Temporal changes in biomarkers of neutrophil extracellular traps and NET-promoting autoantibodies following adenovirus-vectored, mRNA, and recombinant protein COVID-19 vaccination.

Neutrophil extracellular traps (NETs) play a role in innate pathogen defense and also trigger B-cell response by providing antigens. NETs have been linked to vaccine-induced thrombotic thrombocytopenia. We postulated a potential link between NET biomarkers, NET-promoting autoantibodies, and adverse events (AEs) after COVID-19 vaccine boosters. Healthy donors (HDs) who received ChAdOx1-S (A), mRNA-1273 (M), or recombinant protein (MVC-COV1901) vaccines at the National Taiwan University Hospital between 2021 and 2022 were recruited. We measured serial NET-associated biomarkers, citrullinated-histone3 (citH3), and myeloperoxidase (MPO)-DNA. Serum citH3 and MPO-DNA were significantly or numerically higher in HDs who reported AEs (n = 100, booster Day 0/Day 30, p = 0.01/p = 0.03 and p = 0.30/p = 0.35, respectively). We also observed a positive correlation between rash occurrence in online diaries and elevated citH3. A linear mixed model also revealed significantly higher citH3 levels in mRNA-1273/ChAdOx1-S recipients than MVC-COV1901 recipients. Significant positive correlations were observed between the ratios of anti-heparin platelet factor 4 and citH3 levels on Booster Day 0 and naïve and between the ratios of anti-NET IgM and citH3 on Booster Day 30/Day 0 in the AA-M and MM-M group, respectively. The increased levels of citH3/MPO-DNA accompanied by NET-promoting autoantibodies suggest a potential connection between mRNA-1273/ChAdOx1-S vaccines and cardiovascular complications. These findings provide insights for risk assessments of future vaccines.

Clinical characteristics and treatment outcomes among the hospitalized elderly patients with COVID-19 during the late pandemic phase in central Taiwan.

BACKGROUND: There is a lack of information regarding outcomes of elderly patients hospitalized with COVID-19 following the widespread use of COVID-19 vaccines and antiviral agents. METHODS: A retrospective study was conducted between January and August 2022, enrolling patients aged 65 years or older. Patients were categorized into two groups: 'old' (65-79 years) and 'oldest-old' (80 years or more). Multivariate regression was employed to identify independent prognostic factors for in-hospital mortality. RESULTS: A total of 797 patients were enrolled, including 428 old and 369 oldest-old patients. In each subgroup, 66.6 % and 59.6 % of patients received at least one dose of the COVID-19 vaccine, respectively. Approximately 40 % of the patients received oral antiviral agents either before or upon hospital admission. A greater percentage of the oldest-old patients received remdesivir (53.4 % versus 39.7 %, p < 0.001), dexamethasone (49.3 % versus 36.7 %, p < 0.001), and tocilizumab (10.0 % versus 6.8 %, p < 0.001) than old patients. The mortality rate was comparable between the two age subgroups (14 % versus 15.2 %). Independent predictors of in-hospital mortality included disease severity and comorbidities such as end-stage renal disease (ESRD), cirrhosis, solid tumours, and haematologic malignancies. Ageing was not correlated with increased in-hospital mortality across all comorbidity subgroups. CONCLUSIONS: In the later stages of the pandemic, with widespread vaccination and advancements in COVID-19 treatments, outcomes for hospitalized elderly and oldest-old patients with COVID-19 have improved. The influence of age on in-hospital mortality has diminished, while comorbidities such as ESRD, cirrhosis, solid tumours, and hematologic malignancies have been associated with mortality.

Clinical significance of mutations in dihydropteroate synthase in Pneumocystis jirovecii pneumonia among non-HIV-infected patients.

