Impact of vaccination and non-pharmacological interventions on COVID-19: a review of simulation modeling studies in Asia.

Introduction: Epidemiological modeling is widely used to offer insights into the COVID-19 pandemic situation in Asia. We reviewed published computational (mathematical/simulation) models conducted in Asia that assessed impacts of pharmacological and non-pharmacological interventions against COVID-19 and their implications for vaccination strategy. Methods: A search of the PubMed database for peer-reviewed, published, and accessible articles in English was performed up to November 2022 to capture studies in Asian populations based on computational modeling of outcomes in the COVID-19 pandemic. Extracted data included model type (mechanistic compartmental/agent-based, statistical, both), intervention type (pharmacological, non-pharmacological), and procedures for parameterizing age. Findings are summarized with descriptive statistics and discussed in terms of the evolving COVID-19 situation. Results: The literature search identified 378 results, of which 59 met criteria for data extraction. China, Japan, and South Korea accounted for approximately half of studies, with fewer from South and South-East Asia. Mechanistic models were most common, either compartmental (61.0%), agent-based (1.7%), or combination (18.6%) models. Statistical modeling was applied less frequently (11.9%). Pharmacological interventions were examined in 59.3% of studies, and most considered vaccination, except one study of an antiviral treatment. Non-pharmacological interventions were also considered in 84.7% of studies. Infection, hospitalization, and mortality were outcomes in 91.5%, 30.5%, and 30.5% of studies, respectively. Approximately a third of studies accounted for age, including 10 that also examined mortality. Four of these studies emphasized benefits in terms of mortality from prioritizing older adults for vaccination under conditions of a limited supply; however, one study noted potential benefits to infection rates from early vaccination of younger adults. Few studies (5.1%) considered the impact of vaccination among children. Conclusion: Early in the COVID-19 pandemic, non-pharmacological interventions helped to mitigate the health burden of COVID-19; however, modeling indicates that high population coverage of effective vaccines will complement and reduce reliance on such interventions. Thus, increasing and maintaining immunity levels in populations through regular booster shots, particularly among at-risk and vulnerable groups, including older adults, might help to protect public health. Future modeling efforts should consider new vaccines and alternative therapies alongside an evolving virus in populations with varied vaccination histories.

Evidence synthesis and pooled analysis of vaccine effectiveness for COVID-19 mRNA vaccine BNT162b2 as a heterologous booster after inactivated SARS-CoV-2 virus vaccines.

Introduction of primary COVID-19 vaccination has helped reduce severe disease and death caused by SARS-CoV-2 infection. Understanding the protection conferred by heterologous booster regimens informs alternative vaccination strategies that enable programmatic resilience and can catalyze vaccine confidence and coverage. Inactivated SARS-CoV-2 vaccines are among the most widely used vaccines worldwide. This review synthesizes the available evidence identified as of May 26, 2022, on the safety, immunogenicity, and effectiveness of a heterologous BNT162b2 (Pfizer-BioNTech) mRNA vaccine booster dose after an inactivated SARS-CoV-2 vaccine primary series, to help protect against COVID-19. Evidence showed that the heterologous BNT16b2 mRNA vaccine booster enhances immunogenicity and improves vaccine effectiveness against COVID-19, and no new safety concerns were identified with heterologous inactivated primary series with mRNA booster combinations.

Robust SARS-CoV-2 Antibody Responses in Asian COVID-Naïve Subjects 180 Days after Two Doses of BNT162b2 mRNA COVID-19 Vaccine.

BACKGROUND: Subjects with previous COVID-19 have augmented post-vaccination responses. However, the antibody response in COVID-naïve subjects from Southeast Asia is not well known. METHODS: 77 COVID-naïve vaccinees were tested with a full antibody panel [spike antibodies (total (T-Ab), IgG, IgM) and neutralizing antibodies (N-Ab)] pre-vaccination, 10 days after dose 1, and 20/40/60/90/120/150/180 days after dose 2. RESULTS: 10 days after dose 1, 67.6% (48/71)/69.0% (49/71) were T-Ab/IgG positive; only 15.5% (11/71)/14.1% (10/71) were N-Ab/IgM positive. While all (100%) subjects had brisk T-Ab, IgG and N-Ab antibody responses 20 days after complete vaccination, only 79.1% (53/67) were IgM positive. At 180 days (n = 8), T-Ab/IgG/N-Ab were still reactive (lowest T-Ab 186 U/mL, IgG 617 AU/mL, N-Ab 0.39 µg/mL), but IgM was negative in all samples. Spike antibody thresholds of T-Ab 74.1 U/mL (r = 0.95) and IgG 916 AU/mL (r = 0.95) corresponded to N-Ab reactivity (>0.3 µg/mL). Non-linear regression analysis showed that N-Ab would decrease to 0.3 µg/mL by 241 days, whereas T-Ab/IgG would need 470/163 days to reach titers of T-Ab/IgG associated with a N-Ab 0.3 µg/mL (76.4 U/mL and 916 AU/mL respectively). CONCLUSIONS: The antibody responses of T-Ab, IgG and N-Ab remain high and durable even at 180 days. N-Ab titers are expected to remain reactive up to 241 days post-vaccination.

