Extracellular vesicles as potential diagnostic markers for kidney allograft rejection.

Kidney transplantation is a highly effective treatment for end-stage kidney disease. However, allograft rejection remains a significant clinical challenge in kidney transplant patients. Although kidney allograft biopsy is the gold-standard diagnostic method, it is an invasive procedure. Since the current monitoring methods, including screening of serum creatinine and urinary protein, are not of sufficient sensitivity, there is a need for effective post-transplant monitoring to detect allograft rejection at an early stage. Extracellular vesicles are vesicles with a lipid bilayer that originate from different cell types in pathological and physiological conditions. The content of extracellular vesicles reflects the status of cells at the time of their production. This review comprehensively summarizes clinical, in vivo, and in vitro reports that highlight the potential of extracellular vesicles as diagnostic biomarkers for kidney allograft rejection. Clarification would facilitate differentiation between rejection and non-rejection and identification of the mechanisms involved in the allograft rejection. Despite increasing evidence, further research is necessary to establish the clinical utility of extracellular vesicles in the diagnosis and monitoring of allograft rejection in kidney transplant recipients. Using extracellular vesicles as non-invasive biomarkers for diagnosis of kidney allograft rejection could have tremendous benefits in improving patient outcomes and reduce the need for invasive procedures.

Comparative immunohistochemical analysis of inflammatory cytokines in distinct subtypes of Sweet syndrome.

Background: A dysregulated immune response has been implicated in Sweet syndrome (SS) pathogenesis; however, cytokine profiles across different conditions associated with SS - including adult-onset immunodeficiency (AOID) due to anti-interferon (IFN)-γ autoantibodies - remain unknown. Objective: To investigate alterations in inflammatory cytokines in skin lesions of distinct subtypes of SS. Methods: Skin biopsies were collected from 42 AOID- and 52 non-AOID-associated SS patients and 18 healthy controls. The comparative immunohistochemical study was conducted using monoclonal antibodies against interleukin (IL)-1ß, IL-6, IL-17, IFN-γ, and tumor necrosis factor-α on paraffin-embedded sections. The quantitative percentage positivity and intensity were calculated using computer-based image analysis. Results: The results showed stronger and more diffuse dermal immunoreactivity for IFN-γ and IL-17 in the AOID-associated (p < 0.001 and p < 0.001, respectively) and non-AOID-associated SS (p < 0.001 and p < 0.001, respectively) groups. However, no significant differences in the levels of these two cytokines were observed between the AOID- and non-AOID-associated SS groups. Increased expression of IFN-γ together with IL-17 was also noted in almost all subtypes among non-AOID-associated SS. Conclusions: These results demonstrate that IFN-γ and IL-17 are implicated in immunopathology of all SS subtypes, including AOID-associated SS, despite the presence of anti-IFN-γ autoantibodies.

Safety and immunogenicity of CoronaVac and ChAdOx1 heterologous prime-boost vaccines in an overweight population in Chiang Mai, Thailand.

Background: In early 2021, the Ministry of Public Health of Thailand announced heterologous regimens for COVID-19 vaccines using CoronaVac as the first dose followed by ChAdOx1 nCoV-19 at 3 weeks apart. Priority was given to individuals above 60 years old and those who had seven underlying conditions, including obesity. The vaccine regimen was evaluated for safety and immunogenicity in overweight populations in Chiang Mai, Thailand. Methods: Participants who had a COVID-19 vaccination appointment for the heterologous prime-boost regimen were enrolled. Before each immunization and on day 28 following the second dosage, blood samples were taken, and were examined for anti-spike and neutralizing antibodies by using an indirect ELISA and virus neutralization assays. Safety profile of the vaccine regimen was assessed via a self-recorded diary of adverse events after each vaccination. Results: No serious adverse events related to vaccination were reported during study period and the majority of adverse reactions were fatigue and pain at the injection site. The levels of anti-spike IgG were 26.3, 56.4 and 1752.1 BAU/mL at baseline, 21 days after first dose and 28 days after second dose, respectively. At 4 weeks after complete vaccination, the median inhibition rates of neutralizing antibody determined by surrogate neutralization assay against wild type, Delta and Omicron variants were 95.2, 85.0 and 3.8, respectively. Moreover, the NT50 level against wild type and Delta variants determined by pseudotyped virus neutralization assay were 133.3 and 41.7, respectively. The neutralizing activity against Omicron variant was almost lower than cutoff level for detection. Conclusions: The heterologous CoronaVac-ChAdOx1vaccination was safe, well-tolerated and able to induce humoral immunity against wild-type and Delta variants but not against the Omicron variant in overweight population.

