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.

Three-Dimensional Disease Outbreak Surveillance System in a Tertiary Hospital in Singapore: A Proof of Concept

Objective To develop an electronic surveillance system that provides prompt in-depth situational infectious disease risk and linkage analysis for inpatients in a tertiary hospital. Patients and Methods All patients admitted to Singapore General Hospital (SGH), a 1900-bedded tertiary care hospital, are included in routine surveillance. The 3-Dimensional Disease Outbreak Surveillance System (3D-DOSS) was developed to spatiotemporally represent inpatient surveillance data on a "digital twin” of SGH and evaluated for performance in surveillance, contact tracing, and outbreak investigations. This study was conducted over a 12 month period (October 1, 2020 to September 30, 2021). Results The 3D-DOSS surveillance module identified an influenza cluster of 10 inpatients in November 2018, mapping retrospective data between September 2018 and December 2018. Seventy-six clusters of 2 or more linked patients with health care–associated Klebsiella pneumoniae carbapenemase–type carbapenemase-producing Enterobacteriaceae were detected in SGH in 2 years (2018 and 2019). The 3D-DOSS contact tracing module promptly identified 44 primary and 162 secondary inpatient contacts, after exposure to a health care worker with coronavirus disease 2019 in April 2021. For outbreak mapping, 24 patients with OXA-48 were mapped on October 22, 2020, using 3D-DOSS to determine their spatiotemporal distribution. Conclusion The integration of health care data and representation on a virtual hospital digital twin is a useful tool in an outbreak alert and response framework. Infectious disease surveillance systems, which are syndrome-based, that can access real-time data, and can incorporate movement networks, can potentially enhance health care–associated infection prevention and preparedness for disease X.

SG-APSIC1098: Impact of the COVID-19 pandemic on influenza vaccination uptake among healthcare workers

Objectives: Influenza vaccination is encouraged for all healthcare workers (HCWs) to reduce the risk of acquiring the infection and onward transmission to colleagues and patients during the influenza season. Thus, vaccination was introduced at Singapore General Hospital (SGH) in 2007 and has been offered to all HCWs at no cost. The HCW influenza vaccination program is conducted annually in October and biannually during years with vaccine mismatch. However, influenza vaccine uptake remained low among HCWs. We sought to determine the impact of the coronavirus disease 2019 (COVID-19) pandemic on influenza vaccine uptake among HCWs. Methods: At SGH, 2 methods of vaccine delivery are offered: centralized (1-month drop-in system during office hours) and decentralized (administered by vaccination teams in offices or ward staff in inpatient locations). In the 4-year study period between 2018 and 2021, 6 influenza vaccination exercise campaigns were conducted during 8 influenza seasons. During each exercise, ~9,000 HCWs were eligible for vaccination. Results: Prior to the COVID-19 pandemic, vaccine uptake in the Southern Hemisphere was 77.6% (6,964 of 8,977) in 2018 and 84.2% (7,296 of 8,670) in 2019. During the COVID-19 pandemic in 2020, vaccine uptake in the Southern Hemisphere increased by 10% to 94.1% (8,361 of 8,889). In the Northern Hemisphere, vaccine uptake was 79.2% (7,114 of 8,977) in 2018, and this increased by 17.9% to 97.1% (8,926 of 9,194) during the COVID-19 pandemic in 2020. During the 2021 Southern Hemisphere influenza season, no vaccination program was conducted because the risk of influenza was considered low due to the closure of international borders and the implementation of public health measures. In addition, priority was given to COVID-19 vaccination efforts. Conclusions: Increased uptake of the influenza vaccination was observed during the COVID-19 pandemic. Anxiety created by the respiratory disease pandemic and debate surrounding vaccines likely contributed to increased awareness and uptake in influenza vaccine among HCWs.

