Ventilated COVID-19 Patients Research Articles

Comparison of Two Waves of COVID-19 in Critically Ill Patients: A Retrospective Observational Study.

Background The SARS-CoV-2 virus caused the global COVID-19 pandemic, with waxing and waning course. This study was conducted to compare outcomes in the first two waves, in mechanically ventilated patients. Methods This retrospective observational study included all mechanically ventilated COVID-19 patients above 18 years of age, between March 2020 and January 2021. Patients were grouped into first wave from March 2020 to July 2020, and second wave from August 2020 to January 2021. Outcome measures were mortality, the development of acute kidney injury (AKI), and need for renal replacement therapy (RRT). Univariate and multivariate cox regression analysis were used to delineate risk factors for the outcome measures. Results A total of 426 patients, 285 in the first wave and 185 in the second wave, were included. The incidence of AKI was significantly lower in the second wave (72% vs. 63%; p=0.04). There was no significant difference in mortality (70% vs. 63%; p=0.16) and need for RRT (36% vs. 30%; p=0.1). Risk factors for mortality were increasing age and AKI in both waves, and chronic kidney disease (CKD) (adj. HR 1.7; 95% CI 1.02–2.68; p=0.04) in the second wave. Risk factors for AKI were CKD in both the waves, while it was diabetes (adj. HR 1.4; 95% CI 1.02–1.95; p=0.04) and increasing age in the first wave. Remdesivir (adj. HR 0.5; 95% CI 0.3–0.7; p < 0.01) decreased the risk of AKI, and convalescent plasma (adj. HR 0.5; 95% CI 0.3–0.9; p=0.02) decreased the risk of mortality in the first wave, however, such benefit was not observed in the second wave. Conclusions Our study shows a decrease in the incidence of AKI in critically ill patients, however, the reason for this decrease is still unknown. Studies comparing the waves of the pandemic would not only help in understanding disease evolution but also to develop tailored management strategies.

Effects of Different Inhalation Therapy on Ventilator-Associated Pneumonia in Ventilated COVID-19 Patients: A Randomized Controlled Trial.

The effect of routine inhalation therapy on ventilator-associated pneumonia (VAP) in mechanically ventilated patients with the coronavirus disease (COVID-19) has not been well-defined. This randomized controlled trial included 175 eligible adult patients with COVID-19 who were treated with mechanical ventilation at the University Hospital of Split between October 2020 and June 2021. Patients were randomized and allocated to a control group (no routine inhalation) or one of the treatment arms (inhalation of N-acetylcysteine; 5% saline solution; or 8.4% sodium bicarbonate). The primary outcome was the incidence of VAP, while secondary outcomes included all-cause mortality. Routine inhalation therapy had no effect on the incidence of bacterial or fungal VAP nor on all-cause mortality (p > 0.05). Secondary analyses revealed a significant reduction of Gram-positive and methicillin-resistant Staphylococcus aureus (MRSA) VAP in the treatment groups. Specifically, the bicarbonate group had a statistically significantly lower incidence of Gram-positive bacterial VAP (4.8%), followed by the N-acetylcysteine group (10.3%), 5% saline group (19.0%), and control group (34.6%; p = 0.001). This difference was driven by a lower incidence of MRSA VAP in the bicarbonate group (2.4%), followed by the N-acetylcysteine group (7.7%), 5% saline group (14.3%), and control group (34.6%; p < 0.001). Longer duration of ventilator therapy was the only significant, independent predictor of any bacterial or fungal VAP in the multivariate analysis (aOR 1.14, 95% CI 1.01–1.29, p = 0.038 and aOR 1.05, 95% CI 1.01–1.10, p = 0.028, respectively). In conclusion, inhalation therapy had no effect on the overall VAP incidence or all-cause mortality. Further studies should explore the secondary findings of this study such as the reduction of Gram-positive or MRSA-caused VAP in treated patients.

Energy expenditure in COVID-19 mechanically ventilated patients: A comparison of three methods of energy estimation.

