Applicability of lung ultrasound in the assessment of COVID-19 pneumonia: Diagnostic accuracy and clinical correlations

BackgroundThe purpose of this study was to assess the diagnostic accuracy of lung ultrasound (LUS) in determining the severity of coronavirus disease 2019 (COVID-19) pneumonia compared with thoracic computed tomography (CT) and establish the correlations between LUS score, inflammatory markers, and percutaneous oxygen saturation (SpO₂).MethodsThis prospective observational study, conducted at Târgu-Mureș Pulmonology Clinic included 78 patients with confirmed severe acute respiratory syndrome coronavirus-2 infection via nasopharyngeal real-time-polymerase chain reaction (RT-PCR) (30 were excluded). Enrolled patients underwent CT, LUS, and blood tests on admission. Lung involvement was evaluated in 16 thoracic areas, using AB₁ B₂ C (letters represent LUS pattern) scores ranging 0–48.ResultsLUS revealed bilateral B-lines (97.8%), pleural irregularities with thickening/discontinuity (75%), and subpleural consolidations (70.8%). Uncommon sonographic patterns were alveolar consolidations with bronchogram (33%) and pleural effusion (2%). LUS score cutoff values of ≤14 and > 22 predicted mild COVID-19 (sensitivity [Se] = 84.6%; area under the curve [AUC] = 0.72; P = 0.002) and severe COVID-19 (Se = 50%, specificity (Sp) = 91.2%, AUC = 0.69; P = 0.02), respectively, and values > 29 predicted the patients’ transfer to the intensive care unit (Se = 80%, Sp = 97.7%). LUS score positively correlated with CT score (r = 0.41; P = 0.003) and increased with the decrease of SpO₂ (r = −0.49; P = 0.003), with lymphocytes decline (r = −0.52; P = 0.0001). Patients with consolidation patterns had higher ferritin and C-reactive protein than those with B-line patterns (P = 0.01; P = 0.03).ConclusionsLUS is a useful, non-invasive and effective tool for diagnosis, monitoring evolution, and prognostic stratification of COVID-19 patients.     

Diagnostic prediction of COVID-19 based on clinical and radiological findings in a relatively low COVID-19 prevalence area

BackgroundDistinguishing coronavirus disease 2019 (COVID-19) pneumonia from other lung diseases is often difficult, especially in a highly comorbid patient population in a low prevalence region. We aimed to distinguish clinical data and computed tomography (CT) images between COVID-19 and other lung diseases in an advanced care hospital.MethodsWe assessed clinical characteristics, laboratory data, and chest CT images of patients with COVID-19 and non-COVID-19 patients who were suspected of having COVID-19 between February 20 and May 21, 2020, at the University of Tokyo Hospital.ResultsTypical appearance for COVID-19 on CT images were found in 24 of 29 COVID-19 cases and 21 of 168 non-COVID-19 cases, according to the Radiological Society of North America Expert Consensus Statement (for predicting COVID-19, sensitivity 0.828, specificity 0.875, positive predictive value 0.533, negative predictive value 0.967). When we focused on cases with typical CT images, loss of taste or smell, and close contact with COVID-19 patients were exclusive characteristics for the COVID-19 cases. Among laboratory data, high fibrinogen (P < 0.01) and low white blood cell count (P < 0.01) were good predictors for COVID-19 with typical CT images in multivariate analysis.ConclusionsIn a relatively low prevalence region, CT screening has high sensitivity to COVID-19 in patients with suspected symptoms. When chest CT findings are typical for COVID-19, close contact, loss of taste or smell, lower white blood cell count, and higher fibrinogen are good predictors for COVID-19.     