Human Leukocyte Antigen Markers for Distinguishing Pustular Psoriasis and Adult-Onset Immunodeficiency with Pustular Reaction.

Pustular skin diseases, with pustular psoriasis (PP) being the prototype, are immune-mediated diseases characterized by the presence of multiple pustules, resulting from neutrophil accumulation in the layer of epidermis. Sterile skin pustular eruption, like PP, is also observed in 20-30% of patients with adult-onset immunodeficiency syndrome (AOID) and anti-interferon γ autoantibodies (IFN-γ), leading to challenges in classification and diagnosis. While the mechanism underlying this similar phenotype remains unknown, genetic factors in relation to the immune system are suspected of playing an important role. Here, the association between human leukocyte antigen (HLA) genes, which play essential roles in antigen presentation, contributing to immune response, and the presence of skin pustules in AOID and PP was revealed. HLA genotyping of 41 patients from multiple centers in Thailand who presented with multiple sterile skin pustules (17 AOID patients and 24 PP patients) was conducted using a next-generation-sequencing-based approach. In comparison to healthy controls, HLA-B*13:01 (OR = 3.825, 95%CI: 2.08-7.035), C*03:04 (OR = 3.665, 95%CI: 2.102-6.39), and DQB1*05:02 (OR = 2.134, 95%CI: 1.326-3.434) were significantly associated with the group of aforementioned conditions having sterile cutaneous pustules, suggesting a common genetic-related mechanism. We found that DPB1*05:01 (OR = 3.851, p = 0.008) and DRB1*15:02 (OR = 3.195, p = 0.033) have a significant association with pustular reaction in AOID patients, with PP patients used as a control. A variant in the DRB1 gene, rs17885482 (OR = 9.073, p = 0.005), was observed to be a risk factor for PP when using AOID patients who had pustular reactions as a control group. DPB1*05:01 and DRB1*15:02 alleles, as well as the rs17885482 variant in the DRB1 gene, were proposed as novel biomarkers to differentiate PP and AOID patients who first present with multiple sterile skin pustules without known documented underlying conditions.

Changes in atherosclerotic cardiovascular disease risk over time among people living with HIV.

OBJECTIVE: To describe changes in atherosclerotic cardiovascular disease (ASCVD) risk over time among people living with HIV (PLHIV). METHODS: We used data from the TREAT Asia HIV Observational Database (TAHOD) and the Australian HIV Observational Database (AHOD). Five-year ASCVD risk was calculated using the D:A:D equation. Individuals were eligible for inclusion if they were aged ≥18 years, had started ART, had no previous history of ASCVD and had complete ASCVD risk factor data available within the first 5 years of ART initiation. RESULTS: A total of 3368 adults contributed data, 3221 were from TAHOD and 147 were from AHOD. The median age at ART initiation was 36 [IQR 31-43] years for TAHOD participants, and 42 [IQR 35-50] years for AHOD participants. Most TAHOD (70.4%) and AHOD (91.8%) participants were male. Overall, ASCVD risk increased from 0.84% (95% CI 0.81%-0.87%) at ART initiation to 1.34% (95% CI 1.29%-1.39%) after 5 years on ART. After adjusting for traditional and HIV-associated ASCVD risk factors, ASCVD risk increased at a similar rate among sub-populations defined by HIV exposure (heterosexuals, men who have sex with men, people who inject drugs), race/ethnicity (Caucasian and Asian) and nadir CD4 at ART initiation (<200 and ≥200 cells/mm3). CONCLUSIONS: These findings emphasize the growing burden of ASCVD risk among PLHIV and the need to develop interventions that are effective across a broad range of HIV sub-populations.

