Clinical characteristics of patients with coronavirus disease 2019-associated pulmonary aspergillosis on mechanical ventilation: A single-center retrospective study in Japan.

BACKGROUND: Aspergillus is one of the important pathogens that contribute to high mortality in patients with coronavirus disease 2019 (COVID-19) in intensive care units (ICUs). Although incidence rates of Aspergillus coinfection are high globally, a Japanese national survey reported a low incidence. This study aimed to describe the clinical characteristics of patients with COVID-19-associated pulmonary aspergillosis at our institute. METHODS: We identified patients with microbiologically confirmed COVID-19 on mechanical ventilation in the ICU. Of these patients, we identified patients in whom Aspergillus was cultured from the respiratory specimen. RESULTS: Of a total of 169 patients, seven had aspergillosis (4.1%), which included three patients, three patients, and one patient with possible, probable, and proven aspergillosis, respectively, according to the criteria of the European Confederation of Medical Mycology International Society. All patients received systemic steroid therapy. Two patients (one each with proven and probable aspergillosis) had tracheobronchitis diagnosed by bronchoscopy. All patients in whom Aspergillus was repeatedly isolated from samples died. The mortality rates for all cases and probable and proven cases were 57% (4/7) and 75% (3/4), respectively. CONCLUSIONS: The incidence rate of aspergillosis in patients with COVID-19 in the ICU was higher in our institute than that reported by a Japanese national survey (4.1% vs. 0.5%). Repeated detection of Aspergillus might suggest a true Aspergillus infection, such as chronic aspergillosis, rather than colonization. In patients with severe COVID-19 patients, it is important to always keep CAPA in mind.

Transition of antibody titers after the SARS-CoV-2 mRNA vaccine in Japanese healthcare workers.

Since February 2021, healthcare workers in Japan have been preferentially vaccinated with a messenger RNA vaccine (BNT162b2/Pfizer) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While many studies have confirmed that this vaccine is highly effective in reducing hospitalizations and deaths from coronavirus disease 2019 (COVID-19), antibody titers tend to decline at 3 months, leading to a risk of breakthrough infections. Thus, information is needed to support decision making regarding the third vaccination. In this study, we investigated transition of the anti-SARS-CoV-2 spike protein receptor-binding domain (RBD) IgG and neutralizing antibody titers of 37 vaccinated Japanese healthcare workers. Samples were collected six times starting prevaccination until 6 months after the second vaccination. Anti-SARS-CoV-2 RBD IgG levels peaked at 1 week after the second vaccination, then declined over time and decreased to <10% at 6 months after the second vaccination. Additionally, approximately one third of subjects at 6 months after the second vaccination were seronegative for the Omicron variant. Workers with low anti-SARS-CoV-2 RBD IgG levels also had low neutralizing antibody titers. These data support the active use of boosters for healthcare workers, especially for those with low anti-SARS-CoV-2 RBD IgG levels.

Sensitivity and specificity analyses of COVID-19 screening protocol for emergency medical services: A STARD-compliant population-based retrospective study.

During the novel coronavirus disease (COVID-19) pandemic, emergency medical services (EMS) has borne a huge burden in transporting emergency patients. However, the protocol's effect on identifying emergency patients who are likely to have COVID-19 is unknown. We aimed to evaluate the diagnostic accuracy of a prehospital COVID-19 screening protocol for EMS. We conducted this population-based retrospective study in Nara Prefecture, Japan. The Nara Prefectural Government implemented a screening protocol for COVID-19 comprising the following symptom criteria (fever, cough, sore throat, headache, malaise, dysgeusia, or anosmia) and epidemiological criteria (contact history with confirmed COVID-19 cases or people with upper respiratory symptoms, or travel to areas with high infection rate). A patient meeting at least one criterion of each class was considered positive. We evaluated all 51,351 patients from the regional EMS database of the Nara Prefecture (emergency Medical Alliance for Total Coordination of Healthcare) who were registered from June 15, 2020 to May 31, 2021 and had results of COVID-19 reverse transcription polymerase chain reaction (RT-PCR) tests. We assessed the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of this protocol. We also assessed how these outcomes changed by adding vital signs and conducted a 10-fold and 100-fold prevalence simulation. The screening protocol was used for 246/51351 patients (0.5%). Among them, 31 tested positive after EMS transportation. This protocol's sensitivity, specificity, PPV, and NPV were 40.8%, 99.6%, 12.6%, and 99.9%, respectively. With the addition of ≥2 vital signs (body temperature ≥37.5 °C, respiratory rate ≥20 breaths/minute, and oxygen saturation <90%), sensitivity and PPV changed to 61.8% and 1.0%, respectively, while NPV remained 99.9%. With a 10-fold and 100-fold increase in disease, the protocol PPV would be 59.0% and 94.3%, and NPV would be 99.1% and 90.7%, respectively, and with additional vital signs, PPV would be 8.9% and 53.1%, and NPV would be 99.4% and 93.2%, respectively. This COVID-19 screening protocol helped enable EMS transport for patients with COVID-19 with a PPV of 12.6%. Adding other vital sign variables may improve its diagnostic value if the prevalence rate increases.

