Characterizing fitness and immune escape of SARS-CoV-2 EG.5 sublineage using elderly serum and nasal organoid.

SARS-CoV-2 Omicron variant has evolved into sublineages. Here, we compared the neutralization susceptibility and viral fitness of EG.5.1 and XBB.1.9.1. Serum neutralization antibody titer against EG.5.1 was 1.71-fold lower than that for XBB.1.9.1. However, there was no significant difference in virus replication between EG.5.1 and XBB.1.9.1 in human nasal organoids and TMPRSS2/ACE2 over-expressing A549 cells. No significant difference was observed in competitive fitness and cytokine/chemokine response between EG.5.1 and XBB.1.9.1. Both EG.5.1 and XBB.1.9.1 replicated more robustly in the nasal organoid from a younger adult than that from an older adult. Our findings suggest that enhanced immune escape contributes to the dominance of EG.5.1 over earlier sublineages. The combination of population serum susceptibility testing and viral fitness evaluation with nasal organoids may hold promise in risk assessment of upcoming variants. Utilization of serum specimens and nasal organoid derived from older adults provides a targeted risk assessment for this vulnerable population.

The Emergence of Candida auris is Not Associated with Changes in Antifungal Prescription at Hospitals.

Purpose: This study describes the emergence of Candida auris in Hong Kong, focusing on the incidence and trends of different Candida species over time. Additionally, the study analyzes the relationship between C. auris and antifungal prescription, as well as the impact of outbreaks caused by C. auris. Patients and Methods: Data were collected from 43 public hospitals across seven healthcare networks (A to G) in Hong Kong, including Candida species culture and antifungal prescription information. Among 150,267 patients with 206,405 hospitalization episodes, 371,653 specimens tested positive for Candida species. Trends in Candida species and antifungal prescription were analyzed before (period 1: 2015 1Q to 2019 1Q) and after (period 2: 2019 2Q to 2023 2Q) the emergence of C. auris in Hong Kong. Results: Candida albicans was the most prevalent species, accounting for 57.1% (212,163/371,653) of isolations, followed by Candida glabrata (13.1%, 48,666), Candida tropicalis (9.2%, 34,261), and Candida parapsilosis (5.3%, 19,688). C. auris represented 2.0% of all Candida species isolations. Comparing period 2 to period 1, the trend of C. albicans remained stable, while C. glabrata, C. tropicalis, and C. parapsilosis demonstrated a slower increasing trend in period 2 than in period 1. Other species, including C. auris, exhibited a 1.1% faster increase in trend during period 2 compared to period 1. Network A, with the highest antifungal prescription, did not experience any outbreaks, while networks F and G had 40 hospital outbreaks due to C. auris in period 2. Throughout the study period, healthcare networks B to G had significantly lower antifungal prescription compared to network A, ranging from 54% to 78% less than that of network A. Conclusion: There is no evidence showing correlation between the emergence of C. auris and antifungal prescription in Hong Kong. Proactive infection control measures should be implemented to prevent nosocomial transmission and outbreak of C. auris.

Post-COVID-19 Pandemic Rebound of Macrolide-Resistant Mycoplasma pneumoniae Infection: A Descriptive Study.

The rebound characteristics of respiratory infections after lifting pandemic control measures were uncertain. From January to November 2023, patients presenting at a teaching hospital were tested for common respiratory viruses and Mycoplasma pneumoniae using a combination of antigen, nucleic acid amplification, and targeted next-generation sequencing (tNGS) tests. The number and rate of positive tests per month, clinical and microbiological characteristics were analyzed. A rapid rebound of SARS-CoV-2 was followed by a slower rebound of M. pneumoniae, with an interval of 5 months between their peaks. The hospitalization rate was higher, with infections caused by respiratory viruses compared to M. pneumoniae. Though the pediatric hospitalization rate of respiratory viruses (66.1%) was higher than that of M. pneumoniae (34.0%), the 4094 cases of M. pneumoniae within 6 months posed a huge burden on healthcare services. Multivariate analysis revealed that M. pneumoniae-infected adults had more fatigue, comorbidities, and higher serum C-reactive protein, whereas children had a higher incidence of other respiratory pathogens detected by tNGS or pathogen-specific PCR, fever, and were more likely to be female. A total of 85% of M. pneumoniae-positive specimens had mutations detected at the 23rRNA gene, with 99.7% showing A2063G mutation. Days to defervescence were longer in those not treated by effective antibiotics and those requiring a change in antibiotic treatment. A delayed but significant rebound of M. pneumoniae was observed after the complete relaxation of pandemic control measures. No unusual, unexplained, or unresponsive cases of respiratory infections which warrant further investigation were identified.

