Differential white blood cell count in the COVID-19: A cross-sectional study of 148 patients

BackgroundSARS-CoV-2 infection alters various blood parameters, which may indicate disease severity and thus help in better clinical management.AimTo study the association between various hematological parameters and disease severity of COVID-19. To analyze the effects of hypertension and diabetes on neutrophil-lymphocyte ratio and neutrophil-monocyte ratio in patients suffering from COVID-19.Materials and methodsThe study was a cross-sectional study involving 148 laboratory-confirmed cases of SARS-CoV-2 infection. The patients were divided into three groups on the basis of disease severity. Various hematological parameters were analyzed. The effects of hypertension and diabetes on NLR and NMR in COVID-19 patients were evaluated.ResultsOf the 148 patients, 78.4%, 8.1% and 13.5% cases were in the mild, moderate and severe groups, respectively. Mean age was 42.63 ± 16.04 years (IQR: 29, 54.75; Range: 7–74). 58.8% patients were male while the rest (42.2%) were female. Mean TLC (cells/mm³), neutrophil (%), lymphocyte (%), monocyte (%), eosinophil (%), neutrophil-lymphocyte ratio (NLR) and neutrophil-monocyte ratio (NMR) among mild, moderate and severe COVID-19 was statistically significant (p < 0.05). Basophil (%) and lymphocyte-monocyte ratio (LMR) was statistically insignificant among the three groups. Lymphocyte (%), monocyte (%) and eosinophil (%) were negatively correlated to disease severity. Among diabetics, both NLR and NMR were statistically significant (p < 0.05). However, among hypertensive cases, only the NLR was statistically significant.ConclusionOlder age, higher TLC, neutrophilia, lymphopenia, eosinopenia, high NLR and high NMR are associated with severe COVID-19. High NLR and high NMR are indicative of severe disease among diabetic patients. High NLR also indicates severe disease among hypertensive patients.     

Clinical characteristics of liver injury in SARS-CoV-2 Omicron variant- and Omicron subvariant-infected patients

Introduction and ObjectivesLiver injury in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant- and Omicron subvariant-infected patients is unknown at present, and the aim of this study is to summarize liver injury in these patients.Patients and MethodsIn this study, 460 SARS-CoV-2-infected patients were enrolled. Five severe or critical patients were excluded, and 34 patients were also excluded because liver injury was not considered to be related to SARS-CoV-2 infection. Liver injury was compared between Omicron and non-Omicron variants- and between Omicron subvariant-infected patients; additionally, the clinical data related to liver injury were also analyzed.ResultsAmong the 421 patients enrolled for analysis, liver injury was detected in 76 (18.1%) patients, including 46 Omicron and 30 non-Omicron variant-infected patients. The ratios did not differ between Omicron and non-Omicron variant-, Omicron BA.1, BA.2 and BA.5 subvariant-infected patients (P>0.05). The majority of abnormal parameters of liver function tests were mildly elevated (1-3 × ULN), the most frequently elevated parameter of liver function test was γ-glutamyl transpeptidase (GGT, 9.5%, 40/421), and patients with cholangiocyte or biliary duct injury markers were higher than with hepatocellular injury markers. Multivariate analysis showed that age (>40 years old, OR=1.898, 95% CI=1.058–3.402, P=0.032), sex (male gender, OR=2.031, 95% CI=1.211–3.408, P=0.007), serum amyloid A (SAA) level (>10 mg/ml, OR=3.595, 95% CI=1.840–7.026, P<0.001) and vaccination status (No, OR=2.131, 95% CI=1.089–4.173, P=0.027) were independent factors related to liver injury.ConclusionsLiver injury does not differ between Omicron and non-Omicron variants or between Omicron subvariant-infected patients. The elevations of cholangiocyte or biliary duct injury biomarkers are dominant in SARS-CoV-2-infected patients.     

