Human Gut Microbiota and Its Metabolites Impact Immune Responses in COVID-19 and Its Complications.

BACKGROUND & AIMS: We investigate interrelationships between gut microbes, metabolites, and cytokines that characterize COVID-19 and its complications, and we validate the results with follow-up, the Japanese 4D (Disease, Drug, Diet, Daily Life) microbiome cohort, and non-Japanese data sets. METHODS: We performed shotgun metagenomic sequencing and metabolomics on stools and cytokine measurements on plasma from 112 hospitalized patients with SARS-CoV-2 infection and 112 non-COVID-19 control individuals matched by important confounders. RESULTS: Multiple correlations were found between COVID-19-related microbes (eg, oral microbes and short-chain fatty acid producers) and gut metabolites (eg, branched-chain and aromatic amino acids, short-chain fatty acids, carbohydrates, neurotransmitters, and vitamin B6). Both were also linked to inflammatory cytokine dynamics (eg, interferon γ, interferon λ3, interleukin 6, CXCL-9, and CXCL-10). Such interrelationships were detected highly in severe disease and pneumonia; moderately in the high D-dimer level, kidney dysfunction, and liver dysfunction groups; but rarely in the diarrhea group. We confirmed concordances of altered metabolites (eg, branched-chain amino acids, spermidine, putrescine, and vitamin B6) in COVID-19 with their corresponding microbial functional genes. Results in microbial and metabolomic alterations with severe disease from the cross-sectional data set were partly concordant with those from the follow-up data set. Microbial signatures for COVID-19 were distinct from diabetes, inflammatory bowel disease, and proton-pump inhibitors but overlapping for rheumatoid arthritis. Random forest classifier models using microbiomes can highly predict COVID-19 and severe disease. The microbial signatures for COVID-19 showed moderate concordance between Hong Kong and Japan. CONCLUSIONS: Multiomics analysis revealed multiple gut microbe-metabolite-cytokine interrelationships in COVID-19 and COVID-19related complications but few in gastrointestinal complications, suggesting microbiota-mediated immune responses distinct between the organ sites. Our results underscore the existence of a gut-lung axis in COVID-19.

Successful management of persistent COVID-19 using combination antiviral therapy (nirmatrelvir/ritonavir and remdesivir) and intravenous immunoglobulin transfusion in an immunocompromised host who had received CD20 depleting therapy for follicular lymphoma.

The management of persistent symptomatic coronavirus disease 2019 (COVID-19) infections in immunocompromised patients remains unclear. Here, we present the first case of successful antiviral therapy (nirmatrelvir/ritonavir and remdesivir) in combination with intravenous immunoglobulin (IVIg) in a patient who had received CD20 depleting therapy for follicular lymphoma and experienced recurrent COVID-19 relapses. After the patient received IVIg treatment, the viral load decreased without recurrence. Subsequently, it was found that the anti-spike antibody titer in the administered immunoglobulin was high at 9528.0 binding antibody units/mL. Our case highlights the potential of combination therapy with selective IVIg and antiviral drugs for relapsed immunocompromised COVID-19 patients who have received CD20 depleting therapy.

Extracellular aaRSs drive autoimmune and inflammatory responses in rheumatoid arthritis via the release of cytokines and PAD4.

OBJECTIVES: Recent studies demonstrate that extracellular-released aminoacyl-tRNA synthetases (aaRSs) play unique roles in immune responses and diseases. This study aimed to understand the role of extracellular aaRSs in the pathogenesis of rheumatoid arthritis (RA). METHODS: Primary macrophages and fibroblast-like synoviocytes were cultured with aaRSs. aaRS-induced cytokine production including IL-6 and TNF-α was detected by ELISA. Transcriptomic features of aaRS-stimulated macrophages were examined using RNA-sequencing. Serum and synovial fluid (SF) aaRS levels in patients with RA were assessed using ELISA. Peptidyl arginine deiminase (PAD) 4 release from macrophages stimulated with aaRSs was detected by ELISA. Citrullination of aaRSs by themselves was examined by immunoprecipitation and western blotting. Furthermore, aaRS inhibitory peptides were used for inhibition of arthritis in two mouse RA models, collagen-induced arthritis and collagen antibody-induced arthritis. RESULTS: All 20 aaRSs functioned as alarmin; they induced pro-inflammatory cytokines through the CD14-MD2-TLR4 axis. Stimulation of macrophages with aaRSs displayed persistent innate inflammatory responses. Serum and SF levels of many aaRSs increased in patients with RA compared with control subjects. Furthermore, aaRSs released PAD4 from living macrophages, leading to their citrullination. We demonstrate that aaRS inhibitory peptides suppress cytokine production and PAD4 release by aaRSs and alleviate arthritic symptoms in a mouse RA model. CONCLUSIONS: Our findings uncovered the significant role of aaRSs as a novel alarmin in RA pathogenesis, indicating that their blocking agents are potent antirheumatic drugs.

