Artificial intelligence-based point-of-care lung ultrasound for screening COVID-19 pneumoniae: Comparison with CT scans.

BACKGROUND: Although 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). METHODS: We 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. RESULTS: A 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. INTERPRETATION: AI-POCUS using the novel pocket-size ultrasound system showed excellent agreement with CT-validated COVID-19 pneumonia, even when used by a novice observer.

Performance evaluation of the Ortho VITROS SARS-CoV-2 Spike-Specific Quantitative IgG test by comparison with the surrogate virus neutralizing antibody test and clinical assessment.

BACKGROUND: Despite 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. METHODS: The 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. RESULTS: VITROS 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. CONCLUSIONS: Although 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.

Performance evaluation of the Roche Elecsys® Anti-SARS-CoV-2 immunoassays by comparison with neutralizing antibodies and clinical assessment.

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.

Longitudinal Analyses after COVID-19 Recovery or Prolonged Infection Reveal Unique Immunological Signatures after Repeated Vaccinations.

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.

Circulating tumor necrosis factor receptors are associated with mortality and disease severity in COVID-19 patients.

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.

Activation of SARS-CoV-2 neutralizing antibody is slower than elevation of spike-specific IgG, IgM, and nucleocapsid-specific IgG antibodies.

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 < 0.0001). However, the kinetics of the SARS-CoV-2 NT antibody in severe cases were slower than that of anti-S and anti-N specific antibodies. These findings indicate a limitation of using the S-IgG antibody titer, detected by the chemiluminescent immunoassay, as a direct quantitative marker of neutralizing activity capacity. Antibody testing should be carefully interpreted when utilized as a marker for serological responses to facilitate diagnostic, therapeutic, and prophylactic interventions.

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force.

Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.

Molecular characterization of SARS-CoV-2 detected in Tokyo, Japan during five waves: Identification of the amino acid substitutions associated with transmissibility and severity

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.

DOCK2 is involved in the host genetics and biology of severe COVID-19.

Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1-5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.

Successful restart of chemotherapy in a patient with primary mediastinal nonseminomatous germ cell tumor after COVID-19 infection.

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.

Impact of a telemedicine system on work burden and mental health of healthcare providers working with COVID-19: a multicenter pre-post prospective study.

Background: The coronavirus disease 2019 (COVID-19) pandemic impacts not only patients but also healthcare providers. This study seeks to investigate whether a telemedicine system reduces physical contact in addressing the COVID-19 pandemic and mitigates nurses' distress and depression. Methods: Patients hospitalized with COVID-19 in 4 hospitals and 1 designated accommodation measured and uploaded their vital signs to secure cloud storage for remote monitoring. Additionally, a mat-type sensor placed under the bed monitored the patients' respiratory rates. Using the pre-post prospective design, visit counts and health care providers' mental health were assessed before and after the system was introduced. Results: A total of 100 nurses participated in the study. We counted the daily visits for 48 and 69 patients with and without using the telemedicine system. The average patient visits were significantly less with the system (16.3 [5.5-20.3] vs 7.5 [4.5-17.5] times/day, P = .009). Specifically, the visit count for each vital sign assessment was about half with the telemedicine system (all P < .0001). Most nurses responded that the system was easy to use (87.1%), reduced work burden (75.2%), made them feel relieved (74.3%), and was effective in reducing the infection risk in hospitals (79.1%) and nursing accommodations (95.0%). Distress assessed by Impact of Event Scale-Revised and depression by Patient Health Questionnaire-9 were at their minimum even without the system and did not show any significant difference with the system (P = .72 and .57, respectively). Conclusions: Telemedicine-based self-assessment of vital signs reduces nurses' physical contact with COVID-19 patients. Most nurses responded that the system is easy and effective in reducing healthcare providers' infection risk.

Successful treatment with steroid pulse therapy for a COVID-19 case with progressive respiratory failure during treatment for pleural metastasis of breast cancer.

