Diagnostic utility of pharyngeal follicular structures in COVID-19: A large-scale cross-sectional study.

OBJECTIVES: Pharyngeal follicles similar to those seen in influenza have been observed in patients with coronavirus disease 2019 (COVID-19), suggesting their potential as early-stage diagnostic markers. In this study, we examined the diagnostic potential of pharyngeal follicles for COVID-19, particularly the Omicron variant and its subtypes, to obtain basic data for AI-based diagnostic imaging tools. METHODS: A cross-sectional study was conducted from July 21, 2022, to March 31, 2023, at the Tokyo Shinagawa Hospital's fever clinic. Participants aged ≥15 years who underwent real-time polymerase chain reaction testing for COVID-19 and pharyngeal examinations were included. Demographic details, symptom onset, throat pain, and vaccination status were also recorded. Pharyngeal structures were categorized into four groups: follicles, buds, mixed, or absent. RESULTS: Of the 1223 participants, 829 (67.8%) tested positive for COVID-19. Among those who tested positive, 73.6% (95% CI: 70.6%-76.6%) had follicular structures, compared to 52.8% (95% CI: 47.9%-57.7%) of those who tested negative (P = 1.0 × 10-12). Overall, 818 participants exhibited follicular structures (439 with follicles, 281 with buds, and 98 with mixed structures), while 405 lacked any follicular structures. Regression analysis identified throat pain and follicular structures as significant COVID-19 predictors (95% confidence intervals: 2.49-4.85 and 1.43-2.59, respectively). Mixed follicles were identified as a potentially characteristic feature of COVID-19. CONCLUSION: Pharyngeal follicular structures demonstrated high sensitivity for early COVID-19 diagnosis.

Comparison of liver fibrosis scores and fatty liver on computed tomography as risk factors for severity of COVID-19.

Background and Aim: Increased liver fibrosis scores (LFS), such as fibrosis-4 index (FIB-4) or non-alcoholic fatty liver disease fibrosis score (NFS), and fatty liver are known risk factors for severe coronavirus disease 2019 (COVID-19). The purpose of this study was to identify the best scores, which predict the prognosis of COVID-19. Methods: Participants comprised consecutive Japanese COVID-19 patients admitted to our hospital between February 14, 2020, and April 14, 2021. Multivariate logistic regression analysis was performed to evaluate the relationships between LFS (FIB-4, NFS, aspartate aminotransferase-to-platelet ratio index [APRI], BARD score, and hepatic steatosis index [HSI]) or fatty liver on computed tomography (CT), and severity of COVID-19. Results: Of the 415 patients (mean age, 59 years), 177 patients (42.7%) needed oxygen therapy, 90 patients (21.7%) worsened to severe COVID-19, and 45 patients (10.8%) died during admission. Multivariate logistic regression analysis showed that increased FIB-4 and NFS were risk factors for death, severe COVID-19, and oxygen demand; that increased BARD was a risk factor for severe COVID-19 and oxygen demand; and that increased APRI and HSI were not risk factors for any status of COVID-19. Furthermore, increased NFS or BARD and fatty liver were independent risk factors for severe COVID-19 and oxygen demand. Conclusions: This study showed that FIB-4 and NFS were the best liver fibrosis scores that predicted worse prognosis for COVID-19, and that increased NFS or BARD and fatty liver evident on CT represented independent risk factors for severe COVID-19 and oxygen demand.

Nonepisodic angioedema with eosinophilia following a rose-thorn prick injury.

