COVID-19-Induced Eosinophilic Lower Airway Inflammation in Those With Multiple COVID-19 Vaccinations.

A 29-year-old woman was admitted with a diagnosis of ischemic enteritis. She had a coronavirus disease 2019 (COVID-19) infection four weeks before this visit and continued to experience a cough. Four months before, she received the third COVID-19 vaccine. Chest computer tomography revealed scattered ground-glass opacities in both upper lobes. Based on abnormalities in chest imaging, eosinophilia, and a high level of fractional exhaled nitric oxide, she was diagnosed with eosinophilic lower airway inflammation due to COVID-19. Since the visit, the patient had an intermittent fever and no radiological improvement, so systemic corticosteroid treatment was initiated, and the symptoms and clinical findings improved. Clinicians should know the potential association between COVID-19 and eosinophilic lower airway inflammation, which may still occur despite multiple vaccinations.

Educational Effects of Simulation and Non-Simulation Training in Airway Management according to Levels of the Kirkpatrick Model: A Systematic Review and Network Meta-Analysis.

There is insufficient validation of the effectiveness of simulation-based training (Sim) or non-simulation-based training (non-Sim) for teaching airway management to healthcare professionals within the literature. We thus conducted a network meta-analysis comparing the effectiveness of Sim, non-Sim, and no educational intervention (NI) for airway management. The primary endpoints were knowledge scores (KnS) and behavioral performance scores (BpS) corresponding to assessments at levels 2 and 3 of the Kirkpatrick model, respectively. Effect sizes were expressed as standardized mean differences (Std. MD) and 95% credible intervals (CrIs). Regarding KnS, the educational effects of Sim and non-Sim were significantly improved compared to those of NI (Std. MD [95% CI]: 1.110 [0.903-1.316] and 0.819 [0.209-1.429], respectively); there was no significant difference between Sim and non-Sim. The educational effect of Sim in BpS was significantly improved compared to that of non-Sim and NI (0.850 [0.015-1.691] and 0.660 [0.241-1.076]); there were no differences between non-Sim and NI. Surface under the cumulative rank curve values demonstrated that Sim ranked highest in efficacy for KnS and BpS. This study provides valuable information regarding the educational efficacy of Sim and non-Sim in airway management. Larger randomized controlled trials are needed to confirm these findings.

Serum IL-28A/IFN-λ2 is linked to disease severity of COVID-19.

Type III interferons (IFNs) play an important role in respiratory viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to determine whether the expression of serum type III IFNs predicted disease severity among patients with the coronavirus disease (COVID-19). A retrospective cohort study was conducted of patients admitted to a single hospital between March 21, 2020, and March 31, 2021. Patients were divided into mild to moderate I (MM) and moderate II to severe (MS) groups based on the COVID-19 severity classification developed by the Japanese Ministry of Health, Labor and Welfare. A total of 257 patients were included in the analysis. Human interleukin-28A (IL-28A/IFN-λ2) expression was significantly lower, and interleukin (IL)-6 expression was significantly higher in the MS group than in the MM group (both p < 0.001). In addition, IL-28A/IFN-λ2 was statistically significantly inversely correlated with the time from disease onset to negative SARS-CoV-2 PCR results (p = 0.049). Multivariable logistic regression analysis showed that IL-28A/IFN-λ2 was an independent predictor of disease severity (p = 0.021). The low expression of IL-28A/IFN-λ2 may serve as a serum biomarker that predicts the severity of COVID-19, possibly through the mechanism of delayed viral elimination.

Serum cystatin C and CRP are early predictive biomarkers for emergence of hypoxia in COVID-19.

BACKGROUND: In Japan, during the coronavirus disease 2019 (COVID-19) pandemic, patients with non-hypoxia are recommended to recuperate at home or in pre-hospital facilities. However, it was observed that unexpected hypoxia may occur and become severe subsequently in patients whose symptoms were initially expected to improve naturally. The aim of this study is to validate biomarkers that can predict at an early stage the emergence of hypoxia in COVID-19 patients without hypoxia. METHODS: We retrospectively enrolled 193 patients with COVID-19, excluding patients with hypoxia and severe disease from the onset. Participants were classified into two groups according to the emergence of hypoxia during the clinical course, and the laboratory data were compared to identify biomarkers that could predict early the emergence of hypoxia. RESULTS: The areas under the curve for serum cystatin C (CysC) and C-reactive protein (CRP) levels for the emergence of hypoxia during the clinical course were higher than those for other biomarkers (CysC, 0.84 and CRP, 0.83). Multivariate analysis showed that high serum CysC and CRP levels were associated with the emergence of hypoxia during the clinical course. CONCLUSIONS: Elevated serum CysC and CRP levels were associated with the emergence of hypoxia during the clinical course in COVID-19 patients without hypoxia. These findings may help determine the need for hospitalization in initially non-hypoxic COVID-19 patients.

