracheal aspirates in COVID-19-associated pulmonary aspergillosis.

OBJECTIVE: Our aim was to evaluate the performance of two galactomannan (GM) assays (Platelia Aspergillus EIA, Bio-Rad® , and Aspergillus GM LFA, IMMY® ) in tracheal aspirate (TA) samples of consecutive critically ill patients with COVID-19. METHODS: We included critically ill patients, performed GM-EIA and GM-Lateral Flow Assay (GM-LFA) in TA and followed them until development of COVID-19-associated pulmonary aspergillosis (CAPA) or alternate diagnosis. CAPA was defined according to the modified AspICU criteria in patients with SARS-CoV-2 infection. We estimated sensitivity, specificity, positive and negative predictive values for GM-EIA, GM-LFA, the combination of both or either positive results for GM-EIA and GM-LFA. We explored accuracy using different breakpoints, through ROC analysis and Youden index to identify the optimal cut-offs. We described antifungal treatment and 30-day mortality. RESULTS: We identified 14/144 (9.7%) patients with CAPA, mean age was 50.35 (SD 11.9), the median time from admission to CAPA was 8 days; 28.5% received tocilizumab and 30-day mortality was 57%. ROC analysis and Youden index identified 2.0 OD as the best cut-off, resulting in sensitivity and specificity of 57.1% and 81.5% for GM-EIA and 60% and 72.6% for GM-LFA, respectively. CONCLUSIONS: The diagnostic performance of GM in tracheal aspirates improved after using a cut-off of 2 OD. Although bronchoalveolar lavage testing is the ideal test, centres with limited access to bronchoscopy may consider this approach to identify or rule out CAPA.

CLINICAL AND EPIDEMIOLOGICAL CHARACTERISTICS OF PATIENTS DIAGNOSED WITH COVID-19 IN A TERTIARY CARE CENTER IN MEXICO CITY: A PROSPECTIVE COHORT STUDY.

BACKGROUND: Regional information regarding the characteristics of patients with coronavirus disease (COVID)-19 is needed for a better understanding of the pandemic. OBJECTIVE: The objective of the study to describe the clinical features of COVID-19 patients diagnosed in a tertiary-care center in Mexico City and to assess differences according to the treatment setting (ambulatory vs. hospital) and to the need of intensive care (IC). METHODS: We conducted a prospective cohort, including consecutive patients with COVID-19 from February 26, 2020 to April 11, 2020. RESULTS: We identified 309 patients (140 inpatients and 169 outpatients). The median age was 43 years (interquartile range, 33-54), 59.2% men, and 18.6% healthcare workers (12.3% from our center). The median body mass index (BMI) was 29.00 kg/m2 and 39.6% had obesity. Compared to outpatients, inpatients were older, had comorbidities, cough, and dyspnea more frequently. Twenty-nine (20.7%) inpatients required treatment in the IC unit (ICU). History of diabetes (type 1 or 2) and abdominal pain were more common in ICU patients compared to non-ICU patients. ICU patients had higher BMIs, higher respiratory rates, and lower room-air capillary oxygen saturations. ICU patients showed a more severe inflammatory response as assessed by white blood cell count, neutrophil and platelet count, C-reactive protein, ferritin, procalcitonin, and albumin levels. By the end of the study period, 65 inpatients had been discharged because of improvement, 70 continued hospitalized, and five had died. CONCLUSIONS: Patients with comorbidities, either middle-age obese or elderly complaining of fever, cough, or dyspnea, were more likely to be admitted. At admission, patients with diabetes, high BMI, and clinical or laboratory findings consistent with a severe inflammatory state were more likely to require IC.