Outcomes of Heart Failure Related Hospitalizations During the COVID-19 Pandemic.

BACKGROUND:  The incidence and prevalence of heart failure (HF) in the United States has steadily increased in the past few decades. Similarly, the United States has experienced an increase in HF-related hospitalizations which has added to the burden of a resource-stretched healthcare system. With the emergence of the coronavirus disease 2019 (COVID-19) pandemic in 2020, hospitalizations due to the COVID-19 infection sky-rocketed further exacerbating the burden on both patient health and the healthcare system. The focus of this study is to examine how a secondary COVID-19 diagnosis affects the outcome of HF patients, and how a pre-existing diagnosis of heart failure impacts the outcomes of patients hospitalized with COVID-19 infection. METHODS: This was a retrospective observational study of adult patients hospitalized with heart failure and COVID-19 infection in the United States in the years 2019 and 2020. Analysis was conducted using the National Inpatient Sample (NIS) database of the Healthcare Utilization Project (HCUP). The total number of patients included in this study from the NIS database 2020 was 94,745. Of those, 93,798 had heart failure without a secondary diagnosis of COVID-19; 947 had heart failure along with a secondary diagnosis of COVID-19. The primary outcome of our study was in-hospital mortality, length of stay, total hospital charges and time from admission to right heart catheterization, which were compared between the two cohorts.  Results: Our main study findings are that mortality in HF patients with secondary diagnosis of COVID-19 infection was not statistically different compared to those who were without a secondary diagnosis of COVID-19. Our study findings also showed that length of stay (LOS) and hospital costs in HF patients who had a secondary diagnosis of COVID-19 were not statistically different compared to those who did not have the secondary diagnosis. Time from admission to right heart catheterization (RHC) in HF patients who had a secondary diagnosis of COVID-19 was shorter in heart failure with reduced ejection fraction (HFrEF) but not in heart failure preserved ejection fraction (HFpEF) compared to those without secondary diagnoses of COVID-19. Finally, when evaluating hospital outcomes for patients admitted with COVID-19 infection, we found that inpatient mortality increased significantly when they had a pre-existing diagnosis of heart failure. CONCLUSION: The COVID-19 pandemic significantly impacted hospitalization outcomes for patients admitted with heart failure. The time from admission to right heart catheterization was significantly shorter in patients admitted with heart failure reduced ejection fraction who also had a secondary diagnosis of COVID-19 infection. When evaluating hospital outcomes for patients admitted with COVID-19 infection, we found that inpatient mortality increased significantly when they had a pre-existing diagnosis of heart failure. Length of hospital stay and hospital charges also were higher for patients with COVID-19 infection who had pre-existing heart failure. Further studies should focus not just on how medical comorbidities like COVID-19 infection, affect outcomes of heart failure but also on how overall strains on the healthcare system, such as pandemics, may affect the management of conditions such as heart failure.

Impact of COVID-19 Pandemic on the Outcomes of Acute Coronary Syndrome.