BACKGROUND: Dihydropteroate synthase (DHPS) mutations may be associated with trimethoprim-sulfamethoxazole resistance in Pneumocystis jirovecii pneumonia (PCP) and worse clinical outcomes. However, the clinical significance of DHPS mutations in PCP among non-human immunodeficiency virus (HIV)-infected patients remains unclear. METHODS: Patients with PCP in three tertiary referral hospitals in Taiwan between 2016 and 2020 were retrospectively enrolled. Two point mutations, Thr55Ala and Pro57Ser, in the DHPS protein were analysed. Patients with invalid DHPS mutations in the respiratory specimen, chronic respiratory failure, receiving endotracheal intubation for surgical intervention, HIV infection, Pneumocystis jirovecii colonisation, and no lactate dehydrogenase (LDH) data were excluded. The primary outcome was 30-day survival. RESULTS: A total of 215 patients were analysed. Mutants inside DHPS were found in 78 patients (36.3%) and 68 patients (31.6%) died within 30 days. A total of 214 patients (99.5%) received trimethoprim-sulfamethoxazole as the first-line treatment. The rates of mechanical ventilation, 30-day, and in-hospital mortality were similar between wild-type and mutant DHPS PCP. After adjusting for important confounders, LDH > 500 µ/L (adjusted hazard ratio [aHR] = 2.448, P = 0.001), pneumonia severity index > 135 mg/dL (aHR = 1.689, P = 0.049), and having solid tumours (aHR = 1.832, P = 0.034) were independently associated with higher mortality. In subgroup analysis, mutant DHPS PCP patients had less 30-day mortality among patients aged > 65 years (P = 0.049), with lymphopenia (P = 0.040), and those without solid tumour (P = 0.045). CONCLUSIONS: In non-HIV-infected PCP, point mutants inside DHPS may not be associated with trimethoprim-sulfamethoxazole treatment outcomes. Further prospective large-scale studies are warranted.

Chitinase 3-like-1 Expression in the Microenvironment Is Associated with Neutrophil Infiltration in Bladder Cancer.

Bladder cancer is a common cancer with well-established therapeutic strategies. However, recurrence occurs in 50% of patients with non-muscle-invasive bladder cancer, and 20% of patients progress to muscle-invasive bladder cancer. The 5-year survival rate for muscle-invasive bladder cancer patients is disappointingly low, ranging from 36% to 48%. A molecular marker of interest is chitinase 3-like-1 (CHI3L1), which is elevated in various cancers, including bladder cancer. In addition to its role in cancer cells, CHI3L1 also has regulatory abilities in immune cells. Neutrophil infiltration has been shown to positively correlate with overall survival, progression-free survival, and relapse-free survival in bladder cancer patients. However, the relationship between CHI3L1 and neutrophils remain poorly understood. Therefore, this study investigated the relationship between CHI3L1 level and protumor neutrophil infiltration in bladder cancer. We analyzed the GSE128959 dataset and the data of a bladder cancer cohort undergoing chemotherapy. We observed higher expression of CHI3L1 in bladder cancer patients with invasive or chemotherapy-resistance. Our results revealed a positive correlation between CHI3L1 expression and protumor neutrophil infiltration. Elevated CHI3L1 expression was associated with genes which were related to the recruitment and infiltration of neutrophils. Consequently, CHI3L1 may serve as a novel evaluation factor for the degree of neutrophil infiltration in advanced bladder cancer in those scheduled for chemotherapy.

Placebo effects on all-cause mortality of patients with COVID-19 in randomized controlled trials of interleukin 6 antagonists: A systematic review and network meta-analysis.

AIM: Many randomized controlled trials (RCTs) have investigated the use of interleukin 6 antagonists for the treatment of coronavirus disease 2019 (COVID-19), yielding inconsistent results. This network meta-analysis (NMA) aimed to identify the source of these inconsistent results by reassessing whether participants treated with standard of care (SoC) plus placebo have different all-cause mortality from those treated with SoC alone and to reevaluate the efficacy of interleukin 6 antagonists in the treatment of COVID-19. METHODS: We conducted a systematic search for relevant RCTs from the inception of electronic databases through 1 September 2022. The primary outcome was all-cause mortality. The secondary outcomes were the incidences of major medical events, secondary infections, all-cause discontinuation, and serious adverse events. RESULTS: The results of NMA of 33 RCTs showed that patients with COVID-19 treated with SoC plus placebo had lower odds of all-cause mortality than those who received SoC alone (OR, 0.75 [95% confidence interval, 0.58-0.97]). This finding remained consistent after excluding studies with no incident deaths. In addition, when we consider the impact of the widely promoted COVID-19 vaccination and newly developed antiviral treatment strategy, the results from the analysis of the RCT published in 2021 and 2022 remained similar. CONCLUSION: These findings suggest the potential influence of placebo effects on the treatment outcomes of COVID-19 in RCTs. When evaluating the efficacy of treatment strategies for COVID-19, it is crucial to consider the use of placebo in the design of clinical trials.