Negative cerebrospinal fluid ß-d-glucan levels as an indicator for treatment cessation ahead of biochemical resolution: A case report of Candida glabrata meningitis.

Candida infections of the central nervous system (CNS) are rare. We report a case of Candida glabrata meningitis successfully treated with combination antifungal therapy followed by step-down therapy with fluconazole. New-onset hypercalcaemia, an uncommon side effect of the prolonged fluconazole treatment, prompted early treatment cessation. A negative cerebrospinal fluid (CSF) ß-d-glucan supported the decision of treatment cessation despite incomplete resolution of CSF biochemical parameters. No disease relapse was encountered after 2 years post-treatment.

Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and 4vHPV vaccine administered according to two- or three-dose schedules in girls aged 9-14 years: Results to month 36 from a randomized trial.

This observer-blind study (clinicaltrials.gov NCT01462357) compared the immunogenicity and safety of two doses (2D) of the HPV-16/18 AS04-adjuvanted vaccine (2D of AS04-HPV-16/18) vs. two or three doses of the 4vHPV vaccine [2D or 3D of 4vHPV] in 1075 healthy girls aged 9-14 years. Girls were randomized (1:1:1) to receive 2D of AS04-HPV-16/18 at months (M) 0, 6 (N = 359), 2D of 4vHPV at M0, 6 (N = 358) or 3D of 4vHPV at M0, 2, 6 (N = 358). 351, 339 and 346 girls, respectively, returned for the concluding visit at M36. Superiority was demonstrated at M7 and M12; comparison of the immune response to both vaccine antigens was made between 2D of AS04-HPV-16/18 and 2D or 3D of 4vHPV at subsequent time points in the according-to-protocol immunogenicity cohort (ATP-I; N = 958 at M36) and the total vaccinated cohort (TVC: N = 1036 at M36). HPV-16/18-specific T-cell- and B-cell-mediated immune responses and safety were also investigated. At M36, anti-HPV-16/18 ELISA responses in the 2D AS04-HPV-16/18 group remained superior to those of the 2D and 3D 4vHPV groups. In the M36 TVC, geometric mean titers were 2.78-fold (HPV-16) and 6.84-fold (HPV-18) higher for 2D of AS04-HPV-16/18 vs. 2D of 4vHPV and 2.3-fold (HPV-16) and 4.14-fold (HPV-18) higher vs. 3D of 4vHPV. Results were confirmed by vaccine pseudovirion-based neutralisation assay. Numbers of circulating CD4+ T cells and B cells appeared similar across groups. Safety was in line with the known safety profiles of both vaccines. In conclusion, superior HPV-16/18 antibody responses were elicited by 2D of the AS04-HPV-16/18 compared with 2D or 3D of the 4vHPV vaccine in girls aged 9-14 years. CLINICAL TRIAL REGISTRATION: NCT0146235.

Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine administered according to 2- and 3-dose schedules in girls aged 9-14 years: Results to month 12 from a randomized trial.

This observer-blind study (clinicaltrials.gov NCT01462357) compared the immunogenicity and safety of 2 doses of the HPV-16/18 AS04-adjuvanted vaccine (HPV-16/18(2D)) vs. 2 or 3 doses of the HPV-6/11/16/18 vaccine (HPV-6/11/16/18(2D) and HPV-6/11/16/18(3D)) in healthy girls aged 9-14 y. Girls were randomized (1:1:1) to receive HPV-16/18(2D) at months (M) 0,6 (N = 359), HPV-6/11/16/18(2D) at M0,6 (N = 358) or HPV-6/11/16/18(3D) at M0,2,6 (N = 358). The primary objective was non-inferiority/superiority of HPV-16/18 antibodies by ELISA for HPV-16/18(2D) vs. HPV-6/11/16/18(2D) at M7 in the according-to-protocol immunogenicity cohort (ATP-I) and total vaccinated cohort, respectively. Secondary objectives included non-inferiority/superiority of HPV-16/18(2D) vs. HPV-6/11/16/18(3D) at M7, non-inferiority/superiority at M12, HPV-16/18 neutralizing antibodies, frequencies of T-cells/B-cells, reactogenicity and safety. Antibody responses at M7 for HPV-16/18(2D) were superior to those for HPV-6/11/16/18(2D) and HPV-6/11/16/18(3D) (lower limit of 95% confidence interval for geometric mean titer ratio (GMR) was >1): HPV-16/18(2D)/HPV-6/11/16/18(2D) GMRs were 1.69 [1.49-1.91] for anti-HPV-16 and 4.52 [3.97-5.13] for anti-HPV-18; HPV-16/18(2D)/HPV-6/11/16/18(3D) GMRs were 1.72 [1.54-1.93] for anti-HPV-16 and 3.22 [2.82-3.68] for anti-HPV-18; p = 0.0001 for all comparisons. Non-inferiority/superiority was also demonstrated at M12. Among initially seronegative girls in the ATP-I, neutralizing antibody titers were at least 1.8-fold higher for HPV-16/18(2D) vs. HPV-6/11/16/18(2D) and HPV-6/11/16/18(3D) at M7 and M12. Frequencies of HPV-16/18-specific T-cells and B-cells were in similar ranges between groups. Reactogenicity and safety were in line with the known profile of each vaccine. In conclusion, superior HPV-16/18 antibody responses were elicited by 2 doses of the HPV-16/18 AS04-adjuvanted vaccine compared with 2 or 3 doses of the HPV-6/11/16/18 vaccine in girls (9-14 years).

