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.

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.

Consensus statement and recommendations on the treatment of COVID-19: 2021 update.

Many treatments including antiviral and non-antiviral drugs, and critical care are considered for the management of coronavirus disease 2019 (COVID-19). Practice recommendations need to be updated and graded according to the critical evaluation of rapidly emerging literature. In June 2020, Research Center for Epidemic Prevention-National Yang Ming Chiao Tung University formed a task group comprising infectious disease clinicians, pulmonologists, and intensivists with varied areas of expertise. The steering committee prioritized questions and outcomes. The keywords for the searches were COVID-19 and prone position, extracorporeal membrane oxygenation (ECMO), noninvasive positive pressure ventilation (NIPPV), remdesivir, lopinavir, hydroxychloroquine/chloroquine (HCQ/CQ), azithromycin, corticosteroid, tocilizumab, convalescent plasma therapy, and intravenous immunoglobin (IVIG). A systematic review of peer-reviewed literature was performed by the consensus panel. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used in assessing the certainty of evidence and making recommendations. The effects of COVID-19 treatments on mortality and clinical improvement were summarized in 11 tables, and GRADE was presented to define the strength and quality of evidence for recommendation. The consensus recommended that prone position implanted in COVID-19 patients with hypoxic respiratory failure (IIC), careful selection for the support of ECMO (IIB), NIPPV being feasible but a risk of staff contamination (IIC), remdesivir generally administered in mild-to-moderate COVID-19 patients (IA), the use of dexamethasone in critically ill COVID-19 patients (IA), and the use of tociliziumab in hospitalized severe/critical COVID-19 patient with elevated markers of systemic inflammation (IA). The consensus recommended against the use of lopinavir/ritonavir (IB), HCQ/CQ (IA), azithromycin (IA), convalescent plasma therapy (IA), and IVIG (IA). The inception of the consensus and task group has provided much-needed evidence of the efficacy and safety of various therapies for the management of COVID-19 patients, and make a description about the benefits and harms for most treatments.

National surveillance of antimicrobial susceptibilities to dalbavancin, telavancin, tedizolid, eravacycline, omadacycline and other comparator antibiotics and serotype distribution of invasive Streptococcus pneumoniae isolates in adults: results from the Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART) programme in 2017-2020.

OBJECTIVES: The aim of this study was to investigate the trends in serotypes and in vitro antimicrobial susceptibility of Streptococcus pneumoniae causing adult invasive pneumococcal disease (IPD) to dalbavancin, telavancin, tedizolid, eravacycline, omadacycline and other comparator antibiotics from 2017-2020 following implementation of the 13-valent pneumococcal conjugate vaccine (PCV-13) and during the COVID-19 (coronavirus disease 2019) pandemic. METHODS: During the study period, 237 S. pneumoniae isolates were collected from non-duplicate patients, covering 15.0% of IPD cases in Taiwan. Antimicrobial susceptibility testing was performed using a Sensititre® system. A latex agglutination method (ImmuLex™ Pneumotest Kit) was used to determine serotypes. RESULTS: Susceptibility rates were high for vancomycin (100%), teicoplanin (100%) and linezolid (100%), followed by ceftaroline (non-meningitis) (98.3%), moxifloxacin (94.9%) and quinupristin/dalfopristin (89.9%). MIC50 and MIC90 values of dalbavancin, telavancin, tedizolid, eravacycline and omadacycline were generally low. Non-vaccine serotype 23A was the leading cause of IPD across the adult age range. Isolates of serotype 15B were slightly fewer than those of PCV-13 serotypes in patients aged ≥65 years. The overall case fatality rate was 15.2% (36/237) but was especially high for non-PCV-13 serotype 15B (21.4%; 3/14). Vaccine coverage was 44.7% for PCV-13 and 49.4% for the 23-valent pneumococcal polysaccharide vaccine (PPSV-23), but was 57% for both PCV-13 and PPSV-23. CONCLUSION: The incidence of IPD was stationary after PCV-13 introduction and only dramatically decreased in the COVID-19 pandemic in 2020. The MIC50 and MIC90 values of dalbavancin, telavancin, tedizolid, eravacycline, omadacycline were generally low for S. pneumoniae causing adult IPD.

The epidemiology and etiologies of respiratory tract infection in Northern Taiwan during the early phase of coronavirus disease 2019 (COVID-19) outbreak.

BACKGROUND: Coronavirus disease 2019 (COVID-19) manifests symptoms as common etiologies of respiratory tract infections (RTIs). During the pandemic of COVID-19, identifying the etiologies correctly from patients with RTI symptoms was crucial in not only disease control but preventing healthcare system from collapsing. By applying sensitive PCR-based molecular assays, we detected the etiologic agents and delineated the epidemiologic picture of RTIs in the early phase of COVID-19 pandemic. METHODS: From December 2019 to February 2020, we screened patients presented with RTIs using multiplex PCR-based diagnostic assays. Data from pediatric and adult patients were compared with different months and units in the hospital. RESULTS: Of all 1631 patients including 1445 adult and 186 pediatric patients screened, 8 viruses and 4 bacteria were identified. Positive rates were 25% in December, 37% in January, and 20% in February, with pediatric patients having higher positive rates than adults (Ps < 0.001). In pediatric patients, RhV/EnV was the most commonly detected, followed by parainfluenza viruses. Most Mycoplasma pneumoniae infection occurred in pediatric patients. RhV/EnV was the most commonly detected agent in pediatric patients admitted to intensive care units (ICUs), while influenza accounted for the majority of adult cases with critical illness. Noticeably, seasonal coronavirus ranked second in both adult and pediatric patients with ICU admission. CONCLUSION: While we focused on the pandemic of COVID-19, common etiologies still accounted for the majority of RTIs and lead to severe diseases, including other seasonal coronaviruses.

Nationwide surveillance of antimicrobial resistance in invasive isolates of Streptococcus pneumoniae in Taiwan from 2017 to 2019.

BACKGROUND/PURPOSE: Streptococcus pneumoniae causes pneumonia and other invasive diseases, and is a leading cause of mortality in the elderly population. The present study aimed to provide current antimicrobial resistance and epidemiological profiles of S. pneumoniae infections in Taiwan. METHODS: A total of 252 nonduplicate S. pneumoniae isolates were collected from patients admitted to 16 hospitals in Taiwan between January 2017 and December 2019, and were analyzed. The minimum inhibitory concentration of antibiotics was determined using the Vitek 2 automated system for antimicrobial susceptibility testing. Furthermore, epidemiological profiles of S. pneumoniae infections were analyzed. RESULTS: Among the strains analyzed, 88% were recognized as invasive pneumococcal strains. According to the Clinical and Laboratory Standards Institute criteria for non-meningitis, the prevalence of penicillin-non-susceptible S. pneumoniae demonstrated a declining trend from 43.6% in 2017 to 17.2% in 2019. However, the rate of penicillin-non-susceptible S. pneumoniae was 85.7% based on the criteria for meningitis. Furthermore, the prevalence of ceftriaxone-non-susceptible S. pneumoniae was 62.7% based on the criteria for meningitis. Isolates demonstrated higher susceptibility toward doripenem and ertapenem