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Nosocomial SARS-CoV-2 transmission in multi-bedded hospital cubicles over successive pandemic waves: Lower mortality but wider spread with Omicron despite enhanced infection-prevention measures

Published:October 06, 2022DOI:https://doi.org/10.1016/j.idh.2022.09.003

      Highlights

      • Hospital-onset COVID-19 (HA-COVID-19) cases were monitored over 9 months.
      • HA-COVID-19 formed a larger proportion of hospitalized cases during Omicron (vs. Delta).
      • Mortality in HA-COVID-19 was reduced during the Omicron wave.
      • HA-COVID-19 cases identified via daily testing had lower odds of onwards transmission.

      Abstract

      Background

      Increased transmissibility of severe-acute-respiratory-syndrome-coronavirus-2(SARS-CoV-2) variants, such as the Omicron-variant, presents an infection-control challenge. We contrasted nosocomial transmission amongst hospitalized inpatients across successive pandemic waves attributed to the Delta- and Omicron variants, over a 9-month period in which enhanced-infection-prevention-measures were constantly maintained.

      Methods

      Enhanced-infection-prevention-measures in-place at a large tertiary hospital included universal N95-usage, routine-rostered-testing (RRT) for all inpatient/healthcare-workers (HCWs), rapid-antigen-testing (RAT) for visitors, and outbreak-investigation coupled with enhanced-surveillance (daily-testing) of exposed patients. The study-period lasted from 21st June 2021–21st March 2022. Chi-square test and multivariate-logistic-regression was utilized to identify factors associated with onward transmission and 28d-mortality amongst inpatient cases of hospital-onset COVID-19.

      Results

      During the Delta-wave, hospital-onset cases formed 2.7% (47/1727) of all COVID-19 cases requiring hospitalisation; in contrast, hospital onset-cases formed a greater proportion (17.7%, 265/1483; odds-ratio, OR = 7.78, 95%CI = 5.65–10.70) during the Omicron-wave, despite universal N95-usage and other enhanced infection-prevention measures that remained unchanged. The odds of 28d-mortality were higher during the Delta-wave compared to the Omicron-wave (27.7%, 13/47, vs. 10.6%, 28/265, adjusted-odds-ratio, aOR = 2.78, 95%CI = 1.02–7.69). Onward-transmission occurred in 21.2% (66/312) of hospital-onset cases; being on enhanced-surveillance (daily-testing) was independently associated with lower odds of onward-transmission (aOR = 0.18, 95%CI = 0.09–0.38). Costs amounted to $USD7141 per-hospital-onset COVID-19 case.

      Conclusion

      A surge of hospital-onset COVID-19 cases was encountered during the Omicron-wave, despite continuation of enhanced infection-prevention measures; mortality amongst hospital-onset cases was reduced. The Omicron variant poses an infection-control challenge in contrast to Delta; surveillance is important especially in settings where infrastructural limitations make room-sharing unavoidable, despite the high risk of transmission.