Health Behaviors and Attitudes Toward HIV Clinic Among Young Men who Have Sex with Men Living with HIV in Chiang Mai, Thailand: A Mixed Methods Study.

Today, many young men who have sex with men (YMSM) with a new HIV infection were diagnosed and successfully linked to HIV services. Studies on their health behaviors while living with HIV and their attitude toward the HIV clinic are scarce. We characterized common health behaviors of YMSM and assessed their perspective towards the existing HIV services. We collected data from a self-administered questionnaire and in-depth interviews (IDI) using a mixed-method cross-sectional study design. A hundred YMSM, aged 18-24, who attended the HIV clinic were enrolled. Their median age was 23 years (interquartile range, IQR 21-24). Eighty-four (84%) were gay men. Their common health behaviors included 15 (15%) being current smokers and 30 (30%) using alcohol regularly. Sixty-four (64%) reported > 95% antiretroviral treatment adherence, while 32 (32%) self-reported adherence at 80-95%. Fifty-three (53%) reported 100% condom use, while 30 (30%) reported using a condom in > 80% of their sexual activities. From the questionnaire respondents, individual characteristics of providers were the most critical factor affecting participants' willingness to attend HIV services. From the IDI, social disclosure of HIV status was their primary concern, with the presence of self- and anticipating HIV-related stigma issues. In summary, YMSM living with HIV who regularly attended the HIV clinic had a low frequency of health risk behaviors. Most did not socially disclose their serostatus but could manage their health. They were generally satisfied with patient-friendly services while calling to protect their confidentiality and privacy.

Safety and immunogenicity of the third and fourth doses of vaccine against SARS-CoV-2 following a 2-dose regimen of inactivated whole-virion SARS-CoV-2 vaccine.

This study followed healthcare personnel (HCP) who had completed a primary series of CoronaVac and then received the third and fourth doses of COVID-19 vaccine. The primary objective was to determine the seroconversion rate of neutralizing antibodies against wild-type SARS-CoV-2 and VOCs at day 28 after the third dose of vaccine and day 28 after the fourth dose of vaccine. This prospective cohort study was conducted at Maharaj Nakorn Chiang Mai Hospital, a tertiary care hospital affiliated to Chiang Mai University from July 2021 to February 2022. Two hundred and eighty-three participants were assessed for eligibility; 142 had received AZD1222 and 141 BNT162b2 as the third dose. Seroconversion rates using a 30% inhibition cutoff value against wild-type SARS-CoV-2 were 57.2%, 98.6%, 97.8%, and 98.9% at points before and after the third dose, before and after the fourth dose, respectively among those receiving AZD1222 as the third dose. Frequencies were 31.9%, 99.3%, 98.9%, and 100% among those receiving BNT162b2 as the third dose, respectively. The seroconversion rates against B.1.1.529 [Omicron] were 76.1% and 90.2% (p-value 0.010) at 4 weeks after the third dose in those receiving AZD1222 and BNT162b2 as the third dose, respectively. After a booster with the mRNA vaccine, the seroconversion rates increased from 21.7 to 91.3% and from 30.4 to 91.3% in those receiving AZD1222 and BNT162b2 as the third dose, respectively. No serious safety concerns were found in this study. In conclusion, antibody responses waned over time regardless of the vaccine regimen. The booster dose of the vaccine elicited a humoral immune response against SARS-CoV-2 including SARS-CoV-2 variants of concern, including B.1.1.529 [Omicron], which was circulating during the study period. However, the results might not be extrapolated to other Omicron sublineages.

Correction: Narongkiatikhun et al. Immunogenicity and Safety of Homologous and Heterologous Prime-Boost of CoronaVac® and ChAdOx1 nCoV-19 among Hemodialysis Patients: An Observational Prospective Cohort Study. Vaccines 2023, 11, 175.

The authors wish to make the following correction to this paper [...].

Profiles of gut microbiota associated with clinical outcomes in patients with different stages of SARS-CoV-2 infection.