Background: Nonepisodic angioedema with eosinophilia (NEAE) is a condition marked by angioedema and significant eosinophilia and often linked with atopic dermatitis. It predominantly affects young Asian women and occurs more frequently in the autumn and winter. Despite over 100 reported cases, its etiology and pathogenesis remain unclear. Case presentation: A 23-year-old Japanese female florist presented with acute arm swelling following rose-thorn pricks to her hands and fingers in spring. One week later, she developed progressive symmetrical non-pitting edema in her lower legs and a 3 kg weight gain without any rash. She had a history of oral allergy syndrome to apples and pears for which allergen-specific IgE were previously detected. Blood tests showed significant eosinophilia (14,930 cells/µL) and elevated thymus and activation-regulated chemokine (TARC) levels (12,864 pg/mL). Thyroid disease, autoimmune disorders, and hematologic malignancies were ruled out. Normal cardiac markers and a whole-body computed tomography excluded visceral organ involvement. She was diagnosed with NEAE and treated with oral prednisolone, which resolved the edema within 10 days. Prednisolone was tapered gradually on an outpatient basis without recurrence. Conclusion: A review of the literature indicates that NEAE triggered by subcutaneous antigen exposure may not follow the typical age or seasonal patterns. Direct subcutaneous antigen exposure, including rose-thorn pricks, can trigger NEAE. Clinicians should consider NEAE in atypical presentations and thoroughly investigate preceding episodes.

Effectiveness and duration of additional immune defense provided by SARS-CoV-2 infection before and after receiving the mRNA COVID-19 vaccine BNT162b2.

Background: Our investigation focused whether infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) before or after receiving the mRNA COVID-19 vaccine can increase immune protection. And we also investigated relationship of infection acquired. Methods: Three shots of the mRNA coronavirus disease 2019 (COVID-19) vaccine BNT162b2 were administered to 736 healthcare workers at Tokyo Shinagawa Hospital. Serum samples were collected before the first shot (P1), at one month (P2), and at six months (P3) after the second shot and at one month after the third shot (P4). The presence of infection was assessed using IgG against the nucleocapsid (IgG (N) and RBD in the spike protein of SARS-CoV-2. We defined infection before P2 as natural infection (NI) and infection between P2 and P3 as breakthrough infection (BI) and compared susceptibility to further infection between the NI (-) and NI (+) groups and between BI (-) and BI (+) groups. Events in 485 participants who had a complete dataset of IgG (N) and IgG (RBD) from P1 to P4 were analyzed. Results: The presence of SARS-CoV-2 infection before P2 were examined by examining the titers of IgG (N)P1, IgG (N) P2, and IgG (RBD) P1 that exceeded the cutoff values. Consequently, 35 participants (7.22 %) were categorized into the NI (+) group, whereas 450 (92.8 %) were categorized into the NI (-) group. Between P2 and P3, the NI (-) group showed a higher rate of SARS-CoV-2 infection than the NI (+) group; however, there was no significant difference in the infection rate between P3 and P4. The infection rate was significantly lower in the BI (+) group than in the BI (-) group. Pre-primary vaccination infection significantly increased IgG (RBD) levels between P1 and P3. Post-primary vaccination infection significantly increased IgG (RBD) levels between P3 and P4. Conclusions: Infection with SARS-CoV-2 before or after receiving the mRNA COVID-19 vaccine can increase immune protection; however, the duration of this effect may be limited.

Successful Treatment with Mycophenolate Mofetil in a Patieint with Anti-MDA 5 Antibody-positive Interstitial Lung Disease and Posterior Reversible Encephalopathy syndrome: A Case Report.

A 59-year-old woman presented with a rash on the top part of her hands and pain in the wrist joint and was diagnosed with dermatomyositis complicated by interstitial pneumonia positive for anti-melanoma differentiation-associated gene 5 (MDA-5) antibody. However, the patient reported a severe headache following treatment with oral prednisolone and tacrolimus. Posterior reversible encephalopathy syndrome (PRES) was diagnosed based on the brain magnetic resonance imaging findings. Tacrolimus was discontinued, and mycophenolate mofetil was instead administered with a favorable outcome. Mycophenolate mofetil should therefore be considered as an alternative treatment for anti-MDA-5-positive interstitial lung disease in cases where calcineurin inhibitors cannot be used.

Surveillance of seasonal influenza viruses during the COVID-19 pandemic in Tokyo, Japan, 2018-2023, a single-center study.