      Keywords

      Introduction

      While strict infection-prevention measures lower secondary -attack-rates of coronavirus-disease-2019 (COVID-19) in healthcare-facilities [
      • Thompson H.A.
      • Mousa A.
      • Dighe A.
      • Fu H.
      • Arnedo-Pena A.
      • Barrett P.
      • et al.
      Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) setting-specific transmission rates: a systematic review and meta-analysis.
      ], increased transmissibility of severe-acute-respiratory-syndrome-coronavirus-2(SARS-CoV-2) variants, such as the Omicron-variant, presents infection-control challenges [
      • Baker M.A.
      • Rhee C.
      • Tucker R.
      • Badwaik A.
      • Coughlin C.
      • Holtzman M.A.
      • et al.
      Rapid control of hospital-based SARS-CoV-2 Omicron clusters through daily testing and universal use of N95 respirators.
      ]. Various enhanced-infection-prevention measures have been instituted to mitigate nosocomial transmission [
      • Baker M.A.
      • Rhee C.
      • Tucker R.
      • Badwaik A.
      • Coughlin C.
      • Holtzman M.A.
      • et al.
      Rapid control of hospital-based SARS-CoV-2 Omicron clusters through daily testing and universal use of N95 respirators.
      ]. In Singapore, emergence of the Delta-variant precipitated comprehensive enhanced-infection-prevention-measures, including universal N95-usage, routine-rostered-testing (RRT) for all inpatients/healthcare-workers (HCWs), rapid-antigen-testing (RAT) for visitors, and outbreak-investigation coupled with enhanced-surveillance (daily-testing) of exposed patients [
      • Wee L.E.
      • Venkatachalam I.
      • Sim X.Y.J.
      • Tan K.B.
      • Wen R.
      • Tham C.K.
      • et al.
      Containment of COVID-19 and reduction in healthcare-associated respiratory viral infections through a multi-tiered infection control strategy.
      ,
      • Wee L.E.
      • Conceicao E.P.
      • Aung M.K.
      • Oo A.M.
      • Yong Y.
      • Venkatachalam I.
      • et al.
      Rostered routine testing for healthcare workers and universal inpatient screening: the role of expanded hospital surveillance during an outbreak of COVID-19 in the surrounding community.
      ,
      • Wee L.E.
      • Conceicao E.P.
      • Sim X.Y.J.
      • Venkatachalam I.
      • Weng W.P.
      • Zakaria N.D.
      • et al.
      Utilisation of rapid antigen assays for detection of SARS-CoV-2 in a low-incidence setting at emergency department triage: does risk-stratification still matter?.
      ,
      • Wee L.E.
      • Conceicao E.P.
      • Sim J.X.
      • Venkatachalam I.
      • Wijaya L.
      Utilisation of SARS-CoV-2 rapid antigen assays in screening asymptomatic hospital visitors: mitigating the risk in low-incidence settings.
      ]. These measures were maintained throughout community-transmission of Delta- and Omicron-variants, allowing nosocomial inpatient transmission to be contrasted across successive waves.

      Methodology

      Institutional setting, study-period, outcome measures

      Our healthcare-campus hosts a 1785-bedded tertiary-hospital and a 545-bed community-hospital. Patients are housed on general-wards containing a mixture of normal-pressure single rooms and 5–6 bedded cohorted-cubicles (beds six-feet apart). Toilet facilities are en-suite in some wards and located outside the cohorted-cubicle/room in others. Each cohorted-cubicle/single room has its own ventilation system, with ≥six air-exchanges/hour, and air is not recirculated between cubicles/rooms. Toilets have their own ventilation system, with all air exhausted to outdoors. Ward areas are air-conditioned, given heat and humidity in tropical Singapore. Air in transplant wards is HEPA-filtered. Almost 13,000 HCWs work on-campus. 89.6% of HCWs and 65.0% of inpatients received2 doses of mRNA-vaccines by end-June 2021. The study-period lasted from 21st June 2021–21st March 2022. Chi-square test and multivariate-logistic-regression was utilized to identify factors associated with onward transmission and 28d-mortality amongst inpatient cases of hospital-onset COVID-19 using SPSS (version 20.0). Costs arising from hospital-onset COVID-19 cases were also collated.

