A longitudinal environmental surveillance study for SARS-CoV-2 from the emergency department of a teaching hospital in Hong Kong.

BACKGROUND: Understanding factors associated with SARS-CoV-2 exposure risk in the hospital setting may help improve infection control measures for prevention. AIM: To monitor SARS-CoV-2 exposure risk among healthcare workers and to identify risk factors associated with SARS-CoV-2 detection. METHODS: Surface and air samples were collected longitudinally over 14 months spanning 2020-2022 at the Emergency Department (ED) of a teaching hospital in Hong Kong. SARS-CoV-2 viral RNA was detected by real-time reverse-transcription polymerase chain reaction. Ecological factors associated with SARS-CoV-2 detection were analysed by logistic regression. A sero-epidemiological study was conducted in January-April 2021 to monitor SARS-CoV-2 seroprevalence. A questionnaire was used to collect information on job nature and use of personal protective equipment (PPE) of the participants. FINDINGS: SARS-CoV-2 RNA was detected at low frequencies from surfaces (0.7%, N = 2562) and air samples (1.6%, N = 128). Crowding was identified as the main risk factor, as weekly ED attendance (OR = 1.002, P=0.04) and sampling after peak-hours of ED attendance (OR = 5.216, P=0.03) were associated with the detection of SARS-CoV-2 viral RNA from surfaces. The low exposure risk was corroborated by the zero seropositive rate among 281 participants by April 2021. CONCLUSION: Crowding may introduce SARS-CoV-2 into the ED through increased attendances. Multiple factors may have contributed to the low contamination of SARS-CoV-2 in the ED, including hospital infection control measures for screening ED attendees, high PPE compliance among healthcare workers, and various public health and social measures implemented to reduce community transmission in Hong Kong where a dynamic zero COVID-19 policy was adopted.

Historical perspective: other human coronavirus infectious diseases, SARS and MERS

Alphacoronaviruses (HCoV-229E and HCoV-NL63) and betacoronaviruses (HCoV-OC43 and HCoV-HKU1) are common causes of upper respiratory tract infection in humans. SARS-CoV-1 and MERS-CoV emerged in 2002 and 2012, respectively, with the potential of causing severe and lethal disease in humans, termed SARS and MERS, respectively. Bats appear to be the common natural source of SARS-like coronaviruses including SARS-CoV-1, but their role in MERS-CoV is less clear. Civet cats and dromedary camels are the intermediary animal sources for SARS-CoV-1 and MERS-CoV, respectively. Nosocomial outbreaks are hallmarks of SARS and MERS. MERS patients with comorbidities or immunosuppression tend to progress more rapidly to respiratory failure and have a higher case fatality rate than SARS patients. SARS has disappeared since 2004, while there are still sporadic cases of MERS in the Middle East. Continued global surveillance is essential for SARS-like coronaviruses and MERS-CoV to monitor changing epidemiology due to viral variants.Copyright © ERS 2021.