SFTPB (rs11130866) and NR3C1 (rs41423247) gene variants as potential clinical biomarkers for personalized treatment strategy selection in patients with severe COVID-19 pneumonia

BackgroundExploring the pathogenetic mechanisms behind severe lung damage in COVID-19 is crucial. In this study, we decided to focus on two molecular markers that affect surfactant metabolism and lung development: the surfactant protein B (SFTPB) and the glucocorticoid receptor (NR3C1) genes. The aim of our study was to determine the effect of SFTPB (rs11130866) and NR3C1 (rs41423247) gene variants on the course of the disease in patients with COVID-19, and the treatment measures they required.MethodsThe study group included 58 patients with a diagnosis of severe “viral COVID-19 pneumonia.” Determination of SFTPB and NR3C1 gene variants was performed using the PCR-RFLP method.ResultsOur results indicate that the presence of the SFTPB gene CC genotype increases the risk of developing acute respiratory distress syndrome in patients with COVID-19 (χ² = 4.03, p = 0.045, OR = 3.90 [1.19–12.78]). However, patients with the SFTPB gene TT genotype required respiratory support for a shorter period of time. Patients with the NR3C1 gene CC genotype underwent a longer glucocorticoid therapy. Moreover, for patients with the CC genotype, a longer stay in the intensive care unit was detected before lethal outcome.ConclusionsThe obtained results confirm the influence of the SFTPB (rs11130866) and NR3C1 (rs41423247) gene variants on the therapy, course, and severity of the disease in patients with COVID-19. Of course, these results require further study, analysis, and larger, complex, systematic research.     

Comparison of COVID-19 pneumonia during the SARS-CoV-2 Omicron wave and the previous non-Omicron wave in a single facility

BackgroundThe characteristics of coronavirus disease 2019 (COVID-19) pneumonia caused by the severe acute respiratory syndrome coronavirus 2 Omicron variant have not been fully described. Unlike other variants, the Omicron variant replicates rapidly in the bronchus. Therefore, we hypothesized that it would have different computed tomography (CT) findings from non-Omicron variants.MethodsWe enrolled patients with COVID-19 who visited our hospital and underwent chest CT during the first month of the Omicron wave (January 2022; N = 231) and the previous non-Omicron wave (July 2021; N = 87). We retrospectively evaluated the differences in the prevalence rate and CT characteristics of COVID-19 pneumonia between the two waves.ResultsThe prevalence of pneumonia was significantly lower in the Omicron wave group (79/231, 34.2%) compared to the previous wave group (67/87, 77.0%) (P < 0.001). For the predominant distribution pattern of pneumonia, the Omicron wave group revealed a significantly lower rate of the peripheral pattern and a higher rate of the random pattern than the previous wave group. In addition, the Omicron wave group had a significantly lower rate of consolidation than the previous wave group. The ground-glass opacities (GGOs) rate was similar between the two wave groups. For GGOs patterns, cluster-like GGOs along the bronchi on chest CT were more frequently observed during the Omicron wave than during the previous wave.ConclusionThe Omicron wave group had a lower COVID-19 pneumonia prevalence than the previous wave group. Cluster-like GGOs should be noted as a characteristic CT finding of pneumonia during the Omicron wave.     

Patient-centered outcomes at hospital discharge in mechanically ventilated COVID-19 patients in Kobe,Japan: A single-center retrospective cohort study

BackgroundApart from saving the lives of coronavirus disease (COVID-19) patients on mechanical ventilation (MV), recovery from the sequelae of prolonged MV (PMV) is an emerging issue.cMethodsWe conducted a retrospective study among consecutive adult COVID-19 patients admitted to an intensive care unit (ICU) in Kobe, Japan, between March 3, 2020, and January 31, 2021, and received invasive MV. Clinical outcomes included in-hospital mortality and recovery from COVID-19 in survivors regarding organ dysfunction, respiratory symptoms, and functional status at discharge. We compared survivors’ outcomes with MV durations of >14 days and ≤14 days.ResultsWe included 85 patients with a median age of 69 years (interquartile range, 64–75 years); 76 (89%) patients had at least 1 comorbidity, 72 (85%) were non-frail, and 79 (93%) were functionally independent before COVID-19 infection. Eighteen patients (21%) died during hospitalization. At discharge, 59/67 survivors (88%) no longer required respiratory support, 50 (75%) complained of dyspnea, and 40 (60%) were functionally independent. Of the survivors, 23 patients receiving MV for >14 days had a worse recovery from COVID-19 at discharge compared with those on MV for ≤14 days, as observed using the Barthel index (median: 35 [5–65] vs. 100 [85–100]), ICU mobility scale (8 [5–9] vs. 10 [10-10]), and functional oral intake scale (3 [1–7] vs. 7 [7-7]) (P < 0.0001).ConclusionAlthough four-fifths of the patients survived and >50% of survivors demonstrated clinically important recovery in organ function and functional status during hospitalization, PMV was related to poor recovery from COVID-19 at discharge.     