      Definitions

      Hospital-onset COVID-19-infection was defined as-follows [
      European Centre for Disease Prevention and Control
      Surveillance definitions for COVID-19.
      ].
      • Indeterminate-hospital-onset: PCR-positive 3–7d post-admission
      • Probable-hospital-onset: PCR-positive 8–14d post-admission
      • Definite-hospital-onset: PCR-positive ≥15d post-admission
      As inpatient PCR-testing was conducted weekly, prior negative PCR-results up-to 14d prior were utilised to evaluate potential nosocomial-transmission. Incubation-periods were defined as 1–14d prior to positive-PCR. Infectious-period was defined as 2d prior to symptom-onset if symptomatic or 7d prior to positive-PCR if asymptomatic. Significant patient-close-contact was defined as contact within six-feet for ≥15 min [
      • Wee L.E.
      • Conceicao E.P.
      • Sim J.X.
      • Venkatachalam I.
      • Wijaya L.
      Utilisation of SARS-CoV-2 rapid antigen assays in screening asymptomatic hospital visitors: mitigating the risk in low-incidence settings.
      ], during the index-patient's infectious-period. Onward-transmission was defined as >1 hospital-onset COVID-19 cases in the same cohorted-cubicle, or if the index was in a single-room, in the same ward; with overlap during the index-patient's infectious-period; ending when no cases were diagnosed for 14d. Whenever hospital-onset inpatient cases were identified, exposed inpatient close-contacts who had originally shared the cohorted-cubicle were placed on an enhanced-surveillance regimen (d1/4/7 PCR, daily-RAT post-exposure for 7-days) which remained unchanged throughout the study-period; however new admissions were still continuously accepted to the cubicle. Patients who subsequently tested positive (RAT/PCR) were transferred immediately to isolation so as not to cohort COVID-19 patients together with patients who tested negative. Onward-transmission was classified as occurring between or beyond adjacent-beds (six-feet-apart). Fully-vaccinated status was defined according to our Ministry of Health's guidelines [
      • Tan H.X.S.
      • Pung R.
      • Wang L.F.
      • Lye D.C.
      • Ong B.
      • Cook A.R.
      • et al.
      Association of homologous and heterologous vaccine boosters with COVID-19 incidence and severity in Singapore.
      ]; prior to February 2022, receipt of 2 doses of mRNA vaccines was required to maintain fully-vaccinated status, while after February 2022, receipt of a 3rd booster dose was required to maintain fully-vaccinated status for all adults aged ≥18 years.

      Enhanced infection-prevention measures

      Universal-admission-testing for SARS-CoV-2 via PCR and RAT was practiced for all inpatients [
      • Wee L.E.
      • Conceicao E.P.
      • Aung M.K.
      • Oo A.M.
      • Yong Y.
      • Venkatachalam I.
      • et al.
      Rostered routine testing for healthcare workers and universal inpatient screening: the role of expanded hospital surveillance during an outbreak of COVID-19 in the surrounding community.
      ,
      • Wee L.E.
      • Conceicao E.P.
      • Sim X.Y.J.
      • Venkatachalam I.
      • Weng W.P.
      • Zakaria N.D.
      • et al.
      Utilisation of rapid antigen assays for detection of SARS-CoV-2 in a low-incidence setting at emergency department triage: does risk-stratification still matter?.
      ], with weekly-PCR/mid-week RAT thereafter for all asymptomatic patients [
      • Wee L.E.
      • Conceicao E.P.
      • Aung M.K.
      • Oo A.M.
      • Yong Y.
      • Venkatachalam I.
      • et al.
      Rostered routine testing for healthcare workers and universal inpatient screening: the role of expanded hospital surveillance during an outbreak of COVID-19 in the surrounding community.
      ]. This testing regimen remained unchanged through the whole study period. Patients who developed new respiratory symptoms/undifferentiated fever were tested at symptom-onset for SARS-CoV-2 via PCR. Inpatients testing positive were managed in designated COVID-19 wards (isolation-areas comprising negative-pressure rooms) separate from patients who tested negative. HCWs in isolation-areas designated for the management of confirmed/suspected COVID-19 cases donned N95-respirators/disposable gloves/gowns/faceshields as personal-protective-equipment (PPE), with disposal after each use. All HCWs donned N95 respirators in all clinical-areas as a mandatory minimum. Aerosol-generating-procedures (AGPs) outside of the isolation-ward were performed with HCWs using N95-respirators/disposable gloves/gowns/faceshields and in single rooms where feasible. Surgical-mask-usage was mandated for all inpatients and visitors. Two asymptomatic, fully-vaccinated-visitors/inpatient/day were allowed; visitors underwent RAT if visiting ≥30 min [
      • Wee L.E.
      • Conceicao E.P.
      • Sim J.X.
      • Venkatachalam I.
      • Wijaya L.
      Utilisation of SARS-CoV-2 rapid antigen assays in screening asymptomatic hospital visitors: mitigating the risk in low-incidence settings.
      ]. Symptomatic HCWs could access free PCR-testing at Staff Clinic [
      • Wee L.E.
      • Conceicao E.P.
      • Aung M.K.
      • Oo A.M.
      • Yong Y.
      • Venkatachalam I.
      • et al.
      Rostered routine testing for healthcare workers and universal inpatient screening: the role of expanded hospital surveillance during an outbreak of COVID-19 in the surrounding community.
      ].