BackgroundIndirect calorimetry (IC) is the gold standard for measuring resting energy expenditure. Energy expenditure (EE) estimated by ventilator‐derived carbon dioxide consumption (EEVCO2) has also been proposed. In the absence of IC, predictive weight‐based equations have been recommended to estimate daily energy requirements. This study aims to compare simple predictive weight‐based equations with those estimated by EEVCO2 and IC in mechanically ventilated patients of COVID‐19.MethodsRetrospective study of a cohort of critically ill adult patients with COVID‐19 requiring mechanical ventilation and artificial nutrition to compare energy estimations by three methods through the calculation of bias and precision agreement, reliability, and accuracy rates.ResultsIn 58 mechanically ventilated patients, a total of 117 paired measurements were obtained. The mean estimated energy derived from weight‐based calculations was 2576 ± 469 kcal/24 h, as compared with 1507 ± 499 kcal/24 h when EE was estimated by IC, resulting in a significant bias of 1069 kcal/day (95% CI [−2158 to 18.7 kcal]; P < 0.001). Similarly, estimated mean EEVCO2 was 1388 ± 467 kcal/24 h when compared with estimation of EE from IC. A significant bias of only 118 kcal/day (95% CI [−187 to 422 kcal]; P < 0.001), compared by the Bland‐Altman plot, was noted.ConclusionThe energy estimated with EEVCO2 correlated better with IC values than energy derived from weight‐based calculations. Our data suggest that the use of simple predictive equations may potentially lead to overfeeding in mechanically ventilated patients with COVID‐19.

Long-term ketamine infusion-induced cholestatic liver injury in COVID-19-associated acute respiratory distress syndrome

BackgroundA higher-than-usual resistance to standard sedation regimens in COVID-19 patients suffering from acute respiratory distress syndrome (ARDS) has led to the frequent use of the second-line anaesthetic agent ketamine. Simultaneously, an increased incidence of cholangiopathies in mechanically ventilated patients receiving prolonged infusion of high-dose ketamine has been noted. Therefore, the objective of this study was to investigate a potential dose–response relationship between ketamine and bilirubin levels.MethodsPost hoc analysis of a prospective observational cohort of patients suffering from COVID-19-associated ARDS between March 2020 and August 2021. A time-varying, multivariable adjusted, cumulative weighted exposure mixed-effects model was employed to analyse the exposure–effect relationship between ketamine infusion and total bilirubin levels.ResultsTwo-hundred forty-three critically ill patients were included into the analysis. Ketamine was infused to 170 (70%) patients at a rate of 1.4 [0.9–2.0] mg/kg/h for 9 [4–18] days. The mixed-effects model revealed a positively correlated infusion duration–effect as well as dose–effect relationship between ketamine infusion and rising bilirubin levels (p < 0.0001). In comparison, long-term infusion of propofol and sufentanil, even at high doses, was not associated with increasing bilirubin levels (p = 0.421, p = 0.258). Patients having received ketamine infusion had a multivariable adjusted competing risk hazard of developing a cholestatic liver injury during their ICU stay of 3.2 [95% confidence interval, 1.3–7.8] (p = 0.01).ConclusionsA causally plausible, dose–effect relationship between long-term infusion of ketamine and rising total bilirubin levels, as well as an augmented, ketamine-associated, hazard of cholestatic liver injury in critically ill COVID-19 patients could be shown. High-dose ketamine should be refrained from whenever possible for the long-term analgosedation of mechanically ventilated COVID-19 patients.

Corticosteroids and superinfections in COVID-19 patients on invasive mechanical ventilation