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.

Retrospective Study on the Effects of Glucose Abnormality on COVID-19 Outcomes in Japan.

INTRODUCTION: To investigate the effects of glucose abnormality on outcomes of hospitalized coronavirus disease 2019 (COVID-19) patients in Japan. METHODS: This study retrospectively analyzed 393 COVID-19 patients admitted at Juntendo University Hospital. Patients were divided into subgroups according to history of diabetes and blood glucose (BG) levels and subsequently compared in terms of in-hospital death, invasive ventilation, or a composite of both. RESULTS: Patients with glucose abnormality demonstrated more risk factors for serious COVID-19, such as high body mass index, dyslipidemia, and hypertension, and higher biomarkers for inflammation compared to those with normal BG levels. Oxygen inhalation and steroid use were more frequent among patients with than without glucose abnormality. Invasive ventilation was more frequent in patients with diabetes (9.5% vs. 3.2%, p = 0.033) and BG ≥ 140 mg/dl (11.0% vs. 3.1%, p = 0.009) compared with those without diabetes and BG < 140 mg/dl, respectively. Logistic regression analysis showed that BG ≥ 140 mg/dl was a risk factor for invasive ventilation [odds ratio (OR) 2.87, 95% CI 1.04-7.68, p = 0.037] or the composite outcome (OR 3.03, 95% CI 1.21-7.38, p = 0.015) even after adjusting for by age and gender. Kaplan-Meier analysis showed that glucose abnormality was significantly associated with invasive ventilation and that BG ≥ 140 mg/dl was a risk factor for invasive ventilation [hazard ratio (HR) 2.68, 95% CI 1.05-6.82, p = 0.039] and the composite of death and invasive ventilation (HR 2.77, 95% CI 1.21-6.37, p = 0.016) regardless of age and gender. CONCLUSIONS: Glucose abnormality, particularly BG ≥ 140 mg/dl, was associated with serious outcomes among Japanese COVID-19 patients, suggesting the need to consider high BG as a major risk factor for poor clinical course also in Japan.

Performance and usefulness of a novel automated immunoassay HISCL SARS-CoV-2 Antigen assay kit for the diagnosis of COVID-19.

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 < 99, respectively. The kit did not cross-react with human coronaviruses causing seasonal common cold and influenza, and none of the 69 individuals without COVID-19 were diagnosed with positive results. Importantly, 81.8% of the samples with low virus load (< 50 copy numbers) were diagnosed as negative. Thus, using HISCL antigen assay kits may reduce overdiagnosis compared with RT-qPCR tests. The rapid and high-throughput HISCL SARS-CoV-2 Antigen assay kit developed here proved suitable for screening infectious COVID-19 and may help control the pandemic.

A Case of ST-Elevation Acute Myocardial Infarction in a Nonhospitalized Patient with SARS-CoV-2 Pneumonia: Treatment with Primary Percutaneous Coronary Intervention.

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.

COVID-19-induced acute renal tubular injury associated with elevation of serum inflammatory cytokine.

BACKGROUND: Severe acute respiratory syndrome Coronavirus 2 has rapidly spread worldwide, with acute kidney injury (AKI) as one of the manifestations with unknown causal mechanisms. We aimed to investigate tubular injury by assessing tubular markers and their association with the severity of Coronavirus disease 2019 (COVID-19). METHODS: We examined the associations between laboratory markers and urinary levels of N-acetyl-ß-D-glucosaminidase (uNAG), ß2-microglobulin (u ß2MG), α1-microglobulin (u α1MG), and liver-type fatty acid binding protein (L-FABP). We studied 18 COVID-19 patients without previous chronic kidney disease and analyzed the relationship between the urinary biomarkers and inflammatory markers in patients with severe (n = 7) or non-severe (n = 11) COVID-19, defined by requirements of supplemental oxygen. RESULTS: Fourteen patients (78%) showed abnormal urinalysis findings and two (11%) developed AKI. Patients with severe COVID-19 had significantly higher levels of proteinuria, uNAG, uß2MG, uα 1MG, and L-FABP than those with non-severe disease. Serum levels of interleukin-6 (IL-6) were significantly higher on admission in all severe COVID-19 cases and correlated with the levels of L-FABP, uß2MG, uα1MG, uNAG, and proteinuria. Moreover, the changes in serum IL-6 (ΔIL-6) levels from baseline to 7 days after admission significantly correlated with ΔL-FABP and Δuß2MG. CONCLUSIONS: Levels of tubular injury markers, especially L-FABP and uß2MG, were significantly associated with IL-6 levels even in patients with no evident AKI. This suggests that L-FABP and uß2MG could be useful as early detective biomarkers for COVID-19 associated renal injury.

