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Continued demographic shifts in hospitalised patients with COVID-19 from migrant workers to a vulnerable and more elderly local population at risk of severe disease

Open AccessPublished:December 09, 2022DOI:https://doi.org/10.1016/j.ijid.2022.12.007

      Highlights

      • In 2020, COVID-19 predominantly affected young migrant workers in Singapore.
      • Therefore, a low incidence of severe complications was observed in 2020.
      • In 2021, COVID-19 affected Singapore's more elderly and vulnerable local population.
      • Consequently, there was a greater strain on intensive care facilities in 2021.
      • Monitoring COVID-19 demographic shifts help guide healthcare resource allocation.

      Abstract

      Objectives: In the early months of the COVID-19 pandemic in Singapore, the vast majority of infected persons were migrant workers living in dormitories who had few medical comorbidities. In 2021, with the Delta and Omicron waves, this shifted to the more vulnerable, elderly population within the local community. We examined evolving trends among the hospitalised cases of COVID-19.
      Methods: All patients with polymerase chain reaction-positive SARS-CoV-2 admitted from February 2020 to October 2021 were included and subsequently stratified by their year of admission (2020 or 2021). We compared the baseline clinical characteristics, clinical course, and outcomes.
      Results: A majority of cases were seen in 2020 (n = 1359), compared with 2021 (n = 422), due to the large outbreaks in migrant worker dormitories. Nevertheless, the greater proportion of locally transmitted cases outside of dormitories in 2021 (78.7% vs 12.3%) meant a significantly older population with more medical comorbidities had COVID-19. This led to an observably higher proportion of patients with severe disease presenting with raised inflammatory markers, need for therapeutics, supplemental oxygenation, and higher mortality.
      Conclusion: Changing demographics and the characteristics of the exposed populations are associated with distinct differences in clinical presentation and outcomes. Older age remained consistently associated with adverse outcomes.

      Keywords

      1. Introduction

      In a previous study, we examined the first 3 months of the pandemic and the shifting demographics of hospitalised patients with COVID-19 in Singapore [
      • Ngiam JN
      • Chew N
      • Tham SM
      • Beh DL
      • Lim ZY
      • Li TYW
      • Cen S
      • Tambyah PA
      • Santosa A
      • Sia CH
      • Cross GB.
      Demographic shift in COVID-19 patients in Singapore from an aged, at-risk population to young migrant workers with reduced risk of severe disease.
      ]. In summary, the first cases observed were labelled as ‘imported cases’ as they were predominantly returning travellers [
      • Lim RJ
      • Lee TH
      • Lye DCB.
      From SARS to COVID-19: the Singapore journey.
      ]. This subsequently led to a small outbreak within the local community, which was rapidly curbed by aggressive case-finding and quarantining of the affected cases and their contacts (Ministry of Health [[
      Ministry of Health (Singapore)
      Circuit breaker to minimise further spread of COVID-19.
      ]pore] 2020, [
      • Lee VJ
      • Chiew CJ
      • Khong WX.
      Interrupting transmission of COVID-19: lessons from containment efforts in Singapore.
      ]). Similar approaches have been adopted in several other countries to effectively control the cases of COVID-19 in the early stages of the pandemic [
      • Peck KR.
      Early diagnosis and rapid isolation: response to COVID-19 outbreak in Korea.
      ].
      However, although these measures had been effective in limiting the cases within the local community, migrant workers in dormitories with crowded living conditions were not spared [
      • Yi H
      • Ng ST
      • Farwin A
      • Pei Ting Low A
      • Chang CM
      • Lim J
      Health equity considerations in COVID-19: geospatial network analysis of the COVID-19 outbreak in the migrant population in Singapore.
      ,
      Government of Singapore
      Containing COVID-19 spread at foreign worker dormitories.
      ,
      • Chew MH
      • Koh FH
      • Wu JT
      • Ngaserin S
      • Ng A
      • Ong BC
      • Lee VJ.
      Clinical assessment of COVID-19 outbreak among migrant workers residing in a large dormitory in Singapore.
      ]. This large and sustained outbreak in the migrant worker dormitories accounted for the vast majority of hospitalised patients with COVID-19 in Singapore in 2020 [
      • Ngiam JN
      • Chew N
      • Tham SM
      • Beh DL
      • Lim ZY
      • Li TYW
      • Cen S
      • Tambyah PA
      • Santosa A
      • Sia CH
      • Cross GB.
      Demographic shift in COVID-19 patients in Singapore from an aged, at-risk population to young migrant workers with reduced risk of severe disease.
      ]. These migrant workers tended to be young and fit men with few medical comorbidities. As such, they were at low risk for progression to severe COVID-19 or developing life-threatening complications of the disease [
      • Ngiam JN
      • Chew N
      • Tham SM
      • Beh DL
      • Lim ZY
      • Li TYW
      • Cen S
      • Tambyah PA
      • Santosa A
      • Sia CH
      • Cross GB.
      Demographic shift in COVID-19 patients in Singapore from an aged, at-risk population to young migrant workers with reduced risk of severe disease.
      ,
      • Ngiam JN
      • Chew NWS
      • Tham SM
      • Lim ZY
      • Li TYW
      • Cen S
      • Tambyah PA
      • Santosa A
      • Sia CH
      • Cross GB.
      Utility of conventional clinical risk scores in a low-risk COVID-19 cohort.
      ,
      • Kim GU
      • Kim MJ
      • Ra SH
      • Lee J
      • Bae S
      • Jung J
      • Kim SH.
      Clinical characteristics of asymptomatic and symptomatic patients with mild COVID-19.
      ]. Indeed, at that time, due to the active case-finding (a “zero-COVID” approach) and the relatively young and low-risk affected population, Singapore reported among the lowest mortality rates for COVID-19 in the world [,
      • Lim RHF
      • Htun HL
      • Li AL
      • Guo H
      • Kyaw WM
      • Hein AA
      • Ang B
      • Chow A.
      Fending off Delta - Hospital measures to reduce nosocomial transmission of COVID-19.
      ].
      Singapore was able to quickly vaccinate the majority of its population against COVID-19 [
      • Griva K
      • Tan KYK
      • Chan FHF
      • Periakaruppan R
      • Ong BWL
      • Soh ASE
      • Chen MI.
      Evaluating rates and determinants of COVID-19 vaccine hesitancy for adults and children in the Singapore population: strengthening our community's resilience against threats from emerging infections (Socrates) cohort.
      ,
      • Chew NWS
      • Cheong C
      • Kong G
      • Phua K
      • Ngiam JN
      • Tan BYQ
      • Wang B
      • Hao F
      • Tan W
      • Han X
      • Tran BX
      • Hoang MT
      • Pham HQ
      • Vu GT
      • Chen Y
      • Danuaji R
      • Rn K
      • Pv M
      • Talati K
      • Ho CS
      • Sharma AK
      • Ho RC
      • Sharma VK.
      An Asia-Pacific study on healthcare workers' perceptions of, and willingness to receive, the COVID-19 vaccination.
      ], with 80% of the country's population having completed two doses by August 2021 (Ministry of Health [[
      Ministry of Health (Singapore)
      Update on local COVID-19 situation and vaccination progress.
      ]pore] 2021). In addition, the rapid spread of the Delta variant in the third quarter of 2021 raised the concern of overcrowding in healthcare facilities; thus, in comparison to 2020, in 2021, persons with COVID-19 were no longer routinely quarantined in a hospital or care facilities but were allowed to recover at home. People with COVID-19 were, however, required to be hospitalised if they had risk factors for disease progression, such as if they were unvaccinated and/or were more vulnerable to severe disease despite vaccination on account of comorbidities or age. In this study, we described the changing trends in hospitalised patients with COVID-19 as the pandemic progressed in Singapore from 2020 to 2021.

