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Persistent COVID-19 is a well recognized issue of concern in patients with hematological malignancies. Such patients are not only at risk of mortality due to the infection itself, but are also at risk of suboptimal malignancy-related outcomes because of delays and terminations of chemotherapy. We report two lymphoma patients with heavily pretreated persistent COVID-19 in which ensitrelvir brought about radical changes in the clinical course leading to rapid remissions. Patient 1 was on ibrutinib treatment for mantle cell lymphoma when he developed COVID-19 pneumonia which was severe and ongoing for 2 months despite therapy with molnupiravir, multiple courses of remdesivir, one course of sotrovimab, tocilizumab, and steroids. Patient 2 was administered R-CHOP therapy for diffuse large B-cell lymphoma when he developed COVID-19 which was ongoing for a month despite treatment with multiple courses of remdesivir and one course of sotrovimab. A 5-day administration of ensitrelvir promptly resolved the persistent COVID-19 accommodated by negative conversions of RT-qPCR tests in both patients within days. Ensitrelvir is a novel COVID-19 therapeutic that accelerates viral clearance through inhibition of the main protease of SARS-CoV-2, 3-chymotrypsin-like protease, which is vital for viral replication. Ensitrelvir is a promising treatment approach for immunocompromised lymphoma patients suffering from persisting and severe COVID-19.

COVID-19 has a range of complications, from no symptoms to severe pneumonia. It can also affect multiple organs including the nervous system. COVID-19 affects the brain, leading to neurological symptoms such as delirium. Delirium, a sudden change in consciousness, can increase the risk of death and prolong the hospital stay. However, research on delirium prediction in patients with COVID-19 is insufficient. This study aimed to identify new risk factors that could predict the onset of delirium in patients with COVID-19 using machine learning (ML) applied to nursing records. This retrospective cohort study used natural language processing and ML to develop a model for classifying the nursing records of patients with delirium. We extracted the features of each word from the model and grouped similar words. To evaluate the usefulness of word groups in predicting the occurrence of delirium in patients with COVID-19, we analyzed the temporal changes in the frequency of occurrence of these word groups before and after the onset of delirium. Moreover, the sensitivity, specificity, and odds ratios were calculated. We identified (1) elimination-related behaviors and conditions and (2) abnormal patient behavior and conditions as risk factors for delirium. Group 1 had the highest sensitivity (0.603), whereas group 2 had the highest specificity and odds ratio (0.938 and 6.903, respectively). These results suggest that these parameters may be useful in predicting delirium in these patients. The risk factors for COVID-19-associated delirium identified in this study were more specific but less sensitive than the ICDSC (Intensive Care Delirium Screening Checklist) and CAM-ICU (Confusion Assessment Method for the Intensive Care Unit). However, they are superior to the ICDSC and CAM-ICU because they can predict delirium without medical staff and at no cost.

Triglyceride deposit cardiomyovasculopathy (TGCV) is an intractable disease characterized by massive triglyceride (TG) accumulation in the myocardium and coronary arteries caused by genetic or acquired dysfunction of adipose TG lipase (ATGL). A phase IIa trial has been conducted involving patients with idiopathic TGCV using CNT-01 (tricaprin/ trisedecanion) by the Japan TGCV study group, which showed that CNT-01 improved myocardial lipolysis as demonstrated by iodine-123-beta-methyl iodophenyl-pentadecanoic acid (BMIPP) scintigraphy. We evaluated changes in myocardial TG content using proton magnetic resonance spectroscopy (1H-MRS) before/after CNT-01. This report describes a male patient with hypertension, diabetes, angina pectoris, repeated percutaneous coronary intervention, chest pain, and exertional dyspnea that persisted despite standard medications and nitroglycerin. Idiopathic TGCV was diagnosed based on a remarkably reduced washout rate (WR) for BMIPP scintigraphy, high myocardial TG content on 1H-MRS, and no ATGL mutation. After an 8-week, 1.5 g/day CNT-01 administration, the WR of BMIPP increased from 5.1 to 13.3% and the myocardial TG content decreased from 8.4 to 5.9%, with no adverse effects. CNT-01 corrected myocardial lipolysis and subsequently reduced TG content in idiopathic TGCV as evaluated using 1H-MRS, which may be a useful, noninvasive evaluation of therapeutic efficacy.

