Prediction of prognosis in patients with severe COVID-19 pneumonia using CT score by emergency physicians: a single-center retrospective study.

We aimed to develop a method to determine the CT score that can be easily obtained from CT images and examine its prognostic value for severe COVID pneumonia. Patients with COVID pneumonia who required ventilatory management by intubation were included. CT score was based on anatomical information in axial CT images and were divided into three sections of height from the apex to the bottom. The extent of pneumonia in each section was rated from 0 to 5 and summed. The primary outcome was the prediction of patients who died or were managed on extracorporeal membrane oxygenation (ECMO) based on the CT score at admission. Of the 71 patients included, 12 (16.9%) died or required ECMO management, and the CT score predicted death or ECMO management with ROC of 0.718 (0.561-0.875). The death or ECMO versus survival group (median [quartiles]) had a CT score of 17.75 (14.75-20) versus 13 (11-16.5), p = 0.017. In conclusion, a higher score on our generated CT score could predict the likelihood of death or ECMO management. A CT score at the time of admission allows for early preparation and transfer to a hospital that can manage patients who may need ECMO.

Utility of dual-energy computed tomography in the association of COVID-19 pneumonia severity.

Aim: Coronavirus disease 2019 pneumonia differs from ordinary pneumonia in that it is associated with lesions that reduce pulmonary perfusion. Dual-energy computed tomography is well suited to elucidate the etiology of coronavirus disease 2019 pneumonia, because it highlights changes in organ blood flow. In this study, we investigated whether dual-energy computed tomography could be used to determine the severity of coronavirus disease 2019 pneumonia. Methods: Patients who were diagnosed with coronavirus disease 2019 pneumonia, admitted to our hospital, and underwent dual-energy computed tomography were included in this study. Dual-energy computed tomography findings, plane computed tomography findings, disease severity, laboratory data, and clinical features were compared between two groups: a critical group (18 patients) and a non-critical group (30 patients). Results: The dual-energy computed tomography results indicated that the percentage of flow loss was significantly higher in the critical group compared with the non-critical group (P < 0.001). Additionally, our data demonstrated that thrombotic risk was associated with differences in clinical characteristics (P = 0.018). Receiver operating characteristic analysis revealed that the percentage of flow loss, evaluated using dual-energy computed tomography, could predict severity in the critical group with 100% sensitivity and 77% specificity. However, there were no significant differences in the receiver operating characteristic values for dual-energy computed tomography and plane computed tomography. Conclusion: Dual-energy computed tomography can be used to associate the severity of coronavirus disease 2019 pneumonia with high accuracy. Further studies are needed to draw definitive conclusions.

Early alveolar epithelial cell necrosis is a potential driver of COVID-19-induced acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) with COVID-19 is aggravated by hyperinflammatory responses even after the peak of the viral load has passed; however, its underlying mechanisms remain unclear. In the present study, analysis of the alveolar tissue injury markers and epithelial cell death markers in patients with COVID-19 revealed that COVID-19-induced ARDS was characterized by alveolar epithelial necrosis at an early disease stage. Serum levels of HMGB-1, one of the DAMPs released from necrotic cells, were also significantly elevated in these patients. Further analysis using a mouse model mimicking COVID-19-induced ARDS showed that the alveolar epithelial cell necrosis involved two forms of programmed necrosis, namely necroptosis, and pyroptosis. Finally, the neutralization of HMGB-1 attenuated alveolar tissue injury in the mouse model. Collectively, necrosis, including necroptosis and pyroptosis, is the predominant form of alveolar epithelial cell death at an early disease stage and subsequent release of DAMPs is a potential driver of COVID-19-induced ARDS.

Severity predictors of COVID-19 in SARS-CoV-2 variant, delta and omicron period; single center study.

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.

Prolonged mechanical ventilation in patients with severe COVID-19 is associated with serial modified-lung ultrasound scores: A single-centre cohort study.