      2. Methods

      We retrospectively examined patients consecutively admitted between February 2020 to October 2021 at a single tertiary academic institution in Singapore who had polymerase chain reaction (PCR)-proven COVID-19. Patients who were less than 21 years of age were excluded from this study, as were patients who did not require hospital admission or who were cared for only in community care facilities.
      The study population was divided based on their admission year (2020 or 2021) and subsequently also stratified by age category (<40 years or ≥40 years of age). For each patient, we collected information on their demographic background, clinical presentation, laboratory findings, and other investigations conducted within 24 hours of hospital admission. The progress of each patient was followed, including the use of COVID-19-specific therapeutics (such as remdesivir, dexamethasone, baricitinib, or tocilizumab) and clinical outcomes, such as the presence of pneumonia, need for supplemental oxygen, transfer to intensive care, and in-hospital mortality.
      To compare differences in characteristics between those admitted in 2020 compared with 2021, t-tests were used for continuous variables, while chi-squared tests were used for categorical variables. Data for continuous variables were expressed as means (± 1 SD), while data for categorical variables were expressed as frequencies (and percentages). A P-value of less than 0.05 was considered significant in this study. All data analyses were performed on SPSS version 20.0 (SPSS, Inc., Chicago, Illinois). This study was approved by the National Healthcare Group Domain Specific Review Board (DSRB 2020/00545). The study was conducted in line with the principles laid out by the Declaration of Helsinki. All data were anonymised, and a waiver of written informed consent was obtained before the conduct of the study.

