Recommendations and guidelines for the diagnosis and management of Coronavirus Disease-19 (COVID-19) associated bacterial and fungal infections in Taiwan.

Coronavirus disease-19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2 that has rapidly evolved into a pandemic to cause over 600 million infections and more than 6.6 million deaths up to Nov 25, 2022. COVID-19 carries a high mortality rate in severe cases. Co-infections and secondary infections with other micro-organisms, such as bacterial and fungus, further increases the mortality and complicates the diagnosis and management of COVID-19. The current guideline provides guidance to physicians for the management and treatment of patients with COVID-19 associated bacterial and fungal infections, including COVID-19 associated bacterial infections (CABI), pulmonary aspergillosis (CAPA), candidiasis (CAC) and mucormycosis (CAM). Recommendations were drafted by the 7th Guidelines Recommendations for Evidence-based Antimicrobial agents use Taiwan (GREAT) working group after review of the current evidence, using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations in March 2022, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes the epidemiology, diagnostic methods and treatment recommendations for COVID-19 associated infections. The aim of this guideline is to provide guidance to physicians who are involved in the medical care for patients with COVID-19 during the ongoing COVID-19 pandemic.

Possible transmission of COVID-19 epidemic by a dog as a passive mechanical carrier of SARS-CoV-2, Chongqing, China, 2022.

An outbreak of coronavirus disease 2019 (COVID-19) was reported in Yongchuan district of Chongqing, China in March 2022, while the source was unknown. We aimed to investigate the origin and transmission route of the virus in the outbreak. We conducted field investigations for all cases and collected their epidemiological and clinical data. We performed gene sequencing and phylogenetic analysis for the cases, and draw the epidemic curve and the case relationship chart to analyze interactions and possible transmission mode of the outbreak. A total of 11 cases of COVID-19, including 5 patients and 6 asymptomatic cases were laboratory-confirmed in the outbreak. The branch of the virus was Omicron BA.2 which was introduced into Yongchuan district by a traveler in early March. Patient F and asymptomatic case G had never contact with other positive-infected individuals, but close contact with their pet dog that sniffed the discarded cigarette butts and stepped on the sputum of patient B. Laboratory test results showed that the dog hair and kennel were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the 10 isolates were highly homologous to an epidemic strain in a province of China. The investigation suggested that the contaminated dog by SARS-CoV-2 can act as a passive mechanical carrier of the virus and might transmit the virus to humans through close contact. Our findings suggest that during the COVID-19 pandemic, increasing hygiene measures and hand washing after close contact with pets is essential to minimize the risk of community spread of the virus.

Coronavirus disease 2019 (COVID-19) associated bacterial coinfection: Incidence, diagnosis and treatment.

Coronavirus disease 2019 (COVID-19) emerged as a pandemic that spread rapidly around the world, causing nearly 500 billion infections and more than 6 million deaths to date. During the first wave of the pandemic, empirical antibiotics was prescribed in over 70% of hospitalized COVID-19 patients. However, research now shows a low incidence rate of bacterial coinfection in hospitalized COVID-19 patients, between 2.5% and 5.1%. The rate of secondary infections was 3.7% in overall, but can be as high as 41.9% in the intensive care units. Over-prescription of antibiotics to treat COVID-19 patients fueled the ongoing antimicrobial resistance globally. Diagnosis of bacterial coinfection is challenging due to indistinguishable clinical presentations with overlapping lower respiratory tract symptoms such as fever, cough and dyspnea. Other diagnostic methods include conventional culture, diagnostic syndromic testing, serology test and biomarkers. COVID-19 patients with bacterial coinfection or secondary infection have a higher in-hospital mortality and longer length of stay, timely and appropriate antibiotic use aided by accurate diagnosis is crucial to improve patient outcome and prevent antimicrobial resistance.

A multitope SARS-CoV-2 vaccine provides long-lasting B cell and T cell immunity against Delta and Omicron variants.

