•Patients with COVID-19 were recruited from more than 70 institutes in Japan.•Japan experienced 3 waves of COVID-19 during the first year of the pandemic.•The case fatality rate of 3.2% was ...relatively low.•The data will be used for a genome-wide association study.
The coronavirus disease (COVID-19) pandemic is having a devastating effect worldwide. Host genome differences between populations may influence the severity of COVID-19.
The Japan COVID-19 Task Force is conducting host genome analysis of hospitalized patients with COVID-19 from more than 70 institutions nationwide in Japan. This report describes the clinical characteristics of patients enrolled to date.
The median (interquartile range) age of the 1674 patients included in the analysis was 59 (45–71) years, and more than half of the patients (66.2%) were male. Less than half of the patients (41.2%) had severe disease. The case fatality rate was 3.2%.
Since this is a hospital-based study, the number of severe cases was relatively high, but the case fatality rate was relatively low, when compared to that of other countries. In the future, we will continue to enroll patients and conduct genome analyses of patients with COVID-19.
B-cell receptors (BCRs) play a critical role in adaptive immunity as they generate highly diverse immunoglobulin repertoires to recognize a wide variety of antigens. To better understand immune ...responses, it is critically important to establish a quantitative and rapid method to analyze BCR repertoire comprehensively. Here, we developed "Bcrip", a novel approach to characterize BCR repertoire by sequencing millions of BCR cDNA using next-generation sequencer. Using this method and quantitative real-time PCR, we analyzed expression levels and repertoires of BCRs in a total of 17 peanut allergic subjects' peripheral blood samples before and after receiving oral immunotherapy (OIT) or placebo. By our methods, we successfully identified all of variable (V), joining (J), and constant (C) regions, in an average of 79.1% of total reads and 99.6% of these VJC-mapped reads contained the C region corresponding to the isotypes that we aimed to analyze. In the 17 peanut allergic subjects' peripheral blood samples, we observed an oligoclonal enrichment of certain immunoglobulin heavy chain alpha (IGHA) and IGH gamma (IGHG) clones (P = 0.034 and P = 0.027, respectively) in peanut allergic subjects after OIT. This newly developed BCR sequencing and analysis method can be applied to investigate B-cell repertoires in various research areas, including food allergies as well as autoimmune and infectious diseases.
The severity of chest X-ray (CXR) findings is a prognostic factor in patients with coronavirus disease 2019 (COVID-19). We investigated the clinical and genetic characteristics and prognosis of ...patients with worsening CXR findings during early hospitalization. We retrospectively included 1656 consecutive Japanese patients with COVID-19 recruited through the Japan COVID-19 Task Force. Rapid deterioration of CXR findings was defined as increased pulmonary infiltrates in ≥ 50% of the lung fields within 48 h of admission. Rapid deterioration of CXR findings was an independent risk factor for death, most severe illness, tracheal intubation, and intensive care unit admission. The presence of consolidation on CXR, comorbid cardiovascular and chronic obstructive pulmonary diseases, high body temperature, and increased serum aspartate aminotransferase, potassium, and C-reactive protein levels were independent risk factors for rapid deterioration of CXR findings. Risk variant at the ABO locus (rs529565-C) was associated with rapid deterioration of CXR findings in all patients. This study revealed the clinical features, genetic features, and risk factors associated with rapid deterioration of CXR findings, a poor prognostic factor in patients with COVID-19.
Inherited bone-marrow-failure syndromes (IBMFSs) include heterogeneous genetic disorders characterized by bone-marrow failure, congenital anomalies, and an increased risk of malignancy. Many lines of ...evidence have suggested that p53 activation might be central to the pathogenesis of IBMFSs, including Diamond-Blackfan anemia (DBA) and dyskeratosis congenita (DC). However, the exact role of p53 activation in each clinical feature remains unknown. Here, we report unique de novo TP53 germline variants found in two individuals with an IBMFS accompanied by hypogammaglobulinemia, growth retardation, and microcephaly mimicking DBA and DC. TP53 is a tumor-suppressor gene most frequently mutated in human cancers, and occasional germline variants occur in Li-Fraumeni cancer-predisposition syndrome. Most of these mutations affect the core DNA-binding domain, leading to compromised transcriptional activities. In contrast, the variants found in the two individuals studied here caused the same truncation of the protein, resulting in the loss of 32 residues from the C-terminal domain (CTD). Unexpectedly, the p53 mutant had augmented transcriptional activities, an observation not previously described in humans. When we expressed this mutant in zebrafish and human-induced pluripotent stem cells, we observed impaired erythrocyte production. These findings together with close similarities to published knock-in mouse models of TP53 lacking the CTD demonstrate that the CTD-truncation mutations of TP53 cause IBMFS, providing important insights into the previously postulated connection between p53 and IBMFSs.