      Results

      Over the study-period, 312 hospital-onset cases were identified, of which the majority (53.8%, 168/312) were probable/definite; the remainder were indeterminate. Up to December 2021, whole-genome-sequencing (WGS) revealed that all hospital-onset-cases were attributable to the Delta-variant (N = 47) [
      • Wee L.E.
      • Ko K.K.K.
      • Conceicao E.P.
      • Sim J.X.
      • Rahman N.A.
      • Tan S.Y.L.
      • et al.
      Linking sporadic hospital clusters during a community surge of the SARS-CoV-2 delta variant (B.1.617.2): the utility of whole-genome-sequencing.
      ]. The first Omicron case was identified in a returned traveler on 24th December 2021. By January 2022, all hospital-onset cases demonstrated S-gene dropout on PCR-testing, indicative of the Omicron-variant. During the Delta-wave, hospital-onset cases formed 2.7% (47/1727) of all COVID-19 cases requiring hospitalisation; in contrast, hospital onset-cases formed a greater proportion (17.7%, 265/1483; odds-ratio, OR = 7.78, 95%CI = 5.65–10.70) during the Omicron-wave. The majority of hospital-onset cases (78.8%, 246/312) were fully-vaccinated. Three-fifths (59.6%, 186/312) received therapeutics; 4.5% (14/312) required intensive-care-unit/high-dependency admission; and 13.1% (41/312) demised within 28d of infection. Stratifying by variant (Delta vs. Omicron), 55.3% (26/47) received therapeutics during the Delta-wave, while 60.4% (160/265) received therapeutics during the Omicron-wave (odds ratio, OR = 0.81, 95%CI = 0.44–1.52, p = 0.310). Only 6.4% (3/47) required intensive-care-unit/high-dependency admission during the Delta-wave, while 4.2% (11/265) required intensive-care-unit/high-dependency admission during the Omicron-wave (OR = 1.54, 95%CI = 0.45–5.31, p = 0.701). The majority (76.5%, 36/47) were fully-vaccinated during the Delta-wave, while 79.2% (210/265) were fully vaccinated during the Omicron-wave (OR = 0.86, 95%CI = 0.41–1.79, p = 0.700). On univariate analysis, older age (age≥70 years), higher ISARIC-score (≥7), being immobile, partial/unvaccinated status, pneumonia, high-dependency/intensive-care-unit admission, and infection with the Delta-variant were associated with 28d-mortality (Table 1). On multivariate-logistic-regression, higher ISARIC-score (≥7), immobility, pneumonia, and intensive-care-unit/high-dependency admission were all independently associated with 28-day mortality amongst hospital-onset COVID-19 cases (Table 2). The odds of 28d-mortality were higher during the Delta-wave compared to Omicron (27.7%, 13/47, vs. 10.6%, 28/265, adjusted-odds-ratio, aOR = 2.78, 95%CI = 1.02–7.69).
      Table 1Univariate analysis of risk factors for 28-day mortality amongst hospital-onset COVID-19 cases (N = 312).
      Covariates (index cases)28-day mortality amongst hospital-onset cases (N%)Odds ratio, 95% CI
      Chi-square test.
      P-value
      Clinical characteristics
      Aged<70 years12/141 (8.5)1.00
      Aged≥70 years29/171 (17.0)2.22 (1.07–4.55)0.030∗
      Female17/122 (13.9)1.00
      Male24/190 (12.6)0.89 (0.46–1.74)0.735
      ISARIC score<7
      ISARIC score: risk stratification score that predicts in-hospital mortality for hospitalised COVID-19 patients, derived from the following variables: age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea level, and C reactive protein (score range 0–21 points).