ObjectivesTo determine the incidence and characteristics of superinfections in mechanically ventilated COVID-19 patients, and the impact of dexamethasone as standard therapy. MethodsThis multicentre, observational, retrospective study included patients ≥ 18 years admitted from March 1st 2020 to January 31st 2021 with COVID-19 infection who received mechanical ventilation. Patient characteristics, clinical characteristics, therapy and survival were examined. Results155/156 patients (115 men, mean age 62 years, range 26-84 years) were included. 67 patients (43%) had 90 superinfections, pneumonia dominated (78%). Superinfections were associated with receiving dexamethasone (66% vs 32%, p<0.0001), autoimmune disease (18% vs 5.7%, p<0.016) and with longer ICU stays (26 vs 17 days, p<0,001). Invasive fungal infections were reported exclusively in dexamethasone-treated patients [8/67 (12%) vs 0/88 (0%), p<0.0001]. Unadjusted 90-day survival did not differ between patients with or without superinfections (64% vs 73%, p=0.25), but was lower in patients receiving dexamethasone versus not (58% vs 78%, p=0.007). In multiple regression analysis, superinfection was associated with dexamethasone use [OR 3.7 (1.80–7.61), p<0.001], pre-existing autoimmune disease [OR 3.82 (1.13–12.9), p=0.031] and length of ICU stay [OR 1.05 p<0.001]. ConclusionsIn critically ill COVID-19 patients, dexamethasone as standard of care was strongly and independently associated with superinfections.

Incidence of autoantibodies related to systemic autoimmunity in patients with severe COVID-19 admitted to the intensive care unit.

To assess the prevalence of autoantibodies (AAbs) in mechanically ventilated COVID-19 patients and to investigate whether AAbs influence the clinical outcome. Serum samples were drawn within the first 48 hours upon admission to the intensive care unit (ICU) from 217 consecutive patients, from January 1st, 2021, to May 10th, 2021, and investigated for the presence of AAbs using conventional techniques. Serum samples (n=117) of age- and sex-matched healthy individuals collected before COVID-19 pandemic were used as controls. COVID-19 patients in the ICU had more commonly AAbs compared to age- and sex-matched controls (174/217, 80.2% vs. 73/117, 62.4%, p<0.001). Patients expressed more frequently ANAs (48.4% vs. 21.4%, p<0.001), anti-dsDNA (5.1% vs. 0%, p=0.01), anti-CCP (8.3% vs. 1.7%, p=0.014) and anti-CL IgM AAbs (21.7% vs. 9.4%, p=0.005) than controls, respectively. Simultaneous reactivity against at least three autoantigens, occurred in 144 out of 174 (82.8%) patients. The two groups did not differ in terms of clinicoepidemiologic characteristics or the mortality ratio within the ICU. Patients who died compared to convalescents were older, had higher ferritin, D-dimers levels, APACHE II score, lower oxygen saturation, higher prevalence of comorbidities and cognitive dysfunction. However, AAbs were not found to correlate with the clinical outcome. Patients with severe COVID-19 express AAbs more commonly compared to controls. No correlation was found between AAbs and disease outcome.

Low tidal volume ventilation is associated with mortality in COVID-19 patients-Insights from the PRoVENT-COVID study.

PurposeLow tidal volume ventilation (LTVV) is associated with mortality in patients with acute respiratory distress syndrome. We investigated the association of LTVV with mortality in COVID-19 patients.MethodsSecondary analysis of a national observational study in COVID-19 patients in the first wave of the pandemic. We compared COVID-19 patients that received LTVV, defined as controlled ventilation with a median tidal volume ≤ 6 mL/kg predicted body weight over the first 4 calendar days of ventilation, with patients that did not receive LTVV. The primary endpoint was 28-day mortality. In addition, we identified factors associated with use of LTVV.ResultsOf 903 patients, 294 (32.5%) received LTVV. Disease severity scores and ARDS classification was not different between the two patient groups. The primary endpoint, 28-day mortality, was met in 68 out of 294 patients (23.1%) that received LTVV versus in 193 out of 609 patients (31.7%) that did not receive LTVV (P < 0.001). LTVV was independently associated with 28-day mortality (HR, 0.68 (0.45 to 0.95); P = 0.025). Age, height, the initial tidal volume and continuous muscle paralysis was independently associated with use of LTVV.ConclusionsIn this cohort of invasively ventilated COVID-19 patients, approximately a third of patients received LTVV. Use of LTVV was independently associated with reduced 28-day mortality. The initial tidal volume and continuous muscle paralysis were potentially modifiable factors associated with use of LTVV. These findings are important as they could help clinicians to recognize patients who are at risk of not receiving LTVV.