BackgroundThe Delta and Omicron variants of SARS-CoV-2 are currently responsible for breakthrough infections due to waning immunity. We report phase I/II trial results of UB-612, a multitope subunit vaccine containing S1-RBD-sFc protein and rationally designed promiscuous peptides representing sarbecovirus conserved helper T cell and cytotoxic T lymphocyte epitopes on the nucleocapsid (N), membrane (M), and spike (S2) proteins.MethodWe conducted a phase I primary 2-dose (28 days apart) trial of 10, 30, or 100 µg UB-612 in 60 healthy young adults 20 to 55 years old, and 50 of them were boosted with 100 µg of UB-612 approximately 7 to 9 months after the second dose. A separate placebo-controlled and randomized phase II study was conducted with 2 doses of 100 µg of UB-612 (n = 3,875, 18-85 years old). We evaluated interim safety and immunogenicity of phase I until 14 days after the third (booster) dose and of phase II until 28 days after the second dose.ResultsNo vaccine-related serious adverse events were recorded. The most common solicited adverse events were injection site pain and fatigue, mostly mild and transient. In both trials, UB-612 elicited respective neutralizing antibody titers similar to a panel of human convalescent sera. The most striking findings were long-lasting virus-neutralizing antibodies and broad T cell immunity against SARS-CoV-2 variants of concern (VoCs), including Delta and Omicron, and a strong booster-recalled memory immunity with high cross-reactive neutralizing titers against the Delta and Omicron VoCs.ConclusionUB-612 has presented a favorable safety profile, potent booster effect against VoCs, and long-lasting B and broad T cell immunity that warrants further development for both primary immunization and heterologous boosting of other COVID-19 vaccines.Trial RegistrationClinicalTrials.gov: NCT04545749, NCT04773067, and NCT04967742.FundingUBI Asia, Vaxxinity Inc., and Taiwan Centers for Disease Control, Ministry of Health and Welfare.

Identifying critical outbreak time window of controversial events based on sentiment analysis.

The response of netizens toward controversial events plays an important guiding role in the development of events. Based on the identification of such responses, this study aimed to determine the critical outbreak time window of events. The microblog texts related to an event were divided into seven emotional categories via multi-emotional analysis to capture the subtle emotions of netizens toward an event, i.e., public opinion. By detecting the characteristics of the text and regional coverage of emotions, an emotional coverage index that reflects the intensity of emotional impact was proposed to determine the mainstream emotion of netizens. By capturing the mutation characteristics of the impact intensity of mainstream emotions, the critical time window of the public opinion toward the event was obtained. The experimental results demonstrated that the proposed method can effectively identify the critical outbreak time window of controversial events, which can help authorities in preventing the further aggravation of events.

Add-On Chinese Medicine for Coronavirus Disease 2019 (ACCORD): A Retrospective Cohort Study of Hospital Registries.

Chinese medicine (CM) was extensively used to treat COVID-19 in China. We aimed to evaluate the real-world effectiveness of add-on semi-individualized CM during the outbreak. A retrospective cohort of 1788 adult confirmed COVID-19 patients were recruited from 2235 consecutive linked records retrieved from five hospitals in Wuhan during 15 January to 13 March 2020. The mortality of add-on semi-individualized CM users and non-users was compared by inverse probability weighted hazard ratio (HR) and by propensity score matching. Change of biomarkers was compared between groups, and the frequency of CMs used was analyzed. Subgroup analysis was performed to stratify disease severity and dose of CM exposure. The crude mortality was 3.8% in the semi-individualized CM user group and 17.0% among the non-users. Add-on CM was associated with a mortality reduction of 58% (HR = 0.42, 95% CI: 0.23 to 0.77, [Formula: see text] = 0.005) among all COVID-19 cases and 66% (HR = 0.34, 95% CI: 0.15 to 0.76, [Formula: see text] = 0.009) among severe/critical COVID-19 cases demonstrating dose-dependent response, after inversely weighted with propensity score. The result was robust in various stratified, weighted, matched, adjusted and sensitivity analyses. Severe/critical patients that received add-on CM had a trend of stabilized D-dimer level after 3-7 days of admission when compared to baseline. Immunomodulating and anti-asthmatic CMs were most used. Add-on semi-individualized CM was associated with significantly reduced mortality, especially among severe/critical cases. Chinese medicine could be considered as an add-on regimen for trial use.