Aortic endograft infection by Mycobacterium abscessus subsp. massiliense with acquired clarithromycin resistance: a case report.

BACKGROUND: Mycobacterium abscessus subsp. massiliense (MMA) comprises a group of non-tuberculous, rapidly growing mycobacteria. Although MMA can cause pulmonary diseases, surgical site infections, and disseminated diseases, aortic endograft infection has not been reported. Here, we describe the first case of aortic endograft infection caused by MMA. CASE PRESENTATION: Two months after stent-graft insertion for an abdominal aortic aneurysm, an 85-year-old man was admitted with fever and abdominal pain and was diagnosed with aortic endograft infection. Despite 14 days of meropenem and vancomycin intravenous administration, periaortic fluid pooling increased as compared to that before antibiotic administration. The abscess was drained, and fluorescent acid-fast staining of the abscess fluid revealed bacilli. We conducted genetic tests on the genes hsp65, rpoB, and sodA, performed Whole Genome Sequencing (WGS), and identified the organism as MMA. Intravenous imipenem-cilastatin (IPM/CS), amikacin (AMK), and oral clarithromycin (CAM) were administered. After 2 months, oral CAM and sitafloxacin were administered because the abscess had decreased in size. However, after 6 weeks, the abscess increased in size again. Antimicrobial susceptibility testing of the drainage fluid from the abscess resulted in the isolation of an MMA strain that had acquired resistance to CAM. Intravenous IPM/CS, AMK, and oral linezolid were added to the treatment regimen along with oral CAM and STFX. However, he was not fully cured and died 6 months later. Neither the full-length erythromycin ribosome methyltransferase (erm)(41) gene nor the rrl or rpIV gene mutations were found by Sanger sequencing in the pre- and post-treatment strains. Whole-genome sequence analysis of the post-treatment strain revealed mutations in genes with no previous reports of association with macrolide resistance. CONCLUSIONS: Aortic endograft infection caused by MMA strain is extremely rare; nonetheless, MMA should be suspected as the causative microorganism when broad-spectrum antimicrobials are ineffective.

The safety of plasma apheresis from donors recovering from COVID-19 infection in Japan.

PURPOSE: Since 2020, the novel coronavirus infection (COVID-19) has spread globally. A few studies have investigated the safety of COVID-19 convalescent plasma (CCP) apheresis from COVID-19. This study was the first retrospective observational study of CCP in Japan. METHODS: We recruit donors from April 2020 to November 2021 and plasmapheresis in our center (NCGM: national center for global health and medicine). We set the primary endpoint as the Donors Adverse Event (DAE) occurrence at the time of the CCP collection. Variable selection was used to explore the determinants of DAE. RESULTS: Mean and SD age was 50.5 (10.6) years old. Seventy-three (42.2 %) were female, and 87 (33.3 %) were multiple-times donors. Twelve (6.97 % by donors and 4.6 % in total collections) adverse events occurred. The DAEs were VVR (Vaso Vagal Reaction), paresthesia, hypotension, agitation, dizziness, malaise, and hearing impairment/paresthesia. Half of them were VVR during apheresis. DAE occurred only in first-time donors and more in severe illnesses such as using ventilation and ECMO. From the donor characteristics and variable selection, the risk factors are as follows: younger age, female, the severity of disease at the time of the disease, and lower SBP before initiation. Our DAE incidence did not differ from previous studies. DAEs were more likely to occur in CCP apheresis than in healthy donors. CONCLUSION: We confirm the safety of CCP apheresis in this study, although DAEs were more than healthy donors. More caution should be exercised in the plasma collection for future outbreaks of emerging infectious diseases.

Serum Concentrations of Infliximab and IL-6 for Predicting One-Year Discontinuation of Infliximab Treatment Owing to Secondary Non-response in Patients with Rheumatoid Arthritis.