The balance of comprehensive coagulation and fibrinolytic potential is disrupted in patients with moderate to severe COVID-19.

Coagulation and fibrinolytic mechanisms are enhanced in patients with coronavirus (COVID-19), but disturbances in the balance of both functions in COVID-19 patients remain unclear. We assessed global coagulation and fibrinolysis in plasma from 167 COVID-19 patients (mild/moderate/severe: 62/88/17, respectively) on admission using clot-fibrinolysis waveform analysis (CFWA). Maximum coagulation velocity (|min1|) and maximum fibrinolysis velocity (|FL-min1|) were expressed as ratios relative to normal plasma. Ten patients (6.0%) developed thrombosis, 5 (3.0%) had bleeding tendency, and 13 (7.8%) died during admission. FDP levels increased with severity of COVID-19 symptoms (mild/moderate/severe; median 2.7/4.9/9.9 µg/mL, respectively). The |min1| ratios were elevated in all categories (1.27/1.61/1.58) in keeping with enhanced coagulation potential, with significant differences between mild cases and moderate to severe cases. The |FL-min1| ratios were also elevated in all groups (1.19/1.39/1.40), reflecting enhanced fibrinolytic potential. These data identified coagulation dominance in moderate to severe cases, but balanced coagulation and fibrinolysis in mild cases. There were significant differences in FDP and TAT, but no significant differences in |min1| or |FL-min1| ratios, between patients with and without thrombosis. CFWA monitoring of coagulation and fibrinolysis dynamics could provide valuable data for understanding hemostatic changes and disease status in COVID-19 patients.

Newly developed artificial intelligence algorithm for COVID-19 pneumonia: utility of quantitative CT texture analysis for prediction of favipiravir treatment effect.

PURPOSE: Using CT findings from a prospective, randomized, open-label multicenter trial of favipiravir treatment of COVID-19 patients, the purpose of this study was to compare the utility of machine learning (ML)-based algorithm with that of CT-determined disease severity score and time from disease onset to CT (i.e., time until CT) in this setting. MATERIALS AND METHODS: From March to May 2020, 32 COVID-19 patients underwent initial chest CT before enrollment were evaluated in this study. Eighteen patients were randomized to start favipiravir on day 1 (early treatment group), and 14 patients on day 6 of study participation (late treatment group). In this study, percentages of ground-glass opacity (GGO), reticulation, consolidation, emphysema, honeycomb, and nodular lesion volumes were calculated as quantitative indexes by means of the software, while CT-determined disease severity was also visually scored. Next, univariate and stepwise regression analyses were performed to determine relationships between quantitative indexes and time until CT. Moreover, patient outcomes determined as viral clearance in the first 6 days and duration of fever were compared for those who started therapy within 4, 5, or 6 days as time until CT and those who started later by means of the Kaplan-Meier method followed by Wilcoxon's signed-rank test. RESULTS: % GGO and % consolidation showed significant correlations with time until CT (p < 0.05), and stepwise regression analyses identified both indexes as significant descriptors for time until CT (p < 0.05). When divided all patients between time until CT of 4 days and that of more than 4 days, accuracy of the combined quantitative method (87.5%) was significantly higher than that of the CT disease severity score (62.5%, p = 0.008). CONCLUSION: ML-based CT texture analysis is equally or more useful for predicting time until CT for favipiravir treatment on COVID-19 patients than CT disease severity score.

Corynebacterium pseudodiphtheriticum as a Pathogen in Bacterial Co-Infection in COVID-19 Patients on Mechanical Ventilation.

Many studies have been conducted on ventilator-associated complications (VACs) in patients with coronavirus 2019 (COVID-19). However, in these studies, the causative organisms were similar, and there were no reports on VAC corresponding with Corynebacteria. Coryneforms are frequently cultured in cases of polymicrobial infections and are usually considered contaminants in respiratory specimens. However, Corynebacterium pseudodiphtheriticum or C. striatum is known to be a pathogen in lower respiratory tract infections. We report three cases of VAC, probably due to C. pseudodiphtheriticum, in patients with COVID-19. If purulent lower respiratory tract specimens showed coryneform predominantly upon Gram staining, empirical therapy should be started. Furthermore, species identification and drug susceptibility testing should be performed.

