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BACKGROUND: Growing evidence suggests that some coronavirus disease 2019 (COVID-19) survivors experience a wide range of long-term postacute sequelae. We examined the postacute risk and burden of new-incident cardiovascular, cerebrovascular, and other thrombotic complications after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a highly vaccinated multiethnic Southeast Asian population, during Delta predominance. METHODS: This cohort study used national testing and healthcare claims databases in Singapore to build a cohort of individuals who had a positive SARS-CoV-2 test between 1 September and 30 November 2021 when Delta predominated community transmission. Concurrently, we constructed a test-negative control group by enrolling individuals between 13 April 2020 and 31 December 2022 with no evidence of SARS-CoV-2 infection. Participants in both groups were followed up for a median of 300 days. We estimated risks of new-incident cardiovascular, cerebrovascular, and other thrombotic complications using doubly robust competing-risks survival analysis. Risks were reported using 2 measures: hazard ratio (HR) and excess burden (EB) with 95% confidence intervals. RESULTS: We included 106 012 infected cases and 1 684 085 test-negative controls. Compared with the control group, individuals with COVID-19 exhibited increased risk (HR, 1.157 [1.069-1.252]) and excess burden (EB, 0.70 [.53-.88]) of new-incident cardiovascular and cerebrovascular complications. Risks decreased in a graded fashion for fully vaccinated (HR, 1.11 [1.02-1.22]) and boosted (HR, 1.10 [.92-1.32]) individuals. Conversely, risks and burdens of subsequent cardiovascular/cerebrovascular complications increased for hospitalized and severe COVID-19 cases (compared to nonhospitalized cases). CONCLUSIONS: Increased risks and excess burdens of new-incident cardiovascular/cerebrovascular complications were reported among infected individuals; risks can be attenuated with vaccination and boosting.
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COVID-19 , Trombosis , Humanos , Estudios de Cohortes , Estudios Retrospectivos , COVID-19/complicaciones , COVID-19/epidemiología , SARS-CoV-2 , Trombosis/epidemiología , Trombosis/etiologíaRESUMEN
INTRODUCTION: Data on protection afforded by updated COVID-19 vaccines (bivalent/XBB 1.5 monovalent) against the emergent JN.1 variant remains limited. METHODS: We conducted a retrospective population-based cohort study amongst all boosted Singaporeans aged ≥18 years during a COVID-19 wave predominantly driven by JN.1, from 26th November 2023 to 13th January 2024. Multivariable Cox regression was utilised to assess risk of SARS-CoV-2 infection and COVID-19 associated emergency-department (ED) visits/hospitalizations, stratified by vaccination status/prior infection; with individuals last boosted ≥1 year utilized as the reference category. Vaccination and infection status were classified using national registries. RESULTS: 3,086,562 boosted adult Singaporeans were included in the study population, accounting for 146,863,476 person-days of observation. During the JN.1 outbreak, 28,160 SARS-CoV-2 infections were recorded, with 2,926 hospitalizations and 3,747 ED-visits. Compared with individuals last boosted ≥1 year prior with ancestral monovalent vaccines, receipt of an updated XBB.1.5 booster 8-120 days prior was associated with lower risk of JN.1 infection (adjusted-hazard-ratio, aHR = 0.59[0.52-0.66]), COVID-19 associated ED-visits (aHR = 0.50[0.34-0.73]) and hospitalizations(aHR = 0.58[0.37-0.91]), while receipt of a bivalent booster 121-365 days prior was associated with lower risk of JN.1 infection (aHR = 0.92[0.88-0.95]) and ED-visits (aHR = 0.80[0.70-0.90]). Lower risk of COVID-19 hospitalization during the JN.1 outbreak (aHR = 0.57[0.33-0.97]) was still observed following receipt of an updated XBB.1.5 booster 8-120 days prior, even when analysis was restricted to previously infected individuals. CONCLUSION: Recent receipt of updated boosters conferred protection against SARS-CoV-2 infection and ED-visits/hospitalization during a JN.1 variant wave, in both previously infected and uninfected individuals. Annual booster doses confer protection during COVID-19 endemicity.
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Compared with individuals vaccinated with Pfizer-BioNTech/Comirnaty, recipients of Sinovac-CoronaVac and Sinopharm were 2.37 (95% CI, 2.29-2.46) and 1.62 (95% CI, 1.43-1.85) times more likely to be infected with coronavirus disease 19, respectively, while individuals vaccinated with Moderna were 0.42 (95% CI, 0.25-0.70) times less likely to develop severe disease.