SARS-CoV-2 and the reproductive system: assessment of risk and recommendations for infection control in reproductive departments.

The World Health Organization has declared the outbreak of the coronavirus disease COVID-19, caused by SARS-CoV-2, a pandemic. This novel infectious disease has rapidly become a global health threat. Currently, there are limited data on the extent of reproductive system damage caused by COVID-19. We reviewed the potential risks for complications in the reproductive system caused by COVID-19 infection. In addition, based on the latest American Society for Reproductive Medicine (ASRM), and European Society of Human Reproduction and Embryology (ESHRE), recommendations regarding clinical and patient management, we provide a series of suggestions for infection control measures in reproductive medicine departments. With the gradual restoration of reproductive care services, reproductive departments in epidemic areas should actively seek to minimize COVID-19 infection of both healthcare workers and patients.

Epidemiological and Genomic Analysis of SARS-CoV-2 in 10 Patients From a Mid-Sized City Outside of Hubei, China in the Early Phase of the COVID-19 Outbreak.

A novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing Coronavirus Disease 2019 (COVID-19) pandemic. In this study, we performed a comprehensive epidemiological and genomic analysis of SARS-CoV-2 genomes from 10 patients in Shaoxing (Zhejiang Province), a mid-sized city outside of the epicenter Hubei province, China, during the early stage of the outbreak (late January to early February, 2020). We obtained viral genomes with >99% coverage and a mean depth of 296X demonstrating that viral genomic analysis is feasible via metagenomics sequencing directly on nasopharyngeal samples with SARS-CoV-2 Real-time PCR Ct values <28. We found that a cluster of four patients with travel history to Hubei shared the exact same virus with patients from Wuhan, Taiwan, Belgium, and Australia, highlighting how quickly this virus spread to the globe. The virus from another cluster of two family members living together without travel history but with a sick contact of a confirmed case from another city outside of Hubei accumulated significantly more mutations (9 SNPs vs. average 4 SNPs), suggesting a complex and dynamic nature of this outbreak. Our findings add to the growing knowledge of the epidemiological and genomic characteristics of SARS-CoV-2 and offers a glimpse into the early phase of this viral infection outside of Hubei, China.

Impact of the COVID-19 Pandemic on Partner Relationships and Sexual and Reproductive Health: Cross-Sectional, Online Survey Study.

BACKGROUND: In the past few months, the coronavirus disease (COVID-19) pandemic has caused extensive economic and social damage. OBJECTIVE: The purpose of this study was to assess the impact of COVID-19-related measures on partner relationships and sexual and reproductive health in China. METHODS: From May 1 to 5, 2020, 3500 young Chinese individuals were recruited through WeChat or Weibo to participate in a survey to obtain information on sexual and reproductive health (eg, sexual desire, frequency of sexual intercourse, sexual satisfaction, etc). The questionnaire also collected demographic data (eg, age, race, education, current financial status, sexual orientation, relationship status, etc). RESULTS: In total, 967 participants were included in the sexual health analysis. Due to the COVID-19 pandemic and related containment measures, 22% of participants (n=212) reported a decrease in sexual desire; 41% (n=396) experienced a decrease in the sexual intercourse frequency; 30% (n=291) reported an increase in the frequency of masturbation; 20% (n=192) reported a decrease in alcohol consumption before or during sexual activities, and 31% (n=298) reported a deterioration in partner relationships during the pandemic. The logistic regression analysis indicated that the following influenced partner relationships: accommodations during the pandemic (P=.046; odds ratio [OR] 0.59; 95% CI 0.30-0.86); exclusive relationship status (yes or no) (P<.001; OR 0.44; 95 % CI 0.27-0.73); sexual desire (P=.02; OR 2.01; 95% CI 1.38-2.97); and sexual satisfaction (P<.001; OR 1.92; 95% CI 1.54-2.50). COVID-19 also caused disruptions in reproductive health services such as prenatal and postnatal care, childbirth and abortion services, contraception availability, and the management of sexually transmitted infections. CONCLUSIONS: Our results show that many young people have wide-ranging issues affecting their sexual and reproductive health due to the COVID-19 pandemic and related containment measures. Strategies and guidelines are needed to safeguard the sexual and reproductive health of young people during this pandemic.