      3. Results

      A total of 1781 patients required hospital admission for COVID-19 between February 2020 to October 2021. A total of 1359 patients with COVID-19 were admitted in 2020 and 422 in 2021. The mean age of those admitted in 2021 was 60.0 years compared with 39.4 years in 2020 (P <0.001). Dormitory workers accounted for the majority of the outbreak in 2020, compared with 2021 (83.7% vs 4.0%, P <0.001), with men correspondingly accounting for a much larger proportion in 2020 compared with 2021 (90.8% vs 46.2%, P <0.001) (Table 1). The outbreak in Singapore began with a few cases among returning travellers from February to March 2020, followed by small clusters within the community in April 2020. Alongside the outbreak in the community outside the dormitories, which was brought under control quickly, there was a large, uncontrolled outbreak in migrant worker dormitories, which peaked in May 2020 and only subsided substantially in August 2020. Between August 2020 and the new year, there was little transmission within the dormitories or within the community at large in Singapore despite the loosening of social distancing restrictions. However, once again, in early 2021, with the advent of the Delta variant of concern, a few cases in returning travellers gradually built to a relatively large outbreak of cases among the local population in Singapore, which initially peaked around mid-September 2021 (Figure 1).
      Table 1Demographic shifts in the clinical characteristics of patients admitted with COVID-19 from 2020 to 2021 in a tertiary academic hospital in Singapore.
      ParameterAdmission for COVID-19 in 2020 (n = 1359)Admission for COVID-19 in 2021 (n = 422)P-value
      Demographics
      Age (years)39.4 ( ± 11.3)60.0 ( ± 19.7)<0.001
      Body mass index (kg/m2)25.8 ( ± 5.1)26.0 ( ± 5.8)0.742
      Sex (male)1231 (90.8%)195 (46.2%)<0.001
      Ethnicity<0.001
      Chinese220 (16.2%)252 (59.7%)
      Malay59 (4.3%)67 (15.9%)
      Indian496 (36.5%)63 (14.9%)
      Others584 (42.9%)40 (9.5%)
      Transmission<0.001
      Overseas56 (4.1%)73 (17.3%)
      Local166 (12.3%)332 (78.7%)
      Dormitory1137 (83.7%)17 (4.0%)
      Smoking history99 (7.7%)31 (7.4%)0.816
      Hypertension133 (9.8%)121 (28.7%)<0.001
      Hyperlipidaemia74 (5.4%)99 (23.5%)<0.001
      Diabetes mellitus75 (5.5%)55 (13.0%)<0.001
      Asthma12 (0.9%)19 (4.5%)<0.001
      Chronic kidney disease4 (0.3%)17 (4.0%)<0.001
      Cancer13 (1.0%)19 (4.5%)<0.001
      No previous medical conditions1148 (84.5%)251 (59.5%)<0.001
      Vaccinated against COVID-190 (0.0%)273 (64.7%)<0.001
      Clinical presentation
      Acute respiratory symptoms827 (60.9%)339 (80.3%)<0.001
      Anosmia80 (5.9%)14 (3.3%)0.045
      Asymptomatic illness252 (18.5%)55 (13.0%)0.009
      Admission temperature (°C)37.3 ( ± 0.8)37.1 ( ± 0.8)0.002
      Persistent fever >72 hours149 (11.0%)55 (13.0%)0.244
      Length of time with fever (days)1.2 ( ± 2.3)1.0 ( ± 1.6)0.096
      Systolic blood pressure (mmHg)129.7 ( ± 16.7)131.6 ( ± 21.5)0.060
      Diastolic blood pressure (mmHg)80.7 ( ± 17.7)76.2 ( ± 13.1)<0.001
      Pulse rate (per minute)90.3 ( ± 17.7)85.7 ( ± 14.9)<0.001
      Oxygen saturation (%)98.0 ( ± 2.0)97.6 ( ± 3.0)0.003
      Initial laboratory findings
      Total white cell count (x109/l)6.88 ( ± 2.28)6.22 ( ± 2.28)<0.001
      Haemoglobin count (g/dl)14.9 ( ± 1.5)13.3 ( ± 1.8)<0.001
      Platelet count (x109/l)240 ( ± 65)231 ( ± 77)0.025
      Absolute lymphocyte count (x109/l)2.00 ( ± 1.45)1.48 ( ± 0.74)<0.001
      Serum creatinine (µmol/l)78.7 ( ± 24.4)81.9 ( ± 102.5)0.292
      Estimated glomerular filtration rate (ml/min/1.73m2)104.5 ( ± 17.2)94.9 ( ± 27.8)<0.001
      Serum C-reactive protein (mg/dl)12.5 ( ± 26.4)23.1 ( ± 38.0)<0.001
      Serum ferritin (µg/l)196.1 ( ± 233.5)254.1 ( ± 444.7)0.001
      Serum lactate dehydrogenase (U/l)420.6 ( ± 283.3)418.2 ( ± 168.1)0.881
      Therapeutics
      Dexamethasone10 (0.7%)47 (11.1%)<0.001
      Remdesivir39 (2.9%)47 (11.1%)<0.001
      Sotrovimab0 (0.0%)16 (3.8%)<0.001
      Baricitinib4 (0.3%)5 (1.2%)0.039
      Tocilizumab1 (0.1%)2 (0.5%)0.142
      Clinical outcomes
      Length of hospital stay (days)7.8 ( ± 9.1)7.4 ( ± 7.9)0.356
      Requiring supplemental oxygenation40 (2.9%)46 (10.9%)<0.001
      Pneumonia180 (13.2%)105 (24.9%)<0.001
      Requiring intensive care37 (2.7%)18 (4.2%)0.110