The correlation between SARS-CoV-2 infection and gut microbiota has been a subject of growing interest in recent research endeavors. It is postulated that SARS-CoV-2 might lead to gut dysbiosis by affecting the gut-lung axis and reducing the production of antimicrobial peptides in the gastrointestinal tract. Our comprehensive review of both in vivo and clinical studies has revealed a consistent decline in alpha diversity and increased dissimilarity in beta diversity of gut microbiota in comparison to healthy populations, observed during both the acute and post-infection phases of COVID-19. Furthermore, there is a notable reduction in the number of beneficial butyrate-producing bacteria, alongside an upsurge in opportunistic bacteria. Concomitantly, the functional and metabolic characteristics of gut microbiota are significantly altered. Consequently, COVID-19 patients exhibit a heightened inflammatory state, which has been linked to the severity of the disease in the acute phase and the occurrence of post-acute COVID-19 syndrome (PACS) in the post-infection phase. Notably, certain specific gut microbiota species have emerged as potential candidates for aiding in the diagnosis, prediction of disease severity, or treatment of severe cases of COVID-19. This review also underscores the significance of gut microbiota in the context of post-acute COVID-19 syndrome (PACS) and offers valuable insights into possible biomarkers for diagnosis and therapeutic targets for PACS in the future.

Pythiosis presenting with chronic swelling and painful subcutaneous lesion at right deltoid.

Pythiosis is a fatal disease which has high incidence in tropical regions. In contrast with vascular pythiosis, cutaneous and subcutaneous pythiosis are both uncommon. Here, we report a case of subcutaneous pythiosis in a pregnant farmer manifested with a progressively larger and more painful mass at right deltoid. The tissue culture and molecular test were negative for fungi. The diagnosis was supported by the positivity of serum immunochromatographic test (ICT) for pythiosis. Patients responded well to the combination therapy of itraconazole, terbinafine and azithromycin.

Comparison of antibody responses following natural infection with Severe Acute Respiratory Syndrome Coronavirus 2 or receipt of CoronaVac or ChAdOx1 (AZD1222) vaccination in Chiang Mai, Thailand.

Background: In Thailand, early vaccination initiatives for SARS-CoV-2 relied on CoronaVac (Sinovac Life Sciences) and ChAdOx1 (Oxford-AstraZeneca) vaccines. However, the data of immunogenicity of these two vaccines in Thai populations is limited. This real time, head-to-head comparative study was conducted to investigate antibody (Ab) responses to SARS-CoV-2 following infection or receipt of either CoronaVac or ChAdOx1 vaccination in Chiang Mai, Thailand. Methods: Sera was collected within two months from participants having a history of documented SARS-CoV-2 infection or at one month after the second dose of CoronaVac vaccine. Sera from participants with a history of receiving one dose of ChAdOx1 vaccination was collected twice, at one month following each vaccine dose. Neutralizing antibodies (NAbs) were assessed using the surrogate neutralization test and anti-spike protein antibodies were assessed using an in-house enzyme-linked immunosorbent assay. Results: The prevalence of NAbs against SARS-CoV-2 was 92.1 %, 95.7 %, 64.1 % and 100 % in the infection group, CoronaVac group, ChAdOx1 group after 1st dose, and ChAdOx1 group after 2nd dose, respectively. The inhibition rate in individuals receiving two doses of ChAdOx1 vaccine (90.8%) was significantly higher than individuals who had recovered from natural infection (71.7%) or individuals who had received two doses of CoronaVac vaccine (66.7%). The prevalence of anti-spike Abs was 97.4 %, 97.8 %, 97.4 % and 100 % in the infection group, CoronaVac group, ChAdOx1 group after 1st dose, and ChAdOx1 group after 2nd dose, respectively. Significantly higher levels of anti-spike Abs were observed in the ChAdOx1 group after two doses of vaccination (1975 AU/mL) compared to those who had recovered from natural infection (468.5 AU/mL) and individuals who had received CoronaVac (554.4 AU/mL). Neutralizing activity had a statistically significant positive correlation with levels of anti-spike Abs. Conclusions: ChAdOx1 vaccine may provide superior immunogenicity than CoronaVac and natural infection.

