Immunomodulators for immunocompromised patients hospitalized for COVID-19: a meta-analysis of randomized controlled trials.

Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61-1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64-1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09-0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.

Mortality of intubated patients with COVID-19 during first and subsequent waves: a meta-analysis involving 363,660 patients from 43 countries.

BACKGROUND: We attempted to investigate the change in mortality of intubated patients with coronavirus disease (COVID-19) from first to subsequent waves across several countries. METHODS: We pre-registered our meta-analysis with PROSPERO [Anonymized]. We searched PubMed, Scopus, and gray literature for observational studies reporting data on all-cause mortality of intubated patients with COVID-19 recruited both during first and subsequent waves of the pandemic. We considered studies published after 31 August 2020 up to 12 July 2021. The primary outcome of the meta-analysis was all-cause mortality. We used a random effects model to calculate pooled risk ratio (RR) and 95% confidence intervals (CI). RESULTS: By incorporating data of 363,660 patients from 43 countries included in 28 studies, we found that all-cause mortality of intubated patients with COVID-19 increased from first to subsequent waves (from 62.2% to 72.6%; RR 0.90, 95% CI 0.85-0.94, p < 0.00001). This finding was independent of the geo-economic variation of the included studies and persisted in several pre-specified subgroup and sensitivity analyses. CONCLUSIONS: The robust finding of this meta-analysis suggests that mortality of intubated patients with COVID-19 did not improve over time. Future research should target this group of patients to further optimize their management.

Association between timing of intubation and clinical outcomes of critically ill patients: A meta-analysis.

PURPOSE: Optimal timing of intubation is controversial. We attempted to investigate the association between timing of intubation and clinical outcomes of critically ill patients. METHODS: PubMed was systematically searched for studies reporting on mortality of critically ill patients undergoing early versus late intubation. Studies involving patients with new coronavirus disease (COVID-19) were excluded because a relevant meta-analysis has been published. "Early" intubation was defined according to the authors of the included studies. All-cause mortality was the primary outcome. Pooled risk ratio (RR) and 95% confidence intervals (CI) were calculated using a random effects model. The meta-analysis was registered with PROSPERO (CRD42021284850). RESULTS: In total, 27 studies involving 15,441 intubated patients (11,943 early, 3498 late) were included. All-cause mortality was lower in patients undergoing early versus late intubation (7338 deaths; 45.8% versus 53.5%; RR 0.92, 95% CI 0.87-0.97; p = 0.001). This was also the case in the sensitivity analysis of studies defining "early" as intubation within 24 h from admission in the intensive care unit (6279 deaths; 45.8% versus 53.6%; RR 0.93, 95% CI 0.89-0.98; p = 0.005). CONCLUSION: Avoiding late intubation may be associated with lower mortality in critically ill patients without COVID-19.

Effect of Vitamin C on Clinical Outcomes of Critically Ill Patients With COVID-19: An Observational Study and Subsequent Meta-Analysis.

BACKGROUND: Whether vitamin C provides any benefit when administered in critically ill patients, including those with coronavirus disease (COVID-19), is controversial. We endeavored to estimate the effect of administration of vitamin C on clinical outcomes of critically ill patients with COVID-19 by performing an observational study and subsequent meta-analysis. METHODS: Firstly, we conducted an observational study of critically ill patients with laboratory-confirmed COVID-19 who consecutively underwent invasive mechanical ventilation in an academic intensive care unit (ICU) during the second pandemic wave. We compared all-cause mortality of patients receiving vitamin C ("vitamin C" group) or not ("control" group) on top of standard-of-care. Subsequently, we systematically searched PubMed and CENTRAL for relevant studies, which reported on all-cause mortality (primary outcome) and/or morbidity of critically ill patients with COVID-19 receiving vitamin C or not treatment. Pooled risk ratio (RR) and 95% confidence intervals (CI) were calculated using a random effects model. The meta-analysis was registered with PROSPERO. RESULTS: In the observational study, baseline characteristics were comparable between the two groups. Mortality was 20.0% (2/10) in the vitamin C group vs. 47.6% (49/103; p = 0.11) in the control group. Subsequently, the meta-analysis included 11 studies (6 observational; five randomized controlled trials) enrolling 1,807 critically ill patients with COVID-19. Mortality of patients receiving vitamin C on top of standard-of-care was not lower than patients receiving standard-of-care alone (25.8 vs. 34.7%; RR 0.85, 95% CI 0.57-1.26; p = 0.42). CONCLUSIONS: After combining results of our observational cohort with those of relevant studies into a meta-analysis of data from 1,807 patients, we found that administration vitamin C as opposed to standard-of-care alone might not be associated with lower of mortality among critically ill patients with COVID-19. Additional evidence is anticipated from relevant large randomized controlled trials which are currently underway. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier: CRD42021276655.