Secondary non-response to infliximab (IFX) occurs in some patients with rheumatoid arthritis (RA). Although therapeutic drug monitoring (TDM) is a useful tool to optimize IFX therapy, it is unclear whether it can help to identify the risk of secondary non-response. This study aimed to explore the utility of serum levels of IFX or other biomarkers to predict IFX discontinuation owing to secondary non-response. A single-center, retrospective study was conducted using the Kyoto University Rheumatoid Arthritis Management Alliance cohort database between 2011 and 2020. Serum IFX levels were measured using liquid chromatography-tandem mass spectrometry. An electrochemiluminescence assay was used to quantify serum levels of tumor necrosis factor-α and interleukin-6 and detect anti-drug antibodies. Eighty-four out of 310 patients were eligible for this study. The cutoff levels of biomarkers were determined by receiver operating characteristic analysis. IFX persistence was similar between groups stratified using IFX levels, tumor necrosis factor-α levels, interleukin-6 levels, and anti-drug antibodies positivity. The group with lower IFX and higher interleukin-6 levels had the worst therapy persistence (p = 0.017) and the most frequent disease worsening (90.0%, p < 0.001). Evaluating both interleukin-6 and IFX levels, not just IFX alone, enabled us to identify patients at risk of discontinuing IFX treatment. These findings support the utility of measuring IFX and interleukin-6 levels for successful maintenance therapy for RA.

Clinical efficacy of remdesivir for COVID-19 in children: A propensity-score-matched analysis.

Clinical efficacy of remdesivir in children with COVID-19 is unclear. This propensity-score-matched retrospective cohort study of children with COVID-19 showed that the rate of patients achieving defervescence on Day 4 was higher in the remdesivir group than in the non-remdesivir group, but was not statistically different (86.7% vs 73.3%, P = 0.333).

Comparison of clinical characteristics of COVID-19 in pregnant women between the Delta and Omicron variants of concern predominant periods.

BACKGROUND: Information regarding effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant strains on clinical manifestations and outcomes of coronavirus disease 2019 (COVID-19) in pregnant women is limited. METHODS: A retrospective observational study was conducted using the data from the nationwide COVID-19 registry in Japan. We identified pregnant patients with symptomatic COVID-19 hospitalized during the study period. The Delta and Omicron variants of concern (VOC) predominant periods were defined as August 1 to December 31, 2021 and January 1 to May 31, 2022, respectively. Clinical characteristics were compared between the patients in the Delta and Omicron VOC periods. In addition, logistic regression analysis was performed to identify risk factors for developing moderate-to-severe COVID-19. RESULTS: During the study period, 310 symptomatic COVID-19 cases of pregnant women were identified; 111 and 199 patients were hospitalized during the Delta and Omicron VOC periods, respectively. Runny nose and sore throat were more common, and fatigue, dysgeusia, and olfactory dysfunction were less common manifestations observed in the Omicron VOC period. In the multivariable logistic regression analysis, onset during the later stage of pregnancy (OR: 2.08 [1.24-3.71]) and onset during the Delta VOC period (OR: 2.25 [1.08-4.90]) were independently associated with moderate-to-severe COVID-19, whereas two doses of SARS-CoV-2 vaccine were protective against developing moderate-to-severe COVID-19 (OR: 0.34 [0.13-0.84]). CONCLUSIONS: Clinical manifestations of COVID-19 in pregnant women differed between the Delta and Omicron VOC periods. SARS-CoV-2 vaccination was still effective in preventing severe COVID-19 throughout the Delta and Omicron VOC periods.

A nationwide cross-sectional study using a web-based questionnaire survey of the duration of isolation of COVID-19 inpatients with cancer at Japanese cancer centers.

There is no clear consensus regarding the optimal isolation duration for immunocompromised patients with coronavirus disease 2019 (COVID-19). Therefore, we conducted a questionnaire survey at eight Japanese cancer centers to investigate the practices of infectious disease specialists regarding the duration of isolation for COVID-19 inpatients with cancer. For asymptomatic to severely ill COVID-19 inpatients without severe immunodeficiency, four centers reported at least 10 days of isolation without testing, and two reported at least 20 days. Two centers incorporated polymerase chain reaction (PCR) as a criterion for terminating the isolation of inpatients without severe immunodeficiency. For severely immunocompromised COVID-19 inpatients, at least 20 days of isolation were required in seven facilities, regardless of illness severity. Additionally, seven centers had implemented Ct or antigen quantification test values as criteria for de-isolating severely immunocompromised inpatients. No cases caused nosocomial outbreaks after isolation was terminated based on each facility's criteria for isolation termination. Thus, cancer patients required longer isolation periods than the general population in most facilities, and for those with severe immunodeficiency, the isolation periods were longer and more tightly controlled with tests.