      High-flow nasal cannula2 (0.1%)9 (2.1%)<0.001
      Myocarditis8 (0.6%)4 (0.9%)0.494
      Stroke4 (0.3%)1 (0.2%)0.999
      Acute kidney injury60 (4.4%)15 (3.6%)0.491
      Death5 (0.4%)8 (1.9%)0.004
      Figure 1
      Figure 1Transmission of COVID-19 cases in Singapore over time, comparing local (community) cases with returning travellers (overseas) and migrant worker (dormitory) cases.
      Patients admitted in 2021 had a greater likelihood of having medical comorbidities such as hypertension, diabetes mellitus, and chronic kidney disease. A total of 59.5% had no previous medical conditions in 2021, compared with 84.5% in 2020. Asymptomatic disease was more common among hospitalised patients in 2020 (18.5%) compared with 2021 (13.0%) (Table 1). Those above and below 40 years of age had a comparable prevalence of asymptomatic disease (Table 2). Despite good uptake of the COVID-19 vaccines in the community in Singapore since early 2021 (64.7% of the admitted COVID-19 cases in 2021 had received at least one dose of the vaccination), symptoms of acute respiratory illness (e.g., cough, rhinorrhoea, sore throat) were far more common in 2021 (80.3% vs 60.9%, P <0.001) probably related to the public health policies which did not mandate admission to a hospital or community care facility for all patients who were SARS-CoV-2 positive by PCR in 2021. Anosmia was slightly more common in 2020 compared with 2021 (5.9% vs 3.3%, P-value = 0.045) (Table 1). Older patients (>40 years of age) had a similar prevalence of anosmia compared with their younger counterparts (Table 2). Oxygen saturation at presentation in 2021 was marginally lower compared with 2020 (97.6 ± 3.0 vs 98.0 ± 2.0%, P-value = 0.003), but no significant differences in the duration of fever were found (Table 1). When stratified by age, older patients (>40 years of age) tended to have more persistent fever and marginally lower oxygen saturations at presentation (Table 2).
      Table 2Clinical characteristics of patients admitted with COVID-19 from 2020 to 2021 in a tertiary academic hospital in Singapore, stratified by year of admission and age category.
      ParameterAdmission for COVID-19 in 2020 (n = 1359)Admission for COVID-19 in 2021 (n = 422)P
      A comparison between COVID-19 admissions in 2020 with COVID-19 admissions in 2021.
      value
      Age<40 years (n = 756)Age≥40 years (n = 603)Age<40 years (n = 164)Age>40 years (n = 258)
      Demographics
      Age (years)30.8 ( ± 4.8)50.1 ( ± 7.1)32.3 ( ± 4.5)62.8 ( ± 16.1)<0.001
      Body mass index (kg/m2)24.8 ( ± 4.7)26.5 ( ± 5.3)27.1 ( ± 6.5)25.5 ( ± 5.4)0.062
      Sex (male)690 (91.8%)541 (89.7%)57 (34.8%)138 (53.5%)<0.001
      Ethnicity<0.001
      Chinese42 (5.6%)178 (29.5%)66 (40.2%)186 (72.1%)
      Malay29 (3.8%)30 (5.0%)35 (21.3%)32 (12.4%)
      Indian297 (39.3%)199 (33.0%)33 (20.1%)30 (11.6%)
      Others388 (51.3%)196 (32.5%)32 (19.5%)103 (3.9%)
      Transmission<0.001
      Overseas33 (4.4%)23 (3.8%)43 (26.2%)30 (11.6%)
      Local55 (7.3%)111 (18.4%)108 (65.8%)224 (86.8%)
      Dormitory668 (88.4%)469 (77.8%)13 (7.9%)4 (1.6%)
      Smoking history41 (5.7%)58 (10.3%)4 (2.5%)27 (10.6%)<0.001
      Hypertension15 (2.0%)118 (19.6%)4 (2.4%)117 (45.3%)<0.001
      Hyperlipidaemia6 (0.8%)68 (11.3%)3 (1.8%)96 (37.2%)<0.001
      Diabetes mellitus9 (1.2%)66 (10.9%)1 (0.6%)54 (20.9%)<0.001
      Asthma7 (0.9%)5 (0.8%)3 (1.8%)16 (6.2%)<0.001
      Chronic kidney disease2 (0.3%)2 (0.4%)0 (0.0%)3 (1.2%)<0.001
      Cancer2 (0.3%)11 (2.0%)0 (0.0%)13 (5.1%)<0.001
      No previous medical conditions722 (95.5%)426 (70.6%)151 (92.1%)100 (38.8%)<0.001
      Vaccinated against COVID-190 (0.0%)0 (0.0%)84 (51.2%)189 (73.3%)<0.001
      Clinical presentation
      Acute respiratory symptoms475 (62.8%)352 (58.4%)129 (78.7%)210 (81.4%)<0.001
      Anosmia40 (5.3%)40 (6.6%)7 (4.3%)7 (2.7%)0.114
      Asymptomatic illness93 (12.3%)159 (26.4%)29 (17.7%)26 (10.1%)<0.001
      Admission temperature (°C)37.4 ( ± 0.8)37.1 ( ± 0.7)37.0 ( ± 0.6)37.3 ( ± 0.9)<0.001
      Persistent fever >72 hours74 (9.8%)75 (12.4%)14 (8.5%)41 (15.9%)0.029
      Length of time with fever (days)1.2 ( ± 2.3)1.2 ( ± 2.3)0.7 ( ± 1.3)1.1 ( ± 1.7)0.061
      Systolic blood pressure (mmHg)127.2 ( ± 15.1)132.9 ( ± 18.1)120.1 ( ± 14.8)138.9 ( ± 22.0)<0.001
      Diastolic blood pressure (mmHg)80.0 ( ± 11.4)81.5 ( ± 12.5)74.5 ( ± 12.3)77.3 ( ± 13.4)<0.001
