Inhaled Pulmonary Vasodilators in COVID-19 Infection: A Systematic Review and Meta-Analysis.

Introduction: Inhaled pulmonary vasodilators (IPVD) have been previously studied in patients with non-coronavirus disease-19 (COVID-19) related acute respiratory distress syndrome (ARDS). The use of IPVD has been shown to improve the partial pressure of oxygen in arterial blood (PaO2), reduce fraction of inspired oxygen (FiO2) requirements, and ultimately increase PaO2/FiO2 (P/F) ratios in ARDS patients. However, the role of IPVD in COVID-19 ARDS is still unclear. Therefore, we performed this meta-analysis to evaluate the role of IPVD in COVID-19 patients. Methods: Comprehensive literature search of PubMed, Embase, Web of Science and Cochrane Library databases from inception through April 22, 2022 was performed for all published studies that utilized IPVD in COVID-19 ARDS patients. The single arm studies and case series were combined for a 1-arm meta-analysis, and the 2-arm studies were combined for a 2-arm meta-analysis. Primary outcomes for the 1-arm and 2-arm meta-analyzes were change in pre- and post-IPVD P/F ratios and mortality, respectively. Secondary outcomes for the 1-arm meta-analysis were change in pre- and post-IPVD positive end-expiratory pressure (PEEP) and lung compliance, and for the 2-arm meta-analysis the secondary outcomes were need for endotracheal intubation and hospital length of stay (LOS). Results: 13 single arm retrospective studies and 5 case series involving 613 patients were included in the 1-arm meta-analysis. 3 studies involving 640 patients were included in the 2-arm meta-analysis. The pre-IPVD P/F ratios were significantly lower compared to post-IPVD, but there was no significant difference between pre- and post-IPVD PEEP and lung compliance. The mortality rates, need for endotracheal intubation, and hospital LOS were similar between the IPVD and standard therapy groups. Conclusion: Although IPVD may improve oxygenation, our investigation showed no benefits in terms of mortality compared to standard therapy alone. However, randomized controlled trials are warranted to validate our findings.

High-Flow Nasal Cannula Versus Noninvasive Ventilation in Patients With COVID-19.

BACKGROUND: High-flow nasal cannula (HFNC) oxygen and noninvasive ventilation (NIV) have been widely used in patients with acute hypoxic respiratory failure (AHRF) due to COVID-19. However, the impact of HFNC versus NIV on clinical outcomes of COVID-19 is uncertain. Therefore, we performed this meta-analysis to evaluate the effect of HFNC versus NIV in COVID-19-related AHRF. METHODS: Several electronic databases were searched through February 10, 2022, for eligible studies comparing HFNC and NIV in COVID-19-related AHRF. Our primary outcome was intubation. The secondary outcomes were mortality, hospital length of stay (LOS), and PaO2 /FIO2 changes. Pooled risk ratio (RR) and mean difference (MD) with the corresponding 95% CI were obtained using a random-effect model. Prediction intervals were calculated to indicate the variance in outcomes that would be expected if new studies were conducted in the future. RESULTS: Nineteen studies involving 3,606 subjects (1,880 received HFNC and 1,726 received NIV) were included. There were no differences in intubation (RR 1.01 [95% CI 0.85-1.20], P = .89) or LOS (MD 0.38 d [95% CI -0.61 to 1.37], P = .45) between groups, with consistent results on the subgroup of randomized controlled trials (RCTs). Mortality was lower in NIV (RR 0.81 [95% CI 0.66-0.98], P = .03). However, the prediction interval was 0.41-1.59, and subgroup analysis of RCTs showed no difference in mortality between groups. There was a greater improvement in PaO2 /FIO2 with NIV (MD 22.80 [95% CI 5.30-40.31], P = .01). CONCLUSIONS: Our study showed that despite the greater improvement in PaO2 /FIO2 with NIV, intubation rates and LOS were similar between HFNC and NIV. Although mortality was lower with HFNC than NIV, the prediction interval included the null value, and there was no difference in mortality between HFNC and NIV on a subgroup of RCTs. Future large-scale RCTs are necessary to support our findings.

Pulse versus nonpulse steroid regimens in patients with coronavirus disease 2019: A systematic review and meta-analysis.

Systemic steroids are associated with reduced mortality in hypoxic patients with coronavirus disease 2019 (COVID-19). However, there is no consensus on the doses of steroid therapy in these patients. Several studies showed that pulse dose steroids (PDS) could reduce the progression of COVID-19 pneumonia. However, data regarding the role of PDS in COVID-19 is still unclear. Therefore, we performed this meta-analysis to evaluate the role of PDS in COVID-19 patients compared to nonpulse steroids (NPDS). Comprehensive literature search of PubMed, Embase, Cochrane Library, and Web of Science databases from inception through February 10, 2022 was performed for all published studies comparing PDS to NPDS therapy to manage hypoxic patients with COVID-19. Primary outcome was mortality. Secondary outcomes were the need for endotracheal intubation, hospital length of stay (LOS), and adverse events in the form of superimposed infections. A total of 10 observational studies involving 3065 patients (1289 patients received PDS and 1776 received NPDS) were included. The mortality rate was similar between PDS and NPDS groups (risk ratio [RR]: 1.23, 95% confidence interval [CI]: 0.92-1.65, p = 0.16). There were no differences in the need for endotracheal intubation (RR: 0.71, 95%: CI 0.37-1.137, p = 0.31), LOS (mean difference: 1.93 days; 95% CI: -1.46-5.33; p = 0.26), or adverse events (RR: 0.93, 95% CI: 0.56-1.57, p = 0.80) between the two groups. Compared to NPDS, PDS was associated with similar mortality rates, need for endotracheal intubation, LOS, and adverse events. Given the observational nature of the included studies, randomized controlled trials are warranted to validate our findings.