Development and Evaluation of an In-House Real-Time RT-PCR Targeting nsp10 Gene for SARS-CoV-2 Detection.

The emergence of SARS-CoV-2 mutations poses significant challenges to diagnostic tests, as these mutations can reduce the sensitivity of commonly used RT-PCR assays. Therefore, there is a need to design diagnostic assays with multiple targets to enhance sensitivity. In this study, we identified a novel diagnostic target, the nsp10 gene, using nanopore sequencing. Firstly, we determined the analytical sensitivity and specificity of our COVID-19-nsp10 assay. The COVID-19-nsp10 assay had a limit of detection of 74 copies/mL (95% confidence interval: 48-299 copies/mL) and did not show cross-reactivity with other respiratory viruses. Next, we determined the diagnostic performance of the COVID-19-nsp10 assay using 261 respiratory specimens, including 147 SARS-CoV-2-positive specimens belonging to the ancestral strain and Alpha, Beta, Gamma, Delta, Mu, Eta, Kappa, Theta and Omicron lineages. Using a LightMix E-gene RT-PCR assay as the reference method, the diagnostic sensitivity and specificity of the COVID-19-nsp10 assay were found to be 100%. The median Cp values for the LightMix E-gene RT-PCR and our COVID-19-nsp10 RT-PCR were 22.48 (range: 12.95-36.60) and 25.94 (range 16.37-36.87), respectively. The Cp values of the COVID-19-nsp10 RT-PCR assay correlated well with those of the LightMix E-gene RT-PCR assay (Spearman's ρ = 0.968; p < 0.0001). In conclusion, nsp10 is a suitable target for a SARS-CoV-2 RT-PCR assay.

Rat hepatitis E virus (Rocahepevirus ratti) exposure in cats and dogs, Hong Kong.

Hepatitis E virus (HEV) variants infecting humans belong to two species: Paslahepevirus balayani (bHEV) and Rocahepevirus ratti (rat hepatitis E virus; rHEV). R. ratti is a ubiquitous rodent pathogen that has recently been recognized to cause hepatitis in humans. Transmission routes of rHEV from rats to humans are currently unknown. In this study, we examined rHEV exposure in cats and dogs to determine if they are potential reservoirs of this emerging human pathogen. Virus-like particle-based IgG enzymatic immunoassays (EIAs) capable of differentiating rHEV & bHEV antibody profiles and rHEV-specific real-time RT-PCR assays were used for this purpose. The EIAs could detect bHEV and rHEV patient-derived IgG spiked in dog and cat sera. Sera from 751 companion dogs and 130 companion cats in Hong Kong were tested with these IgG enzymatic immunoassays (EIAs). Overall, 13/751 (1.7%) dogs and 5/130 (3.8%) cats were sero-reactive to HEV. 9/751 (1.2%) dogs and 2/130 (1.5%) cats tested positive for rHEV IgG, which was further confirmed by rHEV immunoblots. Most rHEV-seropositive animals were from areas in or adjacent to districts reporting human rHEV infection. Neither 881 companion animals nor 652 stray animals carried rHEV RNA in serum or rectal swabs. Therefore, we could not confirm a role for cats and dogs in transmitting rHEV to humans. Further work is required to understand the reasons for low-level seropositivity in these animals.

Antibiotic use in hospitalized patients with COVID-19: a population-based study in Hong Kong.