      Pulse rate (per minute)92.0 ( ± 18.3)88.1 ( ± 16.6)87.6 ( ± 15.2)84.6 ( ± 14.7)<0.001
      Oxygen saturation (%)98.2 ( ± 1.4)97.7 ( ± 2.6)98.4 ( ± 1.3)97.1 ( ± 3.6)<0.001
      Initial laboratory findings
      Total white cell count (x109/l)6.89 ( ± 2.18)6.87 ( ± 2.39)6.56 ( ± 2.20)6.03 ( ± 2.30)<0.001
      Haemoglobin count (g/dl)15.2 ( ± 1.4)14.4 ( ± 1.5)13.5 ( ± 1.8)13.2 ( ± 1.8)<0.001
      Platelet count (x109/l)238 ( ± 62)242 ( ± 68)253 ( ± 75)219 ( ± 75)<0.001
      Absolute lymphocyte count (x109/l)2.07 ( ± 1.79)1.91 ( ± 0.86)1.60 ( ± 0.74)1.41 ( ± 0.73)<0.001
      Serum creatinine (µmol/l)77.9 ( ± 14.8)79.7 ( ± 32.5)62.2 ( ± 17.9)92.8 ( ± 126.0)<0.001
      Estimated glomerular filtration rate (ml/min/1.73m2)111.0 ( ± 15.4)96.4 ( ± 15.9)115.0 ( ± 17.6)83.9 ( ± 26.4)<0.001
      Serum C-reactive protein (mg/dl)28.2 ( ± 1.1)23.9 ( ± 1.0)12.9 ( ± 1.2)45.1 ( ± 2.9)<0.001
      Serum ferritin (µg/l)149.9 ( ± 132.5)257.3 ( ± 311.6)105.4 ( ± 145.5)330.7 ( ± 521.4)<0.001
      Serum lactate dehydrogenase (U/l)409.4 ( ± 298.6)434.3 ( ± 262.7)368.3 ( ± 123.4)444.7 ( ± 182.3)0.019
      Therapeutics
      Dexamethasone3 (0.4%)7 (1.2%)2 (1.2%)45 (17.4%)<0.001
      Remdesivir4 (0.5%)35 (5.8%)3 (1.8%)44 (17.1%)<0.001
      Sotrovimab0 (0.0%)0 (0.0%)0 (0.0%)16 (6.2%)<0.001
      Baricitinib0 (0.0%)4 (0.7%)0 (0.0%)5 (1.9%)0.001
      Tocilizumab0 (0.0%)1 (0.2%)0 (0.0%)2 (0.8%)0.066
      Clinical outcomes
      Length of hospital stay (days)7.7 ( ± 9.1)8.0 ( ± 9.1)6.9 ( ± 7.8)7.7 ( ± 7.9)0.519
      Requiring supplemental oxygenation9 (1.2%)31 (5.1%)1 (0.6%)45 (17.4%)<0.001
      Pneumonia49 (6.5%)131 (21.7%)13 (7.9%)92 (35.7%)<0.001
      Requiring intensive care8 (1.1%)29 (4.8%)3 (1.8%)15 (5.8%)<0.001
      High-flow nasal cannula1 (0.1%)1 (0.2%)1 (0.6%)8 (3.1%)<0.001
      Myocarditis3 (0.4%)5 (0.8%)1 (0.6%)3 (1.2%)0.569
      Stroke1 (0.1%)3 (0.5%)0 (0.0%)1 (0.4%)0.537
      Acute kidney injury27 (3.6%)33 (5.5%)1 (0.6%)14 (5.4%)0.025
      Death2 (0.3%)3 (0.5%)0 (0.0%)8 (3.1%)<0.001
      a A comparison between COVID-19 admissions in 2020 with COVID-19 admissions in 2021.
      Patients in 2021 were more likely to present with lower lymphocyte count (1.48 ± 0.74 vs 2.00 ± 1.45 × 109/l, P <0.001), higher C-reactive protein concentrations (23.1 ± 38.0 vs 12.5 ± 26.4 mg/dl, P <0.001), and higher serum ferritin concentrations (254.1 ± 444.7 vs 196.1 ± 233.5 µg/l, P-value = 0.001) (Table 1). Older patients (>40 years of age) across both the years of the study consistently had higher levels of C-reactive protein and serum ferritin levels compared with their younger counterparts (Table 2). In 2021, a greater proportion of patients received COVID-19-specific drugs than in 2020, including dexamethasone (11.1% vs 0.7%, P <0.001), remdesivir (11.1% vs 2.9%, P <0.001), and baricitinib (1.2% vs 0.3%, P-value = 0.039). Sotrovimab, a neutralising monoclonal antibody, was also only available in Singapore in 2021, and 16 patients (3.8%) of the cohort in 2021 received this medication (Table 1). Similarly, across both the years of study, older patients (>40 years of age) were more likely to receive COVID-19-specific therapeutics than those that were younger (Table 2).
      No difference in the length of hospital stay was found between the two study periods (7.8 ± 9.1 days in 2020 and 7.4 ± 7.9 days in 2021, P-value = 0.356) mainly because discharge policies changed in tandem with admission policies, meaning that in 2021, patients were not kept in hospital until they had tested negative for COVID-19 on PCR. As shown in Figure 2, Figure 3, the proportion of cases who had pneumonia and required intensive care fell dramatically in 2020 and then rose again in June 2021 when the vulnerable, elderly population were once again exposed to COVID-19 (Figures 2 and 3) A higher proportion of patients required supplemental oxygenation in 2021 (10.9%) compared with 2020 (2.9%, P <0.001), and there was higher mortality among those admitted in 2021 (1.9% vs 0.4%, P-value = 0.004). Across both years of study, older patients consistently had a higher proportion of patients with adverse outcomes, such as requiring supplemental oxygenation, intensive care, and death (Table 2).
      Figure 2
      Figure 2Percentage of hospitalised COVID-19 patients with pneumonia over time.
      Figure 3
      Figure 3Percentage of hospitalised COVID-19 patients requiring intensive care over time.