Background: We aimed to investigate the diagnostic value of energy loss (EL) and baseline CT fractional flow reserve (CT-FFR) computed using computational fluid dynamics to predict functional progression of coronary stenosis in patients with type 2 diabetes mellitus. Methods: This single-center prospective study included 61 patients with type 2 diabetes mellitus (mean age, 61 years ±9 [SD]; 43 men) showing 20–70 % stenosis who underwent serial coronary CT performed at 2-year interval between October 2015 and March 2020. A mesh-free simulation was performed to calculate the CT-FFR and EL. Functional progression was defined as ≥ 0.05 decrease in CT-FFR on the second coronary CT. Models using baseline CT-FFR and EL were compared by analyzing the receiver operating characteristic (ROC) curve. Results: Of the 94 vessels evaluated, 25 vessels (27 %) showed functional progression. EL at distal stenosis (ELdis) of vessels with functional progression was higher than that of vessels without functional progression (27.6 W/m3 [interquartile range (IQR): 15.0, 53.0] vs. 5.7 W/m3 [IQR: 2.3, 10.1], p

Abstract Background This study aimed to compare the coronary plaque characterization by cardiovascular magnetic resonance (CMR) and near-infrared spectroscopy (NIRS)-intravascular ultrasound (IVUS) (NIRS-IVUS), and to determine whether pre–percutaneous coronary intervention (PCI) evaluation using CMR identifies high-intensity plaques (HIPs) at risk of peri-procedural myocardial infarction (pMI). Although there is little evidence in comparison with NIRS-IVUS findings, which have recently been shown to identify vulnerable plaques, we inferred that CMR-derived HIPs would be associated with vulnerable plaque features identified on NIRS-IVUS. Methods 52 patients with stable coronary artery disease who underwent CMR with non-contrast T1-weighted imaging and PCI using NIRS-IVUS were studied. HIP was defined as a signal intensity of the coronary plaque-to-myocardial signal intensity ratio (PMR) ≥ 1.4, which was measured from the data of CMR images. We evaluated whether HIPs were associated with the NIRS-derived maximum 4-mm lipid-core burden index (maxLCBI4mm) and plaque morphology on IVUS, and assessed the incidence and predictor of pMI defined by the current Universal Definition using high-sensitive cardiac troponin-T. Results Of 62 lesions, HIPs were observed in 30 lesions (48%). The HIP group had a significantly higher remodeling index, plaque burden, and proportion of echo-lucent plaque and maxLCBI4mm ≥ 400 (known as large lipid-rich plaque [LRP]) than the non-HIP group. The correlation between the maxLCBI4mm and PMR was significantly positive (r = 0.51). In multivariable logistic regression analysis for prediction of HIP, NIRS-derived large LRP (odds ratio [OR] = 5.41; 95% confidence intervals [CIs] 1.65–17.8, p = 0.005) and IVUS-derived echo-lucent plaque (OR = 5.12; 95% CIs 1.11–23.6, p = 0.036) were strong independent predictors. Furthermore, pMI occurred in 14 of 30 lesions (47%) with HIP, compared to only 5 of 32 lesions (16%) without HIP (p = 0.005). In multivariable logistic regression analysis for prediction of incidence of pMI, CMR-derived HIP (OR = 5.68; 95% CIs 1.53–21.1, p = 0.009) was a strong independent predictor, but not NIRS-derived large LRP and IVUS-derived echo-lucent plaque. Conclusions There is an important relationship between CMR-derived HIP and NIRS-derived large LRP. We also confirmed that non-contrast T1-weighted CMR imaging is useful for characterization of vulnerable plaque features as well as for pre-PCI risk stratification. Trial registration The ethics committee of Juntendo Clinical Research and Trial Center approved this study on January 26, 2021 (Reference Number 20-313).

Abstract Cancer patients are considered highly susceptible to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. However, it is not well known when chemotherapy can be safely restarted in cancer patients after coronavirus disease 2019 (COVID‐19). Here, we describe the case of an 18‐year‐old man diagnosed with primary mediastinal nonseminomatous germ cell tumor (PMNSGCT) in which chemotherapy could be safely restarted after COVID‐19. On day 11 of the third cycle of bleomycin, etoposide, plus cisplatin (BEP), he was diagnosed with mild COVID‐19. On day 16 after the onset of COVID‐19 (day 26 of third cycle of BEP), chemotherapy for his PMNSGCT was restarted. He received surgery after the fourth cycle of BEP without recurrence of COVID‐19. Chemotherapy could be restarted and followed by surgery in this post‐COVID‐19 patient who had experienced mild illness after the discharge criteria were met and all symptoms had disappeared. We report this case with a review of the literature on restarting chemotherapy after SARS‐CoV2 infection.