During the pandemic, health care resources were primarily focused on treating COVID-19 infections and its related complications, with various Clinical units were converted to COVID-19 units, This study aims to investigate the impact of the COVID-19 pandemic on the clinical course of patients who had developed acute coronary syndrome (ACS) including ST-elevation myocardial infarction (STEMI). In this large nationwide observational study utilizing National Inpatient Sample 2019 and 2020.The primary outcomes of our study were in-hospital mortality, length of stay (LOS), total hospital charges and time from admission to percutaneous coronary intervention (PCI). Using the National Inpatient Sample 2020 database we found 32,355,827 hospitalizations in 2020 and 521,484 of which had a primary diagnosis of STEMI that met our criteria. Patients with COVID-19 infection were similar in mean age, more likely to be men, were treated in the same hospital settings as those without COVID-19 and had higher rates of diabetes with chronic complications. These patients had a similar prevalence of traditional coronary artery disease risk factors including hypertension, peripheral vascular disease and obesity. There was higher inpatient mortality (adjusted odds ratios 3.10; 95% CI, 2.40-4.02; P < 0.01) and LOS (95% CI 1.07-2.25; P < 0.01) in STEMI patient with concurrent COVID-19 infection. The average time from admission to PCI was significantly higher among unstable angina (UA) and None ST-segment elevated myocardial infarction (NSTEMI) in patients with a secondary diagnosis of COVID-19 infection compared to patients without: 0.45 days (95% CI: .155-758; P < 0.01). The COVID-19 pandemic had a significant impact on the treatment of patients with ACS, resulting in increased inpatient mortality, higher costs, and longer lengths of stay. During the pandemic, for patients with UA and NSTEMI the time from admission to PCI was significantly longer in patients with a secondary diagnosis of COVID-19 compared to patients without. When comparing ACS outcomes between pre-pandemic to pandemic periods (2019 versus 2020), the 2020 data showed higher mortality, higher hospital costs, and a decrease in LOS. Finally, the time from admission to PCI was longer for UA and NSTEMI in 2020 but not for patients with STEMI.

In-Hospital Mortality and Morbidity in Cancer Patients with COVID-19: A Nationwide Analysis from the United States.

Background: Coronavirus disease 2019 (COVID-19) caused significant mortality and mortality worldwide. There is limited information describing the outcomes of COVID-19 in cancer patients. Methods: We utilized the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (NIS) 2020 database to collect information on cancer patients hospitalized for COVID-19 in the United States. Using the International Classification of Diseases, 10th revision, Clinical Modification (ICD-10-CM) coding system, adult (≥18 years) patients with COVID-19 were identified. Adjusted analyses were performed to assess for mortality, morbidity, and resource utilization among cancer patients. Results: A total of 1,050,045 patients were included. Of them, 27,760 had underlying cancer. Cancer patients were older and had more comorbidities. The all-cause in-hospital mortality rate in cancer patients was 17.58% vs. 11% in non-cancer. After adjusted logistic regression, cancer patients had a 21% increase in the odds of all-cause in-hospital mortality compared with those without cancer (adjusted odds ratio (aOR) 1.21, 95%CI 1.12−1.31, p-value < 0.001). Additionally, an increased odds in acute respiratory failure rate was found (aOR 1.14, 95%CI 1.06−1.22, p-value < 0.001). However, no significant differences were found in the odds of septic shock, acute respiratory distress syndrome, and mechanical ventilation between the two groups. Additionally, no significant differences in the mean length of hospital stay and the total hospitalization charges between cancer and non-cancer patients. Conclusion: Cancer patients hospitalized for COVID-19 had increased odds of all-cause in hospital mortality and acute respiratory failure compared with non-cancer patients.

Association between Body Mass Index and Hospital Outcomes for COVID-19 Patients: A Nationwide Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused significant morbidity and mortality worldwide. There is limited information describing the hospital outcomes of COVID-19 patients in regard to specific body mass index (BMI) categories. METHODS: We utilized the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (NIS) 2020 database to collect information on patients hospitalized for COVID-19 in the United States. Using the International Classification of Diseases, 10th revision, Clinical Modification (ICD-10-CM) coding system, adult patients (≥18 years of age) with a primary hospitalization for COVID-19 were identified. Adjusted analyses were performed to assess for mortality, morbidity, and resource utilization, and compare the outcomes among patients categorized according to BMI. RESULTS: A total of 305,284 patients were included in this study. Of them, 248,490 had underlying obesity, defined as BMI ≥ 30. The oldest patients were observed to have BMI < 19, while youngest patients were in the BMI > 50 category. BMI < 19 category had the highest crude in-hospital mortality rate. However, after adjusted regression, patients with BMI > 50 (adjusted odds ratio (aOR) 1.63, 95% CI 1.48-1.79, p-value < 0.001) had the highest increased odds, at 63%, of in-hospital mortality compared to all other patients in the study. Patients with BMI > 50 also had the highest increased odds of needing invasive mechanical ventilation (IMV) and mortality associated with IMV compared to all other patient, by 37% and 61%, respectively. Obese patients were noted to have shorter average hospital length of stay (LOS), by 1.07 days, compared to non-obese patients, but there was no significant difference in average hospitalization charges. CONCLUSION: Among obese patients primarily hospitalized with COVID-19, those with BMI ≥ 40 had significantly increased rates of all-cause in-hospital mortality, need for IMV, mortality associated with IMV, and septic shock. Overall, obese patients had shorter average hospital LOS, however, did not have significantly higher hospitalization charges.

