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.

Serum inflammatory and brain injury biomarkers in COVID-19 patients admitted to intensive care unit: A pilot study.

Background: The aim of this study was to measure serum brain injury biomarkers in patients with COVID-19 admitted to intensive care unit (ICU), without evidence of brain impairment, and to determine potential correlations with systemic inflammatory markers, illness severity, and outcome. Methods: In patients admitted to the ICU with COVID-19, without clinical evidence of brain injury, blood S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE) and interleukin-6 (IL-6) were measured on admission. Clinical, routine laboratory data and illness severity were recorded. Comparisons between 28-day survivors and non-survivors and correlations of neurological biomarkers to other laboratory data and illness severity, were analyzed. Results: We included 50 patients, median age 64 [IQR 58-78] years, 39 (78%) males, 39 (78%) mechanically ventilated and 11 (22%) under high flow nasal oxygen treatment. S100B and NSE were increased in 19 (38%) and 45 (90%) patients, respectively. S100B was significantly elevated in non-survivors compared to survivors: 0.15 [0.10-0.29] versus 0.11 [0.07-0.17] µg/L, respectively, (p = 0.03), and significantly correlated with age, IL-6, arterial lactate, noradrenaline dose, illness severity and lymphocyte count. IL-6 was significantly correlated with C-reactive protein, noradrenaline dose and organ failure severity. NSE was correlated only with lactate dehydrogenase. Conclusion: Brain injury biomarkers were frequently elevated in COVID-19 ICU patients, in the absence of clinical evidence of brain injury. S100B was significantly correlated with IL-6, low lymphocyte count, hypoperfusion indices, illness severity, and short-term outcome. These findings indicate a possible brain astrocytes and neurons involvement, also suggesting a broader role of S100B in systemic inflammatory response.

Acute Arterial Ischemic Stroke Following COVID-19 Vaccination: A Systematic Review and Meta-analysis.

BACKGROUND: Acute arterial-ischemic-stroke (AIS) has been reported as a rare adverse-event following COVID-19-vaccination with mRNA or viral-vector vaccines. However, data are sparse regarding the risk of post-vaccination AIS and its potential association with thrombotic-thrombocytopenia-syndrome (TTS). METHODS: A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs), pharmacovigilance registries, registry-based studies, observational cohorts and case-series was performed with the aim to calculate: (1) the pooled proportion of patients presenting with AIS following COVID-19-vaccination; (2) the prevalence of AIS after mRNA and vector-based vaccination; (3) the proportion of TTS among post-vaccination AIS-cases. Patient characteristics were assessed as secondary outcomes. RESULTS: Two RCTs, three cohort and eleven registry-based studies comprising 17,481 AIS-cases among 782,989,363 COVID-19-vaccinations were included in the meta-analysis. The pooled proportion of AIS following exposure to any COVID-19-vaccine type was 4.7 cases per 100,000 vaccinations (95%CI:2.2-8.1; I2=99.9%). The pooled proportion of AIS following mRNA-vaccination (9.2 cases per 100,000 vaccinations; 95%CI: 2.5-19.3; I2=99.9%) did not differ compared to adenovirus-based-vaccination (2.9 cases per 100,000 vaccinations; 95%CI: 0.3-7.8; I2=99.9%). No differences regarding demographics were disclosed between patients with AIS following mRNA- or vector-based vaccination. The pooled proportion of TTS among post-vaccination AIS-cases was 3.1% (95%CI: 0.7-7.2%; I2=78.8%). CONCLUSIONS: The pooled proportion of AIS following COVID-19 vaccination is comparable to the prevalence of AIS in the general population and much lower than the AIS prevalence among SARS-CoV-2-infected patients. TTS is very uncommonly reported in patients with AIS following COVID-19 vaccination.

Occurrence of Severe SARS-CoV-2 Infection in Fully Vaccinated Solid Organ Transplant Recipients.

The present study presents the clinical outcome of SARS-CoV-2 disease in relation to the humoral response in fully vaccinated solid organ transplant (SOT) recipients. Our patient cohort consists of 455 SOT recipients, vaccinated with one of the 2 approved mRNA vaccines. The antibody response was measured 1 month after the second dose, and previously infected patients have been excluded. Of the 449 remaining patients, 15 (3.34%) tested positive, using SARS-CoV-2 polymerase chain reaction. Their mean age was 43.7 ±14.4 years, and median time from transplantation was 7.8 years (1.2-30.2). Eleven patients (73.3%) had been vaccinated with BNT162b2 and 4 (26.7%) with the mRNA1273 vaccine. At the time of infection 9 (60%) patients had a negative (<50 AU/mL) antibody titer, and 6 (40%) had a positive one (>50 AU/mL). Median antibody titer, 27.4± 14.0 days after the second dose, measured at 13 AU/mL (0-7480 AU/mL). Renal function did not appear to be affected by the disease. Τhe mean estimated glomerular filtration rate at diagnosis was 48 ± 15 mL/min, and when in a 29-day (1-101) median follow-up was 53.9± 20.9 mL/min. Of the 15 patients, 7 had mild symptoms and were not hospitalized, and of the remaining 8 (53.3%) who needed hospitalization 7 had severe disease and 2 of them expired. The study confirms the variable and often severe course of coronavirus 2019 infection in SOT recipients, even after their full vaccination, highlighting the need to vaccinate their close relatives and to accelerate the implementation of the booster dose of vaccine.