Abstract COVID-19 antibody testing has been developed to investigate humoral immune response in SARS-CoV-2 infection. To assess the serological dynamics and neutralizing potency following SARS-CoV-2 infection, we investigated the neutralizing (NT) antibody, anti-spike, and anti-nucleocapsid antibodies responses using a total of 168 samples obtained from 68 SARS-CoV-2 infected patients. Antibodies were measured using an authentic virus neutralization assay, the high-throughput laboratory measurements of the Abbott Alinity quantitative anti-spike receptor-binding domain IgG (S-IgG), semiquantitative anti-spike IgM (S-IgM), and anti-nucleocapsid IgG (N-IgG) assays. The quantitative measurement of S-IgG antibodies was well correlated with the neutralizing activity detected by the neutralization assay (r = 0.8943, p

Genetic mechanisms influencing COVID-19 susceptibility are not well understood. Here, the authors analyzed whole blood RNA-seq data of 465 Japanese individuals with COVID-19, highlighting thousands of fine-mapped variants affecting expression and splicing of genes, as well as the presence of COVID-19 severity-interaction eQTLs.

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients are at high risk for developing severe conditions if other comorbidities are present, such as advanced cancer. Although the regulation of immune response is thought to play an important role in the treatment of coronavirus disease 2019 (COVID-19), physicians often have difficulties in selecting the most appropriate treatment. Furthermore, the impact that interrupting breast cancer treatment due to a COVID-19 infection has on patient outcomes is still unknown. Herein we report a case of advanced breast cancer in a patient whose COVID-19 acute respiratory failure was successfully treated with minimal interruption to their anticancer therapy for recurrent breast cancer. Case presentation A 48-year-old woman developed carcinomatous pleurisy after curative surgery for breast cancer. One month after the initiation of targeted therapy with palbociclib and fulvestrant, the pleural effusion decreased, but soon after she developed a COVID-19 infection. Dexamethasone (8 mg/day) was administered due to a prolonged fever, but her respiratory symptoms got worse and pneumonia appeared on a computed tomography (CT) scan 7 days after hospitalization. Thus, steroid pulse therapy (methylprednisolone 1000 mg/day) was administered for 3 days. Her respiratory condition rapidly improved. Two weeks after hospital discharge, complete regression of pneumonia was confirmed on CT scan, and her targeted therapy was resumed at the same dose and strength. More than 6 months later, her metastatic disease remains stable while on the same treatment. Retrospective analysis of the patient's neutralizing antibodies found the neutralizing activity was low in the early stages of infection, but became high after recovery. This suggests the patient acquired an immunity to SARS-CoV-2 through the infection, despite having a mild myelosuppression due to treatment for recurrent breast cancer. Conclusions Steroid pulse therapy is available worldwide, and may have an important role in cancer patients who develop severe pneumonia from SARS-CoV-2, by enabling them to avoid any long-term disruption to anticancer therapy. Moreover, it might also be useful when antiviral therapies lose their efficacy due to mutations of the virus, such as the Omicron variant. A critical element in cases such as this one is that treatment decisions are made by a team of specialists, including pulmonologists.