A living WHO guideline on drugs for covid-19

Clinical question What is the role of drug interventions in the treatment and prevention of covid-19? Recommendations The first version on this living guidance focuses on corticosteroids. It contains a strong recommendation for systemic corticosteroids in patients with severe and critical covid-19, and a weak or conditional recommendation against systemic corticosteroids in patients with non-severe covid-19. Corticosteroids are inexpensive and are on the World Health Organisation list of essential medicines. How this guideline was created This guideline reflects an innovative collaboration between the WHO and the MAGIC Evidence Ecosystem Foundation, driven by an urgent need for global collaboration to provide trustworthy and living covid-19 guidance. A standing international panel of content experts, patients, clinicians, and methodologists, free from relevant conflicts of interest, produce recommendations for clinical practice. The panel follows standards, methods, processes, and platforms for trustworthy guideline development using the GRADE approach. We apply an individual patient perspective while considering contextual factors (that is, resources, feasibility, acceptability, equity) for countries and healthcare systems. The evidence A living systematic review and network meta-analysis, supported by a prospective meta-analysis, with data from eight randomised trials (7184 participants) found that systemic corticosteroids probably reduce 28 day mortality in patients with critical covid-19 (moderate certainty evidence;87 fewer deaths per 1000 patients (95% confidence interval 124 fewer to 41 fewer)), and also in those with severe disease (moderate certainty evidence;67 fewer deaths per 1000 patients (100 fewer to 27 fewer)). In contrast, systemic corticosteroids may increase the risk of death in patients without severe covid-19 (low certainty evidence;absolute effect estimate 39 more per 1000 patients, (12 fewer to 107 more)). Systemic corticosteroids probably reduce the need for invasive mechanical ventilation, and harms are likely to be minor (indirect evidence). Understanding the recommendations The panel made a strong recommendation for use of corticosteroids in severe and critical covid-19 because there is a lower risk of death among people treated with systemic corticosteroids (moderate certainty evidence), and they believe that all or almost all fully informed patients with severe and critical covid-19 would choose this treatment. In contrast, the panel concluded that patients with non-severe covid-19 would decline this treatment because they would be unlikely to benefit and may be harmed. Moreover, taking both a public health and a patient perspective, the panel warned that indiscriminate use of any therapy for covid-19 would potentially rapidly deplete global resources and deprive patients who may benefit from it most as potentially lifesaving therapy. Updates This is a living guideline. Work is under way to evaluate other interventions. New recommendations will be published as updates to this guideline. Readers note This is version 1 of the living guideline, published on 4 September (BMJ 2020;370:m3379) version 1. Updates will be labelled as version 2, 3 etc. When citing this article, please cite the version number. Submitted August 28 Accepted August 31Copyright © Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to.

Human Coronavirus Infections—Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and SARS-CoV-2

Three novel coronaviruses have emerged as new lethal zoonotic pathogens of humans during the past 17 years: The Severe Acute Respiratory Syndrome (SARS) coronavirus (SARS-CoV), the Middle East Respiratory Syndrome (MERS) coronavirus (MERS-CoV), and most recently SARS-CoV-2. SARS-CoV first surfaced as a human pathogen in Guangdong, China in November 2002 and rapidly spread worldwide with 8098 cases and 774 deaths before the end of the epidemic. SARS-like CoVs have been detected in horseshoe bats with high sequence homology with human or civet isolates, suggesting that bats could be a natural reservoir of a close ancestor of SARS-CoV. No cases of SARS have been reported since January 2004. MERS-CoV was first reported in September 2012, after it was isolated from respiratory samples from a patient in Jeddah, Saudi Arabia who died in June 2012. How humans acquire MERS-CoV infection is not yet known although bats and dromedary camels are intermediary reservoirs. MERS-CoV continues to circulate in the Middle East. As of May 22, 2019, 2428 cases of laboratory-confirmed MERS-CoV cases reported to the World Health Organization, including 838 deaths (34.5% mortality) have been reported from 27 countries. While the majority of MERS cases occur in the Middle East, travel related MERS cases have been reported from all continents. Large health care associated outbreaks of MERS-CoV have occurred in Saudi Arabia, United Arab Emirates, and the Republic of Korea. SARS-CoV-2 emerged from Wuhan, China in December 2019, and by March 2020 had established as a pandemic which has caused massive disruption in multiple countries. The eventual mortality caused by this virus remains to be seen. All three viruses cause a similar wide range of nonspecific clinical manifestations from mild upper respiratory tract illness to severe respiratory, gastrointestinal and other extra-pulmonary disease. Early recognition of cases, improved compliance with internationally recommended infection control protocols, and rapid implementation of infection control measures are required to prevent health care facility-associated outbreaks, and in the case of SARS-CoV-2 for control of community spread as well. Treatment is supportive and there are no specific antivirals or vaccines available for both SARS and MERS. © 2022 Elsevier Ltd. All rights reserved

No association between protonpump inhibitor use and adverse clinical outcomes of COVID-19: A territory-wide cohort study of 8,675 patients

