Given the ongoing SARS-CoV-2 pandemic, identification of immunogenic targets against the coronavirus spike glycoprotein will provide crucial advances towards the development of sensitive diagnostic ...tools and potential vaccine candidate targets. In this study, using pools of overlapping linear B-cell peptides, we report two IgG immunodominant regions on SARS-CoV-2 spike glycoprotein that are recognised by sera from COVID-19 convalescent patients. Notably, one is specific to SARS-CoV-2, which is located in close proximity to the receptor binding domain. The other region, which is localised at the fusion peptide, could potentially function as a pan-SARS target. Functionally, antibody depletion assays demonstrate that antibodies targeting these immunodominant regions significantly alter virus neutralisation capacities. Taken together, identification and validation of these neutralising B-cell epitopes will provide insights towards the design of diagnostics and vaccine candidates against this high priority coronavirus.
We compared serial intervals and incubation periods for SARS-CoV-2 Omicron BA.1 and BA.2 subvariants and Delta variants in Singapore. Median incubation period was 3 days for BA.1 versus 4 days for ...Delta. Serial interval was 2 days for BA.1 and 3 days for BA.2 but 4 days for Delta.
Memory T cells induced by previous pathogens can shape susceptibility to, and the clinical severity of, subsequent infections
. Little is known about the presence in humans of pre-existing memory T ...cells that have the potential to recognize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we studied T cell responses against the structural (nucleocapsid (N) protein) and non-structural (NSP7 and NSP13 of ORF1) regions of SARS-CoV-2 in individuals convalescing from coronavirus disease 2019 (COVID-19) (n = 36). In all of these individuals, we found CD4 and CD8 T cells that recognized multiple regions of the N protein. Next, we showed that patients (n = 23) who recovered from SARS (the disease associated with SARS-CoV infection) possess long-lasting memory T cells that are reactive to the N protein of SARS-CoV 17 years after the outbreak of SARS in 2003; these T cells displayed robust cross-reactivity to the N protein of SARS-CoV-2. We also detected SARS-CoV-2-specific T cells in individuals with no history of SARS, COVID-19 or contact with individuals who had SARS and/or COVID-19 (n = 37). SARS-CoV-2-specific T cells in uninfected donors exhibited a different pattern of immunodominance, and frequently targeted NSP7 and NSP13 as well as the N protein. Epitope characterization of NSP7-specific T cells showed the recognition of protein fragments that are conserved among animal betacoronaviruses but have low homology to 'common cold' human-associated coronaviruses. Thus, infection with betacoronaviruses induces multi-specific and long-lasting T cell immunity against the structural N protein. Understanding how pre-existing N- and ORF1-specific T cells that are present in the general population affect the susceptibility to and pathogenesis of SARS-CoV-2 infection is important for the management of the current COVID-19 pandemic.
Abstract Introduction Antiviral treatment can reduce the burden of COVID-19. But utilisation can be suboptimal, even in a setting like Singapore where it is fully subsidized for those with selected ...medical conditions and older adults (≥ 50 years). We hence investigated the factors affecting awareness, acceptance, and initiative to request Paxlovid. Methods We assessed the Paxlovid awareness, factors impacting its uptake in a survey conducted from August 2022 to September 2022 through the SOCRATES cohort. Multivariable logistic regression was used to investigate associations between sociodemographics, perceptions, and attitudes with the key study outcomes. Results Among respondents to the Paxlovid survey, 54% were aware of Paxlovid. On being provided essential details about Paxlovid, 75% reported they would likely be receptive to taking it if prescribed, and 38% indicated the initiative to request for it if it was not suggested by their doctors. Factors associated with awareness of Paxlovid include aged 40 years old and above, higher education, citing websites as an information source, greater trust in healthcare providers (aOR: 1.65, 95% CI 1.26 – 2.15) and government communications (aOR: 0.69, 95% CI 0.55 – 0.86), and higher perceived risk of COVID-19 infection (aOR: 1.25, 95% CI 1.10 – 1.42). Factors associated with acceptance to take Paxlovid include male gender, citing trust in healthcare providers (aOR: 1.49, 95% CI 1.11 – 1.99) and government communications (aOR: 1.38, 95% CI 1.09 – 1.76), and higher perceived severity of COVID-19 (aOR: 1.23, 95% CI 1.07 – 1.42). Factors associated with initiative to request Paxlovid include male gender, having pre-existing diabetes and higher perceived severity of COVID-19 (aOR: 1.24, 95% CI 1.09 – 1.40). The most common reasons for why respondents might not take Paxlovid were concerns about side effects (64%), concerns about costs (29%), and the perception that COVID-19 is a mild (25%). Conclusion The majority of our respondents would take Paxlovid if it was prescribed to them, but a much smaller proportion would have the initiative to request for this. Key factors that may influence uptake are COVID-19 threat perceptions, trust in healthcare and government, and perceptions of the drug’s side effects and cost.