Background: Hong Kong experienced four epidemic waves caused by the ancestral strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2020-2021 and a large Omicron wave in 2022. Few studies have assessed antibacterial prescribing for coronavirus disease 2019 (COVID-19) inpatients throughout the pandemic. Objectives: To describe inpatient antibacterial prescribing and explore factors associated with their prescription. Methods: Electronic health records of patients with COVID-19 admitted to public hospitals in Hong Kong from 21 January 2020 to 30 September 2022 were used to assess the prevalence and rates of inpatient antibacterial drug use (days of therapy/1,000 patient days [DOT/1,000 PD]). We used multivariable logistic regression to investigate potential associations between patients' baseline characteristics and disease severity and prescription of an antibacterial drug during hospital admission. Results: Among 65,810 inpatients with COVID-19, 54.0% were prescribed antibacterial drugs (550.5 DOT/1,000 PD). Compared to waves 1-2 (46.7%; 246.9 DOT/1,000 PD), the prescriptions were lowest during wave 4 (28.0%; 246.9; odds ratio (OR): 0.39, 95% CI: 0.31-0.49) and peaked in early wave 5 (64.6%; 661.2; 0.82, 0.65-1.03). Older age (≥80 years: OR 2.66, 95% CI, 2.49-2.85; 60-79 years: 1.59, 1.51-1.69, compared with 20-59 years), more severe disease (fatal: 3.64, 3.2-4.16; critical: 2.56, 2.14-3.06, compared with severe), and COVID-19 vaccine doses (two doses: 0.74, 0.69-0.78; three doses: 0.69, 0.64-0.74; four doses: 0.52, 0.44-0.62, compared with unvaccinated) were associated with inpatient antibacterial drug use. Conclusions: Antibacterial prescribing changed over time for hospitalized patients with confirmed COVID-19 and was potentially related to patients' demographics, medical conditions, and COVID-19 vaccination status as well as healthcare capacity during epidemic waves.

Determination of seroprevalence and kinetics of humoral response using mpox virus A29 protein.

BACKGROUND: Mpox virus (MPXV), previously known as monkeypox virus, has spread globally in 2022. An accurate and convenient antibody test is essential for the determination of seroprevalence and for studying immune response after natural infection or vaccination. Most seroprevalence or vaccine studies used either live MPXV (or vaccinia virus [VACV]) or inactivated MPXV (or VACV) culture lysate for serological assays, but MPXV culture can only be performed in biosafety level 3 (BSL-3) facilities. Here, we developed and evaluated an enzyme immunoassay (EIA) based on the MPXV A29 surface envelope protein. METHODS: We compared the specificity of the MPXV A29, VACV A27, and VACV lysate EIA using serum specimens collected prior to the global spread of MPXV. Next, we performed these EIAs for serum specimens collected from two mpox patients and an MVA-BN vaccine recipient. We also assessed the kinetics of plasmblast and MPXV A29-specific B-cell response. RESULTS: Using sera collected from different age groups in Hong Kong, we found that most individuals, including those born before 1981 who have received the smallpox vaccine, tested negative using the MPXV A29 protein. MPXV A29-specific antibody could be detected in the serum of mpox patients and an MVA-BN recipient. In a mpox patient, the frequency of plasmablast and MPXV A29-specific B cell peaked on day 8 post-symptom onset and gradually decreased. Finally, we demonstrated that antibodies against the A29 protein can be used for immunofluorescence staining of MPXV-infected cells. CONCLUSIONS: MPXV A29 protein is suitable for studying the immune response against MPXV infection.

Since early 2022, mpox (monkeypox) has been reported in many countries where the disease is not regularly found to occur. The aim of the study was to develop and evaluate the performance of laboratory assays based on the mpox virus surface protein, named A29. We found our assays could accurately distinguish naturally infected cases from smallpox vaccine recipients as well as those who were neither infected nor vaccinated. Our assays provide a useful tool for studying the host immune response to mpox virus.

Humoral and cellular immunity against different SARS-CoV-2 variants in patients with chronic kidney disease.

Chronic kidney disease (CKD) patients are at higher risk of severe COVID-19. Humoral and cellular immunity from prior infection or vaccination are important for protection, but the neutralizing antibody (nAb) response against SARS-CoV-2 variants is impaired. We investigated the variant-specific nAb and T cell immunity among CKD patients. Adult CKD patients were recruited between August and October 2022. nAb against the SARS-CoV-2 (ancestral strains and four Omicron sublineages) and T cell response were measured using the live virus neutralization assay and interferon-gamma release assay (IGRA). The correlation between nAb/T-cell response and subsequent infection after recruitment were also determined. Among the 88 recruited patients, 95.5% had prior infection or had completed the primary vaccine series. However, only 77.3% had detectable nAb against at least one SARS-CoV-2 strains, 59.1% tested positive in IGRA, and 52.3% had detectable nAb and tested positive in the IGRA. The nAb geometic mean titers (GMTs) against XBB.1, BA.5 and BA.2.3.20 were significantly lower than those against BA.2 and ancestral strain. Prior SARS-CoV-2 infection was associated with elevated nAb and T cell response. More kidney transplant recipients (KTRs) showed absent nAb and T cell response (36.8% vs. 10.1%), despite a higher prevalence of vaccine booster in this population (94.7% vs. 50.7%). Lower levels of nAb titer and T cell response were significantly associated with subsequent infection. A considerable proportion of CKD patients, especially KTRs, showed absence of humoral and cellular protective immunity against SARS-CoV-2. Strategies to improve immunogenicity in this population are urgently needed.

