Vaccination Status and Number of Vaccine Doses Are Independently Associated with the PaO2/FiO2 Ratio on Admission in Hospitalized COVID-19 Patients.

INTRODUCTION: Coronavirus Disease-19 (COVID-19) vaccines reduce the risk of severe disease and mortality. However, the association between vaccination status and number of doses and the PaO2/FiO2 ratio, a clinical measure of hypoxemia associated with an increased risk of intensive care treatment and mortality, has not been investigated. METHODS: We retrospectively assessed a consecutive series of 116 patients admitted to hospital with a primary diagnosis of COVID-19 between January and April 2022. Demographic, clinical, and laboratory data were collected within 24 h from admission. RESULTS: There was a significant positive relationship between the number of vaccine doses and the PaO2/FiO2 ratio (r = 0.223, p = 0.012). This association remained significant after adjusting for confounders. Vaccinated patients had significantly higher PaO2/FiO2 ratios than the unvaccinated (median: 250; IQR: 195-309 vs. 200; IQR: 156-257, p = 0.013). CONCLUSION: These results highlight the importance of the number of vaccine doses received in reducing the degree of hypoxia on admission in hospitalized COVID-19 patients.

Comparison of Clinical Features, Complete Blood Count Parameters, and Outcomes between Two Distinct Waves of COVID-19: A Monocentric Report from Italy.

BACKGROUND: Since the beginning of the SARS-CoV-2 pandemic, the ability to predict the trajectory of the disease has represented a major challenge for clinicians. There is recent evidence that complete blood cell count (CBC)-derived inflammation indexes have predictive value in COVID-19. We aimed to describe any changes in the clinical features, CBC-derived ratios, and outcomes of patients admitted to our hospital across two temporally distinct waves. METHODS: We retrospectively assessed and compared the clinical characteristics and blood cell count values of patients hospitalized during the second and fourth waves of COVID-19, and explored any outcome differences in terms of the level of respiratory support required and transfer to intensive care. RESULTS: We observed that fourth-wave patients were older, less male-predominant, and carried more comorbidities compared to the second-wave patients but, nevertheless, experienced more favorable outcomes. A strong internal correlation was documented for both waves between outcomes and CBC-derived ratios, with the fourth-wave cases displaying lower admission values of the neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation index (SII). No significant differences were found for lymphocyte-to-monocyte ratio (LMR), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI). CONCLUSIONS: We observed that both admission values of CBC-derived indexes and adverse respiratory outcomes decreased from the second to the fourth wave of COVID-19. These data represent a contribution to the existing knowledge on the role of CBC-derived indexes as a potential tool to help clinicians to quickly differentiate in-hospital patients at increased risk of serious illness and death.

Serum hydroxybutyrate dehydrogenase and COVID-19 severity and mortality: a systematic review and meta-analysis with meta-regression.

Alterations in cardiac and renal biomarkers have been reported in coronavirus disease 19 (COVID-19). We conducted a systematic review and meta-analysis to investigate serum concentrations of hydroxybutyrate dehydrogenase (HBDH), a combined marker of myocardial and renal injury, in hospitalized COVID-19 patients with different disease severity and survival status. We searched PubMed, Web of Science and Scopus, between December 2019 and April 2021, for studies reporting HBDH in COVID-19. Risk of bias was assessed using the Newcastle-Ottawa scale, publication bias was assessed with the Begg's and Egger's tests, and certainty of evidence was assessed using GRADE. In 22 studies in 15,019 COVID-19 patients, serum HBDH concentrations on admission were significantly higher in patients with high disease severity or non-survivor status when compared to patients with low severity or survivor status (standardized mean difference, SMD = 0.90, 95% CI 0.74 to 1.07, p < 0.001; moderate certainty of evidence). Extreme between-study heterogeneity was observed (I2 = 93.5%, p < 0.001). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and the direction of the effect size were not substantially modified. A significant publication bias was observed. In meta-regression, the SMD of HBDH concentrations was significantly associated with markers of inflammation, sepsis, liver damage, non-specific tissue damage, myocardial injury, and renal function. Higher HBDH concentrations were significantly associated with higher COVID-19 severity and mortality. This biomarker of cardiac and renal injury might be useful for risk stratification in COVID-19. (PROSPERO registration number: CRD42021258123).

The PaO2/FiO2 ratio on admission is independently associated with prolonged hospitalization in COVID-19 patients.