Characteristics of preventive intervention acceptance for international travel among clients aged 60 years and older from a Japanese multicenter pretravel consultation registry.

OBJECTIVES: Pretravel consultation (PTC) is important for older adults owing to health problems associated with overseas travel. Although older adults in Japan, their PTC characteristics are less known. This study aimed to investigate the epidemiology of clients aged ≥ 60 years based on data from the Japan Pre-travel Consultation Registry (J-PRECOR). METHODS: Clients aged ≥ 60 years who visited J-PRECOR cooperative hospitals from February 1, 2018, to May 31, 2022, were included. The primary endpoint was a comparison of prescriptions for vaccines for hepatitis A, tetanus toxoid, and malaria prophylaxis in travelers to high-risk malaria countries in yellow fever vaccination (YFV)-available facilities with and without YFV. RESULTS: In total, 1000 clients (median age: 67 years) were included. Although 523 clients were immunized with YFV, only 38.6% of the 961 unimmunized clients were vaccinated with the tetanus toxoid-containing vaccine. Malaria chemoprophylaxis was prescribed to 25.7% of clients traveling for ≤55 days. At YFV-capable institutes, 557 clients traveling to yellow fever risk countries took PTC, 474 of whom received YFV and 83 were unvaccinated. Lower age (odds rate 0.85 per 1 year; 95% CI 0.80-0.90) and lower hepatitis A vaccination rate (0.29; 95% CI 0.14-0.63) were significantly associated with YFV. CONCLUSIONS: Preventive interventions other than YFV should be offered to older adults.

Two Cases of Breakthrough Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infections Caused by the Omicron Variant (B.1.1.529 Lineage) in International Travelers to Japan.

In November 2021, the World Health Organization designated a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern, Omicron (PANGO lineage B.1.1.529). We report on the first 2 cases of breakthrough coronavirus disease 2019 (COVID-19) caused by Omicron in Japan among international travelers returning from the country with undetected infection. The spread of infection by Omicron were considered.

Clinical Characteristics and Outcomes of Coronavirus Disease 2019 (COVID-19) in Pregnant Women: A Propensity Score-Matched Analysis of Data From the COVID-19 Registry Japan.

BACKGROUND: Several studies have investigated whether pregnancy is a risk factor for developing severe coronavirus disease 2019 (COVID-19); however, the results remain controversial. In addition, the information regarding risk factors for developing severe COVID-19 in pregnant women is limited. METHODS: A retrospective cohort study analyzing the data from the nationwide COVID-19 registry in Japan was conducted. Propensity score-matched analysis was performed to compare COVID-19 severity between pregnant and nonpregnant women. Multivariate analysis was also conducted to evaluate risk factors for developing moderate-to-severe COVID-19 in pregnant women. RESULTS: During the study period, 254 pregnant and 3752 nonpregnant women of reproductive age were identified. After propensity score matching, 187 pregnant women and 935 nonpregnant women were selected. A composite outcome of moderate-to-severe COVID-19 was more frequently observed in pregnant women than that of nonpregnant women (n = 18 [9.6%] vs n = 46 [4.9%]; P = .0155). In multivariate analysis, the presence of underlying diseases and being in the second-to-third trimester of pregnancy were recognized as risk factors for moderate-to-severe COVID-19 in pregnant women (odds ratio [95% confidence interval]: 5.295 [1.21-23.069] and 3.871 [1.201-12.477], respectively). CONCLUSIONS: Pregnancy could be a risk factor for moderate-to-severe COVID-19 for women in Japan. In addition to the presence of comorbidities, advanced pregnancy stages may contribute to greater risks for developing moderate-to-severe COVID-19 in pregnant women.

Duration of Infectious Virus Shedding by SARS-CoV-2 Omicron Variant-Infected Vaccinees.

To determine virus shedding duration, we examined clinical samples collected from the upper respiratory tracts of persons infected with severe acute respiratory syndrome coronavirus 2 Omicron variant in Japan during November 29-December 18, 2021. Vaccinees with mild or asymptomatic infection shed infectious virus 6-9 days after onset or diagnosis, even after symptom resolution.

N-terminus of Etanercept is Proteolytically Processed by Dipeptidyl Peptidase-4.