Low-density lipoprotein cholesterol levels are associated with poor clinical outcomes in COVID-19

Background and aimsSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the sole causative agent of coronavirus infectious disease-19 (COVID-19).Methods and resultsWe performed a retrospective single-center study of consecutively admitted patients between March 1st and May 15th^, 2020, with a definitive diagnosis of SARS-CoV-2 infection. The primary end-point was to evaluate the association of lipid markers with 30-days all-cause mortality in COVID-19.A total of 654 patients were enrolled, with an estimated 30-day mortality of 22.8% (149 patients). Non-survivors had lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) levels during the entire course of the disease. Both showed a significant inverse correlation with inflammatory markers and a positive correlation with lymphocyte count. In a multivariate analysis, LDL-c ≤ 69 mg/dl (hazard ratio [HR] 1.94; 95% confidence interval [CI] 1.14–3.31), C-reactive protein >88 mg/dl (HR 2.44; 95% CI, 1.41–4.23) and lymphopenia <1000 (HR 2.68; 95% CI, 1.91–3.78) at admission were independently associated with 30-day mortality. This association was maintained 7 days after admission. Survivors presented with complete normalization of their lipid profiles on short-term follow-up.ConclusionHypolipidemia in SARS-CoV-2 infection may be secondary to an immune-inflammatory response, with complete recovery in survivors. Low LDL-c serum levels are independently associated with higher 30-day mortality in COVID-19 patients.     

Hypocalcemia is associated with severe COVID-19: A systematic review and meta-analysis

Background and aimsHypocalcemia is commonly in critically ill patients and studies have shown that hypocalcemia is prevalent in patients with COVID-19. This meta-analysis aimed to evaluate the prognostic performance of hypocalcemia in patients with coronavirus disease 2019 (COVID-19).MethodsWe performed a systematic literature search on PubMed, Scopus, and Embase with keywords “SARS-CoV-2″ OR″COVID-19″ OR ″2019-nCoV” AND “hypocalcemia” up until 10 December 2020. The key exposure was hypocalcemia, defined as serum calcium below study-defined cut-off points. The main outcome was poor outcome, which was a composite of mortality and severity. The effect estimate of the main outcome was reported as odds ratio (OR) and its 95% confidence interval (95% CI). We also generate sensitivity, specificity, positive and negative likelihood ratio (PLR & NLR), diagnostic odds ratio (DOR), and area under curve (AUC).ResultsThere are 2032 patients from 7 studies included in this systematic review and meta-analysis. The incidence of poor outcome in this study was 26%. Serum calcium was lower in patients with poor outcome (mean difference ?0.173 mmol/L [-0.259, ?0.087], p < 0.001; I²: 31.3%). Hypocalcemia was associated with poor outcome (OR 3.19 [2.02, 5.06], p < 0.001; I²: 32.86%); with sensitivity of 0.74 [0.53, 0.88], specificity of 0.54 [0.29, 0.77], PLR of 1.6 [1.1, 2.3], NLR of 0.49 [0.35, 0.66], DOR of 3 [2, 5], and AUC of 0.70 [0.66, 0.74]. In this pooled analysis, the post-test probability was 36% in patients with hypocalcemia and 15% in patients without hypocalcemia.ConclusionHypocalcemia was associated with poor outcome in COVID-19 patients.PROSPERO ID: CRD42020225506.     

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.     

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.     

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.     

Decrease in hemoglobin level predicts increased risk for severe respiratory failure in COVID-19 patients with pneumonia