      4. Discussion

      In this retrospective analysis of the first 1781 patients admitted with COVID-19 to our hospital between February 2020 to October 2021, we examined the differences in the patient profile between those admitted in the year 2020 compared with those admitted in 2021. The key findings were that (i) the outbreak in 2020 encompassed predominantly a young migrant worker population, whereas, in 2021, the patient profile was largely elderly patients from the community with comorbidities; (ii) patients were significantly more unwell in 2021 with a higher proportion of pneumonia, severe disease at presentation, higher inflammatory markers, and a greater prevalence in the use of COVID-19-specific drugs; and (iii) that despite the availability of effective COVID-19 therapeutics and effective vaccination in 2021 (where 64% of the hospitalised cohort in 2021 had received at least one dose of the vaccine, and 54.5% had two or more doses of vaccination), there remained a higher proportion of patients with adverse outcomes, including mortality, among the hospitalised cohort. Furthermore, another consistent finding was that despite the changes in the circulating virus strains, and introduction of COVID-19-specific therapeutics and effective vaccination across the years, we consistently found that (iv) older age was uniformly associated with more severe illness and adverse clinical outcomes among those hospitalised with COVID-19.
      A broad overview of the changes to the community measures implemented and COVID-19 management in response to the pandemic from 2020 to 2021 is summarised in Table 3. Our study demonstrated that COVID-19 patients who were younger and had fewer medical comorbidities appeared to be protected against the development of moderate to severe disease, even if infected with the original Wuhan strain or in the absence of vaccination. This original Wuhan strain had been associated with much higher overall excess mortality in Europe and North America [
      • Bonanad C
      • García-Blas S
      • Tarazona-Santabalbina F
      • Sanchis J
      • Bertomeu-González V
      • Fácila L
      • Ariza A
      • Núñez J
      • Cordero A.
      The effect of age on mortality in patients with COVID-19: a meta-analysis with 611,583 subjects.
      ,
      • Ho FK
      • Petermann-Rocha F
      • Gray SR
      • Jani BD
      • Katikireddi SV
      • Niedzwiedz CL
      • Foster H
      • Hastie CE
      • Mackay DF
      • Gill JMR
      • O'Donnell C
      • Welsh P
      • Mair F
      • Sattar N
      • Celis-Morales CA
      • Pell JP
      Is older age associated with COVID-19 mortality in the absence of other risk factors? General population cohort study of 470,034 participants.
      ].
      Table 3Overview of community measures and changes to COVID-19 management in Singapore from 2020 to 2021.
      DateCommunity measures
      Ministry of Health Singapore. Updates on COVID-19 Situation. https://www.moh.gov.sg/covid-19 (accessed 02 April 2022)
      COVID-19 management/therapeutics
      National Centre for Infectious Diseases Singapore. Treatment Guidelines for COVID-19. https://www.ncid.sg/Health-Professionals/Diseases-and-Conditions/Pages/COVID-19.aspx (accessed 02 April 2022)
      January - March 202023 January 2020: First case of COVID-19 diagnosed in Singapore

      4 February 2020: First case of local transmission in Singapore

      7 February 2020: DORSCON Orange

      20 March 2020: Launch of contact-tracing app
      All COVID-19 patients admitted to tertiary hospitals for initial evaluation and monitoring, then subsequently discharged to community facilities for further isolation
      April - June 20204 April 2020: Several clusters identified in migrant worker dormitories

      7 April 2020: “Circuit-breaker” measure start in the community

      9 April 2020: “Stay-home notices” for returning travellers from all countries

      1 June 2020: Phase 1 of Singapore's reopening (end of circuit-breaker measures)

      19 June 2020: Phase 2 of Singapore's reopening
      2 April 2020: NCID Singapore releases Interim Treatment Guidelines for COVID-19 (version 1.0)

      10 April 2020: Large community isolation facility opens in the Expo to isolate COVID-19 patients during the recovery period

      10 June 2020: Remdesivir approved for use in COVID-19 treatment in Singapore by the Health Sciences Authority

      16 June 2020: Preliminary results of RECOVERY trial announced - Dexamethasone for the use in COVID-19
      June - December 202028 December 2020: Phase 3 of Singapore's reopening30 December 2020: Start of the COVID-19 vaccination campaign
      January - June 20218 May 2021: Back to phase 2 measures due to rise in cases from the Delta variant

      16 May 2021: Back to phase 2 heightened alert measures

      14 June 2021: Phase 3 heightened alert measures
      4 January 2021: Baricitinib recommended for severe COVID-19 as part of the NCID Interim Treatment Guidelines (version 5.0)

      14 June 2021: Tocilizumab recommended for severe COVID-19 as part of the NCID Interim Treatment Guidelines (version 6.0)

      30 June 2021: Sotrovimab receives interim authorisation in Singapore from the Health Sciences Authority
      July - December 202122 July 2021: Return to phase 2 (heightened alert) measures to curb COVID-19

      13 October 2021: Vaccination-differentiated measures implemented (e.g., only fully vaccinated individuals may enter shopping malls)
      29 August 2021: 80% of the population is vaccinated against COVID-19