Background Evidence regarding the use of proton-pump inhibitors (PPIs) in COVID-19 patients remains elusive. We examined the impact of PPI use on clinical outcomes of COVID-19 patients in a territory-wide cohort. Methods We performed a retrospective cohort study using data from an electronic healthcare database managed by the Hospital Authority, Hong Kong. COVID-19 patients diagnosed virologically between 23 January 2020 and 1 January 2021 in Hong Kong were identified. The primary endpoint was a composite of intensive care unit admission, use of invasive mechanical ventilation, and/or death. PPI user was identified by PPI use within 12 months before the diagnosis of COVID-19. In subgroup analysis, current PPI users were defined as patients who used PPIs within 1 month before the diagnosis of COVID-19;past PPI users were defined as patients who used PPIs 1 to 12 months before COVID-19 diagnosis. We performed sensitivity analysis after excluding patients with short-term new NSAID use within 1 month before COVID-19 diagnosis to minimize reverse causation bias. Results We identified 8,675 COVID-19 patients (mean age 46 years, 49% male, 97.6% of all the reported cases in Hong Kong);579 (6.7%) patients had used PPI. PPI users were older, more likely to have comorbidities, concomitant medications and unfavorable laboratory parameters than non-users. Of 8,675 COVID-19 patients, 500 (5.8%) developed the primary endpoint. After propensity score (PS) balancing for patients' demographics, comorbidities, laboratory parameters, and use of medications, PPI use was not associated with the development of primary endpoint in PS weighting (weighted hazard ratio [HR] 1.11, 95% confidence interval [CI] 0.83-1.47, P=0.482) (IDDF2021-ABS- 0122 Figure 1. Cumulative incidence of primary endpoint (a composite endpoint of intensive care unit [ICU] admission, use of invasive mechanical ventilation [IMV], and death) in COVID-19 patients who were and were not proton- pump inhibitor (PPI) users after propensity score (PS) weighting in a single multiple imputation data set.), and PS matching analysis (weighted HR 0.81, 95%CI 0.57-1.14, P=0.228) (IDDF2021-ABS-0122 Figure 2. Cumulative incidence of primary endpoint (a composite endpoint of intensive care unit [ICU] admission, use of invasive mechanical ventilation [IMV], and death) in COVID-19 patients who were and were not proton-pump inhibitor (PPI) users after propensity score (PS) matching in a single multiple imputation data set). Consistent non-association was observed after multivariable adjustment (adjusted HR 0.84, 95%CI 0.66- 1.07, P=0.151), in subgroups of current and past PPI users, and in sensitivity analysis after excluding short-term new NSAID users. Conclusions PPI use is not associated with adverse clinical outcomes in COVID-19 patients. The result remains robust after PS weighting, PS matching, multivariable adjustment, and subgroup analyses.

Baseline characteristics associated with clinical improvement and mortality in hospitalized patients with moderate COVID-19

Background: Remdesivir (RDV) has been shown to shorten recovery time and was well tolerated in patients with severe COVID-19. Here we report baseline characteristics associated with clinical improvement at day (d) 14. Methods: We enrolled hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation >94% on room air, and radiological evidence of pneumonia. Patients were randomized 1:1:1 to receive 5d or 10d of intravenous RDV once daily plus standard of care (SoC), or SoC only. For this analysis, patients were followed through discharge, d14, or death. Baseline demographic and disease characteristics associated with clinical improvement in oxygen support (≥2-point improvement on a 7-category ordinal scale ranging from discharge to death) were evaluated using multivariable logistic regression methods. Results: 584 patients were randomized and treated (5/10d RDV, n=384;SoC: n=200). 159 (27%) were ≥65y, 227 (39%) female, 328 (61%) white, 102 (19%) Asian, and 99 (19%) Black. 252 participants (43%) were enrolled in Europe, 260 (45%) North America (NA), and 72 (12%) in Asia. Most patients (483 [83%]) were not on supplemental oxygen but required medical care at baseline. In a multivariable model, 5/10d RDV was significantly positively associated with clinical improvement (adjusted odds ratio [OR] 1.69, 95% CI: 1.08, 2.65;p=0.0226). Significant covariables positively associated with clinical improvement included age < 65y (p< 0.0001) and region of treatment (Europe and NA vs Asia, p< 0.0001 each;Table);other examined factors were not significantly associated with clinical improvement, including gender, race, ethnicity, baseline oxygen support, duration of symptoms and hospitalization, obesity, and baseline transaminase levels. Conclusion: In moderate COVID-19 patients, after adjusting for treatment arm, age < 65y and region (NA vs Asia;Europe vs Asia) were associated with higher rates of clinical improvement. These observations recapitulate younger age as positive prognostic factor, and highlight the differences in the impact of the pandemic globally.

