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1.
Viruses ; 14(5):967, 2022.
Article in English | MDPI | ID: covidwho-1820423

ABSTRACT

As countries transition from pandemic mitigation to endemic COVID-19, mass testing may blunt the impact on the healthcare system of the liminal wave. We used GeoDEMOS-R, an agent-based model of Singapore's population with demographic distributions and vaccination status. A 250-day COVID-19 Delta variant model was run at varying maximal rapid antigen test sensitivities and frequencies. Without testing, the number of infections reached 1,021,000 (899,400–1,147,000) at 250 days. When conducting fortnightly and weekly mass routine rapid antigen testing 30 days into the outbreak at a maximal test sensitivity of 0.6, this was reduced by 12.8% (11.3–14.5%) and 25.2% (22.5–28.5%). An increase in maximal test sensitivity of 0.2 results a corresponding reduction of 17.5% (15.5–20.2%) and 34.4% (30.5–39.1%). Within the maximal test sensitivity range of 0.6–0.8, test frequency has a greater impact than maximal test sensitivity with an average reduction of 2.2% in infections for each day removed between tests in comparison to a 0.43% average reduction per 1% increase in test frequency. Our findings highlight that mass testing using rapid diagnostic tests can be used as an effective intervention for countries transitioning from pandemic mitigation to endemic COVID-19.

4.
Clin Infect Dis ; 2022 Mar 22.
Article in English | MEDLINE | ID: covidwho-1758703

ABSTRACT

BACKGROUND: The impact of SARS-CoV-2 vaccination status and paediatric age on transmission of the Delta variant is key to preventing COVID-19 spread. In Singapore, quarantine of all close-contacts, and quarantine-entry and exit PCR testing, enabled evaluation of these factors. METHODS: This retrospective cohort study included all household close-contacts between March 1, 2021 and August 31, 2021. Logistic regression using generalized estimating equations was used to determine risk factors associated with SARS-CoV-2 acquisition and symptomatic disease. FINDINGS: Among 8470 Delta variant-exposed household close-contacts linked to 2583 indices, full-vaccination of the index with BNT162b2 or mRNA-1273 was associated with significant reduction in SARS-CoV-2 acquisition by contacts (adjusted odds ratio [aOR]:0.56, 95% robust confidence interval [RCI]:0.44-0.71 and aOR:0.51, 95%RCI:0.27-0.96 respectively).Compared to young adults (18-29y), children (0-11y) were significantly more likely to transmit (aOR:2.37 [95%RCI:1.57-3.60]) and acquire (aOR:1.43 [95%RCI:1.07-1.93]) infection, taking into account vaccination status.Longer duration from completion of vaccination among contacts was associated with decline in protection against acquisition (first-month aOR:0.42, 95%RCI:0.33-0.55; fifth-month aOR:0.84, 95%RCI:0.55-0.98; p<0.0001 for trend) and symptomatic disease (first-month aOR:0.30, 95%RCI:0.23-0.41; fifth-month aOR;0.62, 95%RCI:0.38-1.02; p<0.0001 for trend). Contacts immunized with mRNA-1273 had significant reduction in acquisition (aOR:0.73, 95%RCI:0.58-0.91) compared to BNT162b2. CONCLUSIONS: Among household close-contacts, vaccination prevented onward SARS-CoV-2 transmission and there was increased risk of SARS-CoV-2 acquisition and transmission among children compared with young adults. Time after completion of vaccination and vaccine type affected SARS-CoV-2 acquisition.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319425

ABSTRACT

Starting with a handful of SARS-CoV-2 infections in dormitory residents in late March 2020, rapid tranmission in their dense living environments ensued and by October 2020, more than 50,000 acute infections were identified across various dormitories. Extensive epidemiological, serological and phylogentic investigations, supported by simulation models, helped to reveal the factors of transmission and impact of control measures in a dormitory. We find that asymptomatic cases and symptomatic cases who did not seek medical attention were major drivers of the outbreak. Furthermore, each resident has about 30 close contacts and each infected resident spread to 4.4 (IQR 3.5–5.3) others at the start of the outbreak. The final attack rate of the current outbreak was 76.2% (IQR 70.6%–98.0%) and could be reduced by further 10% under a modified dormitory housing condition. These findings are important when designing living environments in a post COVID-19 future to reduce disease spread and facilitate rapid implementation of outbreak control measures.