Effect of Prone Positioning on Clinical Outcomes of Non-Intubated Subjects With COVID-19.

BACKGROUND: Awake prone positioning (APP) has been recently proposed as an adjunctive treatment for non-intubated coronavirus disease 2019 (COVID-19) patients requiring oxygen therapy to improve oxygenation and reduce the risk of intubation. However, the magnitude of the effect of APP on clinical outcomes in these patients remains uncertain. We performed a comparative systematic review and meta-analysis to evaluate the effectiveness of APP to improve the clinical outcomes in non-intubated subjects with COVID-19. METHODS: The primary outcomes were the need for endotracheal intubation and mortality. The secondary outcome was hospital length of stay. Pooled risk ratio (RR) and mean difference with the corresponding 95% CI were obtained by the Mantel-Haenszel method within a random-effect model. RESULTS: A total of 14 studies (5 randomized controlled trials [RCTs] and 9 observational studies) involving 3,324 subjects (1,495 received APP and 1,829 did not) were included. There was a significant reduction in the mortality rate in APP group compared to control (RR 0.68 [95% CI 0.51-0.90]; P = .008, I2 = 52%) with no significant effect on intubation (RR 0.85 [95% CI 0.66-1.08]; P = .17, I2 = 63%) or hospital length of stay (mean difference -3.09 d [95% CI-10.14-3.96]; P = .39, I2 = 97%). Subgroup analysis of RCTs showed significant reduction in intubation rate (RR 0.83 [95% CI 0.72-0.97]; P = .02, I2 = 0%). CONCLUSIONS: APP has the potential to reduce the in-hospital mortality rate in COVID-19 subjects with hypoxemia without a significant effect on the need for intubation or length of hospital stay. However, there was a significant decrease in the need for intubation on subgroup analysis of RCTs. More large-scale trials with a standardized protocol for prone positioning are needed to better evaluate its effectiveness in this select population.

Clinical significance of micronutrient supplements in patients with coronavirus disease 2019: A comprehensive systematic review and meta-analysis.

BACKGROUND AND AIMS: Micronutrient supplements such as vitamin D, vitamin C, and zinc have been used in managing viral illnesses. However, the clinical significance of these individual micronutrients in patients with Coronavirus disease 2019 (COVID-19) remains unclear. We conducted this meta-analysis to provide a quantitative assessment of the clinical significance of these individual micronutrients in COVID-19. METHODS: We performed a comprehensive literature search using MEDLINE, Embase, and Cochrane databases through December 5th, 2021. All individual micronutrients reported by ≥ 3 studies and compared with standard-of-care (SOC) were included. The primary outcome was mortality. The secondary outcomes were intubation rate and length of hospital stay (LOS). Pooled risk ratios (RR) and mean difference (MD) with corresponding 95% confidence intervals (CI) were calculated using the random-effects model. RESULTS: We identified 26 studies (10 randomized controlled trials and 16 observational studies) involving 5633 COVID-19 patients that compared three individual micronutrient supplements (vitamin C, vitamin D, and zinc) with SOC. Nine studies evaluated vitamin C in 1488 patients (605 in vitamin C and 883 in SOC). Vitamin C supplementation had no significant effect on mortality (RR 1.00, 95% CI 0.62-1.62, P = 1.00), intubation rate (RR 1.77, 95% CI 0.56-5.56, P = 0.33), or LOS (MD 0.64; 95% CI -1.70, 2.99; P = 0.59). Fourteen studies assessed the impact of vitamin D on mortality among 3497 patients (927 in vitamin D and 2570 in SOC). Vitamin D did not reduce mortality (RR 0.75, 95% CI 0.49-1.17, P = 0.21) but reduced intubation rate (RR 0.55, 95% CI 0.32-0.97, P = 0.04) and LOS (MD -1.26; 95% CI -2.27, -0.25; P = 0.01). Subgroup analysis showed that vitamin D supplementation was not associated with a mortality benefit in patients receiving vitamin D pre or post COVID-19 diagnosis. Five studies, including 738 patients, compared zinc intake with SOC (447 in zinc and 291 in SOC). Zinc supplementation was not associated with a significant reduction of mortality (RR 0.79, 95% CI 0.60-1.03, P = 0.08). CONCLUSIONS: Individual micronutrient supplementations, including vitamin C, vitamin D, and zinc, were not associated with a mortality benefit in COVID-19. Vitamin D may be associated with lower intubation rate and shorter LOS, but vitamin C did not reduce intubation rate or LOS. Further research is needed to validate our findings.