Abstract Background Coronary computed tomography angiography examinations are increasingly becoming established as a minimally invasive method for diagnosing coronary diseases. However, although various imaging and processing methods have been developed, coronary artery calcification remains a major limitation in the evaluation of the vascular lumen. Subtraction coronary computed tomography angiography (Sub-CCTA) is a method known to be able to reduce the influence of coronary artery calcification and is therefore feasible for improving the diagnosis of significant stenosis in patients with severe calcification. However, Sub-CCTA still involves some problems, such as the increased radiation dose due to plain (mask) imaging, extended breath-holding time, and misregistration due to differences in the imaging phase. Therefore, we considered using artificial intelligence instead of Sub-CCTA to visualize the coronary lumen with high calcification. Given this background, the present study aimed to evaluate the diagnostic performance of a deep learning-based lumen extraction method (DL-LEM) to detect significant stenosis on CCTA in 99 consecutive patients (891 segments) with severe coronary calcification from November 2015 to March 2018. We also estimated the impact of DL-LEM on the medical economics in Japan. Results The DL-LEM slightly improved the per-segment diagnostic accuracy from 74.5 to 76.4%, and the area under the curve (AUC) slightly improved from 0.752 to 0.767 (p = 0.030). When analyzing the 228 segments that could not be evaluated because of severe calcification on the original CCTA images, the DL-LEM improved the accuracy from 35.5 to 42.5%, and the AUC improved from 0.500 to 0.587 (p = 0.00018). As a result, DL-LEM analysis could have avoided invasive coronary angiography in 4/99 cases (per patient). From the calculated results, it was estimated that the number of exams that can be avoided in Japan in one year is approximately 747 for invasive coronary angiography, 219 for fractional flow reserve, and 248 for nuclear exam. The total amount of medical fee that could be reduced was 225,629,368 JPY. Conclusions These findings suggest that the DL-LEM may improve the diagnostic performance in detecting significant stenosis in patients with severe coronary calcification. In addition, the results suggest that not a small medical economic effect can be expected.

The COVID-19 antibody test was developed to investigate the humoral immune response to SARS-CoV-2 infection. In this study, we examined whether S antibody titers measured using the anti-SARS-CoV-2 IgG II Quant assay (S-IgG), a high-throughput test method, reflects the neutralizing capacity acquired after SARS-CoV-2 infection or vaccination. To assess the antibody dynamics and neutralizing potency, we utilized a total of 457 serum samples from 253 individuals: 325 samples from 128 COVID-19 patients including 136 samples from 29 severe/critical cases (Group S), 155 samples from 71 mild/moderate cases (Group M), and 132 samples from 132 health care workers (HCWs) who have received 2 doses of the BNT162b2 vaccinations. The authentic virus neutralization assay, the surrogate virus neutralizing antibody test (sVNT), and the Anti-N SARS-CoV-2 IgG assay (N-IgG) have been performed along with the S-IgG. The S-IgG correlated well with the neutralizing activity detected by the authentic virus neutralization assay (0.8904. of Spearman's rho value, p < 0.0001) and sVNT (0.9206. of Spearman's rho value, p < 0.0001). However, 4 samples (2.3%) of S-IgG and 8 samples (4.5%) of sVNT were inconsistent with negative results for neutralizing activity of the authentic virus neutralization assay. The kinetics of the SARS-CoV-2 neutralizing antibodies and anti-S IgG in severe cases were faster than the mild cases. All the HCWs elicited anti-S IgG titer after the second vaccination. However, the HCWs with history of COVID-19 or positive N-IgG elicited higher anti-S IgG titers than those who did not have it previously. Furthermore, it is difficult to predict the risk of breakthrough infection from anti-S IgG or sVNT antibody titers in HCWs after the second vaccination. Our data shows that the use of anti-S IgG titers as direct quantitative markers of neutralizing capacity is limited. Thus, antibody tests should be carefully interpreted when used as serological markers for diagnosis, treatment, and prophylaxis of COVID-19.

BackgroundAlthough lung ultrasound has been reported to be a portable, cost-effective, and accurate method to detect pneumonia, it has not been widely used because of the difficulty in its interpretation. Here, we aimed to investigate the effectiveness of a novel artificial intelligence-based automated pneumonia detection method using point-of-care lung ultrasound (AI-POCUS) for the coronavirus disease 2019 (COVID-19).MethodsWe enrolled consecutive patients admitted with COVID-19 who underwent computed tomography (CT) in August and September 2021. A 12-zone AI-POCUS was performed by a novice observer using a pocket-size device within 24 h of the CT scan. Fifteen control subjects were also scanned. Additionally, the accuracy of the simplified 8-zone scan excluding the dorsal chest, was assessed. More than three B-lines detected in one lung zone were considered zone-level positive, and the presence of positive AI-POCUS in any lung zone was considered patient-level positive. The sample size calculation was not performed given the retrospective all-comer nature of the study.ResultsA total of 577 lung zones from 56 subjects (59.4 ± 14.8 years, 23% female) were evaluated using AI-POCUS. The mean number of days from disease onset was 9, and 14% of patients were under mechanical ventilation. The CT-validated pneumonia was seen in 71.4% of patients at total 577 lung zones (53.3%). The 12-zone AI-POCUS for detecting CT-validated pneumonia in the patient-level showed the accuracy of 94.5% (85.1%- 98.1%), sensitivity of 92.3% (79.7%- 97.3%), specificity of 100% (80.6%- 100%), positive predictive value of 95.0% (89.6% - 97.7%), and Kappa of 0.33 (0.27-0.40). When simplified with 8-zone scan, the accuracy, sensitivity, and sensitivity were 83.9% (72.2%- 91.3%), 77.5% (62.5%- 87.7%), and 100% (80.6%- 100%), respectively. The zone-level accuracy, sensitivity, and specificity of AI-POCUS were 65.3% (61.4%- 69.1%), 37.2% (32.0%- 42.7%), and 97.8% (95.2%- 99.0%), respectively.InterpretationAI-POCUS using the novel pocket-size ultrasound system showed excellent agreement with CT-validated COVID-19 pneumonia, even when used by a novice observer.