Serum gasdermin D levels are associated with the chest computed tomography findings and severity of COVID-19

BackgroundThe role of programmed cell death, especially pyroptosis and apoptosis, in unfavorable immune responses in COVID-19 remains to be elucidated.MethodsWe conducted a cross-sectional analysis to investigate the association between the serum gasdermin D (GSDMD) levels, a pyroptotic marker, and caspase-cleaved cytokeratin 18 fragment (M30), an apoptotic marker, and the clinical status and abnormal chest computed tomography (CT) findings in patients with COVID-19.ResultsIn this study, 46 patients diagnosed with COVID-19 were divided into the following three groups according to the disease severity: mild to moderate group (n = 10), severe group (n = 14), and critical group (n = 22). The serum GSDMD levels were higher in the critical group than in the mild to moderate group (P = 0.016). In contrast, serum M30 levels were lower in the critical group than in the severe group (P = 0.048). Patients who required mechanical ventilation or died had higher serum GSDMD levels than those who did not (P = 0.007). Area of consolidation only and of ground glass opacity plus consolidation positively correlated with serum GSDMD levels (r = 0.56, P < 0.001 and r = 0.53, P < 0.001, respectively).ConclusionHigher serum GSDMD levels are associated with critical respiratory status and the consolidation area on chest CT in patients with COVID-19, suggesting that excessive activation of pyroptosis may affect the clinical manifestations in patients with COVID-19.     

Myocardial Injury on CMR in Patients With COVID-19 and Suspected Cardiac Involvement

BackgroundMyocardial injury in patients with COVID-19 and suspected cardiac involvement is not well understood.ObjectivesThe purpose of this study was to characterize myocardial injury in a multicenter cohort of patients with COVID-19 and suspected cardiac involvement referred for cardiac magnetic resonance (CMR).MethodsThis retrospective study consisted of 1,047 patients from 18 international sites with polymerase chain reaction–confirmed COVID-19 infection who underwent CMR. Myocardial injury was characterized as acute myocarditis, nonacute/nonischemic, acute ischemic, and nonacute/ischemic patterns on CMR.ResultsIn this cohort, 20.9% of patients had nonischemic injury patterns (acute myocarditis: 7.9%; nonacute/nonischemic: 13.0%), and 6.7% of patients had ischemic injury patterns (acute ischemic: 1.9%; nonacute/ischemic: 4.8%). In a univariate analysis, variables associated with acute myocarditis patterns included chest discomfort (OR: 2.00; 95% CI: 1.17-3.40, P = 0.01), abnormal electrocardiogram (ECG) (OR: 1.90; 95% CI: 1.12-3.23; P = 0.02), natriuretic peptide elevation (OR: 2.99; 95% CI: 1.60-5.58; P = 0.0006), and troponin elevation (OR: 4.21; 95% CI: 2.41-7.36; P < 0.0001). Variables associated with acute ischemic patterns included chest discomfort (OR: 3.14; 95% CI: 1.04-9.49; P = 0.04), abnormal ECG (OR: 4.06; 95% CI: 1.10-14.92; P = 0.04), known coronary disease (OR: 33.30; 95% CI: 4.04-274.53; P = 0.001), hospitalization (OR: 4.98; 95% CI: 1.55-16.05; P = 0.007), natriuretic peptide elevation (OR: 4.19; 95% CI: 1.30-13.51; P = 0.02), and troponin elevation (OR: 25.27; 95% CI: 5.55-115.03; P < 0.0001). In a multivariate analysis, troponin elevation was strongly associated with acute myocarditis patterns (OR: 4.98; 95% CI: 1.76-14.05; P = 0.003).ConclusionsIn this multicenter study of patients with COVID-19 with clinical suspicion for cardiac involvement referred for CMR, nonischemic and ischemic patterns were frequent when cardiac symptoms, ECG abnormalities, and cardiac biomarker elevations were present.     