Genetic epidemiology using whole genome sequencing and haplotype networks revealed the linkage of SARS-CoV-2 infection in nosocomial outbreak.

BACKGROUND: A characteristic feature of SARS-CoV-2 is its ability to transmit from pre- or asymptomatic patients, complicating the tracing of infection pathways and causing outbreaks. Despite several reports that whole genome sequencing (WGS) and haplotype networks are useful for epidemiologic analysis, little is known about their use in nosocomial infections. AIM: We aimed to demonstrate the advantages of genetic epidemiology in identifying the link in nosocomial infection by comparing single nucleotide variations (SNVs) of isolates from patients associated with an outbreak in Showa University Hospital. METHODS: We used specimens from 32 patients in whom COVID-19 had been diagnosed using clinical reverse transcription-polymerase chain reaction tests. RNA of SARS-CoV-2 from specimens was reverse-transcribed and analysed using WGS. SNVs were extracted and used for lineage determination, phylogenetic tree analysis, and median-joining analysis. FINDINGS: The lineage of SARS-CoV-2 that was associated with outbreak in Showa University Hospital was B.1.1.214, which was consistent with that found in the Kanto metropolitan area during the same period. Consistent with canonical epidemiological observations, haplotype network analysis was successful for the classification of patients. Additionally, phylogenetic tree analysis revealed three independent introductions of the virus into the hospital during the outbreak. Further, median-joining analysis indicated that four patients were directly infected by any of the others in the same cluster. CONCLUSION: Genetic epidemiology with WGS and haplotype networks is useful for tracing transmission and optimizing prevention strategies in nosocomial outbreaks.

Extracorporeal Membrane Oxygenation for Secondary Organizing Pneumonia after Severe SARS-CoV-2 Infection: A Case Report.

(Background) COVID-19 is caused by SARS-CoV-2 infection and may result in unfavorable outcomes. A recent large-scale study showed that treatment with dexamethasone leads to favorable outcomes in patients with severe COVID-19, and the use of extracorporeal membrane oxygenation (ECMO) has also been shown to improve outcomes. Recently, secondary organizing pneumonia (SOP) has been reported after SARS-CoV-2 infection, but the diagnostic and treatment strategies are still unclear. (Case presentation) Here, we report a patient with severe COVID-19 who developed SOP even after the use of dexamethasone, for whom the introduction of ECMO on the 19th day after hospitalization led to a favorable outcome. (Conclusions) Life-threatening SOP may evolve even after the use of dexamethasone, and the late-phase introduction of ECMO may save such patients with COVID-19.

Clinical features and mechanism of liver injury in patients with mild or moderate coronavirus disease 2019.

BACKGROUND AND AIM: We aimed to identify clinical features that suggest that coronavirus disease 2019 (COVID-19) should be a differential diagnosis in patients presenting with a chief complaint of fever and abnormal liver function. METHODS: We retrospectively studied the presence or absence of abnormal liver function in 216 patients diagnosed with mild-moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection between February and September 2020. RESULTS: Abnormal liver function was observed in 51 patients with mild-moderate COVID-19. The median peak aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels were 57.5, 75.5, and 332.5 U/L, respectively. The median number of days from symptom onset to peak AST, ALT, and LDH were 8.5, 9, and 8.5, respectively. The median peak LDH/AST ratio was 9.0. Low lymphocyte-to-white blood cell ratio and elevated LDH were found to be independent contributing factors for intensive care unit (ICU) admission on a multivariate analysis. CONCLUSIONS: AST-predominant AST/ALT/LDH elevation peaking 8-9 days after symptom onset and not accompanied by elevated alkaline phosphatase or gamma-glutamyl transferase may be a useful clinical feature for differentiating COVID-19 from other diseases. Since the median LDH/AST ratio was 9.0, it seems that the abnormal liver function caused by SARS-CoV-2 is an indirect damage to liver cells due to elevated cytokine levels caused by liver-infiltrating lymphocytes. SARS-CoV-2 infection should be considered in patients presenting with a chief complaint of fever and liver injury; those with a high lymphocyte-to-white blood cell ratio or and a high LDH/AST ratio may be admitted to the ICU.