•We analyzed the serum uric acid levels and hyperuricemia in patients with COVID-19.•High serum uric acid levels were associated with the requirement of invasive mechanical ventilation.•Low serum ...uric acid levels were also associated with the requirement of invasive mechanical ventilation.
This study aimed to identify the relationship between abnormal serum uric acid levels or a history of hyperuricemia and COVID-19 severity in the Japanese population.
We included 1523 patients enrolled in the Japan COVID-19 Task Force cohort between February 2020 and May 2021. We compared the clinical characteristics, including co-morbidities, laboratory findings, and outcomes, particularly invasive mechanical ventilation (IMV), among patients with and without abnormal uric acid levels or a history of hyperuricemia.
Patients with high serum uric acid levels were older and had higher body weight and body mass index than those without. In addition, the multiple logistic regression analysis revealed a significant association between high serum uric acid levels or a history of hyperuricemia and an increased risk of IMV (odds ratio OR = 1.77; P = 0.03/OR = 1.56; P = 0.04). Moreover, patients with low uric acid levels on admission were also associated significantly with the requirement of IMV (OR = 5.09; P <0.0001).
Abnormal serum uric acid levels or a history of hyperuricemia were significantly associated with COVID-19 severity in the Japanese cohort.
•Smoking and chronic obstructive pulmonary disease are known risk factors of severe COVID-19.•Cumulative smoking exposure was positively associated with COVID-19 outcomes.•In patients aged <65 years, ...chronic obstructive pulmonary disease affected disease severity in those with >30 pack-years.
Smoking and chronic obstructive pulmonary disease (COPD) are risk factors for severe COVID-19. However, limited literature exists on the effect of COPD and smoking on COVID-19 outcomes. This study examined the impact of smoking exposure in pack-years (PY) and COPD on COVID-19 outcomes among smokers in Japan.
The study included 1266 smokers enrolled by the Japan COVID-19 task force between February 2020 and December 2021. PY and COPD status was self-reported by patients. Patients were classified into the non-COPD (n = 1151) and COPD (n = 115) groups; the non-COPD group was further classified into <10 PY (n = 293), 10-30 PY (n = 497), and >30 PY (n = 361). The study outcome was the need for invasive mechanical ventilation (IMV).
The incidence of IMV increased with increasing PY and was highest in the COPD group (<10 PY = 7.8%, 10-30 PY = 12.3%, >30 PY = 15.2%, COPD = 26.1%; P <0.001). A significant association was found for IMV requirement in the >30 PY and COPD groups through univariate (odds ratio OR: >30 PY = 2.11, COPD = 4.14) and multivariate (OR: >30 PY = 2.38; COPD = 7.94) analyses. Increasing PY number was also associated with increased IMV requirement in patients aged <65 years.
Cumulative smoking exposure was positively associated with COVID-19 outcomes in smokers.
Abstract
Background
Respiratory symptoms are associated with coronavirus disease 2019 (COVID-19) outcomes. However, the impacts of upper and lower respiratory symptoms on COVID-19 outcomes in the ...same population have not been compared. The objective of this study was to characterize upper and lower respiratory symptoms and compare their impacts on outcomes of hospitalized COVID-19 patients.
Methods
This was a multicenter, retrospective cohort study; the database from the Japan COVID-19 Task Force was used. A total of 3314 COVID-19 patients were included in the study, and the data on respiratory symptoms were collected. The participants were classified according to their respiratory symptoms (Group 1: no respiratory symptoms, Group 2: only upper respiratory symptoms, Group 3: only lower respiratory symptoms, and Group 4: both upper and lower respiratory symptoms). The impacts of upper and lower respiratory symptoms on the clinical outcomes were compared. The primary outcome was the percentage of patients with poor clinical outcomes, including the need for oxygen supplementation via high-flow oxygen therapy, mechanical ventilation, and extracorporeal membrane oxygenation or death.