Glycemic control metrics using flash glucose monitoring and hospital complications in patients with COVID-19

Background and aimsFew studies have reported on the use of continuous glucose monitoring (CGM) during the Covid-19 pandemic. We aimed to examine glycemic control metrics using flash glucose monitoring during insulin treatment and the clinical outcome in hospitalized patients with COVID-19.MethodsProspective, single-center cohort of adult patients diagnosed with type 2 diabetes or hyperglycemia and COVID-19 infection treated with basal bolus insulin regimen. Glycemic control was assessed with the use of intermittent Freestyle Libre flash glucose monitoring during the hospital stay. Outcome of interest were time in range [TIR], time above [TAR] and below [TBR] range, glycemic variability [coefficient of variation [% CV]), and differences in a composite of complications including ICU admission, acute respiratory distress syndrome (ARDS) and acute kidney injury.ResultsA total of 60 patients were included (44 known diabetes and 16 new onset hyperglycemia). In total 190,080 data points of CGM were available, of which 72.5% of values were within the target area [TIR (70–180 mg/dL)], 22% TAR (>180 mg/dL), and 3% were TBR (<70 mg/dL). During treatment, the coefficient of variation (% CV) was 30%. There were no association with TIR, but patients with TAR >180 mg/dl had higher rates of a composite of complications (22.5% vs 16%, p = 0.04).ConclusionsBasal bolus insulin regimen was safe and effective in achieving inpatient glycemic control in most patients with COVID-19. The association between TAR and complications indicates the need for improved inpatient glycemic control in hospitalized patients with COVID-19.     

Anti-Saccharomyces cerevisiae antibodies in patients with COVID-19

Background and study aimAnti-Saccharomyces cerevisiae antibodies (ASCA) have been described in many autoimmune diseases (AIDs). Coronavirus disease 2019 (COVID-19) could trigger AIDs. This study aimed to determine the frequency of ASCA in patients with COVID-19.Patients and methodsThis study included 88 adult patients with severe COVID-19, 51 mild COVID-19, and 160 healthy blood donors. ASCA of isotype immunoglobulin (Ig)G and IgA were detected by enzyme-linked immunosorbent assay.ResultsThe frequency of ASCA (IgG or IgA) was significantly higher in patients with severe COVID-19 (21.6 % vs 3.7 %, p < 10^?3) and in patients with mild COVID-19 than in the healthy controls (13.7 % vs 3.7 %, p = 0.03). ASCA-IgA was significantly more frequent in patients with severe COVID-19 than in healthy controls (15.9 % vs 0.6 %, p < 10^?3). ASCA-IgG was significantly more frequent in patients with mild COVID-19 than in healthy controls (13.7 % vs 3.1 %, p = 0.02). ASCA (IgG or IgA) were more frequent in severe than in mild COVID-19, but the difference was not statistically significant (21.6 % vs 13.7 %). ASCA-IgA was significantly more frequent in patients with severe than those with mild COVID-19 (15.9 % vs 0 %, p = 0.003). The mean ASCA-IgG and ASCA-IgA levels were significantly higher in patients with severe COVID-19 than in healthy controls (5.8 U/mL ± 11.8 vs 2.3 U/mL ± 2.8, p < 10^?3 and 9.2 U/mL ± 21.5 vs 3.4 U/mL ± 1.7, respectively, p < 10^?3). The mean ASCA-IgG levels were significantly higher in patients with mild COVID-19 than in healthy controls (6.2 U/mL ± 12.9 vs 2.3 U/mL ± 2.8, p < 10^?3). The mean ASCA-IgA levels were significantly higher in patients with severe than in those with mild COVID-19 (9.2 U/mL ± 21.5 vs 2.6 U/mL ± 1.2, p = 0.03).ConclusionASCA was more frequent in patients with COVID-19 than in healthy controls.     