      14 September 2021: COVID-19 booster vaccination for senior citizens above 60 years of age

      10 October 2021: Home recovery programme is the default for most of the population
      NCID, National Centre of Infectious Diseases.
      a Ministry of Health Singapore. Updates on COVID-19 Situation. https://www.moh.gov.sg/covid-19 (accessed 02 April 2022)
      b National Centre for Infectious Diseases Singapore. Treatment Guidelines for COVID-19. https://www.ncid.sg/Health-Professionals/Diseases-and-Conditions/Pages/COVID-19.aspx (accessed 02 April 2022)
      Besides patient-related factors, differences seen between the two study periods were also likely to be due to a change in public health policy: in 2020, all COVID-19 patients were required to be isolated in a care facility or hospital, while in 2021, patients with COVID-19 were instead encouraged to recover at home (Ministry of Health [[
      Ministry of Health (Singapore)
      Eligible for home recovery programme.
      ]pore] 2022). Only those deemed to be at greater risk of moderate to severe disease were hospitalised, namely those who were not vaccinated, partially vaccinated, who were in an older age category, or who had medical comorbidities, reflective of the demographic change we saw in our inpatient cohort in 2021. This meant that the hospitalised cohort was more selected and reflected only those at risk of more severe disease and progression, placing a significant burden on intensive care facilities in 2021 [
      • Cai Y
      • Kwek S
      • Tang SSL
      • Saffari SE
      • Lum E
      • Yoon S
      • Ansah JP
      • Matchar DB
      • Kwa AL
      • Ang KA
      • Thumboo J
      • Ong MEH
      • Graves N.
      Impact of the COVID-19 pandemic on a tertiary care public hospital in Singapore: resources and economic costs.
      ].
      Additionally, the circulating viral strain was also likely to have differed across these two periods: the Delta variant was the predominant strain in Singapore in 2021 compared with the original Wuhan strain, which affected the majority of the migrant worker population in Singapore in 2020 [
      • Chia PY
      • Ong SWX
      • Chiew CJ
      • Ang LW
      • Chavatte JM
      • Mak TM
      • Cui L
      • Kalimuddin S
      • Chia WN
      • Tan CW
      • Chai LYA
      • Tan SY
      • Zheng S
      • Lin RTP
      • Wang L
      • Leo YS
      • Lee VJ
      • Lye DC
      • Young BE.
      Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine breakthrough infections: a multicentre cohort study.
      ]. The Delta variant was associated with increased transmissibility and was reported to have more pneumonia compared with the original Wuhan strain, which may have impacted our findings [
      • Choi JY
      • Smith DM.
      SARS-CoV-2 variants of concern.
      ,
      • Lin L
      • Liu Y
      • Tang X
      • He D.
      The disease severity and clinical outcomes of the SARS-CoV-2 variants of concern.
      ]. It was difficult to tease out the relative contribution of vaccination uptake, the changes in strain, and the changes in demographics on the outcomes of hospitalised patients with COVID-19. All these factors were likely to have contributed to the observed changes in the clinical profile and patient outcomes. However, the consistent age-related differences in mortality in both years in our cohort suggest that demographics played a major contributing role in outcomes.
      Finally, the increase in the use of COVID-19-specific therapeutics would likely also have been related to better-established international guidelines on COVID-19 management and increasing global experience in the efficacy and safety of these therapeutic agents [
      • National Institutes of Health
      Coronavirus disease 2019 (COVID-19) treatment guidelines.
      ,
      • Nicola M
      • O'Neill N
      • Sohrabi C
      • Khan M
      • Agha M
      • Agha R.
      Evidence-based management guideline for the COVID-19 pandemic - Review article.
      ,
      • Andrews N
      • Tessier E
      • Stowe J
      • Gower C
      • Kirsebom F
      • Simmons R
      • Gallagher E
      • Thelwall S
      • Groves N
      • Dabrera G
      • Myers R
      • Campbell CNJ
      • Amirthalingam G
      • Edmunds M
      • Zambon M
      • Brown K
      • Hopkins S
      • Chand M
      • Ladhani SN
      • Ramsay M
      Lopez Bernal J. Duration of protection against mild and severe disease by Covid-19 vaccines.
      ]. Furthermore, the National Centre for Infectious Disease in Singapore also released and updated interim treatment guidelines for COVID-19 [
      National Centre for Infectious Diseases Singapore
      Treatment guidelines for COVID-19.
      ]. These guidelines were first released on April 02, 2020 and updated over the years to guide the use and improve the uptake of COVID-19-specific therapeutics in Singapore, such as remdesivir, dexamethasone, sotrovimab, tocilizumab, and baricitinib, where clinically indicated. The higher uptake of COVID-19-specific therapeutics within the hospitalised cohort in 2021 compared with 2020 may reflect the more severe disease in this population, but improved knowledge and confidence in their use, together with the established treatment guidelines, may also have been contributory.
      Several countries in Asia had also adopted a strict containment strategy for COVID-19 early in the pandemic. For example, South Korea and China both rapidly enforced strategies early in the pandemic in 2020 to test, contact trace, and treat cases of COVID-19 [
      • Chen H
      • Shi L
      • Zhang Y
      • Wang X
      • Jiao J
      • Yang M
      • Sun G.
      Response to the COVID-19 pandemic: comparison of strategies in six countries.
      ] together with quarantine for contacts and various social distancing measures. Other similar strategies included enforcing border controls and restricting entry into the country in 2020 [
      • Olufadewa II
      • Adesina MA
      • Ekpo MD
      • Akinloye SJ
      • Iyanda TO
      • Nwachukwu P
      • Kodzo LD.
      Lessons from the coronavirus (COVID-19) pandemic response in China, Italy and the U.S.: a guide for Africa and low-and-middle-income countries.
      ]. Despite efforts in containment, these countries still saw relatively large outbreaks of COVID-19 cases but with very low levels of mortality [
      • Chen H
      • Shi L
      • Zhang Y
      • Wang X
      • Jiao J
      • Yang M
      • Sun G.
      Response to the COVID-19 pandemic: comparison of strategies in six countries.
      ].
      However, containment strategies were resource-intensive and had significant socio-economic impacts on countries that adopted their use [
      • Jiao J
      • Shi L
      • Chen H
      • Wang X
      • Yang M
      • Yang J
      • Liu M
      • Yi X
      • Sun G.
      Containment strategy during the COVID-19 pandemic among three Asian low and middle-income countries.
      ]. Several countries, including Singapore, shifted towards aiming to effectively vaccinate and protect their vulnerable population against COVID-19 while easing other restrictions as economies and global trade began to recover [
      • Tsou HH
      • Kuo SC
      • Lin YH
      • Hsiung CA
      • Chiou HY
      • Chen WJ
      • Wu SI
      • Sytwu HK
      • Chen PC
      • Wu MH
      • Hsu YT
      • Wu HY
      • Lee FJ
      • Shih SM
      • Liu DP
      • Chang SC.
      A comprehensive evaluation of COVID-19 policies and outcomes in 50 countries and territories.
      ]. In most countries, similar “waves” of cases of COVID-19 were observed, which each new circulating variant of the virus. With its highly vaccinated population, although the hospitalised cohort appeared more ill in 2021 compared with 2020, Singapore continued to observe relatively low mortality rates among patients infected with COVID-19. Indeed, these patterns have also been seen in other countries with high vaccination rates [
      • Ziakas PD
      • Kourbeti IS
      • Mylonakis E.
      Comparative analysis of mortality from coronavirus disease 2019 across the European Union countries and the effects of vaccine coverage.
      ].
      As the pandemic situation continues to evolve in Singapore, as it does around the world, accurate interpretation of clinical case data is critically important. With changes in public health policies at every jurisdiction and the discovery of new variants against which vaccines, monoclonal antibodies, and antiviral agents may have reduced efficacy, we will no doubt continue to field new challenges in managing COVID-19 and discovering how it impacts various sectors in our communities.