INTRODUCTION: The early identification of factors that predict the length of hospital stay (HS) in patients affected by coronavirus desease (COVID-19) might assist therapeutic decisions and patient flow management. METHODOLOGY: We collected, at the time of admission, routine clinical, laboratory, and imaging parameters of hypoxia, lung damage, inflammation, and organ dysfunction in a consecutive series of 50 COVID-19 patients admitted to the Respiratory Disease and Infectious Disease Units of the University Hospital of Sassari (North-Sardinia, Italy) and alive on discharge. RESULTS: Prolonged HS (PHS, >21 days) patients had significantly lower PaO2/FiO2 ratio and lymphocytes, and significantly higher Chest CT severity score, C-reactive protein (CRP) and lactic dehydrogenase (LDH) when compared to non-PHS patients. In univariate logistic regression, Chest CT severity score (OR = 1.1891, p = 0.007), intensity of care (OR = 2.1350, p = 0.022), PaO2/FiO2 ratio (OR = 0.9802, p = 0.007), CRP (OR = 1.0952, p = 0.042) and platelet to lymphocyte ratio (OR = 1.0039, p = 0.036) were significantly associated with PHS. However, in multivariate logistic regression, only the PaO2/FiO2 ratio remained significantly correlated with PHS (OR = 0.9164; 95% CI 0.8479-0.9904, p = 0.0275). In ROC curve analysis, using a threshold of 248, the PaO2/FiO2 ratio predicted PHS with sensitivity and specificity of 60% and 91%, respectively (AUC = 0.780, 95% CI 0.637-0.886 p = 0.002). CONCLUSIONS: The PaO2/FiO2 ratio on admission is independently associated with PHS in COVID-19 patients. Larger prospective studies are needed to confirm this finding.

Cholesterol and Triglyceride Concentrations, COVID-19 Severity, and Mortality: A Systematic Review and Meta-Analysis With Meta-Regression.

Lipid profile alterations have been observed in patients with coronavirus disease 2019 (COVID-19) in relation to disease severity and mortality. We conducted a systematic review and meta-analysis with meta-regression of studies reporting total, HDL, and LDL-cholesterol, and triglyceride concentrations in hospitalized patients with COVID-19. We searched PubMed, Web of Science and Scopus, between January 2020 and January 2021, for studies describing lipid concentrations, COVID-19 severity, and survival status (PROSPERO registration number: CRD42021253401). Twenty-two studies in 10,122 COVID-19 patients were included in the meta-analysis. Pooled results showed that hospitalized patients with severe disease or non-survivor status had significantly lower total cholesterol (standardized mean difference, SMD = -0.29, 95% CI -0.41 to -0.16, p < 0.001), LDL-cholesterol (SMD = -0.30, 95% CI -0.41 to -0.18, p < 0.001), and HDL-cholesterol (SMD = -0.44, 95% CI -0.62 to -0.26, p < 0.001), but not triglyceride (SMD = 0.04, 95% CI -0.10 to -0.19, p = 0.57), concentrations compared to patients with milder disease or survivor status during follow up. Between-study heterogeneity was large-to-extreme. In sensitivity analysis, the effect size of different lipid fractions was not affected when each study was in turn removed. The Begg's and Egger's t-tests did not show evidence of publication bias, except for studies investigating LDL-cholesterol. In meta-regression, significant associations were observed between the SMD of LDL-cholesterol and age and hypertension, and between the SMD of triglycerides and study endpoint and aspartate aminotransferase. In our systematic review and meta-analysis, lower total, HDL, and LDL-cholesterol, but not triglyceride, concentrations were significantly associated with COVID-19 severity and mortality. Cholesterol concentrations might be useful, in combination with other clinical and demographic variables, for risk stratification and monitoring in this group. Systematic Review Registration: PROSPERO registration number: CRD42021253401.

INR and COVID-19 severity and mortality: A systematic review with meta-analysis and meta-regression.

OBJECTIVES: D-dimer elevations, suggesting a pro-thrombotic state and coagulopathy, predict adverse outcomes in coronavirus disease 2019 (COVID-19). However, the clinical significance of other coagulation markers, particularly the international normalized ratio (INR), is not well established. We conducted a systematic review and meta-analysis of the INR in COVID-19. METHODS: A literature search was conducted in PubMed, Web of Science and Scopus, between January 2020 and February 2021, for studies reporting INR values, measures of COVID-19 severity, and mortality (PROSPERO registration number: CRD42021241468). RESULTS: Thirty-eight studies in 7440 COVID-19 patients with low disease severity or survivor status during follow up (50 â€‹% males, mean age 57 years) and 2331 with high severity or non-survivor status (60 â€‹% males, mean age 69 years) were identified. The INR was significantly prolonged in patients with severe disease or non-survivor status than in patients with mild disease or survivor status (standard mean difference, SMD, 0.60; 95 â€‹% confidence interval, CI 0.42 to 0.77; p â€‹< â€‹0.001). There was extreme between-study heterogeneity (I2 â€‹= â€‹90.2 â€‹%; p â€‹< â€‹0.001). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and direction of the effect size was not modified. The Begg's and Egger's t-tests did not show publication bias. In meta-regression, the SMD of the INR was significantly associated with C-reactive protein (p â€‹= â€‹0.048) and D-dimer (p â€‹= â€‹0.001). CONCLUSIONS: Prolonged INR values were significantly associated with COVID-19 severity and mortality. Both INR prolongation and D-dimer elevations can be useful in diagnosing COVID-19-associated coagulopathy and predicting clinical outcomes.