Severe Pediatric Adenovirus 7 Disease in Singapore Linked to Recent Outbreaks across Asia.

During November 2012-July 2013, a marked increase of adenovirus type 7 (Ad7) infections associated with severe disease was documented among pediatric patients in Singapore. Phylogenetic analysis revealed close genetic links with severe Ad7 outbreaks in China, Taiwan, and other parts of Asia.

Neurology of the H1N1 pandemic in Singapore: a nationwide case series of children and adults.

Neurologic complications have long been associated with influenza. A novel strain of influenza A (H1N1) first described in humans to have outbreak potential in 2009 in Mexico went on to become the first influenza pandemic of this century. We evaluated the neurologic complications of the novel influenza A (H1N1) 2009 in children and adults admitted to all public hospitals in Singapore during the influenza A (H1N1) 2009 pandemic between May 2009 and March 2010. All patients were positive for novel H1N1 infection and presented with neurologic symptoms prior to oseltamivir treatment. Ninety-eight patients (median age 6.6 years, range 0.4-62.6) were identified; 90 % were younger than 18 years; 32 % suffered from preexisting neurological, respiratory, or cardiac disease; and 66 % presented with seizures. Of those presenting with seizures, new onset seizures were the most common manifestation (n = 40, 61.5 %), followed by breakthrough seizures (n = 18, 27.7 %) and status epilepticus (n = 7, 10.8 %). Influenza-associated encephalopathy occurred in 20 %. The majority of children (n = 88) presented with seizures (n = 63, 71.6 %), encephalopathy (n = 19, 21.6 %), and syncope (n = 4, 4.5 %). Among adults, a wider range of neurological conditions were seen, with half of them presenting with an exacerbation of their underlying neurological disease. The neurological symptoms developed at a median of 2 days after the onset of systemic symptoms. The median length of hospital stay was 3 days, and 79 % were monitored in general wards. Neurologic complications associated with the novel influenza A (H1N1) 2009 strain were generally mild and had a good outcome. They occurred more frequently in patients with underlying neurological disorders. Seizures and encephalopathy were the most common manifestations, similar to other influenza virus strains.

Immunogenicity and tolerability of an AS03(A)-adjuvanted prepandemic influenza vaccine: a phase III study in a large population of Asian adults.

The immunogenicity and lot-to-lot consistency of an AS03-adjuvanted H5N1 vaccine were evaluated in 1206 Asian adults, randomised to receive two doses of adjuvanted (3.75 microg haemagglutinin) or diluent-mixed vaccines, 21 days apart. Post-Dose 2, 96.0% of vaccinees in the H5N1-AS03 group demonstrated a four-fold increase in neutralising antibody titres against the vaccine strain A/Vietnam/1194/2004 and 91.4% against strain A/Indonesia/05/2005. Haemagglutination-inhibiting antibodies (titre > or = 1:40) against A/Vietnam/1194/2004 and A/Indonesia/05/2005 strains were observed in 94.3% and 50.2% of subjects, respectively. Lot-to-lot consistency of the AS03-adjuvanted vaccine combinations was demonstrated. The AS03-adjuvanted vaccine was well tolerated, induced a high frequency of immune responses to the vaccine strain, allowed antigen sparing and promoted cross-clade immunity. These characteristics make it suitable for presumptive use if an H5N1 pandemic were considered to be imminent.

Chikungunya in Singapore: imported cases among travelers visiting friends and relatives.

Chikungunya infections were detected in Singapore among returning travelers who had visited friends and relatives (VFR) in India and Malaysia. These sporadic imported cases occurred over a year before the 2008 chikungunya outbreaks in Singapore, demonstrating the potential for introducing this emerging viral infection into new areas via VFR travel.