Impact of COVID-19 pandemic on carbapenem-resistant Enterobacterales incidence in the South-East Asia region: an observational study.

The COVID-19 pandemic led to an initial increase in the incidence of carbapenem-resistant Enterobacterales (CRE) from clinical cultures in South-East Asia hospitals, which was unsustained as the pandemic progressed. Conversely, there was a decrease in CRE incidence from surveillance cultures and overall combined incidence. Further studies are needed for future pandemic preparedness.

Environmental contamination and evaluation of healthcare-associated SARS-CoV-2 transmission risk in temporary isolation wards during the COVID-19 pandemic.

BACKGROUND: Temporary isolation wards have been introduced to meet demands for airborne-infection-isolation-rooms (AIIRs) during the COVID-19 pandemic. Environmental sampling and outbreak investigation was conducted in temporary isolation wards converted from general wards and/or prefabricated containers, in order to evaluate the ability of such temporary isolation wards to safely manage COVID-19 cases over a period of sustained use. METHODS: Environmental sampling for SARS-CoV-2 RNA was conducted in temporary isolation ward rooms constructed from pre-fabricated containers (N = 20) or converted from normal-pressure general wards (N = 47). Whole genome sequencing (WGS) was utilized to ascertain health care-associated transmission when clusters were reported amongst HCWs working in isolation areas from July 2020 to December 2021. RESULTS: A total of 355 environmental swabs were collected; 22.4% (15/67) of patients had at least one positive environmental sample. Patients housed in temporary isolation ward rooms constructed from pre-fabricated containers (adjusted-odds-ratio, aOR = 10.46, 95% CI = 3.89-58.91, P = .008) had greater odds of detectable environmental contamination, with positive environmental samples obtained from the toilet area (60.0%, 12/20) and patient equipment, including electronic devices used for patient communication (8/20, 40.0%). A single HCW cluster was reported amongst staff working in the temporary isolation ward constructed from pre-fabricated containers; however, health care-associated transmission was deemed unlikely based on WGS and/or epidemiological investigations. CONCLUSION: Environmental contamination with SARS-CoV-2 RNA was observed in temporary isolation wards, particularly from the toilet area and smartphones used for patient communication. However, despite intensive surveillance, no healthcare-associated transmission was detected in temporary isolation wards over 18 months of prolonged usage, demonstrating their capacity for sustained use during succeeding pandemic waves.

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.

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.

Relapsing COVID-19 infection as a manifestation of Good syndrome: a case report and literature review.

Good syndrome (GS) is a rare acquired immunodeficiency disease characterized by the presence of thymoma with combined B and T cell immunodeficiency in adults. Recurrent bacterial infections, particularly sinopulmonary infections caused by encapsulated bacteria, remain the most common infective presentation of GS; however, relapsing viral infections have also been reported, likely due to impaired T cell-mediated immunity. Relapsing COVID-19 infection, however, has not been previously reported as a manifestation of GS. We present two cases of relapsing COVID-19 infection in patients with GS; in one case, relapsing COVID-19 was the first manifestation of newly diagnosed GS.

Healthcare-associated multispecies outbreaks of OXA-48-positive carbapenemase-producing Enterobacteriaceae in a Singapore tertiary-care hospital.

OBJECTIVE: To describe OXA-48-like carbapenem-producing Enterobacteriaceae (CPE) outbreaks at Singapore General Hospital between 2018 and 2020 and to determine the risk associated with OXA-48 carriage in the 2020 outbreak. DESIGN: Outbreak report and case-control study. SETTING: Singapore General Hospital (SGH) is a tertiary-care academic medical center in Singapore with 1,750 beds. METHODS: Active surveillance for CPE is conducted for selected high-risk patient cohorts through molecular testing on rectal swabs or stool samples. Patients with CPE are isolated or placed in cohorts under contact precautions. During outbreak investigations, rectal swabs are repeated for culture. For the 2020 outbreak, a retrospective case-control study was conducted in which controls were inpatients who tested negative for OXA-48 and were selected at a 1:3 case-to-control ratio. RESULTS: Hospital wide, the median number of patients with healthcare-associated OXA-48 was 2 per month. In the 3-year period between 2018 and 2020, 3 OXA-48 outbreaks were investigated and managed, involving 4 patients with Klebsiella pneumoniae in 2018, 55 patients with K. pneumoniae or Escherichia coli in 2019, and 49 patients with multispecies Enterobacterales in 2020. During the 2020 outbreak, independent risk factors for OXA-48 carriage on multivariate analysis (49 patients and 147 controls) were diarrhea within the preceding 2 weeks (OR, 3.3; 95% CI, 1.1-10.7; P = .039), contact with an OXA-48-carrying patient (OR, 8.7; 95% CI, 1.9-39.3; P = .005), and exposure to carbapenems (OR, 17.2; 95% CI, 2.2-136; P = .007) or penicillin (OR, 16.6; 95% CI, 3.8-71.0; P < .001). CONCLUSIONS: Multispecies OXA-48 outbreaks in our institution are likely related to a favorable ecological condition and selective pressure exerted by antimicrobial use. The integration of molecular surveillance epidemiology of the healthcare environment is important in understanding the risk of healthcare-associated infection to patients.