Clinical and Immune Features of Hospitalized Pediatric Patients With Coronavirus Disease 2019 (COVID-19) in Wuhan, China.

Importance: The epidemiologic and clinical characteristics of pediatric patients with coronavirus disease 2019 (COVID-19) have been reported, but information on immune features associated with disease severity is scarce. Objective: To delineate and compare the immunologic features of mild and moderate COVID-19 in pediatric patients. Design, Setting, and Participants: This single-center case series included 157 pediatric patients admitted to Wuhan Children's Hospital with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data were collected from January 25 to April 18, 2020. Exposures: Documented SARS-CoV-2 infection. Main Outcomes and Measures: Clinical and immunologic characteristics were collected and analyzed. Outcomes were observed until April 18, 2020. Results: Of the 157 pediatric patients with COVID-19, 60 (38.2%) had mild clinical type with pneumonia, 88 (56.1%) had moderate cases, 6 (3.8%) had severe cases, and 3 (1.9%) were critically ill. The 148 children with mild or moderate disease had a median (interquartile range [IQR]) age of 84 (18-123) months, and 88 (59.5%) were girls. The most common laboratory abnormalities were increased levels of alanine aminotransferase (ALT) (median [IQR], 16.0 [12.0-26.0] U/L), aspartate aminotransferase (AST) (median [IQR], 30.0 [23.0-41.8] U/L), creatine kinase MB (CK-MB) activity (median [IQR], 24.0 [18.0-34.0] U/L), and lactate dehydrogenase (LDH) (median [IQR], 243.0 [203.0-297.0] U/L), which are associated with liver and myocardial injury. Compared with mild cases, levels of inflammatory cytokines including interleukin 6, tumor necrosis factor α, and interferon γ were unchanged, whereas the level of immune suppressive interleukin 10 was markedly increased in moderate cases compared with mild cases (median [IQR], 3.96 [3.34-5.29] pg/mL vs 3.58 [3.10-4.36] pg/mL; P = .048). There was no statistically significant difference in absolute number of lymphocytes (including T cells and B cells) between mild and moderate cases, but moderate cases were associated with a decrease in neutrophil levels compared with mild cases (median [IQR], 2310/µL [1680/µL-3510/µL] vs 3120/µL [2040/µL-4170/µL]; P = .01). Immunoglobin G and the neutrophil to lymphocyte ratio were negatively associated with biochemical indices related to liver and myocardial injury (immunoglobulin G, ALT: r, -0.3579; AST: r, -0.5280; CK-MB activity: r, -0.4786; LDH: r, -0.4984; and neutrophil to lymphocyte ratio, ALT: r, -0.1893; AST: r, -0.3912; CK-MB activity: r, -0.3428; LDH: r, -0.3234), while counts of lymphocytes, CD4+ T cells, and interleukin 10 showed positive associations (lymphocytes, ALT: r, 0.2055; AST: r, 0.3615; CK-MB activity: r, 0.338; LDH: r, 0.3309; CD4+ T cells, AST: r, 0.4701; CK-MB activity: r, 0.4151; LDH: r, 0.4418; interleukin 10, ALT: r, 0.2595; AST: r, 0.3386; CK-MB activity: r, 0.3948; LDH: r, 0.3794). Conclusions and Relevance: In this case series, systemic inflammation rarely occurred in pediatric patients with COVID-19, in contrast with the lymphopenia and aggravated inflammatory responses frequently observed in adults with COVID-19. Gaining a deeper understanding of the role of neutrophils, CD4+ T cells, and B cells in the pathogenesis of SARS-CoV-2 infection could be important for the clinical management of COVID-19.