Immunogenicity and Safety of Homologous and Heterologous Prime-Boost of CoronaVac® and ChAdOx1 nCoV-19 among Hemodialysis Patients: An Observational Prospective Cohort Study.

BACKGROUND: Vaccines that prevent SARS-CoV-2 infection are considered the most promising approach to modulating the pandemic. There is scarce evidence on the efficacy and safety of different vaccine prime-boost combinations in MHD patients since most clinical trials have used homologous mRNA vaccine regimens. METHODS: This prospective observational study assessed the immunogenicity and safety of homologous CoronaVac® (SV-SV), ChAdOx1 nCoV-19 (AZD1222) (AZ-AZ), and the heterologous prime-boost of SV-AZ, among MHD patients. RESULTS: A total of 130 MHD participants were recruited. On day 28, after the second dose, seroconversion results of the surrogate virus neutralization test were not different between vaccine regimens. The magnitude of the receptor-binding domain-specific IgG was highest among the SV-AZ. Different vaccine regimens had a distinct impact on seroconversion, for which the heterologous vaccine regimen demonstrated a higher probability of seroconversion (OR 10.12; p = 0.020, and OR 1.81; p = 0.437 for SV-AZ vs. SV-SV, and SV-AZ vs. AZ-AZ, respectively). There were no serious adverse events reported in any of the vaccine groups. CONCLUSIONS: Immunization with SV-SV, AZ-AZ, and SV-AZ could generate humoral immunity without any serious adverse events among MHD patients. Using the heterologous vaccine prime-boost seemed to be more efficacious in terms of inducing immunogenicity.

Cryptococcal Meningitis: Differences between Patients with and without HIV-Infection.

Background: Cryptococcal meningitis is one of the most devastating infections, particularly in HIV-infected individuals. The increased use of immunosuppressants led to an increase in the incidence of cryptococcosis in HIV-uninfected individuals. This study aimed to compare the characteristics between groups. Methods: This retrospective cohort study was conducted from 2011 to 2021 in northern Thailand. Individuals diagnosed with cryptococcal meningitis aged ≥15 years were enrolled onto the study. Results: Out of 147 patients, 101 were individuals infected with HIV and 46 were non-infected. Factors associated with being infected with HIV included age < 45 years (OR 8.70, 95% CI 1.78-42.62), white blood cells < 5000 cells/cu.mm. (OR 7.18, 95% CI 1.45-35.61), and presence of fungemia (OR 5.86, 95% CI 1.17-42.62). Overall, the mortality rate was 24% (18% in HIV-infected vs. 37% in HIV-uninfected individuals, p-value = 0.020). Factors associated with mortality included concurrent pneumocystis pneumonia (HR 5.44, 95% CI 1.55-19.15), presence of alteration of consciousness (HR 2.94, 95% CI 1.42-6.10), infection caused by members of C. gattii species complex (HR 4.19, 95% CI 1.39-12.62), and anemia (HR 3.17, 95% CI 1.17-8.59). Conclusions: Clinical manifestations of cryptococcal meningitis differed between patients with and without HIV-infection in some aspects. Increasing awareness in physicians of this disease in HIV-uninfected individuals may prompt earlier diagnosis and timely treatment.

Comparison of Immunogenicity and Reactogenicity of Five Primary Series of COVID-19 Vaccine Regimens against Circulating SARS-CoV-2 Variants of Concern among Healthy Thai Populations.