Antimicrobial susceptibility of Bacteroides fragilis group organisms in Hong Kong, 2020-2021.

OBJECTIVES: This retrospective study analyzed the susceptibility levels of Bacteroides fragilis group (BFG) in a hospital-based laboratory where disk diffusion test (DDT) was routinely performed. Isolates non-susceptible to imipenem and metronidazole by DDT were further investigated using a gradient method. METHODS: The DDT and MIC susceptibility data of clindamycin, metronidazole, moxifloxacin and imipenem obtained on Brucella blood agar for 1264 non-duplicated isolates during 2020-2021 were analyzed. Species identification was obtained by matrix-assisted laser desorption ionization time-of-flight mass spectrometry and 16S rRNA sequencing. Interpretative agreement of DDT results using the 2015 EUCAST tentative and 2021 CA-SFM breakpoints was compared against MIC as the reference. RESULTS: The dataset included 604 B. fragilis (483 division I, 121 division II isolates), 415 non-fragilis Bacteroides, 177 Phocaeicola and 68 Parabacteroides. Susceptibility rates for clindamycin (22.1-62.1%) and moxifloxacin (59.9-80.9%) were low and many had no inhibition zones. At the EUCAST and CA-SFM breakpoints, 83.0 and 89.4% were imipenem-susceptible, and 89.6% and 97.4 were metronidazole-susceptible. MIC testing confirmed 11.4% and 2.8% isolates as imipenem-non-susceptible and metronidazole-resistant, respectively. Significant numbers of false-susceptibility and/or false-resistance results were observed at the CA-SFM breakpoint but not the EUCAST breakpoint. Higher rates of imipenem and/or metronidazole resistance were detected in B. fragilis division II, B. caccae, B. ovatus, B. salyersiae, B. stercoris and Parabacteroides. Co-resistance to imipenem and metronidazole was detected in 3 B. fragilis division II isolates. CONCLUSIONS: The data demonstrated emerging BFG resistance to several important anti-anaerobic antibiotics and highlights the importance of anaerobic susceptibility testing in clinical laboratories to guide therapy.

A Pilot Study of Short-Course Oral Vitamin A and Aerosolised Diffuser Olfactory Training for the Treatment of Smell Loss in Long COVID.

Background: Olfactory dysfunction (OD) is a common neurosensory manifestation in long COVID. An effective and safe treatment against COVID-19-related OD is needed. Methods: This pilot trial recruited long COVID patients with persistent OD. Participants were randomly assigned to receive short-course (14 days) oral vitamin A (VitA; 25,000 IU per day) and aerosolised diffuser olfactory training (OT) thrice daily (combination), OT alone (standard care), or observation (control) for 4 weeks. The primary outcome was differences in olfactory function by butanol threshold tests (BTT) between baseline and end-of-treatment. Secondary outcomes included smell identification tests (SIT), structural MRI brain, and serial seed-based functional connectivity (FC) analyses in the olfactory cortical network by resting-state functional MRI (rs-fMRI). Results: A total of 24 participants were randomly assigned to receive either combination treatment (n = 10), standard care (n = 9), or control (n = 5). Median OD duration was 157 days (IQR 127-175). Mean baseline BTT score was 2.3 (SD 1.1). At end-of-treatment, mean BTT scores were significantly higher for the combination group than control (p < 0.001, MD = 4.4, 95% CI 1.7 to 7.2) and standard care (p = 0.009) groups. Interval SIT scores increased significantly (p = 0.009) in the combination group. rs-fMRI showed significantly higher FC in the combination group when compared to other groups. At end-of-treatment, positive correlations were found in the increased FC at left inferior frontal gyrus and clinically significant improvements in measured BTT (r = 0.858, p < 0.001) and SIT (r = 0.548, p = 0.042) scores for the combination group. Conclusions: Short-course oral VitA and aerosolised diffuser OT was effective as a combination treatment for persistent OD in long COVID.