7.
J Migr Health ; 5: 100079, 2022.
Article in English | MEDLINE | ID: covidwho-1654788

ABSTRACT

Introduction: COVID-19 transmission within overcrowded migrant worker dormitories is an ongoing global issue. Many countries have implemented extensive control measures to prevent the entire migrant worker population from becoming infected. Here, we explore case count outcomes when utilizing lockdown and testing under different testing measures and transmissibility settings. Methods: We built a mathematical model which estimates transmission across 10 different blocks with 1000 individuals per block under different parameter combinations and testing conditions over the period of 1 month. We vary parameters including differences in block connectivity, underlying recovered proportions at the time of intervention, case importation rates and testing protocols using either PCR or rapid antigen testing. Results: We estimate that a relatively transmissible environment with fortnightly PCR testing at a relatively low initial recovered proportion of 40%, low connectivity where 10% of contacts occurred outside of the infected individuals' block and a high importation rate of 1 100 000 per day, results in an average of 39 (95%Interval: 9-121) new COVID-19 cases after one month of observation. Similar results were observed for weekly rapid antigen testing at 33 (9-95) cases. Interpretation: Our findings support the need for either fortnightly PCR testing or weekly rapid antigen testing in high population density environments such as migrant worker dormitories. Repeated mass testing is highly effective, preventing localized site outbreaks and reducing the need for site wide lockdowns or other extensive social distancing measures within and outside of dormitories.

8.
Int J Infect Dis ; 116: 365-373, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1641323

ABSTRACT

OBJECTIVES: Super-spreading events caused by overdispersed secondary transmission are crucial in the transmission of COVID-19. However, the exact level of overdispersion, demographics, and other factors associated with secondary transmission remain elusive. In this study, we aimed to elucidate the frequency and patterns of secondary transmission of SARS-CoV-2 in Japan. METHODS: We analyzed 16,471 cases between January 2020 and August 2020. We generated the number of secondary cases distribution and estimated the dispersion parameter (k) by fitting the negative binomial distribution in each phase. The frequencies of the secondary transmission were compared by demographic and clinical characteristics, calculating the odds ratio using logistic regression models. RESULTS: We observed that 76.7% of the primary cases did not generate secondary cases with an estimated dispersion parameter k of 0.23. The demographic patterns of primary-secondary cases differed between phases, with 20-69 years being the predominant age group. There were higher proportions of secondary transmissions among older individuals, symptomatic patients, and patients with 2 days or more between onset and confirmation. CONCLUSIONS: The study showed the estimation of the frequency of secondary transmission of SARS-CoV-2 and the characteristics of people who generated the secondary transmission.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Demography , Humans , Japan/epidemiology
9.
Emerg Microbes Infect ; 10(1): 2141-2150, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1532382

ABSTRACT

BACKGROUND: We studied humoral and cellular responses against SARS-CoV-2 longitudinally in a homogeneous population of healthy young/middle-aged men of South Asian ethnicity with mild COVID-19. METHODS: In total, we recruited 994 men (median age: 34 years) post-COVID-19 diagnosis. Repeated cross-sectional surveys were conducted between May 2020 and January 2021 at six time points - day 28 (n = 327), day 80 (n = 202), day 105 (n = 294), day 140 (n = 172), day 180 (n = 758), and day 280 (n = 311). Three commercial assays were used to detect anti-nucleoprotein (NP) and neutralizing antibodies. T cell response specific for Spike, Membrane and NP SARS-CoV-2 proteins was tested in 85 patients at day 105, 180, and 280. RESULTS: All serological tests displayed different kinetics of progressive antibody reduction while the frequency of T cells specific for different structural SARS-CoV-2 proteins was stable over time. Both showed a marked heterogeneity of magnitude among the studied cohort. Comparatively, cellular responses lasted longer than humoral responses and were still detectable nine months after infection in the individuals who lost antibody detection. Correlation between T cell frequencies and all antibodies was lost over time. CONCLUSION: Humoral and cellular immunity against SARS-CoV-2 is induced with differing kinetics of persistence in those with mild disease. The magnitude of T cells and antibodies is highly heterogeneous in a homogeneous study population. These observations have implications for COVID-19 surveillance, vaccination strategies, and post-pandemic planning.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Adult , Antibodies, Neutralizing/blood , Cross-Sectional Studies , Humans , Male , Nucleocapsid Proteins/immunology
10.
Lancet Reg Health West Pac ; 17: 100299, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1506512

