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Although the two‐dose mRNA vaccination regime provides protection against SARS‐CoV‐2, older adults have been shown to exhibit poorer vaccination responses. In addition, the role of vaccine‐induced T‐cell responses is not well characterised. We aim to assess the impact of age on immune responses after two doses of the BNT162b2 mRNA vaccine, focussing on antigen‐specific T‐cells. A prospective 3‐month study was conducted on 15 young (median age 31 years, interquartile range (IQR) 25–35 years) and 14 older adults (median age 72 years, IQR 70–73 years). We assessed functional, neutralising antibody responses against SARS‐CoV‐2 variants using ACE‐2 inhibition assays, and changes in B and T‐cell subsets by high‐dimensional flow cytometry. Antigen‐specific T‐cell responses were also quantified by intracellular cytokine staining and flow cytometry. Older adults had attenuated T‐helper (Th) response to vaccination, which was associated with weaker antibody responses and decreased SARS‐CoV‐2 neutralisation. Antigen‐specific interferon‐γ (IFNγ)‐secreting CD4+ T‐cells to wild‐type and Omicron antigens increased in young adults, which was strongly positively correlated with their neutralising antibody responses. Conversely, this relationship was negative in older adults. Hence, older adults' relative IFNγ‐secreting CD4+ T cell deficiency might explain their poorer COVID‐19 vaccination responses. Further exploration into the aetiology is needed and would be integral in developing novel vaccination strategies and improving infection outcomes in older adults. [ABSTRACT FROM AUTHOR]

Long‐term complications from coronavirus disease 2019 (COVID‐19) are concerning, as survivors can develop subclinical multiorgan dysfunction. It is unknown if such complications are due to prolonged inflammation, and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccination may reduce sequela. We conducted a prospective longitudinal study on hospitalized patients over 24 months. Clinical symptoms were collected by self‐reporting during follow‐up, along with blood samples for quantification of inflammatory markers and immune cell frequencies. All patients were given one dose of mRNA vaccine at 12−16 months. Their immune profiles at 12 and 24 months were compared. Approximately 37% and 39% of our patients reported post‐COVID‐19 symptoms at 12 and 24 months, respectively. The proportion of symptomatic patients with more than one symptom decreased from 69% at 12 months to 56% at 24 months. Longitudinal cytokine profiling revealed a cluster of individuals with persistently high inflammatory cytokine levels 12 months after infection. Patients with prolonged inflammation showed elevated terminally differentiated memory T cells in their blood; 54% had symptoms at 12 months. The majority of inflammatory markers and dysregulated immune cells in vaccinated patients recovered to a healthy baseline at 24 months, even though symptoms persisted. Post‐COVID‐19 symptoms can linger for 2 years after the initial infection and are associated with prolonged inflammation. Prolonged inflammation in hospitalized patients resolves after 2 years. We define a set of analytes associated with persistent inflammation and presence of symptoms, which could be useful biomarkers for identifying and monitoring high‐risk survivors. [ABSTRACT FROM AUTHOR]

Waning antibody levels against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and the emergence of variants of concern highlight the need for booster vaccinations. This is particularly important for the elderly population, who are at a higher risk of developing severe coronavirus disease 2019 (COVID‐19) disease. While studies have shown increased antibody responses following booster vaccination, understanding the changes in T and B cell compartments induced by a third vaccine dose remains limited. We analyzed the humoral and cellular responses in subjects who received either a homologous messenger RNA(mRNA) booster vaccine (BNT162b2 + BNT162b2 + BNT162b2; "BBB") or a heterologous mRNA booster vaccine (BNT162b2 + BNT162b2 + mRNA‐1273; "BBM") at Day 0 (prebooster), Day 7, and Day 28 (postbooster). Compared with BBB, elderly individuals (≥60 years old) who received the BBM vaccination regimen display higher levels of neutralizing antibodies against the Wuhan and Delta strains along with a higher boost in immunoglobulin G memory B cells, particularly against the Omicron variant. Circulating T helper type 1(Th1), Th2, Th17, and T follicular helper responses were also increased in elderly individuals given the BBM regimen. While mRNA vaccines increase antibody, T cell, and B cell responses against SARS‐CoV‐2 1 month after receiving the third dose booster, the efficacy of the booster vaccine strategies may vary depending on age group and regimen combination. [ABSTRACT FROM AUTHOR]