Factores de riesgo de muerte hospitalaria en pacientes con infarto agudo de miocardio durante la pandemia de la COVID-19

Introduction and objectivesDespite advances in treatment, patients with acute myocardial infarction (AMI) still exhibit unfavorable short- and long-term prognoses. In addition, there is scant evidence about the clinical outcomes of patients with AMI and coronavirus disease 2019 (COVID-19). The objective of this study was to describe the clinical presentation, complications, and risk factors for mortality in patients admitted for AMI during the COVID-19 pandemic.MethodsThis prospective, multicenter, cohort study included all consecutive patients with AMI who underwent coronary angiography in a 30-day period corresponding chronologically with the COVID-19 outbreak (March 15 to April 15, 2020). Clinical presentations and outcomes were compared between COVID-19 and non-COVID-19 patients. The effect of COVID-19 on mortality was assessed by propensity score matching and with a multivariate logistic regression model.ResultsIn total, 187 patients were admitted for AMI, 111 with ST-segment elevation AMI and 76 with non-ST-segment elevation AMI. Of these, 32 (17%) were diagnosed with COVID-19. GRACE score, Killip-Kimball classification, and several inflammatory markers were significantly higher in COVID-19-positive patients. Total and cardiovascular mortality were also significantly higher in COVID-19-positive patients (25% vs 3.8% [P < .001] and 15.2% vs 1.8% [P = .001], respectively). GRACE score > 140 (OR, 23.45; 95%CI, 2.52–62.51; P = .005) and COVID-19 (OR, 6.61; 95%CI, 1.82-24.43; P = .02) were independent predictors of in-hospital death.ConclusionsDuring this pandemic, a high GRACE score and COVID-19 were independent risk factors associated with higher in-hospital mortality.Full English text available from:www.revespcardiol.org/en     

Impacto de los inhibidores de la enzima de conversión de la angiotensina y los antagonistas del receptor de la angiotensina II en la COVID-19 en una población occidental. Registro CARDIOVID

Introduction and objectivesCoronavirus disease (COVID-19) has been designated a global pandemic by the World Health Organization. It is unclear whether previous treatment with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) affects the prognosis of COVID-19 patients. The aim of this study was to evaluate the clinical implications of previous treatment with ACEI/ARB on the prognosis of patients with COVID-19 infection.MethodsSingle-center, retrospective, observational cohort study based on all the inhabitants of our health area. Analyses of main outcomes (mortality, heart failure, hospitalization, intensive care unit [ICU] admission, and major acute cardiovascular events [a composite of mortality and heart failure]) were adjusted by multivariate logistic regression and propensity score matching models.ResultsOf the total population, 447 979 inhabitants, 965 patients (0.22%) were diagnosed with COVID-19 infection, and 210 (21.8%) were under ACEI or ARB treatment at the time of diagnosis. Treatment with ACEI/ARB (combined and individually) had no effect on mortality (OR, 0.62; 95%CI, 0.17-2.26; P = .486), heart failure (OR, 1.37; 95%CI, 0.39-4.77; P = .622), hospitalization rate (OR, 0.85; 95%CI, 0.45-1.64; P = .638), ICU admission (OR, 0.87; 95%CI, 0.30-2.50; P = .798), or major acute cardiovascular events (OR, 1.06; 95%CI, 0.39-2.83; P = .915). This neutral effect remained in a subgroup analysis of patients requiring hospitalization.ConclusionsPrevious treatment with ACEI/ARB in patients with COVID-19 had no effect on mortality, heart failure, requirement for hospitalization, or ICU admission. Withdrawal of ACEI/ARB in patients testing positive for COVID-19 would not be justified, in line with current recommendations of scientific societies and government agencies.     

A systematic review and meta-analysis comparing the clinical characteristics and outcomes of COVID-19 and influenza patients on ECMO