ABSTRACT

BACKGROUND: Impact of the Delta variant and vaccination on SARS-CoV-2 transmission remains unclear. In Singapore, quarantine of all close contacts, including entry and exit PCR testing, provided the opportunity to determine risk of infection by the Delta variant compared to other variants, vaccine efficacy against SARS-CoV-2 acquisition, symptomatic or severe COVID-19, and risk factors associated with SARS-CoV-2 acquisition and symptomatic disease. METHODS: This retrospective cohort study included all close contacts between September 1, 2020 and May 31, 2021. Regardless of symptoms, all were quarantined for 14 days with entry and exit PCR testing. Household contacts were defined as individuals who shared a residence with a Covid-19 index case. Secondary attack rates among household close contacts of Delta variant-infected indexes and other variant-infected indexes were derived from prevalence of diagnosed cases among contacts. Relative risk ratios and bootstrapping at the cluster level was used to determine risk of infection by the Delta variant compared to other variants and vaccine efficacy against SARS-CoV-2 acquisition, symptomatic or severe COVID-19. Logistic regression using generalized estimating equations was used to determine risk factors associated with SARS-CoV-2 acquisition and symptomatic disease. FINDINGS: Of 1024 household contacts linked to 301 PCR-confirmed index cases, 753 (73.5%) were linked to Delta-infected indexes and 248 (24.2%) were exposed to indexes with other variants. Household secondary attack rate among unvaccinated Delta-exposed contacts was 25.8% (95% boostrap confidence interval [BCI] 20.6-31.5%) compared with 12.9% (95%BCI 7.0-20.0%) among other variant-exposed contacts. Unvaccinated Delta-exposed contacts were more likely to be infected than those exposed to other variants (Relative risk 2.01, 95%CI 1.24-3.84). Among Delta-exposed contacts, complete vaccination had a vaccine effectiveness of 56.4% (95%BCI 32.6-75.8%) against acquisition, 64.1% (95%BCI 37.8-85.4%) against symptomatic disease and 100% against severe disease. Among Delta-exposed contacts, vaccination status (adjusted odds ratio [aOR] 0.33, 95% robust confidence interval [RCI] 0.17-0.63) and older age of the index (aOR 1.20 per decade, 95%RCI 1.03-1.39) was associated with increased risk of SARS-CoV-2 acquisition by the contact. Vaccination status of the index was not associated with a statistically-significant difference for contact SARS-CoV-2 acquisition (aOR 0.73, 95%RCI 0.38-1.40). INTERPRETATION: Increased risk of SARS-CoV-2 Delta acquisition compared with other variants was reduced with vaccination. Close-contacts of vaccinated Delta-infected indexes did not have statistically significant reduced risk of acquisition compared with unvaccinated Delta-infected indexes.

12.
J Travel Med ; 28(7)2021 10 11.
Article in English | MEDLINE | ID: covidwho-1462388

ABSTRACT

BACKGROUND: The COVID-19 pandemic has resulted in the closure or partial closure of international borders in almost all countries. Here, we investigate the efficacy of imported case detection considering quarantine length and different testing measures for travellers on arrival. METHODS: We examine eight broad border control strategies from utilizing quarantine alone, pre-testing, entry and exit testing, and testing during quarantine. In comparing the efficacy of these strategies, we calculate the probability of detecting travellers who have been infected up to 2 weeks pre-departure according to their estimated incubation and infectious period. We estimate the number of undetected infected travellers permitted entry for these strategies across a prevalence range of 0.1-2% per million travellers. RESULTS: At 14-day quarantine, on average 2.2% (range: 0.5-8.2%) of imported infections are missed across the strategies, leading to 22 (5-82) imported cases at 0.1% prevalence per million travellers, increasing up to 430 (106-1641) at 2%. The strategy utilizing exit testing results in 3.9% (3.1-4.9%) of imported cases being missed at 7-day quarantine, down to 0.4% (0.3-0.7%) at 21-day quarantine, and the introduction of daily testing, as the most risk averse strategy, reduces the proportion further to 2.5-4.2% at day 7 and 0.1-0.2% at day 21 dependent on the tests used. Rapid antigen testing every 3 days in quarantine leads to 3% being missed at 7 days and 0.7% at 14 days, which is comparable to PCR testing with a 24-hour turnaround. CONCLUSIONS: Mandatory testing, at a minimal of pre-testing and on arrival, is strongly recommended where the length of quarantining should then be determined by the destination country's level of risk averseness, pandemic preparedness and origin of travellers. Repeated testing during quarantining should also be utilized to mitigate case importation risk and reduce the quarantining duration required.