PURPOSE: Biologics are structurally heterogeneous and can undergo biotransformation in the body. Etanercept (ETN) is a fusion protein composed of a soluble tumor necrosis factor (TNF) receptor and the Fc portion of human immunoglobulin G1. The N-terminus of ETN has a putative sequence cleaved by dipeptidyl peptidase-4 (DPP-4). The purpose of this study was to investigate the biotransformation of ETN in humans and mice and evaluate its effects on functional properties. METHODS: An analytical method using liquid chromatography-mass spectrometry (LC-MS/MS) was established. The N-terminal heterogeneity of ETN was assessed in the serum of patients with rheumatoid arthritis or mice receiving ETN. The in vitro N-terminal truncation was explored using recombinant DPP-4. The binding affinity to TNF-α or TNF-ß was investigated using an in-house enzyme-linked immunosorbent assay. RESULTS: In the formulations, about 90% of ETN had an intact N-terminus, while the N-terminal truncated form was most abundant in the serum of the patients with rheumatoid arthritis and mice. Recombinant human DPP-4 cleaved two amino acids from the N-terminus of ETN in vitro. Sitagliptin, a DPP-4 inhibitor, inhibited N-terminal truncation both in vivo and in vitro. However, N-terminal truncation did not affect the binding ability to TNF-α or TNF-ß and the pharmacokinetics of ETN. ETN biosimilars exhibited similar characteristics to the reference product in vivo and in vitro. CONCLUSIONS: ETN undergoes N-terminal truncation in the body, and DPP-4 cleaves exogenous ETN via N-terminal proteolysis. The application of an MS-based assay will detect novel biotransformation of therapeutic proteins.

A rapid and universal liquid chromatograph-mass spectrometry-based platform, refmAb-Q nSMOL, for monitoring monoclonal antibody therapeutics.

Accurate quantitation of antibodies is critical for development of monoclonal antibody therapeutics (mAbs). Therapeutic drug monitoring has been applied to measure levels of mAbs in clinics for dose adjustment for autoimmune disease. Trough levels of mAbs can be a biomarker for cancer immunotherapy. Thus, the deployment of a rapid and universal platform for mAb monitoring may benefit processes ranging from drug development to clinical practice for a wide spectrum of diseases. However, mAb monitoring often requires development and conduct of an individual ligand binding assay such as ELISA, which is impractical to scale. We streamlined quantitation of antibody therapeutics by a nano-surface and molecular-orientation limited (nSMOL) proteolysis assay using LC-MS with a universal reference antibody (refmAb-Q), for accurate multiplexed quantitation of unique signature peptides derived from mAbs. This innovative refmAb-Q nSMOL platform may provide a practical solution for quantitating an ever-increasing number of mAbs from developmental to clinical use settings.

Chromosomal coharboring of blaIMP-60 and mcr-9 in Enterobacter asburiae isolated from a Japanese woman with empyema: a case report.

BACKGROUND: Polymyxin E (colistin) is a last-resort antibiotic to treat infections caused by carbapenemase-producing Enterobacteriaceae (CPE). However, reports of CPEs resistant to colistin have been increasing, and the mcr genes are emerging as resistance mechanisms. Among them, plasmid-mediate mcr-9 is known to be associated with colistin resistance, whereas reports on chromosomal mcr-9 and its association with colistin resistance in humans are few. CASE PRESENTATION: We identified Enterobacter asburiae harboring mcr-9 and blaIMP-60 in the pleural fluid of a patient with empyema. The long-read sequencing technique revealed that these genes were located on its chromosome. Despite the lack of exposure to colistin, the organism showed microcolonies in the inhibition circle in the E-test and disk diffusion test. Antibiotic susceptibility testing by broth microdilution confirmed its resistance to colistin. CONCLUSION: Our case report showed that mcr-9 can be present not only on plasmids but also on the chromosome in E. asburiae, and that the presence of mcr-9 on its chromosome may influence its susceptibility to colistin.

Evaluation of the QIAstat-Dx Respiratory SARS-CoV-2 panel, a rapid multiplex PCR method for the diagnosis of COVID-19.