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COVID-19 , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , ARN Mensajero , Singapur/epidemiología , Vacunas de Productos InactivadosRESUMEN
BACKGROUND: In Singapore, quarantine of all close contacts with entry and exit polymerase chain reaction testing enabled evaluation of the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and pediatric age on transmission of the Delta variant. METHODS: This retrospective cohort study included all household close contacts between 1 March 2021 and 31 August 2021. RESULTS: Among 8470 Delta variant-exposed contacts linked to 2583 indices, full-vaccination of the index with BNT162b2 or mRNA-1273 was associated with reduction in acquisition by contacts (adjusted odds ratio [aOR], 0.56; 95% robust confidence interval [RCI], .44-.71 and aOR, 0.51; 95% RCI, .27-.96, respectively). Compared with young adults (aged 18-29 years), children (aged 0-11 years) 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, vaccination considered. Longer duration from vaccination completion among contacts was associated with decline in protection against acquisition (first-month aOR, 0.42; 95% RCI, .33-.55; fifth-month aOR, 0.84; 95% RCI, .55-.98; P < .0001 for trend) and symptomatic disease (first-month aOR, 0.30; 95% RCI, .23-.41; fifth-month aOR, 0.62; 95% RCI, .38-1.02; P < .0001 for trend). Contacts immunized with mRNA-1273 had significant reduction in acquisition (aOR, 0.73; 95% RCI, .58-.91) compared with BNT162b2. CONCLUSIONS: Among household close contacts, vaccination prevented onward SARS-CoV-2 transmission and there was in-creased 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.
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COVID-19 , SARS-CoV-2 , Adolescente , Adulto , Vacuna BNT162 , COVID-19/epidemiología , COVID-19/prevención & control , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Estudios Retrospectivos , SARS-CoV-2/genética , Vacunación , Adulto JovenRESUMEN
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.
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COVID-19 , SARS-CoV-2 , COVID-19/epidemiología , Estudios de Cohortes , Humanos , Estudios Retrospectivos , SARS-CoV-2/genéticaRESUMEN
BACKGROUND: Three clusters of coronavirus disease 2019 (COVID-19) linked to a tour group from China, a company conference, and a church were identified in Singapore in February, 2020. METHODS: We gathered epidemiological and clinical data from individuals with confirmed COVID-19, via interviews and inpatient medical records, and we did field investigations to assess interactions and possible modes of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Open source reports were obtained for overseas cases. We reported the median (IQR) incubation period of SARS-CoV-2. FINDINGS: As of Feb 15, 2020, 36 cases of COVID-19 were linked epidemiologically to the first three clusters of circumscribed local transmission in Singapore. 425 close contacts were quarantined. Direct or prolonged close contact was reported among affected individuals, although indirect transmission (eg, via fomites and shared food) could not be excluded. The median incubation period of SARS-CoV-2 was 4 days (IQR 3-6). The serial interval between transmission pairs ranged between 3 days and 8 days. INTERPRETATION: SARS-CoV-2 is transmissible in community settings, and local clusters of COVID-19 are expected in countries with high travel volume from China before the lockdown of Wuhan and institution of travel restrictions. Enhanced surveillance and contact tracing is essential to minimise the risk of widespread transmission in the community. FUNDING: None.
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Trazado de Contacto , Infecciones por Coronavirus/epidemiología , Brotes de Enfermedades , Neumonía Viral/epidemiología , Vigilancia de la Población , Adulto , Betacoronavirus , COVID-19 , Defensa Civil , Congresos como Asunto , Infecciones por Coronavirus/transmisión , Femenino , Humanos , Control de Infecciones , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/transmisión , Características de la Residencia , SARS-CoV-2 , Singapur , ViajeRESUMEN
BACKGROUND: We hypothesize that comprehensive surveillance of COVID-19 in Singapore has facilitated early case detection and prompt contact tracing and, with community-based measures, contained spread. We assessed the effectiveness of containment measures by estimating transmissibility (effective reproduction number, (Equation is included in full-text article.)) over the course of the outbreak. METHODS: We used a Bayesian data augmentation framework to allocate infectors to infectees with no known infectors and determine serial interval distribution parameters via Markov chain Monte Carlo sampling. We fitted a smoothing spline to the number of secondary cases generated by each infector by respective onset dates to estimate (Equation is included in full-text article.)and evaluated increase in mean number of secondary cases per individual for each day's delay in starting isolation or quarantine. RESULTS: As of April 1, 2020, 1000 COVID-19 cases were reported in Singapore. We estimated a mean serial interval of 4.6 days [95% credible interval (CI) = 4.2, 5.1] with a SD of 3.5 days (95% CI = 3.1, 4.0). The posterior mean (Equation is included in full-text article.)was below one for most of the time, peaking at 1.1 (95% CI = 1.0, 1.3) on week 9 of 2020 due to a spreading event in one of the clusters. Eight hundred twenty-seven (82.7%) of cases infected less than one person on average. Over an interval of 7 days, the incremental mean number of cases generated per individual for each day's delay in starting isolation or quarantine was 0.03 cases (95% CI = 0.02, 0.05). CONCLUSIONS: We estimate that robust surveillance, active case detection, prompt contact tracing, and quarantine of close contacts kept (Equation is included in full-text article.)below one.