Subject(s)
COVID-19 , Communicable Diseases, Imported , Communicable Diseases, Imported/epidemiology , Humans , Pandemics , Quarantine , SARS-CoV-2
14.
J Clin Med ; 9(4)2020 Mar 31.
Article in English | MEDLINE | ID: covidwho-1403623

ABSTRACT

As the novel coronavirus (SARS-CoV-2) continues to spread rapidly across the globe, we aimed to identify and summarize the existing evidence on epidemiological characteristics of SARS-CoV-2 and the effectiveness of control measures to inform policymakers and leaders in formulating management guidelines, and to provide directions for future research. We conducted a systematic review of the published literature and preprints on the coronavirus disease (COVID-19) outbreak following predefined eligibility criteria. Of 317 research articles generated from our initial search on PubMed and preprint archives on 21 February 2020, 41 met our inclusion criteria and were included in the review. Current evidence suggests that it takes about 3-7 days for the epidemic to double in size. Of 21 estimates for the basic reproduction number ranging from 1.9 to 6.5, 13 were between 2.0 and 3.0. The incubation period was estimated to be 4-6 days, whereas the serial interval was estimated to be 4-8 days. Though the true case fatality risk is yet unknown, current model-based estimates ranged from 0.3% to 1.4% for outside China. There is an urgent need for rigorous research focusing on the mitigation efforts to minimize the impact on society.

15.
PLoS Negl Trop Dis ; 14(10): e0008719, 2020 10.
Article in English | MEDLINE | ID: covidwho-1388881

ABSTRACT

An estimated 105 million dengue infections occur per year across 120 countries, where traditional vector control is the primary control strategy to reduce contact between mosquito vectors and people. The ongoing sars-cov-2 pandemic has resulted in dramatic reductions in human mobility due to social distancing measures; the effects on vector-borne illnesses are not known. Here we examine the pre and post differences of dengue case counts in Malaysia, Singapore and Thailand, and estimate the effects of social distancing as a treatment effect whilst adjusting for temporal confounders. We found that social distancing is expected to lead to 4.32 additional cases per 100,000 individuals in Thailand per month, which equates to 170 more cases per month in the Bangkok province (95% CI: 100-242) and 2008 cases in the country as a whole (95% CI: 1170-2846). Social distancing policy estimates for Thailand were also found to be robust to model misspecification, and variable addition and omission. Conversely, no significant impact on dengue transmission was found in Singapore or Malaysia. Across country disparities in social distancing policy effects on reported dengue cases are reasoned to be driven by differences in workplace-residence structure, with an increase in transmission risk of arboviruses from social distancing primarily through heightened exposure to vectors in elevated time spent at residences, demonstrating the need to understand the effects of location on dengue transmission risk under novel population mixing conditions such as those under social distancing policies.


Subject(s)
Communicable Disease Control/methods , Coronavirus Infections/epidemiology , Dengue/transmission , Pneumonia, Viral/epidemiology , Animals , Betacoronavirus , COVID-19 , Coronavirus Infections/prevention & control , Dengue/epidemiology , Humans , Malaysia/epidemiology , Mosquito Vectors , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , SARS-CoV-2 , Singapore/epidemiology , Social Isolation , Thailand/epidemiology
17.
J Infect Dis ; 223(3): 399-402, 2021 02 13.
Article in English | MEDLINE | ID: covidwho-1387901

ABSTRACT

Social distancing (SD) measures aimed at curbing the spread of SARS-CoV-2 remain an important public health intervention. Little is known about the collateral impact of reduced mobility on the risk of other communicable diseases. We used differences in dengue case counts pre- and post implementation of SD measures and exploited heterogeneity in SD treatment effects among different age groups in Singapore to identify the spillover effects of SD measures. SD policy caused an increase of over 37.2% in dengue cases from baseline. Additional measures to preemptively mitigate the risk of other communicable diseases must be considered before the implementation/reimplementation of SARS-CoV-2 SD measures.