Gay, bisexual, and other men who have sex with men (GBMSM) are disproportionately affected by HIV and other sexually transmitted infections (STI). While levels of self-perceived risk of HIV or other ...STI acquisition has been well-established as a factor that is positively associated with HIV or other STI testing, less effort has been made to identify the processes through which GBMSM assess their perceived risk of HIV or other STI acquisition. We conducted a qualitative study exploring the factors influencing self-perceived risk of HIV or other STI among GBMSM. Semi-structured interviews were conducted with 35 self-identified GBMSM in Singapore from October 2017 to June 2018, and the data were analyzed through inductive thematic analysis. Participants reported drawing on individual factors including their own sexual health knowledge and past experiences of risk, interpersonal factors including their sexual partners' attributes or characteristics and perceived trust and familiarity with their sexual partners, and situational factors including the venue and familiarity with such venues where sexual activity took place, in determining their self-perceived risk of HIV or other STI acquisition. The results of this study have implications for HIV and other STI risk education.
Summary Background An outbreak of Zika virus infection was detected in Singapore in August, 2016. We report the first comprehensive analysis of a national response to an outbreak of Zika virus ...infection in Asia. Methods In the first phase of the outbreak, patients with suspected Zika virus infection were isolated in two national referral hospitals until their serum tested negative for the virus. Enhanced vector control and community engagement measures were deployed in disease clusters, including stepped-up mosquito larvicide and adulticide use, community participation in source reduction (destruction of mosquito breeding sites), and work with the local media to promote awareness of the outbreak. Clinical and epidemiological data were collected from patients with confirmed Zika virus infection during the first phase. In the second phase, admission into hospitals for isolation was stopped but vector control efforts continued. Mosquitoes were captured from areas with Zika disease clusters to assess which species were present, their breeding numbers, and to test for Zika virus. Mosquito virus strains were compared with human strains through phylogenetic analysis after full genome sequencing. Reproductive numbers and inferred dates of strain diversification were estimated through Bayesian analyses. Findings From Aug 27 to Nov 30, 2016, 455 cases of Zika virus infection were confirmed in Singapore. Of 163 patients with confirmed Zika virus infection who presented to national referral hospitals during the first phase of the outbreak, Zika virus was detected in the blood samples of 97 (60%) patients and the urine samples of 157 (96%) patients. There were 15 disease clusters, 12 of which had high Aedes aegypti breeding percentages. Captured mosquitoes were pooled into 517 pools for Zika virus screening; nine abdomen pools (2%) were positive for Zika virus, of which seven head and thorax pools were Zika-virus positive. In the phylogenetic analysis, all mosquito sequences clustered within the outbreak lineage. The lineage showed little diversity and was distinct from other Asian lineages. The estimated most recent common ancestor of the outbreak lineage was from May, 2016. With the deployment of vector control and community engagement measures, the estimated reproductive number fell from 3·62 (95% CI 3·48–3·77) for July 31 to Sept 1, 2016, to 1·22 (95% CI 1·19–1·24) 4 weeks later (Sept 1 to Nov 24, 2016). Interpretation The outbreak shows the ease with which Zika virus can be introduced and spread despite good baseline vector control. Disease surveillance, enhanced vector control, and community awareness and engagement helped to quickly curb further spread of the virus. These intensive measures might be useful for other countries facing the same threat. Funding National Medical Research Council Singapore, Centre for Infectious Disease Epidemiology and Research, and A*STAR Biomedical Research Council.