Lung ultrasound (LUS), a rapid, bedside, goal-oriented diagnostic test, can be quantitatively assessed, and the scores can be used to evaluate disease progression. However, little data exists on predicting prolonged mechanical ventilation (PMV) and successful extubation using serial LUS scores. We examined the relationship of PMV with successful extubation in patients with severe coronavirus disease (COVID-19) by using two types of serial LUS scores. One LUS score evaluated both the pleura and lung fields, while the other assessed each separately (modified-LUS score). Both LUS scores were determined for 20 consecutive patients with severe COVID-19 at three timepoints: admission (day-1), after 48 h (day-3), and on the seventh follow-up day (day-7). We compared LUS scores with the radiographic assessment of the lung oedema (RALE) scores and laboratory test results, at the three timepoints. The PMV and successful extubation groups showed no significant differences in mortality, but significant differences occurred on day-3 and day-7 both LUS scores, day-7 RALE score, and day-7 PaO2/FiO2 ratio, in the PMV group (p<0.05); and day-3 and day-7 modified-LUS scores, day-7 C-reactive protein levels, and day-7 PaO2/FiO2 ratio, in the successful extubation group (p<0.05). The area under the curves (AUC) of LUS scores on day-3 and day-7, modified-LUS scores on day-3 and day-7,RALE score on day-7, and PaO2/FiO2 ratio on day-7 in the PMV group were 0.98, 0.85, 0.88, 0.98, 0.77, and 0.80, respectively. The AUC of modified-LUS scores on day-3 and day-7, C-reactive protein levels on day-7, and PaO2/FiO2 ratio on day-7 in the successful extubation group were 0.79, 0.90, 0.82, and 0.79, respectively. The modified-LUS score on day 7 was significantly higher than that on day 1 in PMV group (p<0.05). While the LUS score did not exhibit significant differences. The serial modified-LUS score of patients with severe COVID-19 could predict PMV.

Chronic kidney disease and clinical outcomes in patients with COVID-19 in Japan.

BACKGROUND: Identifying predictive factors for coronavirus disease 2019 (COVID-19) is crucial for risk stratification and intervention. Kidney dysfunction contributes to the severity of various infectious diseases. However, the association between on-admission kidney dysfunction and the clinical outcome in COVID-19 patients is unclear. METHODS: This study was a multicenter retrospective observational cohort study of COVID-19 patients, diagnosed by polymerase chain reaction. We retrospectively analyzed 500 COVID-19 patients (mean age: 51 ± 19 years) admitted to eight hospitals in Japan. Kidney dysfunction was defined as a reduced estimated glomerular filtration rate (< 60 mL/min/1.73 m2) or proteinuria (≥ 1 + dipstick proteinuria) on admission. The primary composite outcome included in-hospital death, extracorporeal membrane oxygenation, mechanical ventilation (invasive and noninvasive methods), and intensive care unit (ICU) admission. RESULTS: Overall, 171 (34.2%) patients presented with on-admission kidney dysfunction, and the primary composite outcome was observed in 60 (12.0%) patients. Patients with kidney dysfunction showed higher rates of in-hospital death (12.3 vs. 1.2%), mechanical ventilation (13.5 vs. 4.0%), and ICU admission (18.1 vs. 5.2%) than those without it. Categorical and multivariate regression analyses revealed that kidney dysfunction was substantially associated with the primary composite outcome. Thus, on-admission kidney dysfunction was common in COVID-19 patients. Furthermore, it correlated significantly and positively with COVID-19 severity and mortality. CONCLUSIONS: On-admission kidney dysfunction was associated with disease severity and poor short-term prognosis in patients with COVID-19. Thus, on-admission kidney dysfunction has the potential to stratify risks in COVID-19 patients.

Temporal change in Syndecan-1 as a therapeutic target and a biomarker for the severity classification of COVID-19.

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 microembolism or microvascular endothelial injuries. Here, we report that 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 1 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 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: Temporal change of SDC-1 levels closely reflect the severity of COVID-19, therefore, SDC-1 may be a therapeutic target and a biomarker for the severity classification of Covid-19.

Detection of Iliopsoas Hematoma by Retrospective Radiography in Veno-Venous Extracorporeal Membrane Oxygenation for a COVID-19 Patient.

In coronavirus disease 2019 (COVID-19), veno-venous extracorporeal membrane oxygenation (VV-ECMO) is used to manage respiratory distress. This study's key clinical question was whether COVID-19 could be complicated by hemorrhagic and thrombotic events, such as iliopsoas hematoma (IPH), during the management of ECMO and the method to quickly and effectively detect IPH. A 52-year-old man with fever and dyspnea was diagnosed with COVID-19 pneumonia. He warranted VV-ECMO management on day 9, which was successfully tapered off on day 18. On day 20, computed tomography revealed a unilateral iliopsoas hematoma that was successfully managed with conservative care. However, a retrospective review of abdominal radiography performed on day 14 revealed a positive left psoas sign. When managing severe COVID-19 patients with VV-ECMO, cautious anticoagulative care and abdominal X-ray findings are warranted when considering the diagnosis of iliopsoas hematoma, including circulatory instability, anemia, and pain associated with limb movement.

Rapid screening for severe acute respiratory syndrome coronavirus 2 infection with a combined point-of-care antigen test and an immunoglobulin G antibody test.

