Variation in outcome of invasive mechanical ventilation between different countries for patients with severe COVID-19: A systematic review and meta-analysis
Authors: Elsayed Hany Hasan , Hassaballa Aly Sherif , Ahmed Taha Aly , Gumaa Mohammed , Sharkawy Hazem Youssef , Moharram Assem Adel 
Published: June 2021

Background
COVID 19 is the most recent cause of Adult respiratory distress syndrome ARDS. Invasive mechanical ventilation IMV can support gas exchange in patients failing non-invasive ventilation, but its reported outcome is highly variable between countries. We conducted a systematic review and meta-analysis on IMV for COVID-associated ARDS to study its outcome among different countries.

Methods
CENTRAL, MEDLINE/PubMed, Cochrane Library, and Scopus were systematically searched up to August 8, 2020. Studies reporting five or more patients with end point outcome for severe COVID 19 infection treated with IMV were included. The main outcome assessed was mortality. Baseline, procedural, outcome, and validity data were systematically appraised and pooled with random-effect methods. Subgroup analysis for different countries was performed. Meta-regression for the effect of study timing and patient age and were tested. Publication bias was examined. This trial was registered with PROSPERO under registration number CRD42020190365.

Findings
Our electronic search retrieved 4770 citations, 103 of which were selected for full-text review. Twenty-one studies with a combined population of 37359 patients with COVID-19 fulfilled the inclusion criteria. From this population, 5800 patients were treated by invasive mechanical ventilation. Out of those, 3301 patients reached an endpoint of ICU discharge or death after invasive mechanical ventilation while the rest were still in the ICU. Mortality from IMV was highly variable among the included studies ranging between 21% and 100%. Random-effect pooled estimates suggested an overall in-hospital mortality risk ratio of 0.70 (95% confidence interval 0.608 to 0.797; I2 = 98%). Subgroup analysis according to country of origin showed homogeneity in the 8 Chinese studies with high pooled mortality risk ratio of 0.97 (I2 = 24%, p = 0.23) (95% CI = 0.94–1.00), similar to Italy with a low pooled mortality risk ratio of 0.26 (95% CI 0.08–0.43) with homogeneity (p = 0.86) while the later larger studies coming from the USA showed pooled estimate mortality risk ratio of 0.60 (95% CI 0.43–0.76) with persistent heterogeneity (I2 = 98%, p<0.001). Meta-regression showed that outcome from IMV improved with time (p<0.001). Age had no statistically significant effect on mortality (p = 0.102). Publication bias was excluded by visualizing the funnel plot of standard error, Egger’s test with p = 0.714 and Begg&Mazumdar test with p = 0.334.

Interpretation
The study included the largest number of patients with outcome findings of IMV in this current pandemic. Our findings showed that the use of IMV for selected COVID 19 patients with severe ARDS carries a high mortality, but outcome has improved over the last few months and in more recent studies. The results should encourage physicians to use this facility when indicated for severely ill COVID-19 patients.