To compare immunogenicity and reactogenicity of five COVID-19 vaccine regimens against wild-type SARS-CoV-2 and variants of concern (VoCs) among Thai populations, a prospective cohort study was conducted among healthy participants aged ≥18 years who had never been infected with COVID-19 and were scheduled to get one of the five primary series of COVID-19 vaccine regimens, including CoronaVac/CoronaVac, AZD1222/AZD1222, CoronaVac/AZD1222, AZD1222/BNT162b2, and BNT162b2/BNT162b2. Anti-receptor binding domain (anti-RBD-WT) IgG and neutralizing antibody (NAb-WT) against wild-type SARS-CoV-2 were measured at pre-prime, post-prime, and post-boost visits. NAb against VoCs (NAb-Alpha, NAb-Beta, NAb-Delta, and NAb-Omicron) were assessed at the post-boost visit. Adverse events (AEs) following vaccination were recorded. A total of 901 participants (CoronaVac/CoronaVac: 332, AZD1222/AZD1222: 221, CoronaVac/AZD1222: 110, AZD1222/BNT162b2: 128, and BNT162b2/BNT162b2: 110) were enrolled. Anti-RBD-WT IgG and NAb-WT levels increased substantially after each vaccine dose. At the post-boost visit, BNT162b2/BNT162b2 induced the highest GMC of anti-RBD-WT IgG level (1698 BAU/mL), whereas AZD1222/BNT162b2 induced the highest median NAb-WT level (99% inhibition). NAb levels against VoCs, particularly the Omicron strain, were markedly attenuated for all vaccine regimens (p < 0.001). Overall, no serious AEs following vaccination were observed. All five primary series of COVID-19 vaccine regimens were well-tolerated and elicited robust antibody responses against wild-type SARS-CoV-2 but had attenuated responses against VoCs, particularly the Omicron strain, among healthy Thai populations.

Longitudinal Profiles of Anti-Platelet Factor 4 Antibodies in Thai People Who Received ChAdOx1 nCoV-19 Vaccination.

Anti-platelet factor 4 (anti-PF4) antibodies were identified as pathogenic antibodies for vaccine-induced immune thrombocytopenia and thrombosis (VITT) in subjects receiving ChAdOx1 nCoV-19 vaccinations. We performed a prospective cohort study to determine the prevalence of anti-PF4 and the effect of the ChAdOx1 nCoV-19 vaccine on anti-PF4 in healthy Thai subjects. Anti-PF4 antibodies were measured before and four weeks after receiving the first vaccination. Participants with detectable antibodies were scheduled for repeat anti-PF4 analysis at 12 weeks after the second vaccination. Of 396 participants, ten participants (2.53%; 95% confidence interval [CI], 1.22-4.59) were positive for anti-PF4 before receiving vaccinations. Twelve people (3.03%; 95% CI, 1.58-5.23) had detectable anti-PF4 after the first vaccination. There was no difference in the optical density (OD) values of anti-PF4 antibodies when comparisons were made between pre-vaccination and four weeks after the first vaccination (p = 0.0779). There was also no significant difference in OD values in participants with detectable antibodies. No subjects experienced thrombotic complications. Pain at the injection site was associated with an increased risk of being anti-PF4 positive at an odds ratio of 3.44 (95% CI, 1.06-11.18). To conclude, the prevalence of anti-PF4 was low in Thais and did not significantly change over time.

Reactive Neutrophilic Dermatoses in Adult-Onset Immunodeficiency due to Interferon-Gamma Autoantibody and Their Associated Factors.

BACKGROUND: Adult-onset immunodeficiency (AOID) due to interferon-gamma autoantibody is a rare, acquired immunodeficiency disease. Reactive neutrophilic dermatoses (RND), predominantly Sweet syndrome (SS), and generalized pustular eruption have been reported repeatedly. OBJECTIVES: The aims of this study were to describe the cutaneous manifestations in AOID patients and determine the incidence of RND and associated factors using a larger population size than have been previously reported. METHODS: A retrospective chart review of all confirmed AOID cases in Chiang Mai University Hospital from January 2006 to June 2020 was conducted. The demographics and characteristics of RND including type, onset, and laboratory information in every episode of cutaneous manifestations were collected. Generalized estimating equations of binary logistic regression were used to determine the indicators of RND. RESULTS: A total of 146 patients with confirmed AOID were identified. Of these, 57 cases (39%) developed at least one episode of RND. Thirteen cases (23%) of the patients experienced RND twice during the follow-up period. All recurrence of RND displayed the same cutaneous phenotype, with the exception of 2 cases who had both SS and generalized pustular eruption. Finally, 49 episodes of SS and 22 episodes of generalized pustular eruption were included in the analysis. All patients with RND had concomitant active opportunistic infections, of which most were non-tuberculous mycobacterium (NTM) infection. NTM infection (prevalence odds ratio [POR] 2.87), lymphadenopathy (POR 3.30) as well as lower serum alkaline phosphatase (ALP) level (POR 0.71 for every 100-unit increment in ALP) were found to be significantly associated with RND occurrence. CONCLUSIONS: 39% of our AOID patients experienced RND once during the course of the disease. Notable factors associated with RND occurrence were concomitant NTM infection, lymphadenopathy, and lower level of ALP.