Epidemiology of multidrug-resistant organisms before and during COVID-19 in Hong Kong.

Background: The coronavirus disease 2019 (COVID-19) has influenced antimicrobial consumption and incidence of multidrug-resistant organisms (MDROs). We aimed to study the epidemiology of MDROs before and during the COVID-19 pandemic in Hong Kong. Methods: With the maintenance of infection control measures, we described the trend of MDRO infections, including methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Acinetobacter species (CRA), and extended-spectrum-beta-lactamase-(ESBL)-producing Enterobacterales, in a healthcare region with 3100-bed before (1 January 2016 to 31 December 2019, period 1) and during COVID-19 (1 January 2020 to 30 September 2022, period 2), together with the antimicrobial consumption using piecewise Poisson regression. The epidemiological characteristics of newly diagnosed COVID-19 patients with or without MDRO infections were analyzed. Results: Between period 1 and 2, we observed a significant increase in the trend of CRA infections (P<0.001), while there was no significant increase in the trend of MRSA (P=0.742) and ESBL-producing Enterobacterales (P=0.061) infections. Meanwhile, a significant increase in the trend of carbapenems (P<0.001), extended-spectrum beta-lactam-beta-lactamase inhibitor combinations (BLBI) (P=0.045), and fluoroquinolones (P=0.009) consumption was observed. The observed opportunity (23,540 ± 3703 vs 26,145 ± 2838, p=0.359) and compliance (81.6% ± 0.5% vs 80.1% ± 0.8%, P=0.209) of hand hygiene per year was maintained. In a multivariable model, older age, male sex, referral from residential care home for the elderly, presence of indwelling device, presence of endotracheal tube, and use of carbapenems, use of BLBI, use of proton pump inhibitors and history of hospitalization in the past 3 months were associated with higher risks of infections by MDROs among COVID-19 patients. Conclusion: Infection control measures may control the surge of MDROs despite an increasing trend of antimicrobial consumption.

Epidemiology and risk factors for carbapenemase-producing Enterobacteriaceae carriage in the hospital: A population-based nested case-control study.

OBJECTIVES: This study aims to study the epidemiology of carbapenemase-producing Enterobacteriaceae (CPE) in Hong Kong. METHODS: This is a longitudinal population-based study reporting monthly CPE incidence rate and a nested case-control study for identifying risk factors for CPE carriage. The cases were patients with at least one CPE-positive genotypic test, while the controls were randomly selected from the cohort with negative tests. Up to four controls per case were matched by sex, age group, and admission year-month. The independent risk factors were identified from a conditional logistic regression with potential covariates. RESULTS: From 1 January 2008 to 31 December 2019, 8588 patients received CPE genotyping tests, and 2353 had at least one positive result. Class B carbapenemase was the predominant enzyme in the samples (78.6%). The incidence rate increased from 0.04 in 2015 to 1.62 in 2019 per 10,000 person-year. In the nested case-control study, 1709 cases and 6664 controls were matched. Previous use of any beta-lactam antibiotics (odds ratio:1.37 [1.22-1.53], P < 0.001) was found as an independent risk factor for carriage of CPE. CONCLUSION: The carriage of CPE was found with an increasing trend in Hong Kong. Previous use of any beta-lactam antibiotics is a risk factor for CPE.

Genomic Investigation of Salmonella Typhi in Hong Kong Revealing the Predominance of Genotype 3.2.2 and the First Case of an Extensively Drug-Resistant H58 Genotype.

Typhoid fever is a notable disease in Hong Kong. We noticed two local cases of typhoid fever caused by Salmonella Typhi within a two-week period in late 2022, which had no apparent epidemiological linkage except for residing in the same region of Hong Kong. A phylogenetic study of Salmonella Typhi isolates from Hong Kong Island from 2020 to 2022 was performed, including a whole-genome analysis, the typing of plasmids, and the analysis of antibiotic-resistance genes (ARGs), to identify the dominant circulating strain and the spread of ARGs. A total of seven isolates, from six local cases and an imported case, were identified from positive blood cultures in two hospitals in Hong Kong. Five antibiotic-sensitive strains of genotype 3.2.2 were found, which clustered with another 30 strains originating from Southeast Asia. Whole-genome sequencing revealed clonal transmission between the two index cases. The remaining two local cases belong to genotype 2.3.4 and genotype 4.3.1.1.P1 (also known as the H58 lineage). The genotype 4.3.1.1.P1 strain has an extensively drug-resistant (XDR) phenotype (co-resistance to ampicillin, chloramphenicol, ceftriaxone, ciprofloxacin, and co-trimoxazole). Although the majority of local strains belong to the non-H58 genotype 3.2.2 with a low degree of antibiotic resistance, the introduction of XDR strains with the global dissemination of the H58 lineage remains a concern.