Remdesivir vs standard care in patients with moderate COVID-19

Background: Remdesivir (RDV) shortens time to recovery time in patients with severe COVID-19. Its effect in patients with moderate COVID-19 remains unclear. Methods: We conducted an open-label, phase 3 trial (NCT04252664) involving hospitalized patients with confirmed SARS-CoV-2 infection, evidence of pulmonary infiltrates, and oxygen saturation >94% on room air. Patients were randomly assigned 1:1:1 to receive up to 5d or 10d of RDV with standard of care (SoC), or SoC alone;patients could be discharged prior to completing per-protocol assigned treatment duration. RDV was dosed intravenously at 200 mg on d1, 100 mg daily thereafter. Patients were evaluated daily while hospitalized, and via telephone if discharged. The primary endpoint was clinical status on d11 assessed on a 7-point ordinal scale. Results regarding the primary endpoint are expected to be published before IDWeek 2020;we plan to present d28 results at the meeting. Results: In total, 584 patients underwent randomization and started their assigned treatment (191, 5d RDV;193, 10d RDV;200, SoC). By d11, 3 2 point improvement on the ordinal scale occurred in 70% of patients in the 5d arm, 65% in the 10d arm, and 61% in the SoC arm. Patients in the 5d RDV arm were significantly more likely to have an improvement in clinical status than those receiving SoC (odds ratio [OR], 1.65;95% confidence interval [CI], 1.09-2.48;P=0.017);OR of improvement for the 10d RDV arm compared to SoC was 1.31 (95% CI, 0.88-1.95];p=0.183). This improvement in the 5-day arm over the SOC arm was noted from d6 through d11. We observed a peak of discharges corresponding with the assigned treatment duration of RDV, with increased discharges at d6 in the 5-day arm and at d11 in the 10-day arm. A worsening of clinical status of ≥ 1 point in the ordinal scale was observed more commonly in the SoC am (n=19, 10%) versus the 5d RDV (n=7, 4%) and 10d RDV (n=9, 5%). Conclusion: RDV for up to 5 days was superior to SoC in improving the clinical status of patients with moderate COVID-19 by d11. We will report d28 outcomes at the meeting. (Table Presented).

Liver enzyme elevation and acute liver injury are independently associated with adverse clinical outcomes in patients with COVID-19: A territory-wide cohort study of 1,040 patients in Hong Kong

Background: Different degrees of liver injury were reported in patients infected by Coronavirus disease 2019 (COVID-19) It is possibly caused by systemic inflammation and adverse drug reactions in severe COVID-19 patients under different medical treatments However, the impact of liver injury on adverse clinical outcomes remains unclear We aimed to examine the impact of liver injury on clinical outcomes in COVID-19 patients Methods: All COVID-19 patients reported to the Department of Health between 23 January 2020 and 1 May 2020 in Hong Kong were identified using an electronic database managed by Hospital Authority, Hong Kong, and retrospectively studied Alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) elevation was defined as ALT/AST ≥2x upper limit of normal (ULN) (i.e. 80 U/L) Acute liver injury was defined as ALT and/or AST ≥2xULN, with total bilirubin ≥2xULN (i.e. 38 μmol/L) and/or international normalized ratio (INR) ≥1.7. The primary endpoint was a composite of intensive care unit (ICU) admission, use of invasive mechanical ventilation, and/or death Results: 1,040 COVID-19 patients were identified. Their mean age was 38±18 years, 560 (53 8%) were male, 4 1% and 0 3% had hepatitis B and C virus infection, respectively;53 (5 1%) were admitted to ICU, 22 (2 1%) received invasive mechanical ventilation, and 4 (0 4%) died Among 816 COVID-19 patients who had serial measurement of liver biochemistries, 184 (22 5%) had ALT/ AST elevation and 15 (1 8%) had acute liver injury Acute liver injury was more common in patients who had hepatitis B/C virus infection than those who did not have (9 4% vs. 1 8%, P=0 026) ALT/AST elevation (adjusted odds ratio [aOR] 7 92, 95% CI 4 14-15 14, P<0 001) and acute liver injury (aOR 6 40, 95% CI 1 78-23 07, P=0 005) were independently associated with development of primary endpoint (Table) Use of lopinavirritonavir ± ribavirin + interferon beta (aOR 1 94, 95% CI 1 20- 3 13, P=0 006) and corticosteroids (aOR 3 92, 95% CI 2 14- 7 16, P<0 001) were independently associated with ALT/AST elevation Use of corticosteroids was associated with acute liver injury (aOR 4 76, 95% CI 1 56-14 50, P=0 006), while all 15 patients who developed acute liver injury also usedlopinavir-ritonavir ± ribavirin ± interferon beta Conclusion: ALT/AST elevation and acute liver injury were independently associated with adverse clinical outcomes in COVID-19 patients Use of lopinavir-ritonavir, with or without ribavirin, interferon beta and/or corticosteroids were associated with ALT/AST elevation and acute liver injury in COVID-19 patients.