B-Type Natriuretic Peptide Concentrations, COVID-19 Severity, and Mortality: A Systematic Review and Meta-Analysis With Meta-Regression.

Alterations in cardiac biomarkers have been reported in patients with coronavirus disease 2019 (COVID-19) in relation to disease severity and mortality. We conducted a systematic review and meta-analysis with meta-regression of studies reporting B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) plasma concentrations in COVID-19. We searched PubMed, Web of Science, and Scopus, between January 2020 and 2021, for studies reporting BNP/NT-proBNP concentrations, measures of COVID-19 severity, and survival status (PROSPERO registration number: CRD42021239190). Forty-four studies in 18,856 COVID-19 patients were included in the meta-analysis and meta-regression. In pooled results, BNP/NT-proBNP concentrations were significantly higher in patients with high severity or non-survivor status when compared to patients with low severity or survivor status during follow up (SMD = 1.07, 95% CI: 0.89-1.24, and p < 0.001). We observed extreme between-study heterogeneity (I 2 = 93.9%, p < 0.001). In sensitivity analysis, the magnitude and the direction of the effect size were not substantially modified after sequentially removing individual studies and re-assessing the pooled estimates, (effect size range, 0.99 - 1.10). No publication bias was observed with the Begg's (p = 0.26) and Egger's (p = 0.40) t-tests. In meta-regression analysis, the SMD was significantly and positively associated with D-dimer (t = 2.22, p = 0.03), myoglobin (t = 2.40, p = 0.04), LDH (t = 2.38, p = 0.02), and procalcitonin (t = 2.56, p = 0.01) concentrations. Therefore, higher BNP/NT-proBNP plasma concentrations were significantly associated with severe disease and mortality in COVID-19 patients.

Serum amyloid A concentrations, COVID-19 severity and mortality: An updated systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: An excessive inflammatory response in patients with coronavirus disease 2019 (COVID-19) is associated with high disease severity and mortality. Specific acute phase reactants might be useful for risk stratification. A systematic review and meta-analysis was conducted of studies on serum amyloid A (SAA) in patients with COVID-19. METHODS: The PubMed, Web of Science, and Scopus databases were searched, covering the period January 2020 to December 2020, for studies reporting SAA concentrations, COVID-19 severity, and survival status. RESULTS: Nineteen studies involving 5617 COVID-19 patients were included in the meta-analysis. Pooled results showed that SAA concentrations were significantly higher in patients with severe disease and non-survivors (standard mean difference (SMD) 1.20, 95% confidence interval 0.91-1.49, P < 0.001). Extreme between-study heterogeneity was observed (I2 = 92.4%, P < 0.001). In the sensitivity analysis, the effect size was not significantly affected when each study was removed in turn (range 1.10-1.29). The Begg test (P = 0.030), but not the Egger test (P = 0.385), revealed the presence of publication bias. Pooled SMD values were significantly and positively associated with sex (t = 2.20, P = 0.047) and aspartate aminotransferase (t = 3.44, P = 0.014). CONCLUSIONS: SAA concentrations were significantly and positively associated with higher COVID-19 severity and mortality. This acute phase reactant might assist with risk stratification and monitoring in this group.

Serum albumin concentrations are associated with disease severity and outcomes in coronavirus 19 disease (COVID-19): a systematic review and meta-analysis.

Coronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the most threatening pandemic in modern history. The aim of this systematic review and meta-analysis was to investigate the associations between serum albumin concentrations and COVID-19 disease severity and adverse outcomes. A systematic literature search was conducted in PubMed, from inception to October 30, 2020. Sixty-seven studies in 19,760 COVID-19 patients (6141 with severe disease or poor outcome) were selected for analysis. Pooled results showed that serum albumin concentrations were significantly lower in patients with severe disease or poor outcome (standard mean difference, SMD: - 0.99 g/L; 95% CI, - 1.11 to - 0.88, p < 0.001). In multivariate meta-regression analysis, age (t = - 2.13, p = 0.043), publication geographic area (t = 2.16, p = 0.040), white blood cell count (t = - 2.77, p = 0.008) and C-reactive protein (t = - 2.43, p = 0.019) were significant contributors of between-study variance. Therefore, lower serum albumin concentrations are significantly associated with disease severity and adverse outcomes in COVID-19 patients. The assessment of serum albumin concentrations might assist with early risk stratification and selection of appropriate care pathways in this group.

The Systemic Inflammation Index on Admission Predicts In-Hospital Mortality in COVID-19 Patients.