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COVID-19/prevención & control , Control de Enfermedades Transmisibles/métodos , Política de Salud , Número Básico de Reproducción , Teorema de Bayes , COVID-19/epidemiología , COVID-19/transmisión , Enfermedades Transmisibles Importadas/epidemiología , Enfermedades Transmisibles Importadas/prevención & control , Enfermedades Transmisibles Importadas/transmisión , Trazado de Contacto , Diagnóstico Precoz , Monitoreo Epidemiológico , Humanos , Cadenas de Markov , Tamizaje Masivo , Método de Montecarlo , Singapur/epidemiología , ViajeRESUMEN
We compared indicators of influenza activity in 2020 before and after public health measures were taken to reduce coronavirus disease (COVID-19) with the corresponding indicators from 3 preceding years. Influenza activity declined substantially, suggesting that the measures taken for COVID-19 were effective in reducing spread of other viral respiratory diseases.
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COVID-19/epidemiología , COVID-19/prevención & control , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/prevención & control , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Pandemias/prevención & control , Neumonía Viral/epidemiología , Neumonía Viral/prevención & control , Betacoronavirus/patogenicidad , Betacoronavirus/fisiología , COVID-19/transmisión , Control de Enfermedades Transmisibles/métodos , Control de Enfermedades Transmisibles/organización & administración , Infecciones por Coronavirus/transmisión , Humanos , Incidencia , Gripe Humana/transmisión , Modelos Estadísticos , Orthomyxoviridae/patogenicidad , Orthomyxoviridae/fisiología , Distanciamiento Físico , Neumonía Viral/transmisión , Salud Pública , Factores de Riesgo , SARS-CoV-2 , Singapur/epidemiologíaRESUMEN
OBJECTIVE: To compare the performance of machine learning models against the traditionally derived Combined Assessment of Risk Encountered in Surgery (CARES) model and the American Society of Anaesthesiologists-Physical Status (ASA-PS) in the prediction of 30-day postsurgical mortality and need for intensive care unit (ICU) stay >24âhours. BACKGROUND: Prediction of surgical risk preoperatively is important for clinical shared decision-making and planning of health resources such as ICU beds. The current growth of electronic medical records coupled with machine learning presents an opportunity to improve the performance of established risk models. METHODS: All patients aged 18 years and above who underwent noncardiac and nonneurological surgery at Singapore General Hospital (SGH) between 1 January 2012 and 31 October 2016 were included. Patient demographics, comorbidities, preoperative laboratory results, and surgery details were obtained from their electronic medical records. Seventy percent of the observations were randomly selected for training, leaving 30% for testing. Baseline models were CARES and ASA-PS. Candidate models were trained using random forest, adaptive boosting, gradient boosting, and support vector machine. Models were evaluated on area under the receiver operating characteristic curve (AUROC) and area under the precision-recall curve (AUPRC). RESULTS: A total of 90,785 patients were included, of whom 539 (0.6%) died within 30 days and 1264 (1.4%) required ICU admission >24âhours postoperatively. Baseline models achieved high AUROCs despite poor sensitivities by predicting all negative in a predominantly negative dataset. Gradient boosting was the best performing model with AUPRCs of 0.23 and 0.38 for mortality and ICU admission outcomes respectively. CONCLUSIONS: Machine learning can be used to improve surgical risk prediction compared to traditional risk calculators. AUPRC should be used to evaluate model predictive performance instead of AUROC when the dataset is imbalanced.
