Severity Predictors of COVID-19 in SARS-CoV-2 Variant, Delta and Omicron Period; Single Center Study (preprint)

Background: The outcomes of coronavirus disease 2019 (COVID-19) treatment have improved due to vaccination and the establishment of better treatment regimens. However, the emergence of variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, and the corresponding changes in the characteristics of the disease present new challenges in patient management. This study aimed to analyze predictors of COVID-19 severity caused by the delta and omicron variants of SARS-CoV-2. Methods: We retrospectively analyzed the data of patients who were admitted for COVID-19 at Yokohama City University Hospital from August 2021 to March 2022. Results: A total of 141 patients were included in this study. Of these, 91 had moderate COVID-19, whereas 50 had severe COVID-19. There were significant differences in sex, vaccination status, dyspnea, sore throat symptoms, and body mass index (BMI) (p <0.0001, p <0.001, p <0.001, p=0.02, p< 0.0001, respectively) between the moderate and severe COVID-19 groups. Regarding comorbidities, smoking habit and renal dysfunction were significantly different between the two groups (p=0.007 and p=0.01, respectively). Regarding laboratory data, only LDH level on the first day of hospitalization was significantly different between the two groups (p<0.001). Multiple logistic regression analysis revealed that time from the onset of COVID-19 to hospitalization, BMI, smoking habit, and LDH level were significantly different between the two groups (p<0.03, p=0.039, p=0.008, p<0.001, respectively). The cut-off value for the time from onset of COVID-19 to hospitalization was four days (sensitivity, 0.73; specificity, 0.70). Conclusions: Time from the onset of COVID-19 to hospitalization is the most important factor in the prevention of the aggravation of COVID-19 caused by the delta and omicron SARS-CoV-2 variants. Appropriate medical management within four days after the onset of COVID-19 is essential for preventing the progression of COVID-19, especially in patients with smoking habits.

Interleukin-6 as a predictor of early weaning from invasive mechanical ventilation in COVID-19 patients with acute respiratory distress syndrome (preprint)

Therapeutic efficacy of steroids on acute respiratory distress syndrome (ARDS) requiring mechanical ventilation (MV) has been reported. However, predictive indicators of early weaning from MV in such cases have not yet been defined. Our aim was to clarify clinical utility of interleukin (IL)-6 level in ventilated patients with established ARDS. Clinical, treatment, and outcome data were evaluated in 119 invasively ventilated patients with ARDS caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Plasma levels of IL-6 and C-reactive protein (CRP) were measured on days 1, 4, and 7 after intubation. Fifty-two patients received dexamethasone (steroid group) and the remaining 67 did not (non-steroid group). Duration of MV use was significantly shorter in the steroid group compared to non-steroid group (11.5±0.6 vs. 16.1±1.0 days, P = 0.0005, respectively). Even when restricted to the steroid group, among the post-MV variables, the IL-6 level on day 7 was most closely correlated with the duration of MV use and showed the highest accuracy for withdrawal from MV within 11 days (AUC: 0.88), with optimal cutoff value of 20.6 pg/mL. Collectively, in intubated patients with ARDS due to SARS-CoV-2 who received dexamethasone, plasma IL-6 levels served as a predictor of early withdrawal from MV. 

Combining Blood Glucose and SpO 2 /FiO 2 Ratio Facilitates Prediction of Imminent Ventilatory Needs in Emergency Room COVID-19 patients (preprint)