Real-world effectiveness of COVID-19 vaccination in liver cirrhosis: a systematic review with meta-analysis of 51,834 patients.

SARS-CoV-2 vaccinations were found to be highly effective in phase 3 clinical trials. However, these trials have not reported data regarding the subgroup of liver disease or excluded patients with liver disease. The effectiveness of COVID-19 vaccines among liver cirrhosis (LC) patients is unclear. We conducted this meta-analysis to assess the effectiveness of SARS-CoV-2 vaccination in LC patients. A comprehensive literature search was conducted to include all the relevant studies that compared the outcomes of LC patients who received SARS-CoV-2 vaccines vs. unvaccinated patients. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated by the Mantel-Haenszel method within a random-effect model. Four studies with 51,834 LC patients (20,689 patients received at least one dose vs 31,145 were unvaccinated) were included. COVID-19-related complications, including hospitalization (RR 0.73, 95% CI 0.59-0.91, P = 0.004), mortality (RR 0.29, 95% CI 0.16-0.55, P = 0.0001), and need for invasive mechanical ventilation (RR 0.29, 95% CI 0.11-0.77, P = 0.01), were significantly lower in the vaccinated group compared to the unvaccinated group. SARS-CoV-2 vaccination in LC patients reduced COVID-19-related mortality, intubation, and hospitalization. SARS-CoV-2 vaccination is highly effective in LC. Further prospective studies, preferably randomized controlled trials, are necessary to validate our findings and determine which vaccine is superior in patients with LC.

Risk Factors Associated With Six-Month Mortality in Hospitalized COVID-19 Patients: A Single-Institution Study.

Background Coronavirus disease 2019 (COVID-19) infection can vary from asymptomatic infection to multi-organ dysfunction. The most serious complication of infection with COVID-19 is death. Various comorbid conditions and inflammatory markers have been associated with an increased risk of mortality, specifically within the immediate post-infection period; however, less is known about long-term mortality outcomes. Objectives Our objective is to determine risk factors associated with six-month mortality in hospitalized COVID-19 patients. Methods This is a single-institution, retrospective study. We included patients hospitalized with COVID-19 from the University of Toledo Medical Center in Toledo, Ohio, who were admitted from March 20, 2020, to June 30, 2021. This study was approved by a biomedical institutional review board at the University of Toledo. Patients with available pre-stored blood samples for laboratory testing were included, and hospital charts were assessed up to six months from the date of a positive COVID-19 test result. Two groups were created based on the mortality outcome at six months from COVID-19 positive test results: survivors and non-survivors. The clinical variables or outcomes and laboratory values were compared between the two groups using non-parametric methods due to the small sample size and non-normality of the data. Either the Mann-Whitney U-test for continuous variables or Fisher's exact test for categorical variables was used for statistical analysis. Results Lactate dehydrogenase (LDH) and D-dimer levels on admission were found to be significantly higher in non-survivors than in survivors. The median high D-dimer level in non-survivors was 5.96 micrograms/milliliter (µg/mL) (interquartile range (IQR): 3.95-11.29 µg/mL) vs 1.82 µg/mL (IQR 1.13-5.55 µg/mL) in survivors (p = 0.019). Median LDH levels were also higher in non-survivors vs survivors, i.e., 621.00 international units per liter (IU/L) (IQR 440.00-849.00 IU/L) vs 328.00 IU/L (IQR 274.00-529.00 IU/L), respectively (p = 0.032). The demographic profile, comorbidity profile, and laboratory data (typically associated with short-term mortality, inflammation, and organ dysfunction) were similar between survivors and non-survivors, except for LDH and D-dimer. Conclusion Higher LDH and D-dimer levels on admission were found to be associated with an increased six-month mortality rate in hospitalized COVID-19 patients. These hematologic data can serve as risk stratification tools to prevent long-term mortality outcomes and provide proactive clinical care in hospitalized COVID-19 patients.