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Hospitalización/estadística & datos numéricos , Unidades de Cuidados Intensivos , Aprendizaje Automático , Complicaciones Posoperatorias/mortalidad , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Preoperatorio , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de TiempoRESUMEN
A measles outbreak involving 19 adults in a home for the intellectually disabled occurred in Singapore in 2019. Further investigation, including a serological survey, was conducted. Mass vaccination and infection control measures were implemented, terminating further secondary transmission. Seropositivity among residents aged 40 to 49 years (90.7%; 95% confidence interval = 78.4%, 96.3%) was lower than among the Singapore adult population (P < .001). This sheltered population, like others previously reported in the literature, had lower measles immunity than the general community, possibly because of limited social interaction. Targeted catch-up vaccination for similarly vulnerable populations should be considered.
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Brotes de Enfermedades/prevención & control , Discapacidad Intelectual/terapia , Vacunación Masiva/estadística & datos numéricos , Vacuna Antisarampión/administración & dosificación , Sarampión/epidemiología , Sarampión/prevención & control , Adulto , Femenino , Humanos , Masculino , Sarampión/inmunología , Persona de Mediana Edad , Instituciones Residenciales , Singapur/epidemiologíaRESUMEN
Presymptomatic transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), might pose challenges for disease control. The first case of COVID-19 in Singapore was detected on January 23, 2020, and by March 16, a total of 243 cases had been confirmed, including 157 locally acquired cases. Clinical and epidemiologic findings of all COVID-19 cases in Singapore through March 16 were reviewed to determine whether presymptomatic transmission might have occurred. Presymptomatic transmission was defined as the transmission of SARS-CoV-2 from an infected person (source patient) to a secondary patient before the source patient developed symptoms, as ascertained by exposure and symptom onset dates, with no evidence that the secondary patient had been exposed to anyone else with COVID-19. Seven COVID-19 epidemiologic clusters in which presymptomatic transmission likely occurred were identified, and 10 such cases within these clusters accounted for 6.4% of the 157 locally acquired cases. In the four clusters for which the date of exposure could be determined, presymptomatic transmission occurred 1-3 days before symptom onset in the presymptomatic source patient. To account for the possibility of presymptomatic transmission, officials developing contact tracing protocols should strongly consider including a period before symptom onset. Evidence of presymptomatic transmission of SARS-CoV-2 underscores the critical role social distancing, including avoidance of congregate settings, plays in controlling the COVID-19 pandemic.
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Enfermedades Asintomáticas , Betacoronavirus , Infecciones por Coronavirus/transmisión , Adulto , Análisis por Conglomerados , Trazado de Contacto , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , SARS-CoV-2 , Singapur/epidemiologíaRESUMEN
Coronavirus disease 2019 (COVID-19) was first reported in Wuhan, China, in December 2019, and has since spread globally, resulting in >95,000 confirmed COVID-19 cases worldwide by March 5, 2020 (1). Singapore adopted a multipronged surveillance strategy that included applying the case definition at medical consults, tracing contacts of patients with laboratory-confirmed COVID-19, enhancing surveillance among different patient groups (all patients with pneumonia, hospitalized patients in intensive care units [ICUs] with possible infectious diseases, primary care patients with influenza-like illness, and deaths from possible infectious etiologies), and allowing clinician discretion (i.e., option to order a test based on clinical suspicion, even if the case definition was not met) to identify COVID-19 patients. Containment measures, including patient isolation and quarantine, active monitoring of contacts, border controls, and community education and precautions, were performed to minimize disease spread. As of March 5, 2020, a total of 117 COVID-19 cases had been identified in Singapore. This report analyzes the first 100 COVID-19 patients in Singapore to determine the effectiveness of the surveillance and containment measures. COVID-19 patients were classified by the primary means by which they were detected. Application of the case definition and contact tracing identified 73 patients, 16 were detected by enhanced surveillance, and 11 were identified by laboratory testing based on providers' clinical discretion. Effectiveness of these measures was assessed by calculating the 7-day moving average of the interval from symptom onset to isolation in hospital or quarantine, which indicated significant decreasing trends for both local and imported COVID-19 cases. Rapid identification and isolation of cases, quarantine of close contacts, and active monitoring of other contacts have been effective in suppressing expansion of the outbreak and have implications for other countries experiencing outbreaks.