Impact of baseline alanine aminotransferase levels on the safety and efficacy of remdesivir in severe COVID-19 patients

Background: Remdesivir (RDV), a nucleotide analogue prodrug that inhibits viral RNA polymerases, has demonstrated potent in vitro and in vivo activity against SAR-CoV-2 and favorable clinical efficacy and tolerability in patients with moderate and severe COVID-19 Elevated transaminase levels are commonly seen in patients with severe COVID-19 prior to treatment Here we report safety and clinical outcomes after RDV treatment in patients with normal versus elevated baseline alanine aminotransferase (ALT) levels Methods: We conducted a randomized, open-label, phase 3 trial, involving hospitalized patients with confirmed COVID-19 pneumonia with Sat<94% Patients with screening ALT or AST> 5x the upper limit of normal (ULN) were excluded from the study Patients were randomized 1:1 to receive either 5 or 10 days of intravenous RDV once daily We compared patients with baseline ALT below and above the ULN based on AASLD criteria (ALT 35 U/L for males and 25 U/L for females) Covariates for adjustment included age, sex, race and baseline oxygen support Clinical recovery and all-cause mortality were evaluated using logistic regression Clinical outcomes and adverse events (AEs) were assessed through day 28 Results: Of 397 patients treated with RDV, 215 (54%) had elevated baseline ALT Median ALT was 53 U/L (IQR: 40 - 78 U/L) in the high ALT group Patients with high ALT at time of RDV initiation were younger (median 58 vs 65 years, p<0 001), required less oxygen (p=0 02), and had longer symptom duration (median 10 vs 8 days, p<0.001) prior to first dose of RDV. Incidence of serious AEs, grade ≥3 AEs, and AE leading to discontinuation were similar between groups (Table1). Grade ≥3 hepatobiliary adverse events, particularly transaminase elevations, were not common but numerically higher in the high ALT group (8 8% vs 3 3%, p=0 068) Time to clinical recovery, 2-point clinical improvement, 1-point clinical improvement, room air, and death were similar between groups Conclusion: In severe COVID-19 patients, adverse events and clinical outcomes after RDV initiation were similar among patients with baseline normal ALT and those with elevated ALT (1-5x ULN)(Table Presented).

Inferring super-spreading from transmission clusters of COVID-19 in Hong Kong, Japan, and Singapore.

Super-spreading events in an outbreak can change the nature of an epidemic. Therefore, it is useful for public health teams to determine whether an ongoing outbreak has any contribution from such events, which may be amenable to interventions. We estimated the basic reproductive number (R0) and the dispersion factor (k) from empirical data on clusters of epidemiologically linked coronavirus disease 2019 (COVID-19) cases in Hong Kong, Japan and Singapore. This allowed us to infer the presence or absence of super-spreading events during the early phase of these outbreaks. The relatively large values of k implied that large cluster sizes, compatible with super-spreading, were unlikely.