Immunogenicity of a fractional or full third dose of AZD1222 vaccine or BNT162b2 messenger RNA vaccine after two doses of CoronaVac vaccines against the Delta and Omicron variants.

OBJECTIVES: The study aimed to compare the immunogenicity and safety of fractional (half) third doses of heterologous COVID-19 vaccines (AZD1222 or BNT162b2) to full doses after the two-dose CoronaVac and when boosting after three different extended intervals. METHODS: At 60-<90, 90-<120, or 120-180 days intervals after the two-dose CoronaVac, participants were randomized to full-dose or half-dose AZD1222 or BNT162b2, followed up at day 28, 60, and 90. Vaccination-induced immune responses to Ancestral, Delta, and Omicron BA.1 strains were evaluated by antispike, pseudovirus, and microneutralization and T cell assays. Descriptive statistics and noninferiority cut-offs were reported as geometric mean concentration or titer and concentration or titer ratios comparing baseline to day 28 and day 90 and different intervals. RESULTS: No safety concerns were detected. All assays and intervals showed noninferior immunogenicity between full doses and half doses. However, full-dose vaccines and/or longer 120-180-day intervals substantially improved the immunogenicity (measured by antispike or measured by pseudotyped virus neutralizing titers 50; P <0.001). Seroconversion rates were over 90% against the SARS-CoV-2 strains by all assays. Immunogenicity waned more quickly with half doses than full doses but remained high against the Ancestral or Delta strains. Against Omicron, the day 28 immunogenicity increased with longer intervals than shorter intervals for full-dose vaccines. CONCLUSION: Immune responses after day 28 when boosting at longer intervals after the two-dose CoronaVac was optimal. Half doses met the noninferiority criteria compared with the full dose by all the immune assays assessed.

CD4/CD8 Ratio Recovery Among People Living With HIV Starting With First-Line Integrase Strand Transfer Inhibitors: A Prospective Regional Cohort Analysis.

BACKGROUND: We evaluated trends in CD4/CD8 ratio among people living with HIV (PLWH) starting antiretroviral therapy (ART) with first-line integrase strand transfer inhibitors (INSTI) compared with non-INSTI-based ART, and the incidence of CD4/CD8 ratio normalization. METHODS: All PLWH enrolled in adult HIV cohorts of IeDEA Asia-Pacific who started with triple-ART with at least 1 CD4, CD8 (3-month window), and HIV-1 RNA measurement post-ART were included. CD4/CD8 ratio normalization was defined as a ratio ≥1. Longitudinal changes in CD4/CD8 ratio were analyzed by linear mixed model, the incidence of the normalization by Cox regression, and the differences in ratio recovery by group-based trajectory modeling. RESULTS: A total of 5529 PLWH were included; 80% male, median age 35 years (interquartile range [IQR], 29-43). First-line regimens were comprised of 65% NNRTI, 19% PI, and 16% INSTI. The baseline CD4/CD8 ratio was 0.19 (IQR, 0.09-0.33). PLWH starting with NNRTI- (P = 0.005) or PI-based ART (P = 0.030) had lower CD4/CD8 recovery over 5 years compared with INSTI. During 24,304 person-years of follow-up, 32% had CD4/CD8 ratio normalization. After adjusting for age, sex, baseline CD4, HIV-1 RNA, HCV, and year of ART initiation, PLWH started with INSTI had higher odds of achieving CD4/CD8 ratio normalization than NNRTI- (P < 0.001) or PI-based ART (P = 0.015). In group-based trajectory modeling analysis, INSTI was associated with greater odds of being in the higher ratio trajectory. CONCLUSIONS: INSTI use was associated with higher rates of CD4/CD8 ratio recovery and normalization in our cohort. These results emphasize the relative benefits of INSTI-based ART for immune restoration.