BackgroundDespite the worldwide campaigns of COVID-19 vaccinations, the pandemic is still a major medical and social problem. The Ortho VITROS SARS-CoV-2 spike-specific quantitative IgG (VITROS S-IgG) assay has been developed to assess neutralizing antibody (NT antibody) against SARS-CoV-2 spike (S) antibodies. However, it has not been evaluated in Japan, where the total cases and death toll are lower than the rest of the world.MethodsThe clinical performance of VITROS S-IgG was evaluated by comparing with the NT antibody levels measured by the surrogate virus neutralizing antibody test (sVNT). A total of 332 serum samples from 188 individuals were used. Of these, 219 samples were from 75 COVID-19 patients: 96 samples from 20 severe/critical cases (Group S), and 123 samples from 55 mild/moderate cases (Group M). The remaining 113 samples were from 113 healthcare workers who had received 2 doses of the BNT162b2 vaccine.ResultsVITROS S-IgG showed good correlation with the cPass sVNT assay (Spearman rho = 0.91). Both VITROS S-IgG and cPass sVNT showed significantly higher plateau levels of antibodies in Group S compared to Group M. Regarding the humoral immune responses after BNT162b2 vaccination, individuals who were negative for SARS-CoV-2 nucleocapsid (N)-specific antibodies had statistically lower titers of both S-IgG and sVNT compared to individuals with a history of COVID-19 and individuals who were positive for N-specific antibodies without history of COVID-19. In individuals who were positive for N-specific antibodies, S-IgG and sVNT titers were similar to individuals with a history of COVID-19.ConclusionsAlthough the automated quantitative immunoassay VITROS S-IgG showed a reasonable correlation with sVNT antibodies, there is some discrepancy between Vitros S-IgG and cPass sVNT in milder cases. Thus, VITROS S-IgG can be a useful diagnostic tool in assessing the immune responses to vaccination and herd immunity. However, careful analysis is necessary to interpret the results.

Abstract Here, we aimed to evaluate the clinical performance of a novel automated immunoassay HISCL SARS-CoV-2 Antigen assay kit designed to detect the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This kit comprises automated chemiluminescence detection systems. Western blot analysis confirmed that anti-SARS-CoV antibodies detected SARS-CoV-2N proteins. The best cut-off index was determined, and clinical performance was tested using 115 serum samples obtained from 46 patients with coronavirus disease 2019 (COVID-19) and 69 individuals who tested negative for COVID-19 through reverse transcription quantitative polymerase chain reaction (RT-qPCR). The HISCL Antigen assay kit showed a sensitivity of 95.4% and 16.6% in samples with copy numbers > 100 and