BackgroundExtracorporeal membrane oxygenation (ECMO) is a valuable rescue therapy to treat refractory hypoxemia caused by influenza. The present meta-analysis aimed to compare the clinical characteristics and outcomes of ECMO between COVID-19 and influenza.MethodsWe searched the PubMed, Cochrane Library, SCOPUS, and Web of Science databases from inception to May 1, 2021. The included studies compared the clinical characteristics and outcomes of ECMO between adults with COVID-19 and those with influenza.ResultsThe study included four retrospective cohorts involving a total of 129 patients with COVID-19 and 140 with influenza who were treated using ECMO. Clinical characteristics were similar between the COVID-19 and influenza groups, including body mass index (BMI), diabetes mellitus, hypertension, and immunocompromised status. A higher proportion of patients with COVID-19 on ECMO were male (75.9% vs. 62.9%; P = 0.04). There was no difference between the groups in terms of illness severity based on sequential organ failure assessment (SOFA) score or serum pH. Patients with COVID-19 had a longer mean duration of mechanical ventilation before ECMO (6.63 vs. 3.38 days; P < 0.01). The pooled mortality rate was 43.8%. The mean ECMO duration (14.13 vs. 12.55 days; P = 0.25) and mortality rate (42.6% vs. 45.0%; P = 0.99) were comparable between the groups.ConclusionClinical characteristics, ECMO duration, and mortality were comparable between patients with COVID-19 and those with influenza who required ECMO to treat refractory hypoxemia. The duration of mechanical ventilation before ECMO did not influence outcomes. Patients with COVID-19 benefit from ECMO salvage therapy similarly to those with influenza.     

The association of metabolic syndrome and COVID-19 deterioration

Background and aimsTo evaluate the prevalence and prognostic value of metabolic syndrome (MetS) in patients admitted for coronavirus disease 2019 (COVID-19).Methods and resultsIn this monocentric cohort retrospective study, we consecutively included all adult patients admitted to COVID-19 units between April 9 and May 29, 2020 and between February 1 and March 26, 2021. MetS was defined when at least three of the following components were met: android obesity, high HbA1c, hypertension, hypertriglyceridemia, and low HDL cholesterol. COVID-19 deterioration was defined as the need for nasal oxygen flow ≥6 L/min within 28 days after admission.We included 155 patients (55.5% men, mean age 61.7 years old, mean body mass index 29.8 kg/m²). Fifty-six patients (36.1%) had COVID-19 deterioration. MetS was present in 126 patients (81.3%) and was associated with COVID-19 deterioration (no-MetS vs MetS: 13.7% and 41.2%, respectively, p < 0.01). Logistic regression taking into account MetS, age, gender, ethnicity, period of inclusion, and Charlson Index showed that COVID-19 deterioration was 5.3 times more likely in MetS patients (95% confidence interval 1.3–20.2) than no-MetS patients.ConclusionsOver 81.3% of patients hospitalized in COVID-19 units had MetS. This syndrome appears to be an independent risk factor of COVID-19 deterioration.     

Serum KL-6 level is a useful biomarker for evaluating the severity of coronavirus disease 2019

BackgroundCoronavirus disease 2019 (COVID-19) is currently spreading worldwide. This study examined whether serum Krebs von den Lungen-6 (KL-6) level is a useful biomarker for evaluating the severity of COVID-19.MethodsWe retrospectively examined patients diagnosed with COVID-19 at the Japanese Red Cross Medical Center between February 1, 2020, and May 15, 2020. Patients were divided into four categories based on clinical and radiological findings: mild, moderate, severe, and critical. Patients who presented with a mild or moderate illness and patients who started with or worsened to a severe or critical illness were classified as the non-severe and severe groups, respectively. The two groups were compared for patient characteristics, including serum KL-6 levels. Receiver operating characteristic curves were used to define the optimum cut-off value of serum KL-6 level to evaluate COVID-19 severity.ResultsA total of 54 patients were enrolled, including 33 in the non-severe group and 21 in the severe group, of which four died. Compared with those in the non-severe group, more patients in the severe group were significantly older and had comorbidities. Serum KL-6 levels were significantly higher in the severe group than in the non-severe group both at diagnosis (median, 338 U/mL) and at peak levels within one week after diagnosis (median, 781 U/mL) (both p < 0.001). Serum KL-6 value at peak level (371 U/mL) was used as the optimal cut-off to evaluate disease severity (sensitivity, 85.7%; specificity, 96.6%).ConclusionsSerum KL-6 levels were significantly elevated in severe COVID-19 and is useful for evaluating its severity.     