Validation of telemedicine-based self-assessment of vital signs for patients with COVID-19: A pilot study.

INTRODUCTION: In the ongoing COVID-19 pandemic, the development of a system that would prevent the infection of healthcare providers is in urgent demand. We sought to investigate the feasibility and validity of a telemedicine-based system in which healthcare providers remotely check the vital signs measured by patients with COVID-19. METHODS: Patients hospitalized with confirmed or suspected COVID-19 measured and uploaded their vital signs to secure cloud storage. Additionally, the respiratory rates were monitored using a mat-type sensor placed under the bed. We assessed the time until the values became available on the Cloud and the agreements between the patient-measured vital signs and simultaneous healthcare provider measurements. RESULTS: Between 26 May-23 September 2020, 3835 vital signs were measured and uploaded to the cloud storage by the patients (n=16, median 72 years old, 31% women). All patients successfully learned how to use these devices with a 10-minute lecture. The median time until the measurements were available on the cloud system was only 0.35 min, and 95.2% of the vital signs were available within 5 min of the measurement. The agreement between the patients' and healthcare providers' measurements was excellent for all parameters. Interclass coefficient correlations were as follows: systolic (0.92, p<0.001), diastolic blood pressure (0.86, p<0.001), heart rate (0.89, p<0.001), peripheral oxygen saturation (0.92, p<0.001), body temperature (0.83, p<0.001), and respiratory rates (0.90, p<0.001). CONCLUSIONS: Telemedicine-based self-assessment of vital signs in patients with COVID-19 was feasible and reliable. The system will be a useful alternative to traditional vital sign measurements by healthcare providers during the COVID-19 pandemic.

Combination therapy with plasma exchange and glucocorticoid may be effective for severe COVID-19 infection: A retrospective observational study.

We retrospectively analyzed the characteristics and outcomes of five patients with COVID-19 who were received glucocorticoid (with or without pulse therapy) and therapeutic plasma exchange. The efficacy of the treatment was determined by whether the patient was able to be transferred from the COVID-19 exclusive ICU to the general ward. In comparing patients who received prednisolone pulse therapy (three cases) with those who did not (two cases), 2/3 (66%) and 0/2 (0%) patients could be discharged from the COVID-19 dedicated ICU, respectively. Among five patients who was performed plasma exchange, two elderly male patients who underwent plasma exchange as early as within 8 days of disease exacerbation survived and were able to be transferred to the general ward. This observational study indicates that plasma exchange in conjunction with methylprednisolone pulse therapy at the appropriate time may be an effective treatment for elderly patients with severe COVID-19.

Seroprevalence of anti-SARS-CoV-2 antibodies in Japanese COVID-19 patients.

OBJECTIVES: To determine the seroprevalence of anti-SARS-CoV-2 IgG and IgM antibodies in symptomatic Japanese COVID-19 patients. METHODS: Serum 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. RESULTS: IgG 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. CONCLUSIONS: A serologic anti-SARS-CoV-2 antibody analysis can complement PCR for diagnosing COVID-19 14 days after symptom onset.