Abstract
Background
The impact of SARS-CoV-2 variants of concern (VOCs) on disease severity is unclear. In this retrospective study, we compared the outcomes of patients infected with B.1.1.7, ...B.1.351, and B.1.617.2 with wild-type strains from early 2020.
Methods
National surveillance data from January to May 2021 were obtained and outcomes in relation to VOCs were explored. Detailed patient-level data from all patients with VOC infection admitted to our center between December 2020 and May 2021 were analyzed. Clinical outcomes were compared with a cohort of 846 patients admitted from January to April 2020.
Results
A total of 829 patients in Singapore in the study period were infected with these 3 VOCs. After adjusting for age and sex, B.1.617.2 was associated with higher odds of oxygen requirement, intensive care unit admission, or death (adjusted odds ratio aOR, 4.90; 95% confidence interval CI: 1.43-30.78). Of these patients, 157 were admitted to our center. After adjusting for age, sex, comorbidities, and vaccination, the aOR for pneumonia with B.1.617.2 was 1.88 (95% CI: .95-3.76) compared with wild-type. These differences were not seen with B.1.1.7 and B.1.351. Vaccination status was associated with decreased severity. B.1.617.2 was associated with significantly lower polymerase chain reaction cycle threshold (Ct) values and longer duration of Ct value ≤30 (median duration 18 days for B.1.617.2, 13 days for wild-type).
Conclusions
B.1.617.2 was associated with increased severity of illness, and with lower Ct values and longer viral shedding. These findings provide impetus for the rapid implementation of vaccination programs.
In this retrospective cohort study we found an association between infection with B.1.617.2 (Delta) and increased disease severity. B.1.617.2 was also associated with higher viral loads and prolonged duration of viral shedding. Vaccination remained protective.
Understanding the particle size distribution in the air and patterns of environmental contamination of SARS-CoV-2 is essential for infection prevention policies. Here we screen surface and air ...samples from hospital rooms of COVID-19 patients for SARS-CoV-2 RNA. Environmental sampling is conducted in three airborne infection isolation rooms (AIIRs) in the ICU and 27 AIIRs in the general ward. 245 surface samples are collected. 56.7% of rooms have at least one environmental surface contaminated. High touch surface contamination is shown in ten (66.7%) out of 15 patients in the first week of illness, and three (20%) beyond the first week of illness (p = 0.01, χ
test). Air sampling is performed in three of the 27 AIIRs in the general ward, and detects SARS-CoV-2 PCR-positive particles of sizes >4 µm and 1-4 µm in two rooms, despite these rooms having 12 air changes per hour. This warrants further study of the airborne transmission potential of SARS-CoV-2.
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
Background
Rapid identification of COVID-19 cases, which is crucial to outbreak containment efforts, is challenging due to the lack of pathognomonic symptoms and in settings with limited ...capacity for specialized nucleic acid–based reverse transcription polymerase chain reaction (PCR) testing.
Methods
This retrospective case-control study involves subjects (7–98 years) presenting at the designated national outbreak screening center and tertiary care hospital in Singapore for SARS-CoV-2 testing from 26 January to 16 February 2020. COVID-19 status was confirmed by PCR testing of sputum, nasopharyngeal swabs, or throat swabs. Demographic, clinical, laboratory, and exposure-risk variables ascertainable at presentation were analyzed to develop an algorithm for estimating the risk of COVID-19. Model development used Akaike’s information criterion in a stepwise fashion to build logistic regression models, which were then translated into prediction scores. Performance was measured using receiver operating characteristic curves, adjusting for overconfidence using leave-one-out cross-validation.
Results
The study population included 788 subjects, of whom 54 (6.9%) were SARS-CoV-2 positive and 734 (93.1%) were SARS-CoV-2 negative. The median age was 34 years, and 407 (51.7%) were female. Using leave-one-out cross-validation, all the models incorporating clinical tests (models 1, 2, and 3) performed well with areas under the receiver operating characteristic curve (AUCs) of 0.91, 0.88, and 0.88, respectively. In comparison, model 4 had an AUC of 0.65.