Risk Factors Associated With Six-Month Mortality in Hospitalized COVID-19 Patients: A Single-Institution Study

Background Coronavirus disease 2019 (COVID-19) infection can vary from asymptomatic infection to multi-organ dysfunction. The most serious complication of infection with COVID-19 is death. Various comorbid conditions and inflammatory markers have been associated with an increased risk of mortality, specifically within the immediate post-infection period;however, less is known about long-term mortality outcomes. Objectives Our objective is to determine risk factors associated with six-month mortality in hospitalized COVID-19 patients. Methods This is a single-institution, retrospective study. We included patients hospitalized with COVID-19 from the University of Toledo Medical Center in Toledo, Ohio, who were admitted from March 20, 2020, to June 30, 2021. This study was approved by a biomedical institutional review board at the University of Toledo. Patients with available pre-stored blood samples for laboratory testing were included, and hospital charts were assessed up to six months from the date of a positive COVID-19 test result. Two groups were created based on the mortality outcome at six months from COVID-19 positive test results: survivors and non-survivors. The clinical variables or outcomes and laboratory values were compared between the two groups using non-parametric methods due to the small sample size and non-normality of the data. Either the Mann-Whitney U-test for continuous variables or Fisher's exact test for categorical variables was used for statistical analysis. Results Lactate dehydrogenase (LDH) and D-dimer levels on admission were found to be significantly higher in non-survivors than in survivors. The median high D-dimer level in non-survivors was 5.96 micrograms/milliliter (μg/mL) (interquartile range (IQR): 3.95-11.29 μg/mL) vs 1.82 μg/mL (IQR 1.13-5.55 μg/mL) in survivors (p = 0.019). Median LDH levels were also higher in non-survivors vs survivors, i.e., 621.00 international units per liter (IU/L) (IQR 440.00-849.00 IU/L) vs 328.00 IU/L (IQR 274.00-529.00 IU/L), respectively (p = 0.032). The demographic profile, comorbidity profile, and laboratory data (typically associated with short-term mortality, inflammation, and organ dysfunction) were similar between survivors and non-survivors, except for LDH and D-dimer. Conclusion Higher LDH and D-dimer levels on admission were found to be associated with an increased six-month mortality rate in hospitalized COVID-19 patients. These hematologic data can serve as risk stratification tools to prevent long-term mortality outcomes and provide proactive clinical care in hospitalized COVID-19 patients.

Prevalence and Clinical Significance of Antiphospholipid Antibodies in Hospitalized Patients With COVID-19 Infection.