Many variants of SARS-CoV-2 have emerged around the world. It is therefore important to understand its global viral evolution and the corresponding mutations associated with transmissibility and severity. In this study, we analyzed 112 whole genome sequences of SARS-CoV-2 collected from patients at Juntendo University Hospital in Tokyo and the genome data from entire Japan deposited in Global Initiative on Sharing Avian Influenza Data (GISAID) to examine the relationship of amino acid changes with the transmissibility and the severity of each strain/lineage. We identified 12 lineages, including B.1.1.284, B.1.1.214, R.1, AY.29, and AY.29.1, which were prevalent specifically in Japan. B.1.1.284 was most frequently detected in the second wave, but B.1.1.214 became the predominant lineage in the third wave, indicating that B.1.1.214 has a higher transmissibility than B.1.1.284. The most prevalent lineage during the fourth and fifth wave was B.1.1.7 and AY.29, respectively. In regard to the severity of identified lineages, B.1.1.214 was significantly lower than the reference lineage, B.1.1.284. Analysis of the genome sequence and other traits of each lineage/strain revealed the mutations in S, N, and NSPs that increase the transmissibility and/or severity. These mutations include S: M153T, N: P151L, NSP3: S543P, NSP5: P108S, and NSP12: A423V in B.1.1.284; S: W152L and E484K in R.1; S: H69del, V70del, and N501Y in the Alpha strain; S: L452R, T478K, and P681R in the Delta strain. Furthermore, it is suggested that the transmissibility of B.1.1.214 could be enhanced by the mutations N: M234I, NSP14: P43L, and NSP16: R287I. To address the issue of the virus evolution, it is necessary to continuously monitor the genomes of SARS-CoV-2 and analyze the effects of mutations for developing vaccines and antiviral drugs effective against SARS-CoV-2 variants.

Quantitative measurement of SARS-CoV-2 neutralizing antibodies is highly expected to evaluate immune status, vaccine response, and antiviral therapy. The Elecsys® Anti-SARS-CoV-2 S (Elecsys® anti-S) was developed to measure anti-SARS-CoV-2 S proteins. We sought to investigate whether Elecsys® anti-S can be used to predict neutralizing activities in patients’ serums using an authentic virus neutralization assay. One hundred forty-six serum samples were obtained from 59 patients with COVID-19 at multiple time points. Of the 59 patients, 44 cases were included in Group M (mild 23, moderate 21) and produced 84 samples (mild 35, moderate 49), while 15 cases were included in Group S (severe 11, critical 4) and produced 62 samples (severe 43, critical 19). The neutralization assay detected 73% positive cases, and Elecsys® anti-S and Elecsys® Anti-SARS-CoV-2 (Elecsys® anti-N) showed 72% and 66% positive cases, respectively. A linear correlation between the Elecsys® anti-S assay and the neutralization assay were highly correlated (r = 0.7253, r2 = 0.5261) than a linear correlation between the Elecsys® anti-N and neutralization assay (r = 0.5824, r2 = 0.3392). The levels of Elecsys® anti-S antibody and neutralizing activities were significantly higher in Group S than in Group M after 6 weeks from onset of symptoms (p < 0.05). Conversely, the levels of Elecsys® anti-N were comparable in both groups. Three immunosuppressed patients, including cancer patients, showed low levels of anti-S and anti-N antibodies and neutralizing activities throughout the measurement period, indicating the need for careful follow-up. Our data indicate that Elecsys® anti-S can predict the neutralization antibodies in COVID-19.

Background Although hyperinflammatory response influences the severity of coronavirus disease 2019 (COVID-19), little has been reported about the utility of tumor necrosis factor (TNF)-related biomarkers in reflecting the prognosis. We examined whether TNF receptors (TNFRs: TNFR1, TNFR2) and progranulin (PGRN) levels, in addition to interleukin 6 (IL-6) and C-reactive protein (CRP), are associated with mortality or disease severity in COVID-19 patients. Methods This retrospective study was conducted at Juntendo University Hospital. Eighty hospitalized patients with various severities of COVID-19 were enrolled. Furthermore, serum levels of TNF-related biomarkers were measured using enzyme-linked immunosorbent assay. Results Twenty-five patients died during hospitalization, and 55 were discharged. The median (25th and 75th percentiles) age of the study patients was 70 (61–76) years, 44 (55.0%) patients were males, and 26 (32.5%) patients had chronic kidney disease (CKD). When comparing with patients who received and did not receive treatment at the intensive care unit (ICU), the former had a higher tendency of being male and have diabetes, hypertension, and CKD; had higher levels of white blood cells, D-dimer, and lactate dehydrogenase; and had lower body mass index, estimated glomerular filtration rate, and lymphocyte counts. Significant differences were observed in TNFR, PGRN, IL-6, and CRP levels between each severity (mild–severe) group. Furthermore, the serum levels of TNFR, IL-6, and CRP, but not PGRN, in ICU patients were significantly higher than in the patients who were not admitted to the ICU. Multivariate logistic regression analysis demonstrated that high levels of TNFR2 were only associated with mortality in patients with COVID-19 even after adjustment for relevant clinical parameters. Conclusions High TNFR2 level might be helpful for predicting mortality or disease severity in patients with COVID-19.