Rapid screening and diagnosis of coronavirus disease 2019 in the emergency department is important for controlling infections. When polymerase chain reaction tests cannot be rapidly performed, rapid antigen testing is often used, albeit with insufficient sensitivity. Therefore, we evaluated the diagnostic accuracy of combining rapid antigen and antibody test results. This was a retrospective review of patients who visited our emergency department between February and May 2021 and underwent rapid antigen, immunoglobulin G antibody, and reverse transcription-polymerase chain reaction tests. The study included 1,070 patients, of whom 56 (5.2%) tested positive on reverse transcription-polymerase chain reaction. The sensitivity, specificity, and area under the curve of rapid antigen testing were 73.7%, 100.0%, and 0.87, respectively. The combined rapid antigen and antibody test result had improved diagnostic accuracy, with 91.2% sensitivity, 97.9% specificity, and an area under the curve of 0.95. The results of the rapid antigen and antibody tests could be combined as a reliable alternative to reverse transcription-polymerase chain reaction.

Identification of serum prognostic biomarkers of severe COVID-19 using a quantitative proteomic approach.

The COVID-19 pandemic is an unprecedented threat to humanity that has provoked global health concerns. Since the etiopathogenesis of this illness is not fully characterized, the prognostic factors enabling treatment decisions have not been well documented. Accurately predicting the progression of the disease would aid in appropriate patient categorization and thus help determine the best treatment option. Here, we have introduced a proteomic approach utilizing data-independent acquisition mass spectrometry (DIA-MS) to identify the serum proteins that are closely associated with COVID-19 prognosis. Twenty-seven proteins were differentially expressed between severely ill COVID-19 patients with an adverse or favorable prognosis. Ingenuity Pathway Analysis revealed that 15 of the 27 proteins might be regulated by cytokine signaling relevant to interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF), and their differential expression was implicated in the systemic inflammatory response and in cardiovascular disorders. We further evaluated practical predictors of the clinical prognosis of severe COVID-19 patients. Subsequent ELISA assays revealed that CHI3L1 and IGFALS may serve as highly sensitive prognostic markers. Our findings can help formulate a diagnostic approach for accurately identifying COVID-19 patients with severe disease and for providing appropriate treatment based on their predicted prognosis.

Evaluation of a combination protocol of CT-first triage and active telemedicine methods by a selected team tackling COVID-19: An experimental research study.

BACKGROUND: Many health care workers around the world tackled with COVID-19, however sadly, the infection of many medical care workers were reported. To reduce the risk of infection, we launched selected team (Team COVID) of non-specialists and brought in active telemedicine method and computed tomography (CT)-first protocol. We describe our actual practice and the health status of medical doctors dealing with COVID-19 patients. METHODS: Between April 17, 2020 and May 24, 2020, 10 doctors worked with COVID-19 patients as part of Team COVID. The Team COVID doctors used a CT-first triage protocol for outpatients and telemedicine for inpatients and outpatients. We evaluated paired serum-specific antibodies for SARS-CoV-2 at the initial and end of the study duration and PCR results for SARS-CoV-2 at the end of the study duration. Furthermore, 36-item short-form of the Medical Outcome Study Questionnaire (SF-36) at the beginning and end of the study period were evaluated. RESULTS: Ten doctors worked as Team COVID: seven internal medicine doctors and three surgeons. During the study period, Team COVID treated 165 individuals in the outpatient clinic and isolated hospitalized patients for 315 person-days. There were no positive results of serum-specific antibody testing and PCR testing for SARS-CoV-2 in Team COVID doctors. Furthermore, the SF-36 showed no deterioration in physical and mental QOL status. No in-hospital infection occurred during the study period. CONCLUSIONS: The Team COVID fulfilled the treatment using the active telemedicine and CT-first triage protocol without in hospital infection and excess stress. The combination strategy seems acceptable for both the protection and stress relief among the medical staff.

Combining IL-6 and SARS-CoV-2 RNAaemia-based risk stratification for fatal outcomes of COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic rapidly increases the use of mechanical ventilation (MV). Such cases further require extracorporeal membrane oxygenation (ECMO) and have a high mortality. OBJECTIVE: We aimed to identify prognostic biomarkers pathophysiologically reflecting future deterioration of COVID-19. METHODS: Clinical, laboratory, and outcome data were collected from 102 patients with moderate to severe COVID-19. Interleukin (IL)-6 level and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA copy number in plasma were assessed with ELISA kit and quantitative PCR. RESULTS: Twelve patients died or required ECMO owing to acute respiratory distress syndrome despite the use of MV. Among various variables, a ratio of oxygen saturation to fraction of inspired oxygen (SpO2/FiO2), IL-6, and SARS-CoV-2 RNA on admission before intubation were strongly predictive of fatal outcomes after the MV use. Moreover, among these variables, combining SpO2/FiO2, IL-6, and SARS-CoV-2 RNA showed the highest accuracy (area under the curve: 0.934). In patients with low SpO2/FiO2 (< 261), fatal event-rate after the MV use at the 30-day was significantly higher in patients with high IL-6 (> 49 pg/mL) and SARS-CoV-2 RNAaemia (> 1.5 copies/µL) compared to those with high IL-6 or RNAaemia or without high IL-6 and RNAaemia (88% vs. 22% or 8%, log-rank test P = 0.0097 or P < 0.0001, respectively). CONCLUSIONS: Combining SpO2/FiO2 with high IL-6 and SARS-CoV-2 RNAaemia which reflect hyperinflammation and viral overload allows accurately and before intubation identifying COVID-19 patients at high risk for ECMO use or in-hospital death despite the use of MV.