      3/83 (3.6)1.00
      ISARIC score≥738/229 (16.6)5.31 (1.59–17.69)0.002∗
      Not on hemodialysis34/257 (13.2)1.00
      On hemodialysis7/55 (12.7)0.96 (0.40–2.29)1.00
      Not immunocompromised22/200 (11.0)1.00
      Immunocompromised19/112 (17.0)1.65 (0.85–3.21)0.162
      Not mobile33/118 (28.0)1.00
      Mobile8/194 (4.1)0.11 (0.05–0.25)<0.001∗
      Not fully vaccinated14/66 (21.2)1.00
      Fully vaccinated27/246 (11.0)0.46 (0.22–0.93)0.039∗
      Admission characteristics
      Admitted for ≤7 days prior to diagnosis11/124 (8.9)1.00
      Admitted for >7 days prior to diagnosis30/188 (16.0)1.95 (0.94–4.01)0.087
      Upper-respiratory-tract-infection15/227 (6.6)1.00
      Pneumonia26/85 (30.6)6.23 (3.10–12.52)<0.001∗
      Did not require high-dependency/intensive care36/298 (12.1)1.00
      Required high-dependency/intensive care5/14 (35.7)4.04 (1.28–12.74)0.025∗
      Did not receive therapeutics13/126 (10.3)1.00
      Received therapeutics28/186 (15.1)1.54 (0.76–3.10)0.238
      Cycle-threshold value ≥ 20 at onset19/151 (12.6)1.00
      Cycle-threshold value < 20 at onset22/161 (13.7)1.10 (0.57–2.12)0.867
      Delta variant13/47 (27.7)1.00
      Omicron variant28/265 (10.6)0.31 (0.15–0.65)0.004∗
      ∗ p-value <0.05.
      a Chi-square test.
      b ISARIC score: risk stratification score that predicts in-hospital mortality for hospitalised COVID-19 patients, derived from the following variables: age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea level, and C reactive protein (score range 0–21 points).
      Table 2Multivariate analysis of risk factors for 28-day mortality amongst hospital-onset COVID-19 cases (N = 312).
      Covariates (index cases)Adjusted odds ratio, 95% CI
      Multivariate logistic regression.
      P-value
      Clinical characteristics
      ISARIC score≥7
      ISARIC score: risk stratification score that predicts in-hospital mortality for hospitalised COVID-19 patients, derived from the following variables: age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea level, and C reactive protein (score range 0–21 points).
      (vs. ISARIC <7)
      3.97 (1.05–14.99)0.042
      p-value <0.05.
      Immunocompromised (vs. not immunocompromised)2.00 (0.89–4.53)0.093
      Mobile (vs. immobile)0.11 (0.04–0.28)<0.001
      p-value <0.05.
      Admission characteristics
      Pneumonia (vs. upper-respiratory-tract-infection)4.63 (2.07–10.33)<0.001
      p-value <0.05.
      Required high-dependency/intensive care (vs. general ward care)3.97 (1.03–15.34)0.045
      p-value <0.05.
      Omicron variant (vs. Delta variant)0.36 (0.13–0.98)0.047
      p-value <0.05.
      a p-value <0.05.
      b Multivariate logistic regression.
      c ISARIC score: risk stratification score that predicts in-hospital mortality for hospitalised COVID-19 patients, derived from the following variables: age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea level, and C reactive protein (score range 0–21 points).