BackgroundIn December 2019, the coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), emerged in Wuhan, China, and has since spread throughout the world. This study aimed to investigate the association between the change in laboratory markers during the three days after pneumonia diagnosis and severe respiratory failure in COVID-19 patients.MethodsData of 23 COVID-19 patients with pneumonia, admitted to the Kumamoto City Hospital between February and April 2020 were retrospectively analyzed.ResultsAmong the 23 patients, eight patients received mechanical ventilation (MV) (MV group), and the remaining 15 comprised the non-MV group. The levels of hemoglobin (Hb) and albumin (Alb) decreased in the MV group during the three days after pneumonia diagnosis more than in the non-MV group (median Hb: 1.40 vs. ?0.10 g/dL, P = 0.015; median Alb: 0.85 vs. ?0.30 g/dL, P = 0.020). Univariate logistic regression analysis showed that the decrease in Hb was associated with receiving MV care (odds ratio: 0.313, 95% confidence interval: 0.100–0.976, P = 0.045). Receiver operating characteristic curve analyses showed that the optimal cut-off value for the decrease in Hb level was ?1.25 g/dL, with sensitivity and specificity values of 0.867 and 0.750, respectively.ConclusionsThe decrease in Hb level during the short period after pneumonia diagnosis might be a predictor of worsening pneumonia in COVID-19 patients.     

A systematic review and meta-analysis of the COVID-19 associated liver injury

Introduction and ObjectivesThe novel coronavirus disease 2019 (COVID-19) has affected more than 5 million people globally. Data on the prevalence and degree of COVID-19 associated liver injury among patients with COVID-19 remain limited. We conducted a systematic review and meta-analysis to assess the prevalence and degree of liver injury between patients with severe and non-severe COVID-19.MethodsWe performed a systematic search of three electronic databases (PubMed/MEDLINE, EMBASE and Cochrane Library), from inception to 24^th April 2020. We included all adult human studies (>20 subjects) regardless of language, region or publication date or status. We assessed the pooled odds ratio (OR), mean difference (MD) and 95% confidence interval (95%CI) using the random-effects model.ResultsAmong 1543 citations, there were 24 studies (5961 subjects) which fulfilled our inclusion criteria. The pooled odds ratio for elevated ALT (OR = 2.5, 95%CI: 1.6-3.7, I² = 57%), AST (OR = 3.4, 95%CI: 2.3-5.0, I² = 56%), hyperbilirubinemia (OR = 1.7, 95%CI: 1.2-2.5, I² = 0%) and hypoalbuminemia (OR = 7.1, 95%CI: 2.1-24.1, I² = 71%) were higher subjects in critical COVID-19.ConclusionCOVID-19 associated liver injury is more common in severe COVID-19 than non-severe COVID-19. Physicians should be aware of possible progression to severe disease in subjects with COVID-19-associated liver injury.     

Cardiac Involvement in Patients Recovered From COVID-2019 Identified Using Magnetic Resonance Imaging

ObjectivesThis study evaluated cardiac involvement in patients recovered from coronavirus disease-2019 (COVID-19) using cardiac magnetic resonance (CMR).BackgroundMyocardial injury caused by COVID-19 was previously reported in hospitalized patients. It is unknown if there is sustained cardiac involvement after patients’ recovery from COVID-19.MethodsTwenty-six patients recovered from COVID-19 who reported cardiac symptoms and underwent CMR examinations were retrospectively included. CMR protocols consisted of conventional sequences (cine, T2-weighted imaging, and late gadolinium enhancement [LGE]) and quantitative mapping sequences (T1, T2, and extracellular volume [ECV] mapping). Edema ratio and LGE were assessed in post–COVID-19 patients. Cardiac function, native T1/T2, and ECV were quantitatively evaluated and compared with controls.ResultsFifteen patients (58%) had abnormal CMR findings on conventional CMR sequences: myocardial edema was found in 14 (54%) patients and LGE was found in 8 (31%) patients. Decreased right ventricle functional parameters including ejection fraction, cardiac index, and stroke volume/body surface area were found in patients with positive conventional CMR findings. Using quantitative mapping, global native T1, T2, and ECV were all found to be significantly elevated in patients with positive conventional CMR findings, compared with patients without positive findings and controls (median [interquartile range]: native T1 1,271 ms [1,243 to 1,298 ms] vs. 1,237 ms [1,216 to 1,262 ms] vs. 1,224 ms [1,217 to 1,245 ms]; mean ± SD: T2 42.7 ± 3.1 ms vs. 38.1 ms ± 2.4 vs. 39.1 ms ± 3.1; median [interquartile range]: 28.2% [24.8% to 36.2%] vs. 24.8% [23.1% to 25.4%] vs. 23.7% [22.2% to 25.2%]; p = 0.002; p < 0.001, and p = 0.002, respectively).ConclusionsCardiac involvement was found in a proportion of patients recovered from COVID-19. CMR manifestation included myocardial edema, fibrosis, and impaired right ventricle function. Attention should be paid to the possible myocardial involvement in patients recovered from COVID-19 with cardiac symptoms.     