Abstract We experienced a case of primary percutaneous coronary intervention for ST‐elevation myocardial infarction (STEMI) with coronavirus disease 2019 (COVID‐19) using appropriate infection prevention protocol. However, recanalization was difficult due to severe coagulopathy. Further researches are needed to clarify optimal treatment for STEMI in patients with COVID‐19.

To develop preventive and therapeutic measures against coronavirus disease 2019, the complete characterization of immune response and sustained immune activation following viral infection and vaccination are critical. However, the mechanisms controlling intrapersonal variation in antibody titers against SARS-CoV-2 antigens remain unclear. To gain further insights, we performed a robust molecular and cellular investigation of immune responses in infected, recovered, and vaccinated individuals. We evaluated the serum levels of 29 cytokines and their correlation with neutralizing antibody titer. We investigated memory B-cell response in patients infected with the original SARS-CoV-2 strain or other variants, and in vaccinated individuals. Longitudinal correlation analyses revealed that post-vaccination neutralizing potential was more strongly associated with various serum cytokine levels in recovered patients than in naïve individuals. We found that IL-10, CCL2, CXCL10, and IL-12p40 are candidate biomarkers of serum-neutralizing antibody titer after the vaccination of recovered individuals. We found a similar distribution of virus-specific antibody gene families in triple-vaccinated individuals and a patient with COVID-19 pneumonia for 1 year. Thus, distinct immune responses occur depending on the viral strain and clinical history, suggesting that therapeutic options should be selected on a case-by-case basis. Candidate biomarkers that correlate with repeated vaccination may support the efficacy and safety evaluation systems of mRNA vaccines and lead to the development of novel vaccine strategies.

Background: Computed tomography fractional flow reserve (CT-FFR), which can be acquired on-site workstation using fluid structure interaction during the multiple optimal diastolic phase, has an incremental diagnostic value over conventional coronary computed tomography angiography (CCTA). However, the appropriate location for CT-FFR measurement remains to be clarified. Method: A total of 115 consecutive patients with 149 vessels who underwent CCTA showing 30–90% stenosis with invasive FFR within 90 days were retrospectively analyzed. CT-FFR values were measured at three points: 1 and 2 cm distal to the target lesion (CT-FFR1cm, 2cm) and the vessel terminus (CT-FFRlowest). The diagnostic accuracies of CT-FFR ≤ 0.80 for detecting hemodynamically significant stenosis, defined as invasive FFR ≤ 0.80, were compered. Result: Fifty-five vessels (36.9%) had invasive FFR ≤ 0.80. The accuracy and AUC for CT-FFR1cm and 2cm were comparable, while the AUC for CT-FFRlowest was significantly lower than CT-FFR1cm and 2cm. (lowest/1cm, 2 cm = 0.68 (95 %CI 0.63–0.73) vs 0.79 (0.72–0.86, p = 0.006), 0.80 (0.73–0.87, p = 0.002)) The sensitivity and negative predictive value of CT-FFRlowest were 100%. The reclassification rates from positive CT-FFRlowest to negative CT-FFR1cm and 2cm were 55.7% and 54.2%, respectively. Conclusion: The diagnostic performance of CT-FFR was comparable when measured at 1-to-2 cm distal to the target lesion, but significantly higher than CT-FFRlowest. The lesion-specific CT-FFR could reclassify false positive cases in patients with positive CT-FFRlowest, while all patients with negative CT-FFRlowest were diagnosed as negative by invasive FFR.

ObjectivesTo determine the seroprevalence of anti-SARS-CoV-2 IgG and IgM antibodies in symptomatic Japanese COVID-19 patients.MethodsSerum samples (n = 114) from 34 COVID-19 patients with mild to critical clinical manifestations were examined. The presence and titers of IgG antibody for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were determined by a chemiluminescent microparticle immunoassay (CMIA) using Alinity i SARS-CoV-2 IgG and by an immunochromatographic (IC) IgM/IgG antibody assay using the Anti-SARS-CoV-2 Rapid Test.ResultsIgG was detected by the CMIA in 40%, 88%, and 100% of samples collected within 1 week, 1-2 weeks, and 2 weeks after symptom onset in severe and critical cases, and 0%, 38%, and 100% in mild/moderate cases, respectively. In severe and critical cases, the positive IgG detection rate with the IC assay was 60% within one week and 63% between one and two weeks. In mild/moderate cases, the positive IgG rate was 17% within one week and 63% between one and two weeks; IgM was positive in 80% and 75% of severe and critical cases, and 42% and 88% of mild/moderate cases, respectively. On the CMIA, no anti-SARS-CoV-2 IgG antibodies were detected in COVID-19 outpatients with mild symptoms within 10 days from onset, whereas 50% of samples from severe inpatients were IgG-positive in the same period. The IC assay detected higher IgM positivity earlier from symptom onset in severe and critical cases than in mild/moderate cases.ConclusionsA serologic anti-SARS-CoV-2 antibody analysis can complement PCR for diagnosing COVID-19 14 days after symptom onset.