Role of Early Enteral Nutrition in Mechanically Ventilated COVID-19 Patients.

OBJECTIVES:Current guidance recommends initiation of early enteral nutrition (early EN) within 24–36 hours of ICU admission in critically ill COVID-19 patients. Despite this recommendation, there is quite limited evidence describing the effect of early EN on outcomes in COVID-19 patients. The association between early EN (within 3 d post intubation) and clinical outcomes in adult COVID-19 patients requiring mechanical ventilation (within 2 d post ICU admission) was evaluated.DESIGN:We performed a nationwide observational cohort study using a nationwide administrative-financial database (Premier) in United States.SETTING:Information pertaining to all COVID-19 patients admitted to ICU from 75 hospitals between April and December 2020 was analyzed.PATIENTS:A total of 861 COVID-19 patients were included.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:Clinical outcomes were assessed via regression models to control for patient and hospital characteristics. We identified 513 COVID-19 ICU patients (59.2%) requiring mechanical ventilation who received early EN and had similar baseline characteristics to late EN group. Compared with late EN group, the early EN group had shorter ICU (hazard ratio [HR], 1.39; 95% CI, 1.15–1.68) and hospital length of stays (LOS) (HR, 1.53; 95% CI, 1.23–1.91), fewer mechanical ventilation days (HR, 1.25; 95% CI, 1.01–1.54), and lower cost (–$22,443; 95% CI, –$32,342 to –$12,534). All comparisons were statistically significant (p < 0.05).CONCLUSIONS:In patients with COVID-19 requiring mechanical ventilation, early EN is associated with earlier liberation from mechanical ventilation, shorter ICU and hospital LOS, and decreased cost. Our results are among the first to support guideline recommendations for initiation of early EN in COVID-19 ICU patients. Further, our data show nearly 40% of critically ill COVID-19 patients fail to have early EN initiated, even at 3 d post initiation of mechanical ventilation. These results emphasize the need for targeted strategies promoting initiation of early EN, as this may lead to improved clinical and economic outcomes in severe COVID-19 patients.

Sensitivity and specificity of heat and moisture exchange filters sampling for SARS-CoV-2 detection in mechanically ventilated COVID-19 patients.

We assessed the sensitivity and specificity of SARS-CoV-2 detection by polymerase chain reaction in heat and moisture exchange filters (HMEF) in mechanically ventilated COVID-19 patients. We showed that testing HMEF might obviate the need for a tracheal sample to affirm that a patient is not ready to end isolation.

Do Mechanically Ventilated COVID-19 Patients Present a Higher Case-Fatality Rate Compared With Other Infectious Respiratory Pandemics? A Systematic Review and Meta-Analysis

Background Early reports on COVID-19 patient outcomes showed a marked fatality rate among patients requiring invasive mechanical ventilation (IMV). Objective Our aim was to compare case fatality rate (CFR) outcomes for patients requiring IMV due to severe acute respiratory syndrome (SARS)-associated coronavirus 2 (COVID-19), SARS-associated coronavirus 1, Middle East respiratory syndrome (MERS), and influenza (H1N1). Materials and Methods We searched PubMed, EMBASE, MEDLINE, Google Scholar, and Cochrane Library for relevant studies published between December 2019 and April 2021 for COVID-19, between January 2002 and December 2008 for SARS, between January 2012 and December 2019 for MERS, and between January 2009 and December 2016 for influenza (H1N1). Results Overall, this study included 81 peer-reviewed studies, pertaining to 65,058 patients requiring IMV: 61 studies including 62,809 COVID-19 patients, 4 studies including 148 SARS patients, 9 studies including 875 MERS patients, and 7 studies including 1226 influenza (H1N1) patients. The CFR for COVID-19 patients requiring IMV was not significantly different from the CFR for SARS and influenza (H1N1) patients (45.5% [95% confidence interval (CI), 38.5%–52.8%] vs. 48.1% [95% CI, 39.2%–57.2%] and 39.7% [95% CI, 29.3%–51.3%], respectively). However, CFR for COVID-19 patients was significantly lower compared with that for MERS patients (CFR, 70.6%; 95% CI, 60.9%–78.8%). Conclusions COVID-19 patients requiring IMV show a similar CFR compared with SARS and H1N1 influenza patients but a lower CFR compared with MERS patients. To improve survival in future pandemics, we recommend examining the pros and cons of the liberal use of endotracheal intubation and considering drafting guidelines for the selection of patients to intubate and the timing of intubation.