Clinical impact of combination therapy with baricitinib,remdesivir, and dexamethasone in patients with severe COVID-19

BackgroundCoronavirus disease 2019 (COVID-19) has spread worldwide and is also an important disease in Japan. Thus, the optimal treatment strategy for severe COVID-19 should be established urgently. The effects of combination treatment with baricitinib—a Janus kinase inhibitor, remdesivir, and dexamethasone (BRD) are unknown.MethodsPatients who received combination therapy with BRD at the Japanese Red Cross Medical Center were enrolled in the study. All patients received baricitinib (≤14 d), remdesivir (≤10 d), and dexamethasone (≤10 d). The efficacy and adverse events were evaluated.ResultsIn total, 44 patients with severe COVID-19 were enrolled in this study. The 28-d mortality rate was low at 2.3% (1/44 patients). The need for invasive mechanical ventilation was avoided in most patients (90%, 17/19 patients). Patients who received BRD therapy had a median hospitalization duration of 11 d, time to recovery of 9 d, duration of intensive care unit stay of 6 d, duration of invasive mechanical ventilation of 5 d, and duration of supplemental oxygen therapy of 5 d. Adverse events occurred in 15 patients (34%). Liver dysfunction, thrombosis, iliopsoas hematoma, renal dysfunction, ventilator-associated pneumonia, infective endocarditis, and herpes zoster occurred in 11%, 11%, 2%, 2%, 2%, 2%, and 2% of patients, respectively.ConclusionsCombination therapy with BRD was effective in treating severe COVID-19, and the incidence rate of adverse events was low. The results of the present study are encouraging; however, further randomized clinical studies are needed.     

Comparison of clinical characteristics and outcomes of COVID-19 patients undergoing early versus late intubation from initial hospital admission: A systematic review and meta-analysis

BackgroundThe true impact of intubation and mechanical ventilation in coronavirus disease 2019 (COVID-19) patients remains controversial.MethodsWe searched Pubmed, Cochrane Library, Embase, and Web of Science databases from inception to October 30th, 2021 for studies containing comparative data of COVID-19 patients undergoing early versus late intubation from initial hospital admission. Early intubation was defined as intubation within 48 h of hospital admission. The primary outcomes assessed were all-cause in-hospital mortality, renal replacement therapy (RRT), and invasive mechanical ventilation (IMV) duration.ResultsFour cohort studies with 498 COVID-19 patients were included between February to August 2020, in which 28.6% had early intubation, and 36.0% underwent late intubation. Although the pooled hospital mortality rate was 32.1%, no significant difference in mortality rate was observed (odds ratio [OR] 0.81; 95% confidence interval 0.32–2.00; P = 0.64) among those undergoing early and late intubation. IMV duration (mean 9.62 vs. 11.77 days; P = 0.25) and RRT requirement (18.3% vs. 14.6%; OR 1.19; P = 0.59) were similar regardless of intubation timing. While age, sex, diabetes, and body mass index were comparable, patients undergoing early intubation had higher sequential organ failure assessment (SOFA) scores (mean 7.00 vs. 5.17; P < 0.001).ConclusionsThe timing of intubation from initial hospital admission did not significantly alter clinical outcomes during the early phase of the COVID-19 pandemic. Higher SOFA scores could explain early intubation. With the advancements in COVID-19 therapies, more research is required to determine optimal intubation time beyond the first wave of the pandemic.     

Mean platelet volume modifies the contribution of homocysteine to cardiovascular disease: A real-world study

Background and aimsThe effect of reductions in homocysteine (Hcy) on cardiovascular disease (CVD) was suggested to be modified by platelet activation, but the interaction between Hcy and platelet activation on CVD events is not well studied. Here, we aimed to examine the interaction between Hcy and platelet activation on CVD in a large, real-world population.Methods and resultsA total of 27,234 patients with hypertension (mean 63 years, 48% male) who were registered in Taicang city and free of CVD were prospectively followed up for new CVD events from 2017 to 2020. Hcy and platelet indices including mean platelet volume (MPV) were assayed at baseline. A total of 1063 CVD events were recorded during follow-up. Hcy at baseline was significantly associated with a higher risk of CVD (HR = 1.85, P < 0.001 for log-transformed Hcy). MPV showed a significant interaction effect with Hcy on CVD (HR = 1.20, P = 0.030 for the interaction term). The association between Hcy and CVD was significantly stronger in participants with a large (vs. small) MPV (HR = 2.71 vs. 1.32, P = 0.029 for log-transformed Hcy). For participants with both elevated Hcy and a large MPV, the attributable proportion of CVD events due to their interaction was 0.26 (95% CI: 0.06–0.45).ConclusionsThe association between Hcy and CVD was significantly stronger in patients with hypertension with a larger MPV. MPV may modify the contribution of Hcy to CVD events through synergistic interactions with Hcy. These findings suggest that MPV could be monitored and controlled in the prevention of CVD.     