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.     

SARS-CoV-2 and COVID-19 in diabetes mellitus. Population-based study on ascertained infections,hospital admissions and mortality in an Italian region with ∼5 million inhabitants and ∼250,000 diabetic people

Background and aimsDiabetes conveys an increased risk of infectious diseases and related mortality. We investigated risk of ascertained SARS-CoV-2 infection in diabetes subjects from the Veneto Region, Northeastern Italy, as well as the risk of being admitted to hospital or intensive care unit (ICU), or mortality for COVID-19.Methods and resultsDiabetic subjects were identified by linkage of multiple health archives. The rest of the population served as reference. Information on ascertained infection by SARS-CoV-2, admission to hospital, admission to ICU and mortality in the period from February 21 to July 31, 2020 were retrieved from the regional registry of COVID-19. Subjects with ascertained diabetes were 269,830 (55.2% men; median age 72 years). Reference subjects were 4,681,239 (men 48.6%, median age 46 years). Ratios of age- and gender-standardized rates (RR) [95% CI] for ascertained infection, admission to hospital, admission to ICU and disease-related death in diabetic subjects were 1.31 [1.19–1.45], 2.11 [1.83–2.44], 2.45 [1.96–3.07], 1.87 [1.68–2.09], all p < 0.001. The highest RR of ascertained infection was observed in diabetic men aged 20–39 years: 1.90 [1.04–3.21]. The highest RR of ICU admission and death were observed in diabetic men aged 40–59 years: 3.47 [2.00–5.70] and 5.54 [2.23–12.1], respectively.ConclusionsThese data, observed in a large population of ∼5 million people of whom ∼250,000 with diabetes, show that diabetes not only conveys a poorer outcome in COVID-19 but also confers an increased risk of ascertained infection from SARS-CoV-2. Men of young or mature age have the highest relative risks.     

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.     

Antibody responses to SARS-CoV-2 nucleocapsid and spike proteins in hospitalized patients with COVID-19: A multicenter,retrospective, cross-sectional study in Japan

BackgroundThere are many commercially available automated assays for assessing coronavirus disease 2019 (COVID-19) immune responses; however, owing to insufficient data, their validities remain unknown. Here, we examined antibody responses during acute-phase COVID-19 using four assays that detect anti-spike protein IgM (S-IgM), anti-nucleocapsid protein IgG (N-IgG), anti-spike protein total Ig (S-total Ig), and anti-spike protein IgG (S-IgG).MethodsWe measured antibody levels in 1154 serum samples collected from 286 hospitalized patients with confirmed COVID-19 by a gene amplification method between February and December 2020 in Japan. Sera from 860 healthcare workers were used as negative controls.ResultsThe antibody positivity rates increased on week 2, peaked, and then started to plateau by the beginning of week 3 after symptom onset. On week 1, there were some significant differences in seropositivity rates between assays (p = 0.032): 14.9% (11.0%–19.4%) for S-IgM and 8.9% (6.0%–12.7%) for N-IgG. The seropositivity for the S-total Ig (10.6% [7.3%–14.6%]) assay was considerably better than that for the S-IgG (6.9% [4.3%–10.4%]) assay, although the difference was not statistically significant (p = 0.150). The levels of S-IgM antibodies and the three others peaked on weeks 3 and 5, respectively. All four assays showed high specificities (>99%).ConclusionsAll four assays had good specificities and were suitable for seropositivity detection after week 3 of symptom onset. Assays of IgM alone or total Ig (containing IgM) were better than those of IgG alone as an adjunct serological test for early-stage COVID-19 diagnosis, albeit the use of a serological assay alone is insufficient.     