Osteoprogenitor-GMP crosstalk underpins solid tumor-induced systemic immunosuppression and persists after tumor removal.

Remote tumors disrupt the bone marrow (BM) ecosystem (BME), eliciting the overproduction of BM-derived immunosuppressive cells. However, the underlying mechanisms remain poorly understood. Herein, we characterized breast and lung cancer-induced BME shifts pre- and post-tumor removal. Remote tumors progressively lead to osteoprogenitor (OP) expansion, hematopoietic stem cell dislocation, and CD41- granulocyte-monocyte progenitor (GMP) aggregation. The tumor-entrained BME is characterized by co-localization between CD41- GMPs and OPs. OP ablation abolishes this effect and diminishes abnormal myeloid overproduction. Mechanistically, HTRA1 carried by tumor-derived small extracellular vesicles upregulates MMP-13 in OPs, which in turn induces the alterations in the hematopoietic program. Importantly, these effects persist post-surgery and continue to impair anti-tumor immunity. Conditional knockout or inhibition of MMP-13 accelerates immune reinstatement and restores the efficacies of immunotherapies. Therefore, tumor-induced systemic effects are initiated by OP-GMP crosstalk that outlasts tumor burden, and additional treatment is required to reverse these effects for optimal therapeutic efficacy.

How Taiwan has responded to COVID-19 and how COVID-19 has affected Taiwan, 2020-2022.

From January 2020 to December 2022, there was a total of 8,872,955 confirmed COVID-19 cases in Taiwan. In addition, a total of 15,253 COVID-19 related deaths were reported. During these three years, the government and health authority did many efforts to response this pandemic. In the early pandemic, Taiwan Central Epidemic Command Center was established in the early 2020 to organize associated resource, develop effective policy and implement strict intervention. In response to COVID-19 pandemic, many infection control policy and interventions, including universal mask wearing with increasing production of face mask, hand hygiene, border control, introduce of digital technology incorporating big data, quarantine of COVID-19 cases, travel and gathering restriction, were implemented. In the meanwhile, two COVID-19 vaccines, namely MVC-COV1901 and UB-612, have been developed under the support of government. Furthermore, MVC-COV1901 was taken into clinical practice after received emergency use approval. In addition, two traditional Chinese medicines, including NRICM101 and NRICM102 showed their promising effect against SARS-CoV-2 infection and were recommended as potential therapeutic options for COVID-19. During the pandemic, the nonpharmacologic intervention help reduce many infectious diseases, especially for airborne/droplet-transmitted diseases. However, COVID-19 exhibited some adverse impacts on the healthcare systems, such as emergency medical service on out of hospital cardiac arrest, cancer screening, HIV screening and prevention services, and public health, namely the psychosocial status of healthcare workers. Although the outbreak of SARS-CoV-2 infections may gradually subsided, we should keep monitoring its associated impact and appropriately response to this pandemic.

Highly Mimetic Ex Vivo Lung-Cancer Spheroid-Based Physiological Model for Clinical Precision Therapeutics.