Diagnostic performance between in-house and commercial SARS-CoV-2 serological immunoassays including binding-specific antibody and surrogate virus neutralization test (sVNT).

This study aimed to evaluate the correlation between in-house and commercial binding-specific IgG antibodies and between in-house and commercial SARS-CoV-2 surrogate virus neutralization tests (sVNT). Samples from healthcare workers who received vaccines against SARS-CoV-2 were tested for RBD-specific antibody, S-specific antibody, and in-house ELISA, commercial sVNT, and in-house sVNT, against wild-type SARS-CoV-2. Three hundred and five samples were included in the analysis. The correlation between S-specific binding antibodies and in-house ELISA was 0.96 (95% CI 0.96-0.97) and between RBD-specific antibodies and in-house ELISA was 0.96 (95% CI 0.95-0.97). The Cohen's kappa between in-house sVNT and the commercial test was 0.90 (95% CI 0.80, 1.00). If using 90% inhibition of sVNT as the reference standard, the optimal cut-off value of RBD-specific antibodies was 442.7 BAU/mL, the kappa, sensitivity, and specificity being 0.99, 99%, and 100%, respectively. The optimal cut-off value of S-specific antibodies was 1155.9 BAU/mL, the kappa, sensitivity, and specificity being 0.99, 100%, and 99%, respectively. This study demonstrated a very strong correlation between in-house ELISA and 2 commercial assays. There was also a very strong correlation between in-house and commercial SARS-CoV-2 sVNT, a finding of particular interest which will inform future research.

The Prevalence and Risk Factors for Peripheral Arterial Disease in Adults Living With Human Immunodeficiency Virus.

Adult patients with human immunodeficiency virus (HIV) appear to be at high risk of cardiovascular disease (CVD). Peripheral arterial disease (PAD) is particularly concerning as it is associated with myocardial infarction and stroke. Nevertheless, the incidence of PAD is still unknown. The authors prospectively recruited HIV-infected patients from the outpatient clinic of the Department of Internal Medicine in our center. We assessed ankle-brachial index (ABI) using the VaSera system™ (Fukuda Denshi Co., Ltd). Patients were grouped into 3 ABI levels: an ABI ≤0.90 was considered abnormal and evidence of PAD, an ABI 1.0 to 1.40 was considered normal, and 0.91 to 0.99 was considered borderline. Cardiovascular risk factors were compared across all 3 levels of ABI and were analyzed using multivariate ordinal logistic regression. Eight hundred ninety-two patients were recruited. The mean age was 42.9 ± 10.0 years and 458 (51.4%) were males. There were 704, 149, and 39 patients in the normal, borderline, and abnormal ABI groups, respectively. The latter group of 39 patients was considered to have PAD, yielding a prevalence of 4.37% (95% confidence interval [CI] 3.21-5.93). Sex ratio, age, education levels, smoking rate, body mass index (BMI), blood pressure, prevalence of comorbidities with hypertension and coronary heart disease, median triglyceride level, reduced kidney function and HIV-1 RNA undetectable ratio, duration of HIV diagnosis, and duration on antiretroviral treatment were significantly different among 3 ABI subgroups. Independent risk factors associated with PAD were being female (odds ratio [OR]: 2.86; 95% CI: 1.94-4.22), being <30 years of age (OR: 4.66; 95% CI: 2.78-7.81), being overweight (BMI 25-25.9; OR: 0.39; 95% CI: 0.20-0.76), being obese (BMI: 30; OR: 3.53; 95% CI: 1.51-8.22), having a diastolic blood pressure ≥80 mmHg (OR: 0.50; 95% CI: 0.35-0.71), and having detectable HIV-1 RNA ≥20 copies/mL (OR: 1.85; 95% CI: 1.13-3.03). In conclusion, the prevalence of PAD in HIV-infected Thais was 4.37% in infected patients on therapy attending outpatient clinics. For this population, PAD appears to be relatively poorly correlated with traditional risk factors of CVD.