Conclusions
Rapidly ascertainable clinical and laboratory data could identify individuals at high risk of COVID-19 and enable prioritization of PCR testing and containment efforts. Basic laboratory test results were crucial to prediction models.
A risk score incorporating easily ascertainable demographic, clinical evaluation, and clinical testing covariates to identify patients at high risk of COVID-19 can help prioritize subjects for testing and public health measures to prevent onward transmission, especially in resource-limited settings.
Testing for SARS-CoV-2: Can We Stop at 2? Lee, Tau Hong; Junhao Lin, Ray; Lin, Raymond T P ...
Clinical infectious diseases,
11/2020, Volume:
71, Issue:
16
Journal Article
Peer reviewed
Open access
Abstract
The COVID-19 epidemic requires accurate identification and isolation of confirmed cases for effective control. This report describes the effectiveness of our testing strategy and highlights ...the importance of repeat testing in suspected cases in our cohort.
•Both TAK-003 formulations showed an acceptable safety profile and were immunogenic.•The TDV formulation appears to elicit a more balanced immune response than HD-TDV.•In baseline seronegative ...subjects, response to DENV-2 was less dominant with TDV.•DENV-4 seropositivity rates and GMTs were higher with TDV in these subjects.
Early formulations of Takeda’s tetravalent dengue vaccine candidate (TAK-003) have demonstrated notably higher neutralizing antibody responses against serotype 2 than other serotypes. Here, we assessed the immunogenicity and tolerability in adults living in Singapore of two TAK-003 formulations: an early formulation, referred to as HD-TDV, and a new formulation with 10-fold lower serotype 2 potency, referred to as TDV (NCT02425098).
Subjects aged 21–45 years were stratified by baseline dengue serostatus and randomised 1:1 to receive a single dose of either HD-TDV or TDV. Immunogenicity was evaluated at Days 15, 30, 90, 180, and 365 post-vaccination as geometric mean titres (GMTs) of neutralising antibodies and seropositivity rates. Viremia was assessed per vaccine strain. Solicited and unsolicited adverse events (AEs) were assessed by severity and causality.
Of 351 subjects randomised, 176 received HD-TDV and 175 received TDV. Peak GMTs against all serotypes were observed at Day 30, with highest GMTs against DENV-2 in both groups. In subjects seronegative at baseline, the response to DENV-2 was less dominant with TDV (Day 30 GMTs: 813 for TDV, 10,966 for HD-TDV). In these subjects, DENV-4 seropositivity rates and GMTs were higher with TDV (Day 30 GMTs: 58 for TDV, 21 for HD-TDV; seropositivity rates: 76% for TDV, 60% for HD-TDV). Viremia mainly occurred for TDV-2 in both vaccine groups, with a lower incidence in TDV recipients, and mostly resolved by Day 30. Both vaccine formulations showed an acceptable safety profile with similar overall rates of solicited and unsolicited AEs across vaccine groups.
These results suggest a more balanced immune response with the new formulation TDV compared with the early formulation HD-TDV, particularly in subjects who were seronegative prior to vaccination, and support the choice of the new formulation for the phase 3 efficacy assessment.
Thrombocytopenia is a hallmark of dengue infection, and bleeding is a dreaded complication of dengue fever. Prophylactic platelet transfusion has been used to prevent bleeding in the management of ...dengue fever, although the evidence for its benefit is lacking. In adult dengue patients with platelet count <20,000/mm3 without bleeding, we aimed to assess if prophylactic platelet transfusion was effective in reducing clinical bleeding and other outcomes.