      Onward-transmission occurred in 21.2% (66/312) of hospital-onset cases, with a median of 1.00 (inter-quartile-ratio, IQR = 1.00–2.00) cases arising from exposure to each index-case. During the Delta-wave, epidemiologically-linked cases (N = 26) previously exposed to an index inpatient case were identified on average at 5.65 days (S.D = 2.45) post-exposure. In comparison, during the Omicron-wave, epidemiologically-linked cases (N = 102) were identified at 3.90 days (S.D = 2.09) post-exposure (mean-difference = 1.75, 95%CI = 0.69–2.91). On univariate analysis (Table 3) and multivariate-logistic-regression, being on enhanced-surveillance (d1/4/7 PCR, daily-RAT post-exposure for 7-days) was independently associated with lower odds of onward-transmission (aOR = 0.18, 95%CI = 0.09–0.38), whereas AGPs occurring during the index's infectious period, prior to positive SARS-CoV-2 testing and subsequent isolation (aOR = 4.07, 95%CI = 1.88–8.78, p < 0.001), cycle-threshold-value of <20 on PCR-testing (aOR = 1.85, 95%CI = 1.01–3.48), admission to a cubicle/room with a shared toilet (outside cohorted cubicle or room) (aOR = 1.90, 95%CI = 1.01–3.54), and being in a cohorted-cubicle instead of a single-room (aOR = 13.32, 95%CI = 1.63–109.10) were all independently associated with higher odds of onward-transmission. Onward-transmission beyond immediately-adjacent beds occurred in the majority (63.6%, 42/66) and was independently associated with common-toilet usage by the index-case (OR = 4.12, 95%CI = 1.44–12.07) (Table 3). Costs of COVID-19 therapeutics, isolation, COVID-19-related testing and surveillance of exposed inpatients attributable to all hospital-onset inpatient cases (N = 312) amounted to USD$2,228,055, or USD$7141 per-case (Table 4).
      Table 3Analysis of risk factors for onward transmission of SARS-CoV-2 from hospital-onset COVID-19 cases (N = 312).
      Covariates (index cases)Onward transmission amongst hospital-onset cases (N%)95% CI
      Chi-square test.
      P-valueTransmission beyond immediately-adjacent beds (N%)95% CI
      Chi-square test.
      P-value
      Clinical characteristics
      Aged<60 years15/75 (20.0)1.000.87211/15 (73.3)1.000.543
      Aged≥60 years51/237 (21.5)1.10 (0.56–2.10)31/51 (60.8)0.56 (0.16–2.02)
      Female22/122 (18.0)1.000.32114/22 (63.6)1.001.00
      Male44/190 (23.2)1.37 (0.77–2.43)28/44 (63.6)1.00 (0.34–2.90)
      ISARIC score<7
      ISARIC score: risk stratification score that predicts in-hospital mortality for hospitalised COVID-19 patients, derived from the following variables: age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea level, and C reactive protein (score range 0–21 points).
      15/83 (18.1)1.000.5308/15 (53.3)1.000.374
      ISARIC score≥751/229 (22.3)1.28 (0.69–2.46)34/51 (66.7)1.75 (0.54–5.64)
      Not on hemodialysis57/257 (22.2)1.000.46734/57 (59.6)1.000.139
      On hemodialysis9/55 (16.4)0.68 (0.32–1.50)8/9 (88.9)5.41 (0.63–46.23)
      Not immunocompromised40/200 (20.0)1.000.56426/40 (65.0)1.000.799
      Immunocompromised26/112 (23.2)1.21 (0.69–2.12)16/26 (61.5)0.86 (0.31–2.40)
      Not mobile30/118 (25.4)1.000.15616/30 (53.3)1.000.131
      Mobile36/194 (18.6)0.67 (0.39–1.16)26/36 (72.2)2.28 (0.82–6.33)
      Not fully vaccinated15/66 (22.7)1.000.73610/15 (66.7)1.001.00
      Fully vaccinated51/246 (20.7)0.89 (0.46–1.71)32/51 (62.7)0.84 (0.25–2.84)
      Ward characteristics
      In single room1/20 (5.0)1.000.0881/1 (100.0)1.001.00
      In cohorted cubicle65/292 (22.3)5.43 (0.71–41.7)41/65 (63.1)0.63 (0.52–0.76)
      Dedicated toilet within cohorted cubicle or room23/145 (15.9)1.000.037∗14/23 (60.9)1.000.792
