Incompletely resolved immune dysfunction in people living with HIV (PLWH) on antiretroviral treatment (ART) could differentially impact the CD4+ and CD8+ T cell subsets. In this study, we investigated SARS-CoV-2 vaccine-induced CD4+ and CD8+ T cell responses in 26 PLWH on ART following third-dose mRNA vaccination. Spike-specific CD4+ and CD8+ T cell responses were assessed based on the expression of activation markers, CD137/OX40 and CD137/CD25, respectively, in response to stimulation with overlapping peptides spanning the spike protein. All participants showed spike-specific T cell responses, with CD8+ responses at a higher median frequency than CD4+. Interestingly, 5 participants who showed a higher frequency of spike-specific CD4+, relative to CD8+ T cells, were significantly younger and had higher CD4 counts pre-ART, in comparison to other participants. Further multivariate analysis revealed that only CD4 count pre-ART was an important predictor of elevated spike-specific CD4+ T cell responses; however, no association was observed with neutralizing antibody (nAb) potency towards a SARS-CoV-2 spike. Our results highlight the heterogeneous immune functionality of vaccine-induced, SARS-CoV-2 spike-specific CD4+ and CD8+ T cells in PLHW on ART.

Tuberculosis (TB) is an endemic respiratory disease in several countries, including South Korea. The coronavirus disease 2019 (COVID-19) may pose greater risks to individuals with pre-existing respiratory diseases, but there are few reports on how the state after recovery from TB affects COVID-19 infection and mortality. This study aimed to investigate the susceptibility and mortality of COVID-19 in patients with a history of TB. We retrospectively analyzed data from the National Health Insurance Service of Korea. We extracted individuals with TB from 2011 to 2019 and matched them with a population-based control group. The main outcomes were COVID-19 incidence and death within 30 days of infection. The study included 138,278 matched pairs of individuals with and without a history of TB. COVID-19 incidence was slightly lower in the TB group (38.0% vs. 38.4%, P = 0.023). Subgroup analysis showed significantly lower COVID-19 incidence in the pulmonary TB group compared to controls (P = 0.001). However, the mortality rate was higher in the TB group (0.9% vs. 0.7%, P < 0.001). This study showed that TB has a slightly protective effect against COVID-19 infection but increases the mortality rate. These findings may guide future research on the interaction between TB and COVID-19.

Chronic inflammation and persistent immune activation (IA) during HIV infection are associated with non-AIDS complications. We investigated sociodemographic and clinical characteristics influencing IA and exhaustion (IE), and platelet activation (PA) in newly diagnosed people living with HIV (PLHIV) and identified modifiable factors for early interventions. We analyzed baseline blood samples from 365 PLHIV participating in a trial investigating the effect of aspirin on IA, IE, and PA. We assessed levels of markers of monocyte activation (soluble CD14), platelet activation (soluble P-selectin), T-cell activation (CD4 ⁺ and CD8 ⁺ expressing CD69 and co-expressing CD38 and HLA-DR), and T-cell exhaustion (PD-1). The median (IQR) age of the participants was 37 (28,45) years, with females comprising 64.7%. Advanced age significantly predicted IA and IE, but not PA. Markers of IA and IE, but not PA, inversely correlated with CD4 counts, while directly with HIV viral load (HVL). We show that most Tanzanian PLHIV initiating antiretroviral therapy (ART) have low CD4 counts and high HVL, with a considerable proportion aged above 50 years, characteristics associated with heightened IA and IE. Adjunctive therapy, when available, should target such population and at ART initiation to prevent morbidity and mortality associated with persistent IA and IE.

Hand, foot, and mouth disease (HFMD) caused by enteroviruses is common in children. Recently, coxsackievirus A6 (CVA6) has been identified as a major causative agent. In this study, we conducted a phylogenetic analysis of a part of the VP1 coding region of 194 CVA6 strains detected directly in 767 nasopharyngeal swab or stool samples of HFMD patients in Japan from 2019 to 2024. The detected CVA6 strains were classified into genotype D. Moreover, the strains detected from before 2019 to 2023 belonged to a cluster (cluster 1 and 2), whereas most of the strains detected in 2024 belonged to another cluster (cluster 3). Genetic identity among all detected CVA6 strains was 89.1–100%, and genetic identity within the cluster for each detected strain was 90.6–100% for the before 2019 (cluster 1) strains, 92.6–100% for the 2019–2023 (cluster 2) strains, and 94.5–100% for the 2024 (cluster 3) strains. Most of the strains detected in 2024 were similar to the strains detected in China in 2023, suggesting that the influx of new strains caused the 2024 outbreak in Japan. HFMD is one of the most prevalent diseases worldwide and its pathogenicity and antigenicity may change over time. Surveillance of the influx of new strains from outside Japan will become increasingly important.

Since we reported the first parechovirus A3-associated myalgia (PeVA3-M) outbreak in Yamagata in 2008 as an emerging disease, we have investigated PeVA3 infections as part of the National Epidemiological Surveillance of Infectious Diseases, Japan, in sentinel hospitals and clinics and also performed a specific symptomatic surveillance targeting PeVA3-M. As PeVA3-M has only been reported from Japan, it is necessary to continue the above surveillance. In our surveillance from July 2022 to December 2023, we found 31 PeVA3 infections, including three confirmed or suspected PeVA3-M cases, using PCR and a virus isolation method. Further next-generation sequencing (NGS) analysis was performed for the representative isolates and their original specimens between 2022 and 2023 as well as those between 2003 and 2019. NGS analysis showed that 7,245–7,309 and 7,118–7,287 nucleotides (98.7%–99.8% and 97.1%–99.4% compared with the reference strains) were available from 25 representative isolates and from 6 clinical specimens, respectively. This study indicated that the recombinant PeVA3 strains, which appeared in 2019, remained in circulation in Yamagata between 2022 and 2023. Furthermore, the NGS method is useful for the molecular epidemiological surveillance of PeVA3 infections, although improvements in the method used for the clinical specimens are required.