BACKGROUND: The rapid onset of a systemic pro-inflammatory state followed by acute respiratory distress syndrome is the leading cause of mortality in patients with COVID-19. We performed a retrospective observational study to explore the capacity of different complete blood cell count (CBC)-derived inflammation indexes to predict in-hospital mortality in this group. METHODS: The neutrophil to lymphocyte ratio (NLR), derived NLR (dNLR), platelet to lymphocyte ratio (PLR), mean platelet volume to platelet ratio (MPR), neutrophil to lymphocyte × platelet ratio (NLPR), monocyte to lymphocyte ratio (MLR), systemic inflammation response index (SIRI), systemic inflammation index (SII), and the aggregate index of systemic inflammation (AISI) were calculated on hospital admission in 119 patients with laboratory confirmed COVID-19. RESULTS: Non-survivors had significantly higher AISI, dNLR, NLPR, NLR, SII, and SIRI values when compared to survivors. Similarly, Kaplan-Meier survival curves showed significantly lower survival in patients with higher AISI, dNLR, MLR, NLPR, NLR, SII, and SIRI. However, after adjusting for confounders, only the SII remained significantly associated with survival (HR = 1.0001; 95% CI, 1.0000-1.0001, p = 0.029) in multivariate Cox regression analysis. CONCLUSIONS: The SII on admission independently predicts in-hospital mortality in COVID-19 patients and may assist with early risk stratification in this group.

The De Ritis ratio as prognostic biomarker of in-hospital mortality in COVID-19 patients.

Increased concentrations of serum aspartate transaminase (AST) and alanine transaminase (ALT) are common in COVID-19 patients. However, their capacity to predict mortality, particularly the AST/ALT ratio, commonly referred to as the De Ritis ratio, is unknown. We investigated the association between the De Ritis ratio on admission and in-hospital mortality in 105 consecutive patients with coronavirus disease of 2019 (COVID-19) admitted to three COVID-19 referral centres in Sardinia, Italy. The De Ritis ratio was significantly lower in survivors than nonsurvivors (median: 1.25; IQR: 0.91-1.64 vs 1.67; IQR: 1.38-1.97, P = .002) whilst there were no significant between-group differences in ALT and AST concentrations. In ROC curve analysis, the AUC value of the De Ritis ratio was 0.701 (95% CI 0.603-0.787, P = .0006) with sensitivity and specificity of 74% and 70%, respectively. Kaplan-Meier survival curves showed a significant association between the De Ritis ratio and mortality (logrank test P = .014). By contrast, no associations were observed between the ALT and AST concentrations and mortality (logrank test P = .83 and P = .62, respectively). In multivariate Cox regression analysis, the HR in patients with De Ritis ratios ≥1.63 (upper tertile of this parameter) remained significant after adjusting for age, gender, smoking status, cardiovascular disease, intensity of care, diabetes, respiratory diseases, malignancies and kidney disease (HR: 2.46, 95% CI 1.05-5.73, P = .037). Therefore, the De Ritis ratio on admission was significantly associated with in-hospital mortality in COVID-19 patients. Larger studies are required to confirm the capacity of this parameter to independently predict mortality in this group.

Laboratory test alterations in patients with COVID-19 and non COVID-19 interstitial pneumonia: a preliminary report.

INTRODUCTION: Coronavirus disease 19 (COVID-19) is the greatest pandemic in modern history. Laboratory test alterations have been described in COVID-19 patients, but differences with other pneumonias have been poorly investigated to date, especially in Caucasian populations. The aim of this study was to investigate differences and prognostic potential of routine blood tests in a series of Italian patients with COVID-19 and non-COVID-19 interstitial pneumonia. METHODOLOGY: Clinical data and routine laboratory tests of a consecutive series of 30 COVID-19 patients and 30 age and sex matched patients with non COVID-19 interstitial pneumonia have been retrospectively collected. Differences in laboratory tests between patients with COVID-19 and non COVID-19 pneumonias have been investigated, as well as differences between COVID-19 survivors and non survivors. RESULTS: COVID-19 patients had lower white blood cells, monocytes, neutrophils, and higher platelet counts. In addition, COVID-19 patients showed higher mean platelet volume, lower C reactive protein concentrations, and higher De Ritis ratio. Combined blood cell indexes of systemic inflammation were significantly lower in COVID-19 patients. In further analysis of the COVID-19 group, the neutrophil count, neutrophil to lymphocyte ratio (NLR), derived NLR, systemic inflammation response index and De Ritis ratio, were significantly higher in non survivors than in survivors, while the number of platelets was significantly lower in non survivors. CONCLUSIONS: Our study showed several alterations in blood cell populations and indexes in patients with COVID-19 pneumonia in comparison with patients with non COVID-19 pneumonia. Some of these indexes showed promising prognostic abilities. Further studies are necessary to confirm these results.