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.     

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.     

Prognostic Value of Right Ventricular Longitudinal Strain in Patients With COVID-19

ObjectivesThe aim of this study was to investigate whether right ventricular longitudinal strain (RVLS) was independently predictive of higher mortality in patients with coronavirus disease-2019 (COVID-19).BackgroundRVLS obtained from 2-dimensional speckle-tracking echocardiography has been recently demonstrated to be a more accurate and sensitive tool to estimate right ventricular (RV) function. The prognostic value of RVLS in patients with COVID-19 remains unknown.MethodsOne hundred twenty consecutive patients with COVID-19 who underwent echocardiographic examinations were enrolled in our study. Conventional RV functional parameters, including RV fractional area change, tricuspid annular plane systolic excursion, and tricuspid tissue Doppler annular velocity, were obtained. RVLS was determined using 2-dimensional speckle-tracking echocardiography. RV function was categorized in tertiles of RVLS.ResultsCompared with patients in the highest RVLS tertile, those in the lowest tertile were more likely to have higher heart rate; elevated levels of D-dimer and C-reactive protein; more high-flow oxygen and invasive mechanical ventilation therapy; higher incidence of acute heart injury, acute respiratory distress syndrome, and deep vein thrombosis; and higher mortality. After a median follow-up period of 51 days, 18 patients died. Compared with survivors, nonsurvivors displayed enlarged right heart chambers, diminished RV function, and elevated pulmonary artery systolic pressure. Male sex, acute respiratory distress syndrome, RVLS, RV fractional area change, and tricuspid annular plane systolic excursion were significant univariate predictors of higher risk for mortality (p < 0.05 for all). A Cox model using RVLS (hazard ratio: 1.33; 95% confidence interval [CI]: 1.15 to 1.53; p < 0.001; Akaike information criterion = 129; C-index = 0.89) was found to predict higher mortality more accurately than a model with RV fractional area change (Akaike information criterion = 142, C-index = 0.84) and tricuspid annular plane systolic excursion (Akaike information criterion = 144, C-index = 0.83). The best cutoff value of RVLS for prediction of outcome was −23% (AUC: 0.87; p < 0.001; sensitivity, 94.4%; specificity, 64.7%).ConclusionsRVLS is a powerful predictor of higher mortality in patients with COVID-19. These results support the application of RVLS to identify higher risk patients with COVID-19.     

Adverse reactions to BNT162b2 mRNA COVID-19 vaccine in medical staff with a history of allergy

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) vaccination is progressing globally. Several adverse reactions have been reported with vaccination against COVID-19. It is unknown whether adverse reactions to COVID-19 vaccination are severe in individuals with allergies.MethodsWe administered the COVID-19 vaccine to the medical staff at Yamagata University Hospital from March to August 2021. Subsequently, we conducted an online questionnaire-based survey to investigate the presence of allergy and adverse reactions after vaccination and examine the association between allergy and adverse reactions after immunization.ResultsResponses were collected from 1586 to 1306 participants after the first and second administration of the BNT162b2 mRNA COVID-19 vaccine, respectively. Adverse reactions included injection site pain, injection site swelling, fever, fatigue or malaise, headache, chills, nausea, muscle pain outside the injection site, and arthralgia. The frequency of some adverse reactions and their severity were higher, and the duration of symptoms was longer in participants with allergies than in those without allergies. Although several participants visited the emergency room for treatment after the first and second vaccinations, no participant was diagnosed with anaphylaxis.ConclusionsThis study suggests that the frequency and severity of adverse reactions after injection of BNT162b2 mRNA COVID-19 vaccine were higher in individuals with allergy; however, no severe adverse reactions such as anaphylaxis or death were observed. These results indicate that individuals with allergic histories may tolerate the BNT162b2 mRNA COVID-19 vaccine.     

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.