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Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/prevención & control , Brotes de Enfermedades/prevención & control , Neumonía Viral/epidemiología , Neumonía Viral/prevención & control , Vigilancia de la Población/métodos , Adulto , COVID-19 , Femenino , Humanos , Masculino , Persona de Mediana Edad , Singapur/epidemiologíaAsunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Singapur/epidemiología , Pandemias , COVID-19/epidemiología , COVID-19/virología , SARS-CoV-2/genéticaAsunto(s)
Betacoronavirus , Infecciones por Coronavirus/epidemiología , Neumonía Viral/epidemiología , Viaje , COVID-19 , China , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/diagnóstico , Fiebre/etiología , Humanos , Pandemias , Aislamiento de Pacientes , Neumonía Viral/complicaciones , Neumonía Viral/diagnóstico , Cuarentena , SARS-CoV-2 , Singapur/epidemiologíaRESUMEN
Importance: Studies have reported increased risk of autoimmune sequelae after SARS-CoV-2 infection. However, risk may potentially be attenuated by milder Omicron (B.1.1.529) variant infection and availability of booster vaccination. Objective: To estimate the 300-day risk of new-incident autoimmune sequelae after SARS-CoV-2 Delta or Omicron BA.1 or BA.2 variant infection in adults who received COVID-19 vaccines and boosters, compared with a contemporary control group without infection. Design, Setting, and Participants: This cohort study in Singapore enrolled adults from September 1, 2021, to March 7, 2022, and followed up for 300 days. Participants were adults aged 18 years or older with SARS-CoV-2 infection during the predominance of the Delta and Omicron BA.1 or BA.2 variants and were still alive at 30 days after COVID-19 diagnosis. Exposure: The national SARS-CoV-2 testing registry was used to construct cohorts of adults with SARS-CoV-2 Delta or Omicron BA.1 or BA.2 variant infection (hereafter, cases) and a contemporaneous group with negative polymerase chain reaction or rapid antigen test results (hereafter, controls). Main Outcomes and Measures: New-incident autoimmune diagnoses after SARS-CoV-2 infection. This information was recorded in the MediClaims national health care claims database and identified 31 to 300 days after index date of infection. Risks and excess burdens were estimated using Cox proportional hazards regression model with overlap weights applied. Results: In total, 1â¯766â¯036 adults (915 096 females [51.9%]; mean [SD] age, 49 [18] years) were included in the study population, with 480â¯082 (27.2%) categorized as cases and 1â¯285â¯954 (72.8%) as controls. Of these adults, 73.1% had Chinese, 13.7% Malay, and 9.9% Indian ethnicity. There were 104â¯179 cases and 666â¯575 controls included during the Delta variant-predominance transmission, while 375â¯903 cases and 619â¯379 controls were included during the Omicron variant-predominance transmission. During the Delta variant period, 81.1% of cases had completed primary vaccination; during the Omicron variant period, 74.6% of cases received boosters. No significantly elevated risk of 12 prespecified autoimmune sequelae was recorded across the Omicron and Delta variant cohorts. Elevated risks of inflammatory bowel disease (adjusted hazard ratio [AHR], 2.23; 95% CI, 1.45-3.46; P < .001) and bullous skin disorders (AHR, 4.88; 95% CI, 2.47-9.66; P < .001) were observed only in the subset of COVID-19 cases requiring hospitalization during the predominance of the Omicron variant. While elevated risk of vasculitis (AHR, 5.74; 95% CI, 1.48-22.23; P = .01) was observed in vaccine-breakthrough Omicron variant infections, no increased risk of vasculitis was observed in the corresponding subgroup who received boosters. Conclusions and Relevance: This cohort study observed no significantly elevated long-term risk of autoimmune sequelae after SARS-CoV-2 Delta and Omicron BA.1 or BA.2 variant infection, except for a modestly increased risk of inflammatory bowel disease and bullous skin disorders in the hospitalized subgroup during the predominance of the Omicron variant. Booster vaccination appeared to mitigate the risk of long-term autoimmune sequelae.