Lung cancer remains a major health problem despite the considerable research into prevention and treatment methods. Through a deeper understanding of tumors, patient-specific ex vivo spheroid models with high specificity can be used to accurately investigate the cause, metastasis, and treatment strategies for lung cancer. Biofabricate lung tumors are presented, consisting of patient-derived tumor spheroids, endothelial cells, and lung decellularized extracellular matrix, which maintain a radial oxygen gradient, as well as biophysicochemical behaviors of the native tumors for precision medicine. It is also demonstrated that the developed lung-cancer spheroid model reproduces patient responses to chemotherapeutics and targeted therapy in a co-clinical trial, with 85% accuracy, 86.7% sensitivity, and 80% specificity. RNA sequencing analysis validates that the gene expression in the spheroids replicates that in the patient's primary tumor. This model can be used as an ex vivo predictive model for personalized cancer therapy and to improve the quality of clinical care.

Cryptococcus tetragattii Meningitis Associated with Travel, Taiwan.

Meningitis caused by Cryptococcus tetragattii fungus is rare and has been found in specific geographic regions. We report a case of meningitis caused by C. tetragattii (molecular type VGIV) in an immunocompetent patient in Taiwan. The patient had traveled to Egypt and was positive for granulocyte-macrophage colony-stimulating factor autoantibody.

Disulfiram blocked cell entry of SARS-CoV-2 via inhibiting the interaction of spike protein and ACE2.

Disulfiram is an FDA-approved drug that has been used to treat alcoholism and has demonstrated a wide range of anti-cancer, anti-bacterial, and anti-viral effects. In the global COVID-19 pandemic, there is an urgent need for effective therapeutics and vaccine development. According to recent studies, disulfiram can act as a potent SARS-CoV-2 replication inhibitor by targeting multiple SARS-CoV-2 non-structural proteins to inhibit viral polyprotein cleavage and RNA replication. Currently, disulfiram is under evaluation in phase II clinical trials to treat COVID-19. With more and more variants of the SARS-CoV-2 worldwide, it becomes critical to know whether disulfiram can also inhibit viral entry into host cells for various variants and replication inhibition. Here, molecular and cellular biology assays demonstrated that disulfiram could interrupt viral spike protein binding with its receptor ACE2. By using the viral pseudo-particles (Vpps) of SARS-CoV-2, disulfiram also showed the potent activity to block viral entry in a cell-based assay against Vpps of different SARS-CoV-2 variants. We further established a live virus model system to support the anti-viral entry activity of disulfiram with the SARS-CoV-2 virus. Molecular docking revealed how disulfiram hindered the binding between the ACE2 and wild-type or mutated spike proteins. Thus, our results indicate that disulfiram has the capability to block viral entry activity of different SARS-CoV-2 variants. Together with its known anti-replication of SARS-CoV-2, disulfiram may serve as an effective therapy against different SARS-CoV-2 variants.

Molecular Epidemiological Characteristics of Mycobacterium abscessus Complex Derived from Non-Cystic Fibrosis Patients in Japan and Taiwan.

Mycobacterium abscessus complex (MABC) is a group of emerging, highly antimicrobial-resistant non-tuberculous mycobacteria. Specific MABC clones are spreading globally in patients with cystic fibrosis (CF); however, associated genomic epidemiology is lacking in East Asia, with very few patients with CF. Here, we investigated MABC populations derived from non-CF patients in Japan and Taiwan. Analysis of whole-genome sequencing data of 220 MABC isolates revealed that 112, 105, and 3 were M. abscessus subsp. abscessus (ABS), M. abscessus subsp. massiliense (MAS), and M. abscessus subsp. bolletii (BOL), respectively. Moreover, >50% of ABS and >70% of MAS were related to four predominant clones in the region. Known mutations conferring macrolide resistance were rare (1.4%) and were not enriched in the predominant clones. Conversely, the macrolide-susceptible erm(41) T28C mutation was significantly enriched in one predominant ABS clone. The most predominant ABS clone was genetically related to the previously described dominant circulating clone (DCC)1 in patients with CF, whereas no isolates were related to DCC2; isolates related to DCC3 were not necessarily predominant in our sample set. We found that the erm(41) T28C mutants spread globally, and some of them reacquired the functional erm(41) gene through both point mutation and recombination. This study revealed predominant MABC clones in Japan and Taiwan and their relationship with the globally superadding clones in the patient community with CF. Our study provides insights into the genetic characteristics of globally dominant and area-specific strains isolated from patients with or without CF and differences between globally spread and regionally specific strains. IMPORTANCE Members of Mycobacterium abscessus complex (MABC) are frequently isolated from patients. Studies have reported that predominant clones of MABC (known as dominant circulating clones; DCCs) are distributed worldwide and transmitted from humans to humans in patients with cystic fibrosis (CF). However, associated genomic epidemiology has not yet been conducted in East Asia, including Japan and Taiwan, where there are only a few patients with CF. Using whole-genome sequencing data derived from non-CF patients in Japan and Taiwan, we revealed prevalent clones and the incidence of macrolide resistance-associated mutations in the MABC population in this region. We also clarified the associations between these predominant clones and DCCs in the global CF patient community. Our results would assist further studies in elucidating the genetic characteristics of strains isolated from patients with or without CF, the differences between globally spread and regionally specific strains, and the adaptive evolution of MABC within the host.