We conducted a retrospective non-randomised observational study of dengue patients with platelet count < 20,000/mm3 without bleeding (except petechiae) admitted to Tan Tock Seng Hospital from January 2005 to December 2008. Baseline characteristics and clinical outcomes were compared between the non-transfused vs. transfused groups. Outcomes studied were clinical bleeding, platelet increment, hospital length of stay, intensive care unit admission and death.
Of the 788 patients included, 486 received prophylactic platelet transfusion. There was no significant difference in the presence of clinical bleeding in the two groups (18.2% in non-transfused group vs. 23.5% in transfused group; P = 0.08). Patients in the transfused group took a median of 1 day longer than the non-transfused group to increase their platelet count to 50,000/mm3 or more (3 days vs. 2 days, P <0.0001). The median duration of hospital stay in the non-transfused group was 5 days vs. 6 days in the transfused group (P< 0.0001). There was no significant difference in the proportion requiring ICU admission (non-transfused 0.66% vs. transfused 1.23%, P = 0.44) and death (non-transfused 0% vs. transfused 0.2%, P = 0.43).
Platelet transfusion in absence of bleeding in adult dengue with platelet count <20,000/mm3 did not reduce bleeding or expedite platelet recovery. There was potential harm by slowing recovery of platelet count to >50,000/mm3 and increasing length of hospitalization.
The aim of this study is to explore the notion of destination resources and competitiveness through comparative analyses of tourists' perceptions and satisfaction, using Kinmen Island of Taiwan as an ...example. Based upon an empirical investigation, the study draws upon the effective responses of 577 Taiwanese and Chinese tourists in Kinmen and attempts to discover the interrelationships between tourists' perceptions, satisfaction and how they are related to destination resources, attractions and competitiveness. The results of the study suggest that the Kinmen Island has not effectively utilized its coastal, historical, and natural resources to gain competitiveness. As a result, if the local authority aims to promote tourism via effective utilization of unique resources on the island, management practices related to inherited and created resources must be seriously considered to further establish its international awareness and image.
•We propose a framework to evaluate the competitiveness of the Kinmen Island.•Relationships among perceptions, satisfaction, and competitiveness are explored.•Descriptive statistics, t-tests, and One-way ANOVA are applied for data analyses.•The targeted island hasn't effectively utilized resources to gain competitiveness.•A unique resourced-based image for tourism development is found to be essential.
Aim
People with rheumatic diseases (PRD) remain vulnerable in the era of the COVID‐19 pandemic. We formulated recommendations to meet the urgent need for a consensus for vaccination against ...SARS‐CoV‐2 in PRD.
Methods
Systematic literature reviews were performed to evaluate: (a) outcomes in PRD with COVID‐19; (b) efficacy, immunogenicity and safety of COVID‐19 vaccination; and (c) published guidelines/recommendations for non‐live, non‐COVID‐19 vaccinations in PRD. Recommendations were formulated based on the evidence and expert opinion according to the Grading of Recommendations Assessment, Development and Evaluation methodology.
Results
The consensus comprises 2 overarching principles and 7 recommendations. Vaccination against SARS‐CoV‐2 in PRD should be aligned with prevailing national policy and should be individualized through shared decision between the healthcare provider and patient. We strongly recommend that eligible PRD and household contacts be vaccinated against SARS‐CoV‐2. We conditionally recommended that the COVID‐19 vaccine be administered during quiescent disease if possible. Immunomodulatory drugs, other than rituximab, can be continued alongside vaccination. We conditionally recommend that the COVID‐19 vaccine be administered prior to commencing rituximab if possible. For patients on rituximab, the vaccine should be administered a minimum of 6 months after the last dose and/or 4 weeks prior to the next dose of rituximab. Post‐vaccination antibody titers against SARS‐CoV‐2 need not be measured. Any of the approved COVID‐19 vaccines may be used, with no particular preference.
Conclusion
These recommendations provide guidance for COVID‐19 vaccination in PRD. Most recommendations in this consensus are conditional, reflecting a lack of evidence or low‐level evidence.
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