Background: The concept of active atherosclerotic disease has been accepted for heart valve calcification (HVC). We investigated prevalence, distribution and related factors of HVC in patients who had undergone coronary CT angiography (CCTA). Methods: Subjects were consecutive 200 patients who underwent CCTA. The prevalence and the distribution of HVC using ECG gated non-contrast CT were investigated. Logistic regression analysis and simple regression analysis for factors associated with presence of the calcification and quantitative calcification in the aortic and mitral valve were conducted. Results: HVC was detected in 48.0%. Aortic valve calcification (AVC) was found in 92 cases, the most, followed by mitral valve calcification (MVC) in 25 cases, pulmonary valve in 3 cases, and tricuspid valve in 1 case. Although the left coronary cusp showed the most in 65.2%, no statistic significant difference for Agatston score was detected among each cusp in AVC. Multiple logistic regression analysis showed that age (OR:1.211, 95%C.I.:1.0716–1.1728, p

Background: A novel algorithm has been developed for the on-site analysis of CT-fractional flow reserve (CT-FFR) using fluid structural interactions. There have been no reports on the factors affecting the diagnostic performance of CT-FFR using this algorithm. We evaluated the factors predictive of false-positive CT-FFR findings compared to invasive FFR as a reference standard. Methods: The subjects were 66 consecutive cases (81 vessels) who underwent invasive FFR assessment within 90 days of the detection of 30–90% stenosis of one vessel of the major coronary artery, from among patients with suspected coronary arterial disease who underwent one-rotation scanning by 320-row coronary CT angiography (CCTA). The prospective CCTA mode was used for all patients, with the X-ray exposure set in a range of 70–99% of the RR interval. The FFR was calculated on-site from multiple cardiac phases. Factors associated with a false-positive finding of functional stenosis on CT-FFR, defined as an invasive FFR of ≤0.80, were evaluated using logistic regression analysis. Results: Thirty-nine vessels (48.1%) had an invasive FFR of ≤0.80. CT-FFR and invasive FFR values disagreed in 13 vessels in 13 patients. The values were false positive in 12 of the vessels. In an analysis of patient characteristics, the body mass index (odds ratio, 1.33; 95%CI, 1.06–1.67; p = 0.01) and Image noise (odds ratio, 1.18; 95%CI, 1.01–1.40; p = 0.04) were predictive of false-positive findings. The presence of calcified plaque (odds ratio, 5.16; 95%CI, 1.06–20.85; p = 0.01) was the only significant predictive factor in a vessel-based analysis of lesion characteristics. Conclusions: The presence of calcified plaque exerted a significant effect on the diagnostic performance of CT-FFR, and did so independently of the degree of calcification indicated by the Agatston score. Keywords: Coronary CT angiography, Local computation, Fractional flow reserve, Fluid structure interaction, False positive

Ectopic fat accumulation plays important roles in various metabolic disorders and cardiovascular diseases. Recent studies reported that myocardial triglyceride (TG) content measured by proton magnetic resonance spectroscopy ((1)H-MRS) is associated with aging, diabetes mellitus, and cardiac dysfunction. However, myocardial TG content in athletes has not yet been investigated. We performed (1)H-MRS and cardiac magnetic resonance imaging in 10 male endurance athletes and 15 healthy male controls. Serum markers and other clinical parameters including arterial stiffness were measured. Cardiopulmonary exercise testing was also performed. There were no significant differences in clinical characteristics including age, anthropometric parameters, blood test results, or arterial stiffness between the two groups. Peak oxygen uptakes, end-diastolic volume (EDV), end-systolic volume (ESV), left ventricular (LV) mass, peak ejection rates and peak filling rates were significantly higher in the athlete group than in the control group (all P