BACKGROUND: Coronavirus disease 2019 (COVID-19) infection is associated with an increased risk of arterial thromboembolic events (ATE) and venous thromboembolic events (VTE). Hypercoagulability associated with COVID-19 infection is multifactorial, and underlying pathogenic mechanisms potentially responsible for thrombosis include inflammation resulting in endothelial damage, platelet activation and the presence of antiphospholipid antibodies (APAs). Antiphospholipid antibody syndrome is one of the very few causes which is associated with venous and arterial thromboembolic events. COVID-19 patients have a high prevalence of APAs as well as both ATE and VTE, but their clinical significance in COVID-19 patients is not fully understood yet. OBJECTIVES: In this study, we intend to find the prevalence of APAs in hospitalized COVID-19 patients at the time of diagnosis and determine whether their presence has any clinical significance. METHODS: This is a retrospective single-institution study involving patients hospitalized for the management of COVID-19 infection at The University of Toledo Medical Center. After obtaining approval from the biomedical institutional review board at The University of Toledo, antiphospholipid antibody (APA) testing was done on pre-stored blood samples of these patients and hospital charts were reviewed till six months from the positive COVID-19 test result. Two groups were created based on the patients' APA testing results (APA positive and APA negative) and used for statistical comparison. Any patients with positive lupus anticoagulant (LA) or abnormal titers APA antibodies were labeled as positive. Demographic data, prognostic outcomes and laboratory values were compared either using Mann-Whitney U-test for continuous variables or Fisher's exact test for categorical variables. RESULTS: The prevalence of APAs in hospitalized COVID-19 patients at the time of diagnosis was 39.3% in this study. There was no difference in demographic variables between the APA-positive and APA-negative groups. The prevalence of APAs was higher in smokers, where 91% of the APA-positive patients were smokers. There was no statistically significant difference in prognostic outcomes including six-month mortality between APA-positive and APA-negative patients. The comorbidity profile was the same in the two groups. APA-positive patients were found to have lower nadir of absolute lymphocyte count and higher nadir levels of C-reactive protein during hospitalization. CONCLUSIONS: The prevalence of APA positivity in hospitalized COVID-19 patients is higher in our study than in historical studies involving non-COVID-19 hospitalized patients, particularly in smokers. However, there is no correlation between APA positivity and prognostic outcomes including six-month mortality. At this point, it is unclear whether APAs are just bystanders or have a pathogenic role. Routine testing of APA in COVID-19 patients is not indicated. Further prospective studies to elucidate the persistence and clinical implications of APAs are needed.

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.

Fluvoxamine in Nonhospitalized Patients With Acute COVID-19 Infection and the Lack of Efficacy in Reducing Rates of Hospitalization, Mechanical Ventilation, and Mortality in Placebo-Controlled Trials: A Systematic Review and Meta-Analysis.

BACKGROUND: Recent clinical trials have investigated the use of fluvoxamine in preventing clinical deterioration in nonhospitalized patients with acute COVID-19 infection via stimulation of sigma-1 receptors, which regulates cytokine production and functional inhibition of acid sphingomyelinase activity, which may prevent infection of epithelial cells with SARS-CoV-2. However, the role of fluvoxamine is currently unclear because of a paucity of studies, particularly because the drug is being repurposed as an immunomodulatory and antiviral agent. STUDY QUESTION: Aim of our meta-analysis was to investigate the efficacy of fluvoxamine in nonhospitalized patients with acute COVID-19 infection. DATA SOURCE: Comprehensive literature search of PubMed, Embase, Cochrane Library databases, and Web of Science was performed from inception to February 10, 2022, for studies comparing fluvoxamine versus placebo for outpatient management of COVID-19. STUDY DESIGN: The primary outcome of interest was rate of hospitalization. The secondary outcomes were rates of patients requiring mechanical ventilation and mortality. The random-effects model was used to calculate the risk ratios (RR) and confidence intervals (CI). A P value <0.05 was considered statistically significant. Heterogeneity was assessed using the Higgins I2 index. RESULTS: Three studies (2 randomized controlled trials and one prospective cohort trial) involving 1762 patients were included in the meta-analysis. In patients who received fluvoxamine compared with placebo, there was no significant difference in rates of hospitalization (RR 0.26, 95% CI, 0.04-1.73, P = 0.16, I2 = 62%), mechanical ventilation (RR 0.73, 95% CI, 0.45-1.19, P = 0.21, I2 = 0%), and mortality (RR 0.67, 95% CI, 0.37-1.22, P = 0.19, I2 = 0%). CONCLUSION: Current evidence does not indicate a significant effect of fluvoxamine on the rates of hospitalization, mechanical ventilation, and mortality of patients with COVID-19 infection.

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.