Evaluation of a Lateral Flow Immunoassay for Rapid Detection of CTX-M Producers from Blood Cultures.

Bacteremia caused by extended-spectrum ß-lactamases-producing Enterobacterales has increased rapidly and is mainly attributed to CTX-M enzymes. This study aimed to evaluate the NG-Test® CTX-M MULTI lateral flow assay (CTX-M LFA) for rapid detection of CTX-M producers in blood cultures (BCs) positive for Gram-negative bacilli in spiked and clinical BCs. Retrospective testing was performed on BC bottles spiked with a collection of well-characterized Enterobacterales isolates producing CTX-M (n = 15) and CTX-M-like (n = 27) ß-lactamases. Prospective testing of clinical, non-duplicate BCs (n = 350) was performed in two hospital microbiology laboratories from April 2021 to March 2022 following detection of Gram-negative bacilli by microscopic examination. Results were compared against molecular testing as the reference. In the spiked BCs, the CTX-M LFA correctly detected all CTX-M producers including 5 isolates with hybrid CTX-M variants. However, false-positive results were observed for several CTX-M-like ß-lactamases, including OXY-1-3, OXY-2-8, OXY-5-3, FONA-8, -9, -10, 11, 13 and SFO-1. In clinical BCs, the CTX-M LFA showed 100% (95% CI, 96.0-100%) sensitivity and 99.6% (97.9-100%) specificity. In conclusion, this study showed that rapid detection of CTX-M producers in BC broths can be reliably achieved using the CTX-M LFA, thus providing an opportunity for early optimization of antibiotics.

Infection of healthcare workers despite a high vaccination rate during the fifth wave of COVID-19 due to Omicron variant in Hong Kong.

Background: No nosocomial infection was recorded in our healthcare workers (HCWs) during the early phase of the coronavirus disease 2019 (COVID-19) pandemic. With the emergence of the Omicron variant of increased transmissibility, infection in HCWs occurred as expected. We aimed to study the epidemiology of infection in HCWs and to describe the infection control measures during the outbreak of the Omicron variant. Methods: With daily rapid antigen testing and molecular confirmation test for COVID-19, infected HCWs were interviewed by infection control nurses (ICNs) to investigate the potential source of infection. The epidemiology of COVID-19 in Hong Kong served as reference. Results: During the fifth wave of COVID-19 (31 December 2021 to 31 May 2022), 1,200,068 cases were reported (incidence 95 times higher than in preceding waves in Hong Kong; 162,103 vs 1,707 per million population respectively, P<0.001). The proportion of infected HCWs was significantly higher than that of the general population (24.9%, 1,607/6,452 vs 16.2%, 1,200,068/7,403,100 respectively; P<0.01). The proportion of infected non-clinical staff was significantly higher than that of clinical staff (31.8%, 536/1,687 vs 22.5%, 1,071/4,765 respectively; P<0.001). Of 82.8% (1,330/1,607) infected HCWs interviewed by ICNs, 99.5% (1,324/1,330) had been fully vaccinated; 49.5% (659/1,330) had no identifiable source; 40.7% (541/1,330) were probably infected from household members; 9.8% (130/1,330) had possible exposure to confirmed patients or HCWs, but no lapse in infection control measures or inappropriate use of personal protective equipment was recalled. Conclusion: Omicron variant is highly transmissible such that breakthrough infection occurred despite high level of vaccination.

Correlations of Myeloperoxidase (MPO), Adenosine deaminase (ADA), C-C motif chemokine 22 (CCL22), Tumour necrosis factor alpha (TNFα) and Interleukin-6 (IL-6) mRNA expression in the nasopharyngeal specimens with the diagnosis and severity of SARS-CoV-2 infections.