Subject(s)
COVID-19/transmission , Dengue/transmission , Physical Distancing , Adolescent , Adult , Aged , COVID-19/epidemiology , COVID-19/virology , Child , Child, Preschool , Dengue/epidemiology , Dengue/virology , Humans , Middle Aged , Public Health , Risk Factors , SARS-CoV-2/isolation & purification , Singapore/epidemiology , Young Adult
18.
Sci Rep ; 11(1): 15297, 2021 07 27.
Article in English | MEDLINE | ID: covidwho-1328854

ABSTRACT

Starting with a handful of SARS-CoV-2 infections in dormitory residents in late March 2020, rapid transmission in their dense living environments ensued and by October 2020, more than 50,000 acute infections were identified across various dormitories in Singapore. The aim of the study is to identify combination of factors facilitating SARS-CoV-2 transmission and the impact of control measures in a dormitory through extensive epidemiological, serological and phylogenetic investigations, supported by simulation models. Our findings showed that asymptomatic cases and symptomatic cases who did not seek medical attention were major drivers of the outbreak. Furthermore, each resident had about 30 close contacts and each infected resident spread to 4.4 (IQR 3.5-5.3) others at the start of the outbreak. The final attack rate of the current outbreak was 76.2% (IQR 70.6-98.0%) and could be reduced by further 10% under a modified dormitory housing condition. These findings are important when designing living environments in a post COVID-19 future to reduce disease spread and facilitate rapid implementation of outbreak control measures.


Subject(s)
COVID-19/prevention & control , COVID-19/transmission , Disease Outbreaks/prevention & control , Population Density , SARS-CoV-2/physiology , COVID-19/epidemiology , Disease Outbreaks/statistics & numerical data , Humans , Phylogeny
19.
PLoS Comput Biol ; 17(7): e1009098, 2021 07.
Article in English | MEDLINE | ID: covidwho-1325365

ABSTRACT

Mathematical models have played a key role in understanding the spread of directly-transmissible infectious diseases such as Coronavirus Disease 2019 (COVID-19), as well as the effectiveness of public health responses. As the risk of contracting directly-transmitted infections depends on who interacts with whom, mathematical models often use contact matrices to characterise the spread of infectious pathogens. These contact matrices are usually generated from diary-based contact surveys. However, the majority of places in the world do not have representative empirical contact studies, so synthetic contact matrices have been constructed using more widely available setting-specific survey data on household, school, classroom, and workplace composition combined with empirical data on contact patterns in Europe. In 2017, the largest set of synthetic contact matrices to date were published for 152 geographical locations. In this study, we update these matrices with the most recent data and extend our analysis to 177 geographical locations. Due to the observed geographic differences within countries, we also quantify contact patterns in rural and urban settings where data is available. Further, we compare both the 2017 and 2020 synthetic matrices to out-of-sample empirically-constructed contact matrices, and explore the effects of using both the empirical and synthetic contact matrices when modelling physical distancing interventions for the COVID-19 pandemic. We found that the synthetic contact matrices show qualitative similarities to the contact patterns in the empirically-constructed contact matrices. Models parameterised with the empirical and synthetic matrices generated similar findings with few differences observed in age groups where the empirical matrices have missing or aggregated age groups. This finding means that synthetic contact matrices may be used in modelling outbreaks in settings for which empirical studies have yet to be conducted.


Subject(s)
COVID-19/epidemiology , Age Distribution , COVID-19/virology , Empirical Research , Europe/epidemiology , Geography , Humans , Pandemics , Rural Population , SARS-CoV-2/isolation & purification , Urban Population
20.
Immunology ; 164(1): 135-147, 2021 09.
Article in English | MEDLINE | ID: covidwho-1295026

ABSTRACT

Detecting antibody responses during and after SARS-CoV-2 infection is essential in determining the seroepidemiology of the virus and the potential role of antibody in disease. Scalable, sensitive and specific serological assays are essential to this process. The detection of antibody in hospitalized patients with severe disease has proven relatively straightforward; detecting responses in subjects with mild disease and asymptomatic infections has proven less reliable. We hypothesized that the suboptimal sensitivity of antibody assays and the compartmentalization of the antibody response may contribute to this effect. We systematically developed an ELISA, optimizing different antigens and amplification steps, in serum and saliva from non-hospitalized SARS-CoV-2-infected subjects. Using trimeric spike glycoprotein, rather than nucleocapsid, enabled detection of responses in individuals with low antibody responses. IgG1 and IgG3 predominate to both antigens, but more anti-spike IgG1 than IgG3 was detectable. All antigens were effective for detecting responses in hospitalized patients. Anti-spike IgG, IgA and IgM antibody responses were readily detectable in saliva from a minority of RT-PCR confirmed, non-hospitalized symptomatic individuals, and these were mostly subjects who had the highest levels of anti-spike serum antibodies. Therefore, detecting antibody responses in both saliva and serum can contribute to determining virus exposure and understanding immune responses after SARS-CoV-2 infection.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Immunoglobulin M/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Antigens, Viral/immunology , COVID-19/blood , COVID-19/diagnosis , Enzyme-Linked Immunosorbent Assay , Humans , Saliva
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