Clinical efficacy of antiviral agents against coronavirus disease 2019: A systematic review of randomized controlled trials.

Despite aggressive efforts on containment measures for the coronavirus disease 2019 (COVID-19) pandemic around the world, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously spreading. Therefore, there is an urgent need for an effective antiviral agent. To date, considerable research has been conducted to develop different approaches to COVID-19 therapy. In addition to early observational studies, which could be limited by study design, small sample size, non-randomized design, or different timings of treatment, an increasing number of randomized controlled trials (RCTs) investigating the clinical efficacy and safety of antiviral agents are being carried out. This study reviews the updated findings of RCTs regarding the clinical efficacy of eight antiviral agents against COVID-19, including remdesivir, lopinavir/ritonavir, favipiravir, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir, baloxavir, umifenovir, darunavir/cobicistat, and their combinations. Treatment with remdesivir could accelerate clinical improvement; however, it lacked additional survival benefits. Moreover, 5-day regimen of remdesivir might show adequate effectiveness in patients with mild to moderate COVID-19. Favipiravir was only marginally effective regarding clinical improvement and virological assessment based on the results of small RCTs. The present evidence suggests that sofosbuvir/daclatasvir may improve survival and clinical outcomes in patients with COVID-19. However, the sample sizes for analysis were relatively small, and all studies were exclusively conducted in Iran. Further larger RCTs in other countries are warranted to support these findings. In contrast, the present findings of limited RCTs did not indicate the use of lopinavir/ritonavir, sofosbuvir/ledipasvir, baloxavir, umifenovir, and darunavir/cobicistat in the treatment of patients hospitalized for COVID-19.

Clostridioides difficile infection in patients with hematological malignancy: A multicenter study in Taiwan.

BACKGROUND: Among the individuals with hematological malignancy (HM) complicated with Clostridioides difficile infection (CDI), the variables associated with in-hospital mortality and recurrence of CDI were investigated. MATERIAL AND METHODS: Including adults with HM and those without malignancy suffering from CDI from January 2015 to December 2016 in three hospitals in Taiwan. RESULTS: Totally 314 patients including 77 with HM and 237 patients without malignancy were included. HM patients more often had low leukocyte counts (<500 cells/mL: 28.6% vs. 2.1%) than those without malignancy and more patients without malignancy had severe CDI than patients with HM (31.6% vs. 14.3%, P = .003), according to the severity score of IDSA/SHEA. Patients with HM had a higher recurrence rate of CDI (14.3%, 11/77 vs. 7.2%, 17/237; P = .07) and longer hospital stay (47.2 ± 40.8 days vs. 33.3 ± 37.3 days; P = .006) than those without malignancy. In the multivariate analyses for those with HM and CDI, the in-hospital mortality was associated with vancomycin-resistant Enterococcus (VRE) colonization or infection (odds ratio [OR] 7.72; P = .01), and C. difficile ribotype 078 complex infection (OR 9.22; P = .03). Moreover underlying hematological malignancy (OR 2.74; P = .04) and VRE colonization/infection (OR 2.71; P = .02) were independently associated with CDI recurrence. CONCLUSION: Patients with HM complicated with CDI were often regarded as non-severe infection, but had a similar in-hospital mortality rate as those without malignancy. CDI due to ribotype 078 complex isolates heralded a poor prognosis among HM patients.