The duration of influenza vaccine effectiveness is important for planning vaccination programs. This review found consistent evidence for a decline in effectiveness over a typical temperate winter ...season and that year-round protection, as required in tropical regions, is unlikely.
Abstract
Background
Whether influenza vaccination offers protection for the duration of an influenza season was called into question recently after analysis of data from test-negative design (TND) case-control studies.
Method
The published literature was systematically reviewed to identify TND studies that estimated the change in vaccine effectiveness (VE) with respect to time since vaccination.
Results
Fourteen studies were identified through the literature search as meeting eligibility criteria. Meta-analyses were performed to compare VE 15–90 days after vaccination to VE 91–180 days after vaccination. A significant decline in VE was observed for influenza virus subtype A/H3 (change in VE, −33; 95% confidence interval CI, −57 to −12) and type B (change in VE, −19; 95% CI, −33 to −6). VE declined for influenza virus subtype A/H1, but this difference was not statistically significant (change in VE −8; 95% CI, −27 to 21). A multivariable mixed-effects meta-regression model indicated that the change VE was associated with the proportion of study participants who were cases and the proportion who were vaccinated controls (P < .05). This could reflect biological effects such as (1) mismatch between the vaccine received and the circulating strains (among cases), (2) herd immunity (among controls), or (3) the reduced power of individual TND studies in the later parts of an influenza outbreak.
Conclusions
Exploration of new influenza vaccination strategies must be a priority for influenza control, particularly in tropical countries with year-round influenza virus activity.
Elucidation of the chain of disease transmission and identification of the source of coronavirus disease 2019 (COVID-19) infections are crucial for effective disease containment. We describe an ...epidemiological investigation that, with use of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological assays, established links between three clusters of COVID-19.
In Singapore, active case-finding and contact tracing were undertaken for all COVID-19 cases. Diagnosis for acute disease was confirmed with RT-PCR testing. When epidemiological information suggested that people might have been nodes of disease transmission but had recovered from illness, SARS-CoV-2 IgG serology testing was used to establish past infection.
Three clusters of COVID-19, comprising 28 locally transmitted cases, were identified in Singapore; these clusters were from two churches (Church A and Church B) and a family gathering. The clusters in Church A and Church B were linked by an individual from Church A (A2), who transmitted SARS-CoV-2 infection to the primary case from Church B (F1) at a family gathering they both attended on Jan 25, 2020. All cases were confirmed by RT-PCR testing because they had active disease, except for A2, who at the time of testing had recovered from their illness and tested negative. This individual was eventually diagnosed with past infection by serological testing. ELISA assays showed an optical density of more than 1·4 for SARS-CoV-2 nucleoprotein and receptor binding domain antigens in titres up to 1/400, and viral neutralisation was noted in titres up to 1/320.
Development and application of a serological assay has helped to establish connections between COVID-19 clusters in Singapore. Serological testing can have a crucial role in identifying convalescent cases or people with milder disease who might have been missed by other surveillance methods.
National Research Foundation (Singapore), National Natural Science Foundation (China), and National Medical Research Council (Singapore).
The proportion of asymptomatic carriers and transmission risk factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among household and non-household contacts remains unclear. In ...Singapore, extensive contact tracing by the Ministry of Health for every diagnosed COVID-19 case, and legally enforced quarantine and intensive health surveillance of close contacts provided a rare opportunity to determine asymptomatic attack rates and SARS-CoV-2 transmission risk factors among community close contacts of patients with COVID-19.