Platelet activation and coronavirus disease 2019 mortality: Insights from coagulopathy,antiplatelet therapy and inflammation

BackgroundCoronavirus disease 2019 (COVID-19) is associated with an inflammatory cytokine burst and a prothrombotic coagulopathy. Platelets may contribute to microthrombosis, and constitute a therapeutic target in COVID-19 therapy.AimTo assess if platelet activation influences mortality in COVID-19.MethodsWe explored two cohorts of patients with COVID-19. Cohort A included 208 ambulatory and hospitalized patients with varying clinical severities and non-COVID patients as controls, in whom plasma concentrations of the soluble platelet activation biomarkers CD40 ligand (sCD40L) and P-selectin (sP-sel) were quantified within the first 48 hours following hospitalization. Cohort B was a multicentre cohort of 2878 patients initially admitted to a medical ward. In both cohorts, the primary outcome was in-hospital mortality.ResultsIn cohort A, median circulating concentrations of sCD40L and sP-sel were only increased in the 89 critical patients compared with non-COVID controls: sP-sel 40,059 (interquartile range 26,876–54,678) pg/mL; sCD40L 1914 (interquartile range 1410–2367) pg/mL (P < 0.001 for both). A strong association existed between sP-sel concentration and in-hospital mortality (Kaplan-Meier log-rank P = 0.004). However, in a Cox model considering biomarkers of immunothrombosis, sP-sel was no longer associated with mortality, in contrast to coagulopathy evaluated with D-dimer concentration (hazard ratio 4.86, 95% confidence interval 1.64–12.50). Moreover, in cohort B, a Cox model adjusted for co-morbidities suggested that prehospitalization antiplatelet agents had no significant impact on in-hospital mortality (hazard ratio 1.05, 95% CI 0.80–1.37; P = 0.73).ConclusionsAlthough we observed an association between excessive biomarkers of platelet activation and in-hospital mortality, our findings rather suggest that coagulopathy is more central in driving disease progression, which may explain why prehospitalization antiplatelet drugs were not a protective factor against mortality in our multicentre cohort.     

Clinical characteristics of COVID-19 in Osaka,Japan: Comparison of the first–third waves with the fourth wave

BackgroundThe fourth wave of COVID-19 in Osaka Prefecture, Japan, caused a medical crisis. Here, we aim to identify the risk factors for COVID-19 severity and compare patients between the first–third waves and the fourth wave.MethodsWe performed an observational retrospective study of COVID-19 cases at the National Hospital Organization Kinki-Chuo Chest Medical Center.ResultsWe identified 404 patients (median age: 71.0 years [interquartile range: 56.0–80.0]), of whom 199 (49.1%) had mild disease, 142 (35.2%) had moderate disease, and 63 (15.6%) had severe disease. The overall mortality rate was 5.4% (22/404). Based on multivariate logistic regression analysis, cardiovascular disease, fever, dyspnea, and several inflammatory biomarkers were independent risk factors for moderate to severe disease. For every 1 mg/dL increase in C-reactive protein, 10 IU/L increase in lactate dehydrogenase, and 100 ng/mL increase in ferritin, the risk for moderate to severe disease increased by 18.3%, 12.9%, and 8.9%, respectively. Overall disease severity in the fourth wave was higher than in the first–third waves. However, there was no significant difference in mortality. Because of a shortage of beds, four of the 28 severe patients (14.3%) in the fourth wave could not be transferred to the advanced hospital.ConclusionsCardiovascular disease, fever, dyspnea, and several inflammatory biomarkers were risk factors for moderate to severe COVID-19 in our cohort. During the fourth wave, COVID-19 severity worsened, increasing the number of patients who could not be transferred to beds for severe cases, resulting in a medical crisis in Osaka.