Clinical efficacy and safety of remdesivir in patients with COVID-19: a systematic review and network meta-analysis of randomized controlled trials.

OBJECTIVES: We performed a systematic review and network meta-analysis of randomized controlled trials (RCTs) to provide updated information regarding the clinical efficacy of remdesivir in treating coronavirus disease 2019 (COVID-19). METHODS: PubMed, Embase, Cochrane Library, clinical trial registries of ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched for relevant articles published up to 18 November 2020. RESULTS: Five RCTs, including 13 544 patients, were included in this meta-analysis. Among them, 3839 and 391 patients were assigned to the 10 day and 5 day remdesivir regimens, respectively. Patients receiving 5 day remdesivir therapy presented greater clinical improvement than those in the control group [OR = 1.68 (95% CI 1.18-2.40)], with no significant difference observed between the 10 day and placebo groups [OR = 1.23 (95% CI 0.90-1.68)]. Patients receiving remdesivir revealed a greater likelihood of discharge [10 day remdesivir versus control: OR = 1.32 (95% CI 1.09-1.60); 5 day remdesivir versus control: OR = 1.73 (95% CI 1.28-2.35)] and recovery [10 day remdesivir versus control: OR = 1.29 (95% CI 1.03-1.60); 5 day remdesivir versus control: OR = 1.80 (95% CI 1.31-2.48)] than those in the control group. In contrast, no mortality benefit was observed following remdesivir therapy. Furthermore, no significant association was observed between remdesivir treatment and an increased risk of adverse events. CONCLUSIONS: Remdesivir can help improve the clinical outcome of hospitalized patients with COVID-19 and a 5 day regimen, instead of a 10 day regimen, may be sufficient for treatment. Moreover, remdesivir appears as tolerable as other comparators or placebo.

Longitudinal non-cystic fibrosis trends of pulmonary Mycobacterium abscessus disease from 2010 to 2017: spread of the "globally successful clone" in Asia.

BACKGROUND: Mycobacterium abscessus (MAB) has emerged as the predominant pulmonary non-tuberculous mycobacterial pathogen in parts of Asia, including Taiwan. The reasons for the significant increase in MAB infections in the non-cystic fibrosis (CF) populations are poorly understood. The study aimed to elucidate whether this increase is related to the spread of the globally successful clone of MAB. METHODS: We performed multilocus sequence typing of 371 nonduplicated MAB pulmonary isolates from 371 patients sampled between 2010-2017 at seven hospitals across Taiwan. RESULTS: In total, 183 (49.3%) isolates were M. abscessus subsp. abscessus (MAB-a), 187 (50.4%) were M. abscessus subsp. massiliense (MAB-m), and 1 (0.3%) was M. abscessus subsp. bolletii (MAB-b). MAB-a sequence type (ST)1 (23.7%) and ST127 (3.8%), followed by MAB-m ST48 (16.2%), ST117 (15.1%), ST23 (8.6%) were most common overall. Of MAB-a strains, 50 (27.3%) belonged to novel STs and 38 (10.2%) were singleton strains, while of MAB-m strains, only 10 (5.3%) were novel and 8 (2.2%) were singletons. From 2010 to 2017, the frequency of the historically dominant ST1 declined from 28.6% to 22.5%, whereas the recently emerged globally successful clonal cluster 3, ST23 and ST48, increased from 14.3% to 40.0%. CONCLUSIONS: The dominance of ST1 particularly in the last 2 years of this study appears to be declining, while ST23, reported in outbreaks among CF and post-surgical cohorts across the Americas and Europe, alongside the closely related ST48, is present among non-CF populations in Taiwan. These trends need to be confirmed with further ongoing studies to track the molecular epidemiology of clinical MAB isolates worldwide.

Clinical and molecular epidemiology of human listeriosis in Taiwan.