COVID-19 among healthcare workers of a tertiary-care hospital in Singapore

Background: Singapore General Hospital (SGH) is the largest acute tertiary-care hospital in Singapore. Healthcare workers (HCWs) are at risk of acquiring COVID-19 in both the community and workplaces. SGH has a robust exposure management process including prompt contact tracing, immediate ring fencing, lock down of affected cubicles or single room isolation for patient contacts, and home isolation orders for staff contacts of COVID-19 cases during the containment phase of the pandemic. Contacts were also placed on enhanced surveillance with PCR testing on days 1 and 4 as well as daily antigen rapid tests (ARTs) for 10 days after exposure. Here, we describe the characteristic of HCWs with COVID-19 during the third wave of the COVID-19 pandemic. Methods: This retrospective observational study included all SGH HCWs who acquired COVID-19 during the third wave (ie, the 18-week period from September 1 to December 31, 2021) of the COVID-19 pandemic. Univariate analysis was used to compare characteristics of work-associated infection (WAI) and community-acquired infection (CAI) among HCWs. Results: Among a workforce of >10,000 at SGH, 335 HCWs acquired COVID-19 during study period. CAI (exposure to known clusters or household contact) accounted for 111 HCW infections (33.1%). Also, 48 HCWs (14.3%) had a WAI (ie, acquired at their work places where there was no patient contact). Among WAsI, only 5 HCWs had hospital-acquired infection (confirmed by phylogenetic analysis). The sources of exposure for the remaining 176 HCWs were unknown. Weekly incidence of COVID-19 among HCWs was comparable to the epidemiology curve of all cases in Singapore (Fig. 1 and 2). The mean age of HCWs with COVID-19 was 39.6 years, and most were women. At the time of positive SARS-CoV-2 PCR test, 223 HCWs were symptomatic, and 67 (20.0%) of them had comorbidities. Only 16 HCWs (4.8%) required hospitalization, and all recovered fully with no mortality (Table 1). Being female was associated with community COVID-19 acquisition (OR, 4.6, P Conclusions: During the thrid wave of the COVID-19 pandemic, a higher percentage of HCWs at SGH acquired the infection from the community than from the workplace. Safe management measures, such as universal masking, social distancing, and robust exposure management processes including prompt contact tracing and environmental disinfection, can reduce the risk of COVID-19 in the hospital work environment.Funding: NoneDisclosures: None

Favorable vaccine-induced SARS-CoV-2-specific T cell response profile in patients undergoing immune-modifying therapies.

BACKGROUNDPatients undergoing immune-modifying therapies demonstrate a reduced humoral response after COVID-19 vaccination, but we lack a proper evaluation of the effect of such therapies on vaccine-induced T cell responses.METHODSWe longitudinally characterized humoral and spike-specific T cell responses in patients with inflammatory bowel disease (IBD), who were on antimetabolite therapy (azathioprine or methotrexate), TNF inhibitors, and/or other biologic treatment (anti-integrin or anti-p40) for up to 6 months after completing 2-dose COVID-19 mRNA vaccination.RESULTSWe demonstrate that a spike-specific T cell response was not only induced in treated patients with IBD at levels similar to those of healthy individuals, but also sustained at higher magnitude for up to 6 months after vaccination, particularly in those treated with TNF inhibitor therapy. Furthermore, the spike-specific T cell response in these patients was mainly preserved against mutations present in SARS-CoV-2 B.1.1.529 (Omicron) and characterized by a Th1/IL-10 cytokine profile.CONCLUSIONDespite the humoral response defects, patients under immune-modifying therapies demonstrated a favorable profile of vaccine-induced T cell responses that might still provide a layer of COVID-19 protection.FUNDINGThis study was funded by the National Centre for Infectious Diseases (NCID) Catalyst Grant (FY2021ES) and the National Research Fund Competitive Research Programme (NRF-CRP25-2020-0003).

Highly sensitive and rapid detection of SARS-CoV-2 via a portable CRISPR-Cas13a-based lateral flow assay.