The increasing requirement of mechanical ventilation (MV) due to the novel coronavirus disease (COVID-19) is still a global threat. The aim of this study is to identify markers that can easily stratify the impending use of MV in the emergency room (ER). A total of 106 patients with COVID-19 requiring oxygen support were enrolled. Fifty-nine patients were provided MV 0.5 hours (interquartile range: 0.3 to 1.4) post-admission. Clinical and laboratory data before intubation were collected. Using a multivariate logistic regression model, we identified four markers associated with the impending use of MV, including the ratio of peripheral blood oxygen saturation to fraction of inspired oxygen (SpO 2 /FiO 2 ratio), alanine aminotransferase, blood glucose (BG), and lymphocyte counts. Among these markers, the combination of SpO 2 /FiO 2 ratio and BG, which can be measured easily and immediately, showed higher accuracy in its prediction (AUC: 0.88) compared to SpO 2 /FiO 2 ratio alone (AUC: 0.84). Moreover, even in patients without severe respiratory failure (SpO 2 /FiO 2 ratio > 300), BG (> 138 mg/dL) was predictive of MV use. Measuring BG and SpO 2 /FiO 2 ratio may be a simple and versatile new strategy to accurately identify ER patients with COVID-19 at high risk for the imminent need of MV.

Do Serial Lung Ultrasound Scores Predict Prolonged Mechanical Ventilation in Patients With Severe COVID-19? A Single-centre Retrospective Cohort Study (preprint)

Background: Some patients with severe coronavirus disease (COVID-19) who present with fibrosis on computed tomography (CT) require prolonged mechanical ventilation (PMV). Lung ultrasound (LUS), a rapid, bedside test, has been reported to have findings consistent with those of CT. Thus, this study aimed to assess whether serial LUS scores could predict PMV or successful extubation in severe COVID-19 patients.Methods: LUS was performed for 20 consecutive severe COVID-19 patients at three time points: admission (day 1), after 48 h (day 3), and seventh-day follow-up (day 7). We compared the LUS score with the results of chest X-rays and laboratory tests at three time points. Moreover, we assessed LUS score to determine the inter-rater reliability (IRR) of the results among examiners.Results: While there were no significant differences in mortality in each PMV and successful extubation groups, there were significant differences in LUS scores on day 3 and day 7; XP score on day 7; and P/F ratio on day 7 in the PMV group (p<0.05). There were significant differences in LUS scores on days 3 and 7, C-reactive protein (CRP) levels on day 7, and P/F ratio on day 7 in the successful extubation group (p<0.05). The areas under the curves (AUCs) of LUS score on days 3 and 7, XP score on day 7, and P/F ratio were 0.88, 0.98, 0.77, and 0.80, respectively in the PMV group; and the AUCs of LUS score on days 3 and 7, CRP levels on day 7, and P/F ratio 0.79, 0.90, 0.82, and 0.79, respectively, in the successful extubation group. Variations in serial LUS scores exhibited significant differences between the groups. The serial LUS score on day 7 was higher than that on day 1 in the PMV group but lower in the successful extubation group (p<0.05). However, there was slight IRR agreement in the LUS score changes on days 1 to 7 (κ= 0.15 [95% CI: 0-0.31]). Conclusions: The serial LUS score of severe COVID-19 patients could predicted PMV and successful extubation. To overcome IRR disagreement, the automatic ultrasound judgement, such as deep learning, would be needed.

Annual Changes in Serum Syndecan-1 as a Therapeutic Target and a Biomarker for the Severity Classification of COVID-19 (preprint)

Background: Coronavirus disease 2019 (COVID-19) pneumonitis associated with severe respiratory failure is associated with high mortality. The pathogenesis of COVID-19 is associated with microemboli or microvascular endothelial injuries. Here, we report that serum syndecan-1 (SDC-1), a component of the endothelial glycocalyx, may be a biomarker of severity classification for COVID-19 related to endothelial injury.Methods and analysis: We analyzed the data of COVID-19 patients for one year from February 2020 at Yokohama City University Hospital and Yokohama City University Medical Center Hospital. We selected COVID-19 patients who required admission care, including intensive care, and analyzed the classification of severe and critical COVID-19 retrospectively, using various clinical data and laboratory data with serum SDC-1 by ELISA. Results: We analyzed clinical and laboratory data with SDC-1 in five severe COVID-19 and ten critical COVID-19 patients. In the two groups, their backgrounds were almost the same. In laboratory data, the LDH, CHE, and CRP levels showed significant differences in each group (P=0.032, P <0.0001, and P = 0.007, respectively) with no significant differences in coagulation-related factors (platelet, PT-INR, D-dimer, ISTH score; P=0.200, 0.277, 0.655, and 0.36, respectively). For the clinical data, the SOFA score was significantly different from admission day to day 14 of admission (p<0.0001). The SDC-1 levels of critical COVID-19 patients were significantly higher on admission day and all-time course compared with the levels of severe COVID-19 patients (P=0.009 and P <0.0001, respectively).Conclusions: Annual changes in serum SDC-1 levels closely reflect the severity of COVID-19, therefore, serum SDC-1 may be a therapeutic target and a biomarker for the severity classification of Covid-19.