This retrospective cohort study involved all close contacts of confirmed COVID-19 cases in Singapore, identified between Jan 23 and April 3, 2020. Household contacts were defined as individuals who shared a residence with the index COVID-19 case. Non-household close contacts were defined as those who had contact for at least 30 min within 2 m of the index case. All patients with COVID-19 in Singapore received inpatient treatment, with access restricted to health-care staff. All close contacts were quarantined for 14 days with thrice-daily symptom monitoring via telephone. Symptomatic contacts underwent PCR testing for SARS-CoV-2. Secondary clinical attack rates were derived from the prevalence of PCR-confirmed SARS-CoV-2 among close contacts. Consenting contacts underwent serology testing and detailed exposure risk assessment. Bayesian modelling was used to estimate the prevalence of missed diagnoses and asymptomatic SARS-CoV-2-positive cases. Univariable and multivariable logistic regression models were used to determine SARS-CoV-2 transmission risk factors.
Between Jan 23 and April 3, 2020, 7770 close contacts (1863 household contacts, 2319 work contacts, and 3588 social contacts) linked to 1114 PCR-confirmed index cases were identified. Symptom-based PCR testing detected 188 COVID-19 cases, and 7582 close contacts completed quarantine without a positive SARS-CoV-2 PCR test. Among 7518 (96·8%) of the 7770 close contacts with complete data, the secondary clinical attack rate was 5·9% (95% CI 4·9–7·1) for 1779 household contacts, 1·3% (0·9–1·9) for 2231 work contacts, and 1·3% (1·0–1·7) for 3508 social contacts. Bayesian analysis of serology and symptom data obtained from 1150 close contacts (524 household contacts, 207 work contacts, and 419 social contacts) estimated that a symptom-based PCR-testing strategy missed 62% (95% credible interval 55–69) of COVID-19 diagnoses, and 36% (27–45) of individuals with SARS-CoV-2 infection were asymptomatic. Sharing a bedroom (multivariable odds ratio OR 5·38 95% CI 1·82–15·84; p=0·0023) and being spoken to by an index case for 30 min or longer (7·86 3·86–16·02; p<0·0001) were associated with SARS-CoV-2 transmission among household contacts. Among non-household contacts, exposure to more than one case (multivariable OR 3·92 95% CI 2·07–7·40, p<0·0001), being spoken to by an index case for 30 min or longer (2·67 1·21–5·88; p=0·015), and sharing a vehicle with an index case (3·07 1·55–6·08; p=0·0013) were associated with SARS-CoV-2 transmission. Among both household and non-household contacts, indirect contact, meal sharing, and lavatory co-usage were not independently associated with SARS-CoV-2 transmission.
Targeted community measures should include physical distancing and minimising verbal interactions. Testing of all household contacts, including asymptomatic individuals, is warranted.
Ministry of Health of Singapore, National Research Foundation of Singapore, and National Natural Science Foundation of China.
Abstract
Seasonal influenza epidemics occur year-round in the tropics, complicating the planning of vaccination programs. We built an individual-level longitudinal model of baseline antibody levels, ...time of infection, and the subsequent rise and decay of antibodies postinfection using influenza A(H1N1)pdm09 data from 2 sources in Singapore: 1) a noncommunity cohort with real-time polymerase chain reaction–confirmed infections and at least 1 serological sample collected from each participant between May and October 2009 (n = 118) and 2) a community cohort with up to 6 serological samples collected between May 2009 and October 2010 (n = 760). The model was hierarchical, to account for interval censoring and interindividual variation. Model parameters were estimated via a reversible jump Markov chain Monte Carlo algorithm using custom-designed R (https://www.r-project.org/) and C++ (https://isocpp.org/) code. After infection, antibody levels peaked at 4–7 weeks, with a half-life of 26.5 weeks, followed by a slower decrease up to 1 year to approximately preinfection levels. After the third wave, the seropositivity rate and the population-level antibody titer dropped to the same level as they were at the end of the first pandemic wave. The results of this analysis are consistent with the hypothesis that the population-level effect of individuals’ waxing and waning antibodies influences influenza seasonality in the tropics.
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