Persimmon-derived tannin has antiviral effects and reduces the severity of infection and transmission of SARS-CoV-2 in a Syrian hamster model.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread across the world. Inactivating the virus in saliva and the oral cavity represents a reasonable approach to prevent human-to-human transmission because the virus is easily transmitted through oral routes by dispersed saliva. Persimmon-derived tannin is a condensed type of tannin that has strong antioxidant and antimicrobial activity. In this study, we investigated the antiviral effects of persimmon-derived tannin against SARS-CoV-2 in both in vitro and in vivo models. We found that persimmon-derived tannin suppressed SARS-CoV-2 titers measured by plaque assay in vitro in a dose- and time-dependent manner. We then created a Syrian hamster model by inoculating SARS-CoV-2 into hamsters' mouths. Oral administration of persimmon-derived tannin dissolved in carboxymethyl cellulose before virus inoculation dramatically reduced the severity of pneumonia with lower virus titers compared with a control group inoculated with carboxymethyl cellulose alone. In addition, pre-administration of tannin to uninfected hamsters reduced hamster-to-hamster transmission of SARS-CoV-2 from a cohoused, infected donor cage mate. These data suggest that oral administration of persimmon-derived tannin may help reduce the severity of SARS-CoV-2 infection and transmission of the virus.

Factors associated with viral clearance periods from patients with COVID-19: A retrospective observational cohort study.

INTRODUCTION: Knowledge is limited on the virologic course of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, particularly the time taken for viral clearance and the optimal time to discontinue isolation. This study aims to identify the clinical and demographic factors influencing the time taken for viral clearance in patients with COVID-19 to determine the optimal isolation period. METHODS: This two-center retrospective observational cohort study was conducted between March 1 and June 31, 2020. Patients with COVID-19, which was confirmed by real-time reverse transcription polymerase chain reaction, were included. Data were extracted from medical records. The positive duration, which was defined as the period from the day of symptom onset to the negative conversion day, was assessed using a generalized linear model. RESULTS: We included 63 patients. The mean positive duration was 20 days. The positive duration was significantly shorter for patients younger than 30 years of age and those between 30 and 60 years of age than for patients older than 60 years of age. We observed a more scattered distribution of the positive duration in older patients than in younger patients. CONCLUSIONS: Younger patients who recovered from COVID-19 took less time to clear SARS-CoV-2 than older patients; thus, a classification of the isolation periods based on age could be considered. A uniform viral clearance period for older patients may be difficult to determine because of biases such as underlying medical conditions. Further surveillance measures are recommended to determine the viral clearance time and the optimal isolation period.

Assessing the effects of exposure to a SARS-CoV-2 re-positive patient in healthcare personnel.

OBJECTIVE: To evaluate whether patients with COVID-19 who have tested re-positive with the PCR test for the SARS-CoV-2 virus are infectious is a challenge in the current circumstances. A follow-up survey was conducted with healthcare personnel (HCP) who were exposed to a patient whose PCR test results for SARS-CoV-2 were re-positive 18 days after the initial confirmation of negative PCR results. RESULTS: We studied a total of 15 HCP who had contact exposures (15/15) and aerosol exposures (7/15). None of them tested positive for IgG against SARS-CoV-2 on blood examination. None of them had any symptoms during 10 days of active isolation. All PCR tests conducted using the nasopharyngeal swabs collected from the HCP on day 10 were negative. No apparent infection was found in any of the HCP who had contact exposure with and/or aerosol exposure to the patient whose PCR test results for SARS-CoV-2 were re-positive 18 days after the initial confirmation of negative results of PCR tests for SARS-CoV-2. CLINICAL TRIAL: Trial Registration: No. 170, approved June 10th, 2020 by the ethics committee of Sakai City Medical Center.

Management of a COVID-19 Patient during ECMO: Paying Attention to Acquired von Willebrand Syndrome.

Patients with severe COVID-19 often experience complications including coagulopathy and fatal thrombosis. COVID-19 pneumonia sometimes leads to acute respiratory distress syndrome, requiring extracorporeal membrane oxygenation (ECMO), during which thrombosis and bleeding are major causes of death. Anticoagulation such as heparin is essential for COVID-19 patients on ECMO; however, bleeding might be caused by not only heparin, but also acquired von Willebrand syndrome (AVWS). To date, no study has examined ECMO-related bleeding and AVWS in COVID-19 patients.We report a COVID-19 patient who experienced bleeding from AVWS in addition to disseminated intravascular coagulation (DIC) during ECMO. The level of high-molecular weight VWF multimers decreased during ECMO therapy, and these findings promptly improved after discontinuation of ECMO. Plasma levels of VWF antigen were extremely high, probably due to endothelial cell damage caused by COVID-19. On the other hand, plasma levels of ADAMTS13 activity were moderately reduced, to 20-30% of normal. The patient was successfully treated with cryoprecipitate in bleeding during ECMO without a reduction in heparin, which might have induced thromboembolism. Bleeding found in this patient might be caused by AVWS and DIC.Severe COVID-19 patients are in a thrombotic state and need to receive anticoagulant therapy. However, once they receive ECMO therapy, bleeding symptoms could be observed. In such cases, physicians should think of AVWS in addition to the side effect of heparin and DIC.