      Shared toilet (outside cohorted cubicle or room)43/167 (25.7)1.84 (1.05–3.24)28/43 (65.1)1.20 (0.42–4.32)
      General ward45/224 (20.1)1.000.53826/45 (57.8)1.000.178
      Haematology/oncology/renal ward21/88 (23.9)1.25 (0.69–2.25)16/21 (76.2)2.34 (0.73–7.50)
      General ward62/294 (21.1)1.001.0040/62 (64.5)1.000.618
      High-dependency/intensive-care-unit4/18 (22.2)1.07 (0.34–3.36)2/4 (50.0)0.55 (0.07–4.18)
      Admission events
      Admitted for ≤7 days prior to diagnosis26/124 (21.0)1.001.0017/26 (65.4)1.001.00
      Admitted for >7 days prior to diagnosis40/188 (21.3)1.02 (0.58–1.79)25/40 (62.5)0.88 (0.32–2.47)
      Not on enhanced-surveillance (daily testing) prior to diagnosis55/183 (30.1)1.00<0.001∗35/55 (63.6)1.001.00
      On enhanced-surveillance (daily testing) prior to diagnosis11/129 (8.5)0.22 (0.11–0.43)7/11 (63.6)1.00 (0.26–3.84)
      Did not use common toilet27/116 (23.3)1.000.47812/27 (44.4)1.000.010
      Used common toilet39/196 (19.9)0.82 (0.47–1.43)30/39 (76.9)4.12 (1.44–12.07)
      No aerosol-generating procedure46/263 (17.5)1.00<0.00128/46 (60.9)1.000.583
      Aerosol-generating procedure20/49 (40.8)3.25 (1.69–6.25)14/20 (70.0)1.50 (0.49–4.62)
      No diarrhea62/294 (21.2)1.001.0040/62 (64.5)1.000.618
      Ongoing diarrhea4/18 (22.2)1.07 (0.34–3.36)2/4 (50.0)0.55 (0.07–4.18)
      SARS-CoV-2 testing results
      Cycle-threshold value ≥ 2024/151 (15.9)1.000.03718/24 (75.0)1.000.188
      Cycle-threshold value < 2042/161 (26.1)1.89 (1.01–3.27)24/42 (57.1)0.44 (0.15–1.35)
      Delta variant8/47 (17.0)1.000.5627/8 (87.5)1.000.241
      Omicron variant58/265 (21.5)1.37 (0.61–3.08)35/58 (60.3)0.22 (0.03–1.89)
      ∗ p-value <0.05.
      ↑ Aerosol-generating procedures defined as: nebulizers, high flow nasal cannula, noninvasive positive pressure ventilation, intubation.
      a Chi-square test.
      b ISARIC score: risk stratification score that predicts in-hospital mortality for hospitalised COVID-19 patients, derived from the following variables: age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea level, and C reactive protein (score range 0–21 points).
      Table 4Cost of COVID-19 therapeutics, isolation-ward stay, COVID-19-related laboratory testing and surveillance for exposed inpatients for hospital-onset COVID-19 cases amongst hospitalised inpatients (N = 312).
      Cost of COVID-19 therapeutics, isolation-ward stay, COVID-19-related laboratory testing and surveillance for exposed inpatientsNumber of patient-days (d)/number of tests/number of patientsTotal cost (USD$)
      COVID-19 therapeutics
      Antivirals
      Remdesivir690d362,500
      Nirmatrelvir-ritonavir5d800
      Monoclonal antibodies
      Casirivimab-imdevimab2d2500
      Sotrovimab21d52,000
      Tixagevimab-cilgavimab2d7000
      Anti-IL6/JAK1-2
      Baricitinib6d75
      Tocilizumab3d2300
      COVID-19 in-hospital isolation
      Isolation in hospital's isolation general ward3269d1,242,700
      Isolation in hospital's isolation intensive-care-unit126d98,280
      COVID-19 related-testing
      SARS-CoV-2 PCR624 tests54,000
      SARS-CoV-2 IgG (RBD)165 tests6000
      Costs of surveillance for exposed inpatients to index hospital-onset COVID-19 cases
      SARS-CoV-2 PCR on d1/4/7, as well as daily-RAT for 7 days post-exposure1045 patients399,900
      Total costs2,228,055
      Total cost per patient (N = 312)7141