      5. Limitations

      This was a retrospective single-centre cohort of patients hospitalised with COVID-19. It was a heterogeneous cohort of patients, given that not all patients required hospital admission because they had been clinically unwell or were at significant risk of deterioration. In the clinical context, early in the pandemic, patients had also been admitted for the purpose of isolation and triage before subsequent transfer to isolation facilities within the community. Our study was observational and retrospective in design. We did not capture or examine the cases that were managed directly in these community facilities or who recovered at home, which formed the bulk of the COVID-19 cases in Singapore from 2020 to 2021. The observed differences in trends and outcomes among hospitalised patients with COVID-19 may be a result of a combination of factors, including the changes in circulating viral strain, changes in public health policy (for example, only admitting severely ill patients to the hospital) in addition to the changes in the demographics of the affected population, which we highlighted. Our study had not been designed to estimate the effect size of each factor on the changes in the observed trends and outcomes. Nevertheless, we believe that this snapshot of hospitalised patients gives valuable insight into the profile of hospitalised patients over time and their evolving needs.

      6. Conclusion

      In conclusion, the demographics of individuals affected by COVID-19 in Singapore shifted dramatically from 2020 to 2021. Despite high vaccination uptake rates against COVID-19, the disease has shifted from a predominantly young and low-risk migrant worker population to affect the more vulnerable local community in 2021, with hospitalised patients consequently being more ill and having a greater need for intensive care and higher mortality. With the benefit of hindsight, it is possible to argue that the zero-COVID strategy, which reduced transmission outside the migrant worker dormitories in 2020, was not sustainable in an open society where there is the constant risk of the introduction of new, more transmissible variants of concern. Despite the changes in the circulating viral strains over the study period and the introduction of effective vaccination against COVID-19 and COVID-19-specific therapeutics, older age remained an important risk factor for more severe disease and adverse clinical outcomes among hospitalised patients with COVID-19 in our centre and elsewhere. Further prospective study is warranted to monitor the shifting demographic trends with new and emerging variants of concerns.

      Declarations of competing interest

      The authors have no competing interests to declare.

      Funding

      There was no funding for this study. CHS was supported by the National University of Singapore Yong Loo Lin School of Medicine's Junior Academic Fellowship Scheme.

      Ethical approval

      This study was approved by the hospital's institutional review board (National Healthcare Group (NHG) Domain Specific Review Board (DSRB) 2020/00545)

      Author contributions

      JNN, SC, WG, and MYS contributed to the conception, data collection, analysis, and writing of the manuscript. NWSC, CHS, GBC, and PAT contributed to the conception, data analysis, writing, and critical review of the manuscript.

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