To rapidly identify individuals infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and control the spread of coronavirus disease (COVID-19), there is an urgent need for highly sensitive on-site virus detection methods. A clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (Cas)-based molecular diagnostic method was developed for this purpose. Here, a CRISPR system-mediated lateral flow assay (LFA) for SARS-CoV-2 was established based on multienzyme isothermal rapid amplification, CRISPR-Cas13a nuclease, and LFA. To improve the limit of detection (LoD), the crispr RNA, amplification primer, and probe were screened, in addition to concentrations of various components in the reaction system. The LoD of CRISPR detection was improved to 0.25 copy/µl in both fluorescence- and immunochromatography-based assays. To enhance the quality control of the CRISPR-based LFA method, glyceraldehyde-3-phosphate dehydrogenase was detected as a reference using a triple-line strip design in a lateral flow strip. In total, 52 COVID-19-positive and 101 COVID-19-negative clinical samples examined by reverse transcription polymerase chain reaction (RT-PCR) were tested using the CRISPR immunochromatographic detection technique. Results revealed 100% consistency, indicating the comparable effectiveness of our method to that of RT-PCR. In conclusion, this approach significantly improves the sensitivity and reliability of CRISPR-mediated LFA and provides a crucial tool for on-site detection of SARS-CoV-2.

An outbreak of acute respiratory disease caused by HAdV-55 in Beijing, China, 2020.

Human adenoviruses (HAdVs) can cause acute respiratory diseases (ARDs) worldwide, and HAdV-55 is a reemergent pathogen in recent years. In the study, we investigated an outbreak of ARD at a school due to HAdV-55 in Beijing, China, during the early outbreak of coronavirus disease 2019 (COVID-19). The epidemic prevention team was dispatched to the school to collect epidemiologic data and nasopharyngeal samples. Then, real-time reverse transcription polymerase chain reaction (PCR) and multiplex PCR assays were used to detect severe acute respiratory syndrome coronavirus 2 and other respiratory pathogens, respectively. One representative HAdV-55 isolate was selected and submitted for whole-genome sequencing using a MiSeq system and the whole-genome phylogenetic tree was conducted based on the maximum likelihood method. The outbreak lasted from January 27 to February 6, 2020, and 108 students developed fever, among whom 60 (55.56%) cases were diagnosed with HAdV-55 infection in the laboratory using real-time PCR and 56 cases were hospitalized. All the confirmed cases had a fever and 11 cases (18.33%) presented with a fever above 39°C. Other main clinical symptoms included sore throat (43.33%) and headache (43.33%). We obtained and assembled the full genome of one isolate, BJ-446, with 34 761 nucleotides in length. HAdV-55 isolate BJ-446 was 99.85% identical to strain QS-DLL, which was the first HAdV-55 strain in China isolated from an ARD outbreak in Shanxi in 2006. One and four amino acid mutations were observed in the hexon gene and the coding region of L2 pV 40.1 kDa protein, respectively. We identified the first HAdV-55 infection associated with the ARD outbreak in Beijing since the emergence of COVID-19. The study suggests that improved surveillance of HAdV is needed, although COVID-19 is still prevalent in the world.

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.

Using ARIMA-GARCH Model to Analyze Fluctuation Law of International Oil Price

It is meaningful and of certain theoretical value for the development of economy through analyzing fluctuation rules of international oil prices and forecasting the future trend of international oil prices. By composing the autoregressive integrated moving average (ARIMA) model and the combination model of autoregressive integrated moving average model-generalized autoregressive conditional heteroskedasticity (ARIMA-GARCH) for analyzing and forecasting international oil prices, study shows that the combination model of ARIMA (1,1,0)-GARCH (1,1) is more suitable for short-term forecasting of international oil prices with higher accuracy that the MAPE of forecasting has reduced from 1.549% to 0.045% and the RMSE of forecasting has reduced from 1.032 to 0.071.