Results
Of the 3314 COVID-19 patients, 605, 1331, 1229, and 1149 were classified as Group 1, Group 2, Group 3, and Group 4, respectively. In univariate analysis, patients in Group 2 had the best clinical outcomes among all groups (odds ratio OR: 0.21, 95% confidence interval CI: 0.11–0.39), while patients in Group 3 had the worst outcomes (OR: 3.27, 95% CI: 2.43–4.40). Group 3 patients had the highest incidence of pneumonia, other complications due to secondary infections, and thrombosis during the clinical course.
Conclusions
Upper and lower respiratory tract symptoms had vastly different impacts on the clinical outcomes of COVID-19.
Abstract
Antimicrobial peptides (AMPs) are short peptides that play crucial roles in diverse biological processes and have various functional activities against target organisms. Due to the abuse of ...chemical antibiotics and microbial pathogens’ increasing resistance to antibiotics, AMPs have the potential to be alternatives to antibiotics. As such, the identification of AMPs has become a widely discussed topic. A variety of computational approaches have been developed to identify AMPs based on machine learning algorithms. However, most of them are not capable of predicting the functional activities of AMPs, and those predictors that can specify activities only focus on a few of them. In this study, we first surveyed 10 predictors that can identify AMPs and their functional activities in terms of the features they employed and the algorithms they utilized. Then, we constructed comprehensive AMP datasets and proposed a new deep learning-based framework, iAMPCN (identification of AMPs based on CNNs), to identify AMPs and their related 22 functional activities. Our experiments demonstrate that iAMPCN significantly improved the prediction performance of AMPs and their corresponding functional activities based on four types of sequence features. Benchmarking experiments on the independent test datasets showed that iAMPCN outperformed a number of state-of-the-art approaches for predicting AMPs and their functional activities. Furthermore, we analyzed the amino acid preferences of different AMP activities and evaluated the model on datasets of varying sequence redundancy thresholds. To facilitate the community-wide identification of AMPs and their corresponding functional types, we have made the source codes of iAMPCN publicly available at https://github.com/joy50706/iAMPCN/tree/master. We anticipate that iAMPCN can be explored as a valuable tool for identifying potential AMPs with specific functional activities for further experimental validation.
Organic matter in lake sediments contains information that can be used to reconstruct lake environmental histories over decades or centuries. In this study, we used organic geochemical proxies (i.e., ...total organic carbon TOC, TOC/total nitrogen TN atomic ratios C/N, stable carbon isotope ratios of TOC δ
13
C
TOC
and palmitic acid δ
13
C
C16:0
, and nitrogen isotope ratios of bulk sediment δ
15
N
bulk
) in sediments from Lake Kawaguchi, Japan, to reconstruct detailed histories of the organic matter accumulation and lake productivity over the past 130 years. Vertical profiles of the mass accumulation rate (MAR) of TOC in the eastern lake basin (core KAW14-7A) showed parallel increases with the C/N ratio from the 1960s to the 1980s, indicating an accelerated delivery of terrestrial organic matter via anthropogenic land-use change. In contrast, the C/N ratios in the western and central basins (cores KAW14-1A and KAW14-4B, respectively) were almost constant prior to the 1980s, suggesting that the increasing trends in the TOC MAR values in these cores are most likely attributable to the onset of eutrophication associated with rapid economic growth after the mid-1950s. On the other hand, the δ
15
N
bulk
showed a gradual increase from the late 1870s, providing evidence for anthropogenic nitrogen input to the lake prior to the apparent eutrophication. After the 1960s–1970s, the δ
15
N
bulk
values rapidly increased, demonstrating water deterioration associated with the direct nutrient discharge into the lake from domestic wastewater. The δ
13
C
C16:0
profiles displayed similar increasing trends to δ
15
N
bulk
from the mid-1960s, demonstrating a close relationship between lake productivity and anthropogenic nitrogen input in Lake Kawaguchi. Our geochemical records as a whole clearly show high algal productivity and enhanced deposition of organic matter in recent decades, suggesting that the amelioration of the lake water is a likely consequence of the transfer of nutrients to the sediment by enhanced productivity, rather than a decrease in the amount of nutrient inflow into the lake.
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