Introduction: COVID-19 pandemic led to significant reductions in influenza detection worldwide, fueling debates on whether influenza truly ceased circulating in communities. The number of influenza cases decreased significantly in Japan, raising concerns about the potential risk of decreased immunity to influenza in the population. Our single-center study aimed to investigate influenza trends before and during the COVID-19 pandemic in Tokyo, Japan. Materials and Methods: This cross-sectional study included patients of all ages who visited Tokyo Shinagawa Hospital between April 1, 2018, and March 31, 2023. Influenza and COVID-19 tests were conducted using Quick Navi-Flu2 and polymerase chain reaction (PCR). We analyzed data from before and during the COVID-19 epidemic, based on patient background, hospitalization, and deaths, collected from medical records. Results: A total of 12 577 influenza tests were conducted, with approximately 100 tests consistently performed each month even in the influenza off-season. Throughout the observation period, 962 positive cases were identified. However, no cases were observed for 27 months between March 2020 and November 2022. Influenza A cases were reobserved in December 2022, followed by influenza B cases in March 2023, similar to the influenza incidence reports from Tokyo. The positivity rate during the 2022-2023 winter season was lower than before the COVID-19 epidemic and decreased in elderly patients, with no hospitalizations or deaths observed. Conclusion: This single-center study provided actual trend data for influenza patients before and during COVID-19 outbreaks in Tokyo, which could offer insights into the potential impact and likelihood of influenza virus infection in Japan.

Heterologous SARS-CoV-2 spike protein booster elicits durable and broad antibody responses against the receptor-binding domain.

The immunogenicity of mRNA vaccines has not been well studied when compared to different vaccine modalities in the context of additional boosters. Here we show that longitudinal analysis reveals more sustained SARS-CoV-2 spike receptor-binding domain (RBD)-binding IgG titers with the breadth to antigenically distinct variants by the S-268019-b spike protein booster compared to the BNT162b2 mRNA homologous booster. The durability and breadth of RBD-angiotensin-converting enzyme 2 (ACE2) binding inhibitory antibodies are pronounced in the group without systemic adverse events (AEs) after the S-268019-b booster, leading to the elevated neutralizing activities against Omicron BA.1 and BA.5 variants in the stratified group. In contrast, BNT162b2 homologous booster elicited antibodies to spike N-terminal domain in proportion to the AE scores. High-dimensional immune profiling identifies early CD16+ natural killer cell dynamics with CCR3 upregulation, as one of the correlates for the distinct anti-RBD antibody responses by the S-268019-b booster. Our results illustrate the combinational effects of heterologous booster on the immune dynamics and the durability and breadth of recalled anti-RBD antibody responses against emerging virus variants.

A case of reinfection with a different variant of SARS-CoV-2: case report.

Background: Coronavirus disease 2019 (COVID-19) was previously thought to have a low reinfection rate, but there are concerns that the reinfection rate will increase with the emergence and spread of mutant variants. This report describes the case of a 36-year-old, non-immunosuppressed man who was infected twice by two different variants of COVID-19 within a relatively short period. Case presentation: A 36-year-old Japanese man with no comorbidities was infected with the E484K variant (R.1 lineage) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Symptoms were mild and improved with symptomatic treatment alone. About four months later he presented to another outpatient department with high fever and headache. We diagnosed him as infected with the Alpha variant (B.1.1.7) of SARS-CoV-2 based on SARS-CoV-2 real-time reverse transcription polymerase chain reaction testing (RT-PCR). The patient was hospitalized with high fever. The patient received treatment in the form of anti-inflammatory therapy with corticosteroid and antibacterial chemotherapy. The patient improved without developing severe disease. Conclusion: Concerns have been raised that the reinfection rate of COVID-19 will increase with the emergence of mutant variants. Particularly in mild cases, adequate amounts of neutralizing antibodies may not be produced, and reinfection may thus occur. Continued attention to sufficient infection control is thus essential.