Favourable vaccine-induced SARS-CoV-2 specific T cell response profile in patients undergoing immune-modifying therapies (preprint)

Patients undergoing immune-modifying therapies demonstrate a reduced humoral response after COVID-19 vaccination, but we lack a proper evaluation of the impact of such therapies on vaccine-induced T cell responses. Here, we longitudinally characterised humoral and Spike-specific T cell responses in IBD patients who are on antimetabolite therapy (azathioprine or methotrexate), TNF inhibitors and/or other biologic treatment (anti-integrin or anti-p40) after mRNA vaccination. We demonstrated that a Spike-specific T cell response is not only induced in treated IBD patients at levels similar to healthy individuals, but also sustained at higher magnitude, particularly in those treated with TNF inhibitor therapy. Furthermore, the Spike-specific T cell response in these patients is mainly preserved against mutations present in SARS-CoV-2 B.1.1.529 (Omicron) and characterized by a Th1/IL-10 cytokine profile. Thus, despite the humoral response defects, the favourable profile of vaccine-induced T cell responses might still provide a layer of COVID-19 protection to patients under immune-modifying therapies.

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.

Utilisation of SARS-CoV-2 rapid antigen assays in screening asymptomatic hospital visitors: mitigating the risk in low-incidence settings.

Retrospective contact tracing, enabled by the use of automated visitor-management systems and digital contact tracing, together with rapid antigen detection (RAD) for SARS-CoV-2 among visitors staying ≥ 30 minutes, identified COVID-19 cases in < 0.01% (6/72 605) of hospital visitors to a large hospital campus over an 8-week study period. The potential for nosocomial transmission of SARS-CoV-2 from hospital visitors was thus very low, and could be further mitigated by universal mask-wearing among staff and visitors.

Myocardial Injury at Early Stage and Its Association With the Risk of Death in COVID-19 Patients: A Hospital-Based Retrospective Cohort Study.

Background: There are growing evidence demonstrating that coronavirus disease 2019 (COVID-19) is companied by acute myocardial injury. However, the associations of SARS-CoV-2-induced myocardial injury with the risk of death and prognosis after discharge in COVID-19 patients are unclear. Methods: This prospective cohort study analyzed 355 COVID-19 patients from two hospitals in different regions. Clinical and demographic information were collected and prognosis was followed up. Results: Of 355 hospitalized patients with COVID-19, 213 were mild, 90 severe, and 52 critically ill patients. On admission, 59 (16.7%) patients were with myocardial injury. Myocardial injury was more popular in critically ill patients. Univariate and multivariate logistic regression revealed that male, older age and comorbidity with hypertension were three crucial independent risk factors predicting myocardial injury of COVID-19 patients. Among 59 COVID-19 patients with myocardial injury, 25 (42.4%) died on average 10.9 days after hospitalization. Mortality was increased among COVID-19 patients with myocardial injury (42.4 vs. 3.38%, RR = 12.542, P < 0.001). Follow-up study observed that 4.67% COVID-19 patients with myocardial injury were not fully recovered in 14 days after discharge. Conclusion: Myocardial injury at early stage elevates mortality of COVID-19 patients. Male elderly patients with hypertension are more vulnerable to myocardial injury. SARS-CoV-2-induced myocardial injury has not completely recovered in 14 days after discharge.

Early kidney injury predicts disease progression in patients with COVID-19: a cohort study.