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Enfermedades Autoinmunes , Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiología , COVID-19/inmunología , COVID-19/prevención & control , Femenino , Masculino , SARS-CoV-2/inmunología , Persona de Mediana Edad , Adulto , Singapur/epidemiología , Vacunas contra la COVID-19/inmunología , Enfermedades Autoinmunes/epidemiología , Enfermedades Autoinmunes/inmunología , Estudios de Cohortes , AncianoRESUMEN
BACKGROUND: Individuals with chronic lung disease (CLD) are more susceptible to respiratory viral infections; however, significant heterogeneity exists in the literature on CLD and COVID-19 outcomes. Data are lacking on outcomes with newer variants (eg, Omicron) and in vaccinated and boosted populations. RESEARCH QUESTION: What are the outcomes of SARS-CoV-2 infection in individuals with CLD during Delta and Omicron transmission in a highly vaccinated and boosted population-based cohort? STUDY DESIGN AND METHODS: Outcomes of Delta and Omicron SARS-CoV-2 infection in a highly vaccinated and boosted cohort of adult Singaporeans with CLD (including asthma, COPD, bronchiectasis, and pulmonary fibrosis) were contrasted against matched population control participants. Calendar time-scale Cox regressions were used to compare risk of infection, COVID-19-related hospitalizations, and severe COVID-19 disease, adjusting for sociodemographic factors and comorbidities. RESULTS: Overall, 68,782 individual patients with CLD and 534,364 matched population control participants were included. By the end of the Omicron wave, 92.7% of patients with CLD were boosted. Compared with control participants, patients with CLD showed higher risk of SARS-CoV-2 infection, COVID-19-related hospitalization, and severe COVID-19 during both the Delta wave (infection: adjusted hazards ratio [aHR], 1.22 [95% CI, 1.17-1.28]; hospitalization: aHR, 1.76 [95% CI, 1.61-1.92]; severe COVID-19: aHR, 1.75 [95% CI, 1.50-2.05]) and Omicron wave (infection: aHR, 1.15 [95% CI, 1.14-1.17]; hospitalization: aHR, 1.82 [95% CI, 1.74-1.91]; severe COVID-19: aHR, 2.39 [95% CI, 2.18-2.63]). During Omicron, significantly higher risk of infection, hospitalization, and severe COVID-19 was observed among patients with asthma (severe COVID-19: aHR, 1.31 [95% CI, 1.10-1.55]) and COPD (severe COVID-19: aHR, 1.36 [95% CI, 1.12-1.66]) compared with control participants. Severe exacerbation (requiring hospitalization) in the preceding year was associated with higher risk of poorer outcomes (Delta, severe COVID-19: aHR, 9.84 [95% CI, 6.33-15.28]; Omicron, severe COVID-19: aHR, 19.22 [95% CI, 15.35-24.06]). Risk was attenuated in the boosted group, with numerically lower HRs against hospitalization and severe COVID-19 in the four-dose group compared with the three-dose group. INTERPRETATION: Increased risk of COVID-19-related hospitalization and severe COVID-19 was observed among patients with CLD compared with matched population control participants during Delta and Omicron predominance. Boosting attenuated serious COVID-19 outcomes.
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OBJECTIVES: Studies have reported increased rates of long-term neuropsychiatric sequelae after SARS-CoV-2 infection using electronic health-record (EHR) data; however, the majority were conducted before Omicron and booster rollout. We estimated the long-term risks and excess burdens of pre-specified new-incident neuropsychiatric diagnoses after Delta versus Omicron BA.1/2 infection in a highly-vaccinated and boosted cohort of adult Singaporeans. METHODS: The national SARS-CoV-2 testing registry was used to construct cohorts of Singaporean adults infected during periods of Delta and Omicron BA.1/2 predominance and a contemporaneous test-negative control group. New-incident neuropsychiatric diagnoses recorded in the national health care claims database were identified up to 300 days postinfection. Risks and excess burden were estimated using a doubly robust competing-risks survival analysis. RESULTS: 104 179 and 375 903 infected cases were assigned to Delta and Omicron cohorts and compared against test-negative controls (Delta: N = 666 575 and Omicron: N = 619 379). Elevated risk of cognition or memory disorders was consistently reported across Omicron (Adjusted hazards ratio [aHR], 1.24; 95% CI, 1.12-1.38) and Delta cohorts (aHR, 1.63; 95% CI, 1.39-1.92). Delta-variant infection was associated with an increased risk of anosmia or dysgeusia (aHR, 4.53; 95% CI, 2.78-7.41) and psychosis (aHR, 1.65; 95% CI, 1.22-2.22). By contrast, Omicron-variant infection was associated with a risk of abnormal involuntary movements (aHR, 1.93; 95% CI, 1.32-2.83). Risks of neuropsychiatric sequelae predominantly accrued in hospitalized individuals. DISCUSSIONS: A modestly increased risk of cognition and memory disorders at 300 days after SARS-CoV-2 infection was observed among adult Singaporeans infected during the Delta/Omicron BA.1/2 transmission. There was no overall increased risk of neuropsychiatric sequelae observed across other domains. Variant-specific differences were also observed in individual neuropsychiatric sequelae, including an elevated risk of anosmia or dysgeusia after Delta-variant infection.