Cytokine dynamics in patients with coronavirus disease 2019 (COVID-19) have been studied in blood but seldomly in respiratory specimens. We studied different cell markers and cytokines in fresh nasopharyngeal swab specimens for the diagnosis and for stratifying the severity of COVID-19. This was a retrospective case-control study comparing Myeloperoxidase (MPO), Adenosine deaminase (ADA), C-C motif chemokine ligand 22 (CCL22), Tumour necrosis factor alpha (TNFα) and Interleukin-6 (IL-6) mRNA expression in 490 (327 patients and 163 control) nasopharyngeal specimens from 317 (154 COVID-19 and 163 control) hospitalized patients. Of the 154 COVID-19 cases, 46 died. Both total and normalized MPO, ADA, CCL22, TNFα, and IL-6 mRNA expression levels were significantly higher in the nasopharyngeal specimens of infected patients when compared with controls, with ADA showing better performance (OR 5.703, 95% CI 3.424-9.500, p < 0.001). Receiver operating characteristics (ROC) curve showed that the cut-off value of normalized ADA mRNA level at 2.37 × 10-3 had a sensitivity of 81.8% and specificity of 83.4%. While patients with severe COVID-19 had more respiratory symptoms, and elevated lactate dehydrogenase, multivariate analysis showed that severe COVID-19 patients had lower CCL22 mRNA (OR 0.211, 95% CI 0.060-0.746, p = 0.016) in nasopharyngeal specimens, while lymphocyte count, C-reactive protein, and viral load in nasopharyngeal specimens did not correlate with disease severity. In summary, ADA appears to be a better biomarker to differentiate between infected and uninfected patients, while CCL22 has the potential in stratifying the severity of COVID-19.

Early Treatment of High-Risk Hospitalized Coronavirus Disease 2019 (COVID-19) Patients With a Combination of Interferon Beta-1b and Remdesivir: A Phase 2 Open-label Randomized Controlled Trial.

BACKGROUND: Early antiviral therapy was effective in the treatment of coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of combined interferon beta-1b and remdesivir treatment in hospitalized COVID-19 patients. METHODS: We conducted a multicentre, prospective open-label, randomized-controlled trial involving high-risk adults hospitalized for COVID-19. Patients were randomly assigned to a 5-day interferon beta-1b 16 million units daily and remdesivir 200 mg loading on day 1 followed by 100 mg daily on day 2 to 5 (combination group), or to remdesivir only of similar regimen (control group) (1:1). The primary endpoint was the time to complete alleviation of symptoms (NEWS2 = 0). RESULTS: Two-hundred and twelve patients were enrolled. The median days of starting treatment from symptom onset was 3 days. The median age was 65 years, and 159 patients (75%) had chronic disease. The baseline demographics were similar. There was no mortality. For the primary endpoint, the combination group was significantly quicker to NEWS2 = 0 (4 vs 6.5 days; hazard ratio [HR], 6.59; 95% confidence interval [CI], 6.1-7.09; P < .0001) when compared to the control group. For the secondary endpoints, the combination group was quicker to negative nasopharyngeal swab (NPS) viral load (VL) (6 vs 8 days; HR, 8.16; 95% CI, 7.79-8.52; P < .0001) and to develop seropositive immunoglobulin G (IgG) (8 vs 10 days; HR, 10.78; 95% CI, 9.98-11.58; P < .0001). All adverse events resolved upon follow-up. Combination group (HR, 4.1 95% CI, 1.9-8.6, P < .0001) was the most significant independent factor associated with NEWS2 = 0 on day 4. CONCLUSIONS: Early treatment with interferon beta-1b and remdesivir was safe and better than remdesivir only in alleviating symptoms, and in shortening viral shedding and hospitalization with earlier seropositivity in high-risk COVID-19 patients. CLINICAL TRIALS REGISTRATION: NCT04647695.

Air dispersal of severe acute respiratory coronavirus virus 2 (SARS-CoV-2): Implications for hospital infection control during the fifth wave of coronavirus disease 2019 (COVID-19) due to the SARS-CoV-2 omicron variant in Hong Kong.

We obtained 24 air samples in 8 general wards temporarily converted into negative-pressure wards admitting coronavirus disease 2019 (COVID-19) patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant BA.2.2 in Hong Kong. SARS-CoV-2 RNA was detected in 19 (79.2%) of 24 samples despite enhanced indoor air dilution. It is difficult to prevent airborne transmission of SARS-CoV-2 in hospitals.