Clinical characteristics, physiological features, and outcomes associated with hypercapnia in patients with acute hypoxemic respiratory failure due to COVID-19---insights from the PRoVENT-COVID study.

PurposeWe determined the incidence of hypercapnia and associations with outcome in invasively ventilated COVID–19 patients.MethodsPosthoc analysis of a national, multicenter, observational study in 22 ICUs. Patients were classified as ‘hypercapnic’ or ‘normocapnic’ in the first three days of invasive ventilation. Primary endpoint was prevalence of hypercapnia. Secondary endpoints were ventilator parameters, length of stay (LOS) in ICU and hospital, and mortality in ICU, hospital, at day 28 and 90.ResultsOf 824 patients, 485 (58.9%) were hypercapnic. Hypercapnic patients had a higher BMI and had COPD, severe ARDS and venous thromboembolic events more often. Hypercapnic patients were ventilated with lower tidal volumes, higher respiratory rates, higher driving pressures, and with more mechanical power of ventilation. Hypercapnic patients had comparable minute volumes but higher ventilatory ratios than normocapnic patients. In hypercapnic patients, ventilation and LOS in ICU and hospital was longer, but mortality was comparable to normocapnic patients.ConclusionHypercapnia occurs often in invasively ventilated COVID–19 patients. Main differences between hypercapnic and normocapnic patients are severity of ARDS, occurrence of venous thromboembolic events, and a higher ventilation ratio. Hypercapnia has an association with duration of ventilation and LOS in ICU and hospital, but not with mortality.

Can Lung Ultrasound Be the Ideal Monitoring Tool to Predict the Clinical Outcome of Mechanically Ventilated COVID-19 Patients? An Observational Study.

Background: During the COVID-19 pandemic, lung ultrasound (LUS) has been widely used since it can be performed at the patient’s bedside, does not produce ionizing radiation, and is sufficiently accurate. The LUS score allows for quantifying lung involvement; however, its clinical prognostic role is still controversial. Methods: A retrospective observational study on 103 COVID-19 patients with respiratory failure that were assessed with an LUS score at intensive care unit (ICU) admission and discharge in a tertiary university COVID-19 referral center. Results: The deceased patients had a higher LUS score at admission than the survivors (25.7 vs. 23.5; p-value = 0.02; cut-off value of 25; Odds Ratio (OR) 1.1; Interquartile Range (IQR) 1.0−1.2). The predictive regression model shows that the value of LUSt0 (OR 1.1; IQR 1.0–1.3), age (OR 1.1; IQR 1.0−1.2), sex (OR 0.7; IQR 0.2−3.6), and days in spontaneous breathing (OR 0.2; IQR 0.1–0.5) predict the risk of death for COVID-19 patients (Area under the Curve (AUC) 0.92). Furthermore, the surviving patients showed a significantly lower difference between LUS scores at admission and discharge (mean difference of 1.75, p-value = 0.03). Conclusion: Upon entry into the ICU, the LUS score may play a prognostic role in COVID-19 patients with ARDS. Furthermore, employing the LUS score as a monitoring tool allows for evaluating the patients with a higher probability of survival.

Inflammatory Profiles of Tracheal Biopsies From SARS-CoV-2 Patients.