Background Dengue and Chikungunya viruses can cause large-scale epidemics, with attack rates of up to 80%. In Tanzania, there have been repeated outbreaks of dengue fever, the most recent in 2018 and 2019, mostly affecting the coastal areas. Despite the importance of these viruses, there is limited knowledge on the epidemiology of dengue (DENV) and Chikungunya (CHIKV) in Tanzania. This study was conducted to investigate the prevalence of DENV and CHIKV in Kilombero Valley, Tanzania. Methods A cross-sectional study was conducted at Kibaoni Health Center in Kilombero Valley, Southeastern Tanzania, in the rainy and dry seasons of 2018. Febrile patients of any age and gender were enrolled from the outpatient department. Blood samples were taken and screened for DENV and CHIKV viral RNA by real-time reverse transcription polymerase chain reaction assays. Results Overall, 294 patients were recruited. Most were females (65%), and one-third of patients were aged 14–25 years. DENV and CHIKV were detected in 29 (9.9%) and 3 (1.0%) patients, respectively. DENV was detected across all age groups during both the dry and rainy seasons. Although all 4 DENV serotypes were detected, serotypes 1 and 3 dominated and were present in 14 patients (42.4%) each. Additionally, the study showed DENV-1 and DENV-3 co-infections. Conclusions This study reveals the co-circulation of all 4 DENV serotypes and CHIKV in Kilombero. Importantly, we report the first occurrence of DENV-4 in Tanzania. Unlike previous DENV outbreaks caused by DENV-2, the 2018 outbreak was dominated by DENV-1 and DENV-3. The occurrence of all serotypes suggests the possibility of severe clinical outcomes in future DENV epidemics in Tanzania. [ABSTRACT FROM AUTHOR]

Vaccine immunogenicity in transplant recipients can be impacted by the immunosuppressive (IS) regimens they receive. While BNT162b2 vaccination has been shown to induce an immune response in liver transplant recipients (LTRs), it remains unclear how different IS regimens may affect vaccine immunogenicity after a third BNT162b2 dose in LTRs, which is especially important given the emergence of the Omicron sublineages of SARS-CoV-2. A total of 95 LTRs receiving single and multiple IS regimens were recruited and offered three doses of BNT162b2 during the study period. Blood samples were collected on days 0, 90, and 180 after the first BNT162b2 dose. At each time point, levels of anti-spike antibodies, their neutralizing activity, and specific memory B and T cell responses were assessed. LTRs receiving single IS regimens showed an absence of poor immunogenicity, while LTRs receiving multiple IS regimens showed lower levels of spike-specific antibodies and immunological memory compared to vaccinated healthy controls after two doses of BNT162b2. With a third dose of BNT162b2, spike-specific humoral, memory B, and T cell responses in LTR significantly improved against the ancestral strain of SARS-CoV-2 and were comparable to those seen in healthy controls who received only two doses of BNT162b2. However, LTRs receiving multiple IS regimens still showed poor antibody responses against Omicron sublineages BA.1 and XBB. A third dose of BNT162b2 may be beneficial in boosting antibody, memory B, and T cell responses in LTRs receiving multiple IS regimens, especially against the ancestral Wuhan strain of SARS-CoV-2. However, due to the continued vulnerability of LTRs to presently circulating Omicron variants, antiviral treatments such as medications need to be considered to prevent severe COVID-19 in these individuals., Competing Interests: An application to hold a patent for the SFB assay has been filed (Singapore patent #10202009679P: A Method Of Detecting Antibodies And Related Products). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chang, Goh, Rouers, Fong, Tay, Chavatte, Hor, Loh, Huang, Tan, Neo, Kam, Yeo, Tan, Huang, Wang, Salleh, Ngoh, Wang, Leo, Lin, Lye, Young, Muthiah, Ng, Rénia and COVID-19 Study Group.)

Competing Interests: A patent application for the SFB assay has been filed (Singapore patent 10202009679P: A Method Of Detecting Antibodies And Related Products. YSG, LFPN, and LR). A patent application on the identified linear epitopes S14P5 and S20P2 has also been filed (PCT/SG2021/050178: Antibody-binding linear B cell epitopes of SARS-CoV and SARS-CoV-2. NKWY, SNA, GC, and LFPN). All other authors declare no conflict of interest.