INTRODUCTION: Rapid, simple, and accurate methods are required to diagnose coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to evaluate the performance of the QIAstat-Dx Respiratory SARS-CoV-2 Panel (QIAstat-SARS-CoV-2), a rapid multiplex PCR assay for SARS-CoV-2 detection. METHODS: Nasopharyngeal swabs (NPS) that were obtained from patients with COVID-19 who were diagnosed at the National Center for Global Health and Medicine were used in this study. When the NPS samples were found to be negative for SARS-CoV-2 after treatment, they were used as negative samples. We evaluated the performance of the QIAstat-SARS-CoV-2 comparing SARS-CoV-2 detection with the National Institute of Infectious Diseases in Japan-recommended real-time polymerase chain reaction (RT-PCR) method (NIID-RT-PCR). RESULTS: In total, 45 NPS samples were analyzed. The proportion of overall agreement between QIAstat-SARS-CoV-2 and NIID-RT-PCR on 45 samples was 91.0% with a sensitivity of 84.0% (21/25), specificity at 100% (20/20), negative predictive value at 83.3% (20/24), and positive predictive value at 100% (21/21). There were no patients with co-infections with pathogens other than SARS-CoV-2. CONCLUSIONS: QIAstat-SARS-CoV-2 showed a high agreement in comparison with the NIID-RT-PCR for the detection of SARS-CoV-2. The QIAstat-SARS-CoV-2 also provided a rapid and accurate diagnosis for COVID-19, even when the concurrent detection of other respiratory pathogens was desired, and therefore, has the potential to direct appropriate therapy and infection control precautions.

Comparison of the clinical characteristics and outcomes of COVID-19 in children before and after the emergence of Delta variant of concern in Japan.

Delta variant of concern (VOC) is the current predominant severe acute respiratory coronavirus type 2 strain causing coronavirus disease 2019 (COVID-19); however, information regarding the impact of the Delta VOC on clinical features and outcomes in pediatric patients with COVID-19 is limited. We conducted a retrospective observational study using the data of patients <18 years of age in COVIREGI-JP, the COVID-19 registry in Japan. The patients were divided into two groups according to the timing of enrollment in the registry (pre-Delta VOC era, October 2020 to May 2021; and Delta VOC era, August to October 2021), and the clinical characteristics and outcomes were compared between the two groups. During the study period, 950 and 349 pediatric patients were registered in the pre-Delta VOC and Delta VOC eras, respectively. The median patient age was younger and the proportion of patients with underlying diseases was higher in the Delta VOC era than that in the pre-Delta VOC era (10.0 vs 7.0 years, P < 0.001, and 7.4% [n = 70] vs. 12.6% [n = 44], P = 0.004, respectively). Significantly more patients were admitted to the intensive care unit in the Delta VOC era than in the pre-Delta VOC era (1.4% [ n = 5] vs. 0.1% [n = 1], P = 0.006), but no patient in either group died or required mechanical ventilation or extracorporeal membrane oxygenation throughout the study period, suggesting that the overall outcomes in children with COVID-19 remained favorable even in the Delta VOC era in Japan.

Clinical characteristics of COVID-19 in hospitalized children during the Omicron variant predominant period.

INTRODUCTION: Information regarding the clinical manifestations and outcomes of coronavirus disease 2019 (COVID-19) in children under the Omicron variant predominant period is still limited. METHODS: A nationwide retrospective cohort study was conducted. Pediatric COVID-19 patients (<18 years of age) hospitalized between August 1, 2021 and March 31, 2022 were enrolled. Epidemiological and clinical characteristics between the Delta variant predominant period (August 1 to December 31, 2021) and the Omicron variant predominant period (January 1 to March 31, 2022) were compared. RESULTS: During the study period, 458 cases in the Delta predominant period and 389 cases in the Omicron predominant period were identified. Median age was younger (6.0 vs. 8.0 years, P = 0.004) and underlying diseases were more common (n = 65, 16.7% vs. n = 53, 11.6%) in the Omicron predominant period than those in the Delta variant predominant era. For clinical manifestations, fever ≥38.0 °C at 2 to <13 years old, sore throat at ≥ 13 years, and seizures at 2 to <13 years old were more commonly observed, and dysgeusia and olfactory dysfunction at ≥ 6 years old were less commonly observed in the Omicron variant predominant period. The number of patients requiring noninvasive oxygen support was higher in the Omicron predominant period than that in the Delta predominant period; however, intensive care unit admission rates were similar and no patients died in both periods. CONCLUSIONS: In the Omicron variant predominant period, more pediatric COVID-19 patients experienced fever and seizures, although the overall outcomes were still favorable.

Antibody titers and neutralizing activity in cases of COVID-19 after a single dose of vaccination.

Vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have shown high efficacy in preventing the onset of disease. However, the immune response to infection immediately after the first vaccination remains unknown. We examined the anti-SARS-CoV-2-binding-antibody titers and neutralizing activity in patients who developed coronavirus disease 2019 after the first vaccination. The amount of anti-SARS-CoV-2-binding antibodies and neutralizing activity drastically increased from the first to the second collection. Our results may provide important data on the course of immune response following vaccination.