PurposeAn increasing number of laryngotracheal complications in mechanically ventilated COVID-19 patients has been reported in the last few months. Many etiopathogenetic hypotheses were proposed but no clear explanation of these complications was identified. In this paper we evaluated the possibility that the tracheal mucosa could be a high viral replication site that could weaken the epithelium itself.MethodsSubjects for the COVID-19 group and the control group were selected retrospectively according to specific criteria. Patients’ basic and clinical data were recorded and analyzed. Tracheal samples of both groups were collected during surgical tracheostomies and then analyzed from a histological and genetic-transcriptional point of view.ResultsFour COVID-19 patients were enrolled in this study and compared with four non-COVID-19 patients. No laryngotracheal complications were identified in both groups. The SARS-CoV-2 was detected in one out of four COVID-19 samples. A subepithelial inflammatory lymphomonocyte infiltrate was observed in all patients but two cases of the COVID-19 group showed vasculitis of small subepithelial vessels associated with foci of coagulative necrosis. Two gene sets (HALLMARK_INFLAMMATORY_RESPONSE and HALLMARK_ESTROGEN_RESPONSE_LATE) were significantly deregulated in COVID-19 patients compared to the control group.ConclusionThe altered inflammatory response of the COVID-19 patients could be another possible explanation of the increasing number of laryngotracheal complications.

Analgesia for ventilation - what's new?

The prerequisite for monitoring goal-oriented analgesia and screening for the presence of delirium is the use of validated measuring instruments such as the Richmond Agitation and Sedation Scale as well as an adequate medical and intensive care staffing ratio. The goal, if possible, is an awake, oriented, cooperative patient who is free of pain. In this regard, multimodal analgesic treatment is of great importance. The lowest possible sedation should also be aimed for in COVID-19 patients, although deep sedation is recommended for invasively ventilated COVID-19 patients in the prone position.

Risk factors for Herpes simplex virus (HSV) and Cytomegalovirus (CMV) infections in critically-ill COVID-19 patients.

BackgroundTo assess the prevalence of Herpes simplex and Cytomegalovirus infection in respiratory samples of critically-ill COVID-19 patients, its role in outcome and mortality and the influence of dexamethasone treatment in the early stage of SARS-CoV-2 infection.MethodsAll mechanically ventilated COVID-19 patients treated on ICU between March 2020 and January 2021 were included. Respiratory specimens were tested for Herpes simplex virus (HSV) type 1, 2 and Cytomegalovirus (CMV) by quantitative real-time PCR. Clinical parameters were compared in the cohorts with and without HSV-1- infection.Results134 patients with a median age of 72.5 years (73.0% male, n=98) were included. HSV-1 reactivation occurred in 61 patients (45.5%), after median 9 (7-13) days of mechanical ventilation. The main factor for reactivation was length of stay on ICU (24 days vs 13 days, p<0.001) and duration of mechanical ventilation (417 vs 214 hours, p<0.001). Treatment with dexamethasone and a history of immunosuppression did not associate with HSV-infection in the univariate analysis (39 vs 41, p=0.462 and 27.9% vs 23.3%, p=0.561, respectively). Both ICU and hospital mortality were not significantly different in the cohorts with and without HSV-infection (57.4% vs 45.2%, p=0.219).ConclusionsOur study shows a high prevalence of HSV-infection in critically-ill COVID-19 patients which was unexpectedly higher than the prevalence of CMV-infections and unrelated to dexamethasone treatment. The main risk factors for HSV and CMV in the studied cohorts were the length of ICU stay and duration of mechanical ventilation. Therefore, we recommend routine monitoring of critically ill COVID-19 patients for these viral co-infections and consider treatment in those patients.

Mortality of Mechanically Ventilated COVID-19 Patients in Traditional versus Expanded Intensive Care Units in New York.