An Evaluation of Thrombotic Tendency by Whole-Body Enhanced CT Scan for Critical COVID-19 Pneumonia: A Case Series Study (preprint)

Background: Coronavirus disease (COVID-19) pneumonitis associated with severe respiratory failure has a high mortality rate. Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated intravascular coagulation (DIC)-like massive intravascular clot formation is frequently observed. Coagulopathy has emerged as a significant contributor to thrombotic complications. Although recommendations have been made for anticoagulant use for COVID-19, no guidelines have been specified.Case presentation: We describe four cases of critical COVID-19 with thrombosis detected by enhanced CT scan. The CT findings of all cases demonstrated typical findings of COVID-19 and pulmonary embolism or deep venous thrombus without critical exacerbation. Two patients died of respiratory failure due to COVID-19.Discussion: Previous reports have suggested coagulopathy with thrombotic signs as the main pathological feature of COVID-19, but no previous reports have focused on coagulopathy evaluated by whole-body enhanced CT scan. Changes in hemostatic biomarkers, represented by an increase in D-dimer and fibrin/fibrinogen degradation products, indicated that the essence of coagulopathy was massive fibrin formation. Although there were no clinical symptoms related to their prognosis, critical COVID-19-induced systemic thrombus formation was observed. Conclusions: Therapeutic dose anticoagulants should be considered for critical COVID-19 because of induced coagulopathy, and aggressive follow-up by whole body enhanced CT scan for systemic venous thromboembolism (VTE) is necessary. 

Serum cholinesterase on admission as a predictor of COVID-19 pneumonia severity and mortality (preprint)

Background: Although some predictors of COVID-19 pneumonia severity and mortality have been identified, much of the pathophysiology of this emerging infectious disease remains unclear. We hypothesized that a patient’s cholinesterase level on admission could predict COVID-19 pneumonia severity and mortality. Methods We retrospectively collected data of 26 COVID-19 pneumonia patients from February–May 2020. Outcomes were aggravation of symptoms and in-hospital mortality. We compared receiver operating curves of cholinesterase, C-reactive protein, lymphocytes, albumin, D-dimer, and PaO 2 /FiO 2 ratio and examined prediction accuracy. Regarding the interaction between cholinesterase and other variables, each independent variable was divided into two groups using cutoff values, and interaction terms were created. Results Cholinesterase levels on admission were significantly lower in the severe group than in the mild-to-moderate group (326 vs. 218 IU/L, p = 0.006; area under the curve: 0.81; 95% confidence interval 0.61–0.94). When comparing the area under the curve, cholinesterase was comparable to C-reactive protein, albumin, lymphocytes, and PaO 2 /FiO 2 ratio other than D-dimer in the prediction accuracy of severe cases and mortality. Cholinesterase levels on admission were significantly lower in the death group than in the survival group (274 vs. 187.5 IU/L, p = 0.028; area under the curve: 0.79; 95% interval 0.58–0.93). Regarding the interaction between cholinesterase and established predictors, the prediction accuracy of both severity and death was higher when cholinesterase was combined with each predictor than when cholinesterase was used alone. Conclusions Cholinesterase may reflect the disease state of COVID-19 pneumonia, suggesting that a patient’s cholinesterase level on admission may be useful as a predictor of severity and prognosis.