BACKGROUND: The receptor of severe respiratory syndrome coronavirus 2 (SARS-CoV-2), angiotensin-converting enzyme 2, is more abundant in kidney than in lung tissue, suggesting that kidney might be another important target organ for SARS-CoV-2. However, our understanding of kidney injury caused by Coronavirus Disease 2019 (COVID-19) is limited. This study aimed to explore the association between kidney injury and disease progression in patients with COVID-19. METHODS: A retrospective cohort study was designed by including 2630 patients with confirmed COVID-19 from Huoshenshan Hospital (Wuhan, China) from 1 February to 13 April 2020. Kidney function indexes and other clinical information were extracted from the electronic medical record system. Associations between kidney function indexes and disease progression were analyzed using Cox proportional-hazards regression and generalized linear mixed model. RESULTS: We found that estimated glomerular filtration rate (eGFR) and creatinine clearance (Ccr) decreased in 22.0% and 24.0% of patients with COVID-19, respectively. Proteinuria was detected in 15.0% patients and hematuria was detected in 8.1% of patients. Hematuria (HR 2.38, 95% CI 1.50-3.78), proteinuria (HR 2.16, 95% CI 1.33-3.51), elevated baseline serum creatinine (HR 2.84, 95% CI 1.92-4.21) and blood urea nitrogen (HR 3.54, 95% CI 2.36-5.31), and decrease baseline eGFR (HR 1.58, 95% CI 1.07-2.34) were found to be independent risk factors for disease progression after adjusted confounders. Generalized linear mixed model analysis showed that the dynamic trajectories of uric acid was significantly related to disease progression. CONCLUSION: There was a high proportion of early kidney function injury in COVID-19 patients on admission. Early kidney injury could help clinicians to identify patients with poor prognosis at an early stage.

Fasting plasma glucose and glucose fluctuation are associated with COVID-19 prognosis regardless of pre-existing diabetes.

AIMS: We aimed to investigate the role of Fasting Plasma Glucose (FPG) and glucose fluctuation in the prognosis of COVID-19 patients stratified by pre-existing diabetes. METHODS: The associations of FPG and glucose fluctuation indexes with prognosis of COVID-19 in 2,642 patients were investigated by multivariate Cox regression analysis. The primary outcome was in-hospital mortality; the secondary outcome was disease progression. The longitudinal changes of FPG over time were analyzed by the latent growth curve model in COVID-19 patients stratified by diabetes and severity of COVID-19. RESULTS: We found FPG as an independent prognostic factor of overall survival after adjustment for age, sex, diabetes and severity of COVID-19 at admission (HR: 1.15, 95% CI: 1.06-1.25, P = 1.02 × 10-3). Multivariate logistic regression analysis indicated that the standard deviation of blood glucose (SDBG) and largest amplitude of glycemic excursions (LAGE) were also independent risk factors of COVID-19 progression (P = 0.03 and 0.04, respectively). The growth trajectory of FPG over the first 3 days of hospitalization was steeper in patients with critical COVID-19 in comparison to moderate patients. CONCLUSIONS: Hyperglycemia and glucose fluctuation were adverse prognostic factors of COVID-19 regardless of pre-existing diabetes. This stresses the importance of glycemic control in addition to other therapeutic management.

The associations of serum S100A9 with the severity and prognosis in patients with community-acquired pneumonia: a prospective cohort study.

BACKGROUND: Previous studies found that S100A9 may involve in the pathophysiology of community-acquired pneumonia (CAP). However, the role of S100A9 was unclear in the CAP. The goal was to explore the correlations of serum S100A9 with the severity and prognosis of CAP patients based on a prospective cohort study. METHODS: A total of 220 CAP patients and 110 control subjects were recruited. Demographic and clinical data were collected. Serum S100A9 and inflammatory cytokines were measured. RESULTS: Serum S100A9 was elevated in CAP patients on admission. Serum S100A9 was gradually elevated parallelly with CAP severity scores. Additionally, inflammatory cytokines were increased and blood routine parameters were changed in CAP patients compared with control subjects. Correlation analysis found that serum S100A9 was positively associated with CAP severity scores, blood routine parameters (WBC, NLR and MON) and inflammatory cytokines. Further, logistic regression analysis demonstrated that there were positive associations between serum S100A9 and CAP severity scores. Besides, the prognosis of CAP was tracked. Serum higher S100A9 on the early stage elevated the death of risk and hospital stay among CAP patients. CONCLUSION: Serum S100A9 is positively correlated with the severity of CAP. On admission, serum higher S100A9 elevates the risk of death and hospital stay in CAP patients, suggesting that S100A9 may exert a certain role in the pathophysiology of CAP and regard as a serum diagnostic and managing biomarker for CAP.