RationaleDuring the first wave of the coronavirus disease (COVID-19) pandemic in New York City, the number of mechanically ventilated COVID-19 patients rapidly surpassed the capacity of traditional intensive care units (ICUs), resulting in health systems utilizing other areas as expanded ICUs to provide critical care.ObjectivesTo evaluate the mortality of patients admitted to expanded ICUs compared with those admitted to traditional ICUs.MethodsMulticenter, retrospective, cohort study of mechanically ventilated patients with COVID-19 admitted to the ICUs at 11 Northwell Health hospitals in the greater New York City area between March 1, 2020 and April 30, 2020. Primary outcome was in-hospital mortality up to 28 days after intubation of COVID-19 patients.ResultsAmong 1,966 mechanically ventilated patients with COVID-19, 1,198 (61%) died within 28 days after intubation, 46 (2%) were transferred to other hospitals outside of the Northwell Health system, 722 (37%) survived in the hospital until 28 days or were discharged after recovery. The risk of mortality of mechanically ventilated patients admitted to expanded ICUs was not different from those admitted to traditional ICUs (hazard ratio [HR], 1.07; 95% confidence interval [CI], 0.95–1.20; P = 0.28), while hospital occupancy for critically ill patients itself was associated with increased risk of mortality (HR, 1.28; 95% CI, 1.12–1.45; P < 0.001).ConclusionsAlthough increased hospital occupancy for critically ill patients itself was associated with increased mortality, the risk of 28-day in-hospital mortality of mechanically ventilated patients with COVID-19 who were admitted to expanded ICUs was not different from those admitted to traditional ICUs.

Comparative outcomes of combined corticosteroid and remdesivir therapy with corticosteroid monotherapy in ventilated COVID-19 patients.

Remdesivir (RDV) reduces time to clinical improvement in hospitalized COVID -19 patients requiring supplemental oxygen. Dexamethasone improves survival in those requiring oxygen support. Data is lacking on the efficacy of combination therapy in patients on mechanical ventilation. We analyzed for comparative outcomes between Corticosteroid (CS) therapy with combined Corticosteroid and Remdesivir (CS-RDV) therapy. We conducted an observational cohort study of patients aged 18 to 90 with COVID-19 requiring ventilatory support using TriNetX (COVID-19 Research Network) between January 20, 2020, and February 9, 2021. We compared patients who received at least 48 hours of CS-RDV combination therapy to CS monotherapy. The primary outcome was 28-day all-cause mortality rates in propensity-matched (PSM) cohorts. Secondary outcomes were Length of Stay (LOS), Secondary Bacterial Infections (SBI), and MRSA (Methicillin-Resistant Staphylococcus aureus), and Pseudomonas infections. We used univariate and multivariate Cox proportional hazards models and stratified log-rank tests. Of 388 patients included, 91 (23.5%) received CS-RDV therapy, and 297 (76.5%) received CS monotherapy. After propensity score matching, with 74 patients in each cohort, all-cause mortality was 36.4% and 29.7% in the CS-RDV and CS therapy, respectively (P = 0.38). We used a Kaplan-Meier with a log-rank test on follow up period (P = 0.23), and a Hazards Ratio model (P = 0.26). SBI incidence was higher in the CS group (13.5% vs. 35.1%, P = 0.02) with a similar LOS (13.4 days vs. 13.4 days, P = 1.00) and similar incidence of MRSA/Pseudomonas infections (13.5% vs. 13.5%, P = 1.00) in both the groups. Therefore, CS-RDV therapy is non-inferior to CS therapy in reducing 28-day all-cause in-hospital mortality but associated with a significant decrease in the incidence of SBI in critically ill COVID-19 patients.

Ventilator-Associated Lower Respiratory Tract Bacterial Infections in COVID-19 Compared With Non-COVID-19 Patients.