The U-shaped association of serum iron level with disease severity in adult hospitalized patients with COVID-19.

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that leads to severe respiratory failure (RF). It is known that host exposure to viral infection triggers an iron-lowering response to mitigate pathogenic load and tissue damage. However, the association between host iron-lowering response and COVID-19 severity is not clear. This two-center observational study of 136 adult hospitalized COVID-19 patients analyzed the association between disease severity and initial serum iron, total iron-binding capacity (TIBC), and transferrin saturation (TSAT) levels. Serum iron levels were significantly lower in patients with mild RF than in the non-RF group; however, there were no significant differences in iron levels between the non-RF and severe RF groups, depicting a U-shaped association between serum iron levels and disease severity. TIBC levels decreased significantly with increasing severity; consequently, TSAT was significantly higher in patients with severe RF than in other patients. Multivariate analysis including only patients with RF adjusted for age and sex demonstrated that higher serum iron and TSAT levels were independently associated with the development of severe RF, indicating that inadequate response to lower serum iron might be an exacerbating factor for COVID-19.

Long-Term Decreased Exercise Capacity of COVID-19 Patients Who Received Mechanical Ventilation in Japan: A Case Series.

ABSTRACT: The long-term exercise capacity of coronavirus disease 2019 patients with acute respiratory distress syndrome is not clear. The 6-min walking distance of four patients with coronavirus disease 2019-associated acute respiratory distress syndrome was followed for 6 mos after admission to the hospital. These four patients were admitted to the intensive care unit of our hospital and received mechanical ventilation. Rehabilitation therapy (positioning, postural drainage, and passive range-of-motion exercises) was started after intensive care unit admission. Mobilization therapy, including muscle power training, sitting on the edge of the bed, and endurance training, was performed after the end of sedation. The Medical Research Council sum scores and Barthel Indexes for the patients improved after intensive care unit discharge and completely recovered 6 mos after admission to the hospital. However, the 6-min walking distance of the four patients remained shorter than those of healthy persons of the same age at 6 mos after admission to the hospital. Furthermore, the minimum Spo2 during the 6-min walking test remained less than 96%. It is possible that patients who receive mechanical ventilation due to coronavirus disease 2019-associated acute respiratory distress syndrome have decreased long-term exercise capacity, despite muscle power and activities of daily living recovering completely.

Real-world evaluation of a computed tomography-first triage strategy for suspected Coronavirus disease 2019 in outpatients in Japan: An observational cohort study.

ABSTRACT: The Coronavirus disease 2019 pandemic continues to spread worldwide. Because of the absence of reliable rapid diagnostic systems, patients with symptoms of Coronavirus disease 2019 are treated as suspected of the disease. Use of computed tomography findings in Coronavirus disease 2019 are expected to be a reasonable method for triaging patients, and computed tomography-first triage strategies have been proposed. However, clinical evaluation of a computed tomography-first triage protocol is lacking.The aim of this study is to investigate the real-world efficacy and limitations of a computed tomography-first triage strategy in patients with suspected Coronavirus disease 2019.This was a single-center cohort study evaluating outpatients with fever who received medical examination at Yokohama City University Hospital, prospectively registered between 9 February and 5 May 2020. We treated according to the computed tomography-first triage protocol. The primary outcome was efficacy of the computed tomography-first triage protocol for patients with fever in an outpatient clinic. Efficacy of the computed tomography-first triage protocol for outpatients with fever was evaluated using sensitivity, specificity, positive predictive value, and negative predictive value. We conducted additional analyses of the isolation time of feverish outpatients and final diagnoses.In total, 108 consecutive outpatients with fever were examined at our hospital. Using the computed tomography-first triage protocol, 48 (44.9%) patients were classified as suspected Coronavirus disease 2019. Nine patients (18.8%) in this group were positive for severe acute respiratory syndrome coronavirus 2 using polymerase chain reaction; no patients in the group considered less likely to have Coronavirus disease 2019 tested positive for the virus. The protocol significantly shortened the duration of isolation for the not-suspected versus the suspected group (70.5 vs 1037.0 minutes, P < .001).Our computed tomography-first triage protocol was acceptable for screening patients with suspected Coronavirus disease 2019. This protocol will be helpful for appropriate triage, especially in areas where polymerase chain reaction is inadequate.

An evaluation of venous thromboembolism by whole-body enhanced CT scan for critical COVID-19 pneumonia with markedly rises of coagulopathy related factors: a case series study.

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. 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.