OBJECTIVE: To determine serogroups, multilocus sequence typing (MLST) of Listeria monocytogenes isolates and analyze clinical characteristics of these clones focusing on non-perinatal cases. METHODS: From 2000 to 2015, we analyzed 123 human listeriosis cases at a medical center in northern Taiwan using PCR serogrouping, MLST, and clinical presentations. RESULTS: The annual incidence of listeriosis increased since 2005 with a peak in 2008 (0.2 per 1000 admission) and decreased thereafter. Of the 115 non-perinatal listeriosis cases, we found a male predominance (60%) with an average age of 63.9 years old (standard deviation: 15.3 years), and almost all patients had underlying conditions including malignancies (61.7%), steroid usage (39.1%), diabetes mellitus (31.3%), renal insufficiency (27.8%), and liver cirrhosis (17.4%). Clinical presentations included bacteremia (74.8%), neurolisteriosis (20.0%), and spontaneous bacterial peritonitis (5.2%). The most frequently identified serogroup-sequence types (ST) were IIB-ST87 (30.9%), followed by IIA-ST378 (16.3%) and IIA-ST155 (14.6%). The 30-day all-cause mortality of non-perinatal listeriosis was 25.2% and was associated with age (Hazard ratio: 1.04, 95% C.I. = 1.01-1.07, p = 0.021), steroid usage (Hazard ratio: 2.54, 95% C.I. = 1.06-6.11, p = 0.038) and respiratory distress at presentation (Hazard ratio: 2.59, 95% C.I. = 1.05-6.39, p = 0.038); while no association was found with serogroups (IIA, IIB, and IVB) or three major ST types by multivariable analysis. All 8 mothers of perinatal listeriosis patients survived and three neonates died (mortality, 37.5%), and IIB-ST87 was the major type (62.5%). CONCLUSION: Predominant strains in Taiwan could cause significant morbidity and mortality. Further disease monitoring and source surveillance are warranted despite a declining trend of human listeriosis in Taiwan.

Remdesivir use in the coronavirus disease 2019 pandemic: A mini-review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative viral pathogen of coronavirus disease 2019 (COVID-19), appears to have various clinical presentations and may result in severe respiratory failure. The global SARS-CoV-2-associated viral pneumonia pandemic was first reported in December 2019 in China. Based on known pharmacological mechanisms, many therapeutic drugs have been repurposed to target SARS-CoV-2. Among these drugs, remdesivir appears to be the currently most promising according to several clinical trials and reports of compassionate use. In this mini-review, we summarize the current evidence on the efficacy and challenges of remdesivir for the treatment of coronavirus disease 2019 (COVID-19).

Laboratory diagnosis of COVID-19 in China: A review of challenging cases and analysis.

Since the initial emergence of coronavirus disease 2019 (COVID-19) in Wuhan, Hubei province, China, a rapid spread of the disease occurred around the world, rising to become an international global health concern at pandemic level. In the face of this medical challenge threatening humans, the development of rapid and accurate methods for early screening and diagnosis of COVID-19 became crucial to containing the emerging public health threat, and prevent further spread within the population. Despite the large number of COVID-19 confirmed cases in China, some problematic cases with inconsistent laboratory testing results, were reported. Specifically, a high false-negative rate of 41% on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection by real-time reverse transcription-polymerase chain reaction (qRT-PCR) assays was observed in China. Although serological testing has been applied worldwide as a complementary method to help identify SARS-CoV-2, several limitations on its use have been reported in China. Therefore, the use of both qRT-PCR and serological testing in the diagnosis of COVID-19 in China and elsewhere, presented considerable challenges, but when used in combination, can be valuable tools in the fight against COVID-19. In this review, we give an overview of the advantages and disadvantages of different molecular techniques for SARS-CoV-2 detection that are currently used in several labs, including qRT-PCR, gene sequencing, loop-mediated isothermal amplification (LAMP), nucleic acid mass spectrometry (MS), and gene editing technique based on clustered regularly interspaced short palindromic repeats (CRISPR/Cas13) system. Then we mainly review and analyze some causes of false-negative qRT-PCR results, and how to resolve some of the diagnostic dilemma.