OBJECTIVES:Ventilator-associated lower respiratory tract infections (VA-LRTIs) are associated with prolonged length of stay and increased mortality. We aimed to investigate the occurrence of bacterial VA-LRTI among mechanically ventilated COVID-19 patients and compare these findings to non-COVID-19 cohorts throughout the first and second wave of the pandemic.DESIGN:Retrospective cohort study.SETTING:Karolinska University Hospital, Stockholm, Sweden.PATIENTS:All patients greater than or equal to 18 years treated with mechanical ventilation between January 1, 2011, and December 31, 2020.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:The cohort consisted of 20,223 ICU episodes (479 COVID-19), with a VA-LRTI incidence proportion of 30% (129/426) in COVID-19 and 18% (1,081/5,907) in non-COVID-19 among patients ventilated greater than or equal to 48 hours. The median length of ventilator treatment for COVID-19 patients was 10 days (interquartile range, 5–18 d), which was significantly longer than for all other investigated specific diagnoses. The VA-LRTI incidence rate per 1,000 ventilator days at risk was 31 (95% CI, 26–37) for COVID-19 and 34 (95% CI, 32–36) for non-COVID-19. With COVID-19 as reference, adjusted subdistribution hazard ratios for VA-LRTI was 0.29–0.50 (95% CI, < 1) for influenza, bacterial pneumonia, acute respiratory distress syndrome, and severe sepsis, but 1.38 (95% CI, 1.15–1.65) for specific noninfectious diagnoses. Compared with COVID-19 in the first wave of the pandemic, COVID-19 in the second wave had adjusted subdistribution hazard ratio of 1.85 (95% CI, 1.14–2.99). In early VA-LRTI Staphylococcus aureus was more common and Streptococcus pneumoniae, Haemophilus influenzae, and Escherichia coli less common in COVID-19 patients, while Serratia species was more often identified in late VA-LRTI.CONCLUSIONS:COVID-19 is associated with exceptionally long durations of mechanical ventilation treatment and high VA-LRTI occurrence proportions. The incidence rate of VA-LRTI was compared with the pooled non-COVID-19 cohort, however, not increased in COVID-19. Significant differences in the incidence of VA-LRTI occurred between the first and second wave of the COVID-19 pandemic.

Tracheostomy timing and clinical outcomes in ventilated COVID-19 patients: a systematic review and meta-analysis

BackgroundThe association of tracheostomy timing and clinical outcomes in ventilated COVID-19 patients remains controversial. We performed a meta-analysis to evaluate the impact of early tracheostomy compared to late tracheostomy on COVID-19 patients’ outcomes.MethodsWe searched Medline, Embase, Cochrane, and Scopus database, along with medRxiv, bioRxiv, and Research Square, from December 1, 2019, to August 24, 2021. Early tracheostomy was defined as a tracheostomy conducted 14 days or less after initiation of invasive mechanical ventilation (IMV). Late tracheostomy was any time thereafter. Duration of IMV, duration of ICU stay, and overall mortality were the primary outcomes of the meta-analysis. Pooled odds ratios (OR) or the mean differences (MD) with 95%CIs were calculated using a random-effects model.ResultsFourteen studies with a cumulative 2371 tracheostomized COVID-19 patients were included in this review. Early tracheostomy was associated with significant reductions in duration of IMV (2098 patients; MD − 9.08 days, 95% CI − 10.91 to − 7.26 days, p < 0.01) and duration of ICU stay (1224 patients; MD − 9.41 days, 95% CI − 12.36 to − 6.46 days, p < 0.01). Mortality was reported for 2343 patients and was comparable between groups (OR 1.09, 95% CI 0.79–1.51, p = 0.59).ConclusionsThe results of this meta-analysis suggest that, compared with late tracheostomy, early tracheostomy in COVID-19 patients was associated with shorter duration of IMV and ICU stay without modifying the mortality rate. These findings may have important implications to improve ICU availability during the COVID-19 pandemic.Trial registration The protocol was registered at INPLASY (INPLASY202180088).

Pharmacological repurposed agents for COVID-19

Coronavirus 2019 (COVID-19) pandemic has created a significant global challenge with respect to the search for specific and effective pharmacological agents with fewer adverse effects for treating this disease. To date, no effective therapy for COVID-19 has been established. Recent virological studies suggest an assortment of potential therapeutics, which could be good candidates for minimizing disease development. One of the most effective potential medications is Remdesivir, which has demonstrated in-vitro antiviral activity and is the first COVID-19 drug approved by the United States Food and Drug Administration (FDA). Adjunct medical care is used as an extra treatment method in addition to the essential treatment, for example, glucocorticoids, which cause a decline in the death rate in mechanically ventilated COVID-19 patients. More clinical preliminary studies should be conducted to explore the most effective pharmacological agent for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19. Numerous possible drug-drug interactions (DDIs) that may take place with the COVID-19 repurposed drugs and other medications have been identified. These facts might be beneficial for physicians to screen and identify potential DDIs with adverse consequences, and accordingly styling preventive and management approaches for their avoidance.