      Discussion

      During the Delta-wave, inpatient clusters remained small and sporadic in the setting of comprehensive enhanced infection-prevention measures [
      • Wee L.E.
      • Conceicao E.P.
      • Sim J.X.
      • Aung M.K.
      • Aung M.O.
      • Yong Y.
      • et al.
      Sporadic outbreaks of healthcare-associated COVID-19 infection in a highly-vaccinated inpatient population during a community outbreak of the B.1.617.2 variant: the role of enhanced infection-prevention measures.
      ]. However, a surge in nosocomial transmission occurred with the Omicron-variant, despite continuation of all infection-prevention measures. Mortality was reduced during the Omicron-wave, and was comparable to estimates of mortality attributed to hospital-associated influenza [
      • Godoy P.
      • Torner N.
      • Soldevila N.
      • Rius C.
      • Jane M.
      • Martínez A.
      • et al.
      Working group on the surveillance of severe influenza hospitalized cases in catalonia. Hospital-Acquired influenza infections detected by a surveillance system over six seasons, from 2010/2011 to 2015/2016.
      ]. Daily inpatient-testing for COVID-19 cluster-control was associated with reduced onward-transmission in cohorted-cubicles. Additionally, COVID-19 index cases identified in rooms with shared bathroom facilities had higher odds of onward transmission; likely due to the possibility of fomite transmission [
      • Al Mayahi Z.K.
      • Al Kindi N.
      • Al Shaqsi N.
      • Al Hattali N.
      • Al Hattali A.
      • Salim K.
      • et al.
      Non-respiratory droplet transmission of COVID-19 in the isolation ward of a secondary hospital in Oman: a return to isolation basics.
      ] and increased human traffic in shared facilities. Generalisability is limited by our study's single-site nature; however, continuity of infection-prevention measures allowed contrast between pandemic waves. In conclusion, we highlight the challenge of the Omicron variant when contrasted against Delta and reinforce the importance of reducing onward transmission, especially given infrastructural limitations posed by cohorted rooms [
      • Karan A.
      • Klompas M.
      • Tucker R.
      • Baker M.
      • Vaidya V.
      • Rhee C.
      The risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission from patients with undiagnosed coronavirus disease 2019 (COVID-19) to roommates in a large academic medical center.
      ].

      Ethics

      This study was conducted as part of outbreak-investigation; ethics approval was waived under our institutional-review-board guidelines.

      Authorship statement

      WLE: Conceptualization; data curation; formal analysis; investigation; methodology; writing- original draft; writing-review and editing. EPC, MKA, AMO, YY, SA: Data curation; formal analysis; investigation; methodology; writing-review and editing. KKK: Investigation; methodology; writing-review and editing. IV: Conceptualization; investigation; methodology; supervision; writing-review and editing.

      Conflict of interest

      The authors report no conflicts of interest

      Funding

      This work was not grant-funded. Funding for consumables was provided by the Singapore General Hospital.

      Provenance and peer review

      Not commissioned; externally peer reviewed.

      Acknowledgement

      The authors acknowledge the efforts of all colleagues in combating COVID-19.

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