Downregulation of type III interferons in patients with severe COVID-19.

Coronavirus disease 2019 (COVID-19) is globally rampant, and to curb the growing burden of this disease, in-depth knowledge about its pathophysiology is needed. This was an observational study conducted at a single center to investigate serum cytokine and chemokine levels of COVID-19 patients, based on disease severity. We included 72 consecutive COVID-19 patients admitted to our hospital from March 21 to August 31, 2020. Patients were divided into Mild-Moderate I (mild) and Moderate II-Severe (severe) groups based on the COVID-19 severity classification developed by the Ministry of Health, Labor and Welfare (MHLW) of Japan. We compared the patient characteristics as well as the serum cytokine and chemokine levels on the day of admission between the two groups. Our findings indicated that the severe group had significantly higher levels of serum fibrinogen, d-dimer, lactate dehydrogenase, C-reactive protein, ferritin, Krebs von den Lungen-6, surfactant protein (SP)-D, and SP-A than the mild group. Strikingly, the levels of interleukin (IL)-28A/interferon (IFN)-λ2 were significantly lower in the severe group than in the mild group. We believe that reduced levels of type III interferons (IFN-λs) and alterations in the levels of other cytokines and chemokines may impact the severity of the disease.

Utility of SpO2/FiO2 ratio for acute hypoxemic respiratory failure with bilateral opacities in the ICU.

Acute hypoxemic respiratory failure (AHRF) with bilateral opacities causes fatalities in the intensive care unit (ICU). It is often difficult to identify the causes of AHRF at the time of admission. The SpO2 to FiO2 (S/F) ratio has been recently used as a non-invasive and alternative marker of the PaO2/FiO2 (P/F) ratio in acute respiratory failure. This retrospective cohort study was conducted from October 2010 to March 2019 at the Showa University Hospital, Tokyo, Japan. We enrolled 94 AHRF patients who had bilateral opacities and received mechanical ventilation in ICU to investigate their prognostic markers including S/F ratio. Significant differences were observed for APACHE II, S/F ratio, PaO2/FiO2 (P/F) ratio, and ventilator-free-days at day 28 for ICU mortality, and for age, S/F ratio, P/F ratio, duration of mechanical ventilation, and ventilator-free days at day 28 for hospital mortality. Multivariate logistic regression analysis showed that the S/F ratio was significantly and independently associated with the risk of death during in ICU (p = 0.003) and hospitalization (p = 0.002). The area under the receiver operating characteristic curves (AUC) based on the S/F ratio were significantly greater than those based on simplified acute physiology score (SAPS) II and sequential organ failure assessment (SOFA) for ICU mortality (0.785 in S/F ratio vs. 0.575 in SAPS II, p = 0.012; 0.785 in S/F ratio vs 0.594 in SOFA, p = 0.021) and for hospital mortality (0.701 in S/F ratio vs. 0.502 in SAPS II, p = 0.012; 0.701 in S/F ratio vs. 0.503 in SOFA, p = 0.005). In the subanalysis for bacterial pneumonia and interstitial lung disease groups, the AUC based on the S/F ratio was the greatest among all prognostic markers, including APACHE II, SAPS II, and SOFA. The S/F ratio may be a useful and noninvasive predictive prognostic marker for acute hypoxemic respiratory failure with bilateral opacities in the ICU.

Combination treatment of short-course systemic corticosteroid and favipiravir in a successfully treated case of critically ill COVID-19 pneumonia with COPD.

Use of systemic corticosteroids for the treatment for coronavirus disease 2019 (COVID-19) among chronic obstructive pulmonary disease (COPD) patients is not well described. A 58-year-old man with fever and progressive dyspnea was admitted to the Showa University Hospital, and showed severe respiratory failure which needed mechanical ventilation. His chest computed tomography scanning showed emphysema and bilateral ground-glass opacity caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. He received 30 mg prednisolone for five days with antiviral drug of favipiravir, and was successfully extubated on day five. A SARS-CoV-2 polymerase chain reaction (PCR) test became negative on day 15. He was discharged on day 21. Serum IgM and IgG antibodies against SARS-CoV-2 converted to positive on day 7 and they kept positive on day 54 for both IgM and IgG. Combination treatment of short-course systemic corticosteroid and favipiravir might improve the prognosis for critically ill COVID-19 pneumonia with COPD without negative influence on viral clearance or antibody production.