Linking sporadic hospital clusters during a community surge of the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) B.1.617.2 delta variant: The utility of whole-genome sequencing.

Sporadic clusters of healthcare-associated coronavirus disease 2019 (COVID-19) occurred despite intense rostered routine surveillance and a highly vaccinated healthcare worker (HCW) population, during a community surge of the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) B.1.617.2 δ (delta) variant. Genomic analysis facilitated timely cluster detection and uncovered additional linkages via HCWs moving between clinical areas and among HCWs sharing a common lunch area, enabling early intervention.

Detection of viable SARS-CoV-2 in deep respiratory specimens despite negative nasopharyngeal SARS-CoV-2 RT-PCR: Occult COVID-19 as an unsuspected cause of pulmonary infiltrates in immunocompromised patients.

Background: Prolonged shedding/relapse of COVID-19 infection has been reported, particularly in patients who received anti-CD20 agents (eg. rituximab). However, cases of occult COVID-19, in which SARS-CoV-2 persistence in lung parenchyma is diagnosed despite clearance from nasopharyngeal (NP) specimens, are uncommon. Case summary: We describe two cases of occult COVID-19 in immunocompromised patients. Both patients had received rituximab previously. Both cases initially presented as ground-glass infiltrates on lung imaging; the diagnosis was originally not suspected due to repeated demonstration of negative SARS-CoV-2 from NP specimens, and alternative etiologies were originally considered. Persistence of SARS-CoV-2 in lung parenchyma, however, was demonstrated on bronchoalveolar lavage (BAL) specimens; additionally, isolation of viable SARS-CoV-2 virus and detection of SARS-CoV-2 nucleocapsid and spike-protein antigen in lung tissue on immunohistochemistry close to 3-months from primary infection strongly suggested ongoing viral persistence and replication as a driver of the lung parenchymal changes, which resolved after antiviral treatment. Discussion: Occult COVID-19 can be a cause of unexplained ground-glass infiltrates on lung imaging; negative NP samples do not rule out SARS-CoV-2 persistence and invasive sampling must be considered. The unsuspected presence of viable virus on BAL, however, highlights that procedurists perfoming aerosol-generating-procedures during an ongoing pandemic wave must also practise appropriate infection-prevention precautions to limit potential exposure.

Dominant Carbapenemase-Encoding Plasmids in Clinical Enterobacterales Isolates and Hypervirulent Klebsiella pneumoniae, Singapore.

Dissemination of carbapenemase-encoding plasmids by horizontal gene transfer in multidrug-resistant bacteria is the major driver of rising carbapenem-resistance, but the conjugative mechanics and evolution of clinically relevant plasmids are not yet clear. We performed whole-genome sequencing on 1,215 clinical Enterobacterales isolates collected in Singapore during 2010-2015. We identified 1,126 carbapenemase-encoding plasmids and discovered pKPC2 is becoming the dominant plasmid in Singapore, overtaking an earlier dominant plasmid, pNDM1. pKPC2 frequently conjugates with many Enterobacterales species, including hypervirulent Klebsiella pneumoniae, and maintains stability in vitro without selection pressure and minimal adaptive sequence changes. Furthermore, capsule and decreasing taxonomic relatedness between donor and recipient pairs are greater conjugation barriers for pNDM1 than pKPC2. The low fitness costs pKPC2 exerts in Enterobacterales species indicate previously undetected carriage selection in other ecological settings. The ease of conjugation and stability of pKPC2 in hypervirulent K. pneumoniae could fuel spread into the community.

Whole genome sequencing reveals hidden transmission of carbapenemase-producing Enterobacterales.

Carbapenemase-producing Enterobacterales (CPE) infection control practices are based on the paradigm that detected carriers in the hospital transmit to other patients who stay in the same ward. The role of plasmid-mediated transmission at population level remains largely unknown. In this retrospective cohort study over 4.7 years involving all multi-disciplinary public hospitals in Singapore, we analysed 779 patients who acquired CPE (1215 CPE isolates) detected by clinical or surveillance cultures. 42.0% met putative clonal transmission criteria, 44.8% met putative plasmid-mediated transmission criteria and 13.2% were unlinked. Only putative clonal transmissions associated with direct ward contact decreased in the second half of the study. Both putative clonal and plasmid-mediated transmission associated with indirect (no temporal overlap in patients' admission period) ward and hospital contact did not decrease during the study period. Indirect ward and hospital contact were identified as independent risk factors associated with clonal transmission. In conclusion, undetected CPE reservoirs continue to evade hospital infection prevention measures. New measures are needed to address plasmid-mediated transmission, which accounted for 50% of CPE dissemination.

Dengue and COVID-19: Managing Undifferentiated Febrile Illness during a "Twindemic".

BACKGROUND: During the COVID-19 pandemic, distinguishing dengue from COVID-19 in endemic areas can be difficult, as both may present as undifferentiated febrile illness. COVID-19 cases may also present with false-positive dengue serology. Hospitalisation protocols for managing undifferentiated febrile illness are essential in mitigating the risk from both COVID-19 and dengue. METHODS: At a tertiary hospital contending with COVID-19 during a dengue epidemic, a triage strategy of routine COVID-19 testing for febrile patients with viral prodromes was used. All febrile patients with viral prodromes and no epidemiologic risk for COVID-19 were first admitted to a designated ward for COVID-19 testing, from January 2020 to December 2021. RESULTS: A total of 6103 cases of COVID-19 and 1251 cases of dengue were managed at our institution, comprising a total of 3.9% (6103/155,452) and 0.8% (1251/155,452) of admissions, respectively. A surge in dengue hospitalisations in mid-2020 corresponded closely with the imposition of a community-wide lockdown. A total of 23 cases of PCR-proven COVID-19 infection with positive dengue serology were identified, of whom only two were true co-infections; both had been appropriately isolated upon admission. Average length-of-stay for dengue cases initially admitted to isolation during the pandemic was 8.35 days (S.D. = 6.53), compared with 6.91 days (S.D. = 8.61) for cases admitted outside isolation (1.44 days, 95%CI = 0.58-2.30, p = 0.001). Pre-pandemic, only 1.6% (9/580) of dengue cases were admitted initially to isolation-areas; in contrast, during the pandemic period, 66.6% (833/1251) of dengue cases were initially admitted to isolation-areas while awaiting the results of SARS-CoV-2 testing. CONCLUSIONS: During successive COVID-19 pandemic waves in a dengue-endemic country, coinfection with dengue and COVID-19 was uncommon. Routine COVID-19 testing for febrile patients with viral prodromes mitigated the potential infection-prevention risk from COVID-19 cases, albeit with an increased length-of-stay for dengue hospitalizations admitted initially to isolation.

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.

Sporadic clusters of health care-associated COVID-19 infection occurred in a highly vaccinated health care-workers and patient population, over a 3-month period during ongoing community transmission of the B.1.617.2 variant. Enhanced infection-prevention measures and robust surveillance systems, including routine-rostered-testing of all inpatients and staff and usage of N95-respirators in all clinical areas, were insufficient in achieving zero health care-associated transmission. The unvaccinated and immunocompromised remain at-risk and should be prioritized for enhanced surveillance.

Transmission modes of severe acute respiratory syndrome coronavirus 2 and implications for infection control: a review.

The complete picture regarding transmission modes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. This review summarises the available evidence on its transmission modes, our preliminary research findings and implications for infection control policy, and outlines future research directions. Environmental contamination has been reported in hospital settings occupied by infected patients, and is higher in the first week of illness. Transmission via environmental surfaces or fomites is likely, but decontamination protocols are effective in minimising this risk. The extent of airborne transmission is also unclear. While several studies have detected SARS-CoV-2 ribonucleic acid in air samples, none has isolated viable virus in culture. Transmission likely lies on a spectrum between droplet and airborne transmission, depending on the patient, disease and environmental factors. Singapore's current personal protective equipment and isolation protocols are sufficient to manage this risk.

Strengthening national capacities for pandemic preparedness: a cross-country analysis of COVID-19 cases and deaths.

The International Health Regulations-State Party Annual Reporting (IHR-SPAR) index and the Global Health Security Index (GHSI) have been developed to aid in strengthening national capacities for pandemic preparedness. We examined the relationship between country-level rankings on these two indices, along with two additional indices (the Universal Health Coverage Service Coverage Index and World Bank Worldwide Governance Indicator (n = 195)) and compared them to the country-level reported coronavirus disease (COVID-19) cases and deaths (Johns Hopkins University COVID-19 Dashboard) through 17 June 2020. Ordinary least squares regression models were used to compare weekly reported COVID-19 cases and death rates per million in the first 12 weeks of the pandemic between countries classified as low, middle and high ranking on each index while controlling for country socio-demographic information. Countries with higher GHSI and IHR-SPAR index scores experienced fewer reported COVID-19 cases and deaths but only for the first 8 weeks after the country's first case. For the GHSI, this association was further limited to countries with populations below 69.4 million. For both the GHSI and IHR-SPAR, countries with a higher sub-index score in human resources for pandemic preparedness reported fewer COVID-19 cases and deaths in the first 8 weeks after the country's first reported case. The Universal Health Coverage Service Coverage Index and Worldwide Governance Indicator country-level rankings were not associated with COVID-19 outcomes. The associations between GHSI and IHR-SPAR scores and COVID-19 outcomes observed in this study demonstrate that these two indices, although imperfect, may have value, especially in countries with a population under 69.4 million people for the GHSI. Preparedness indices may have value; however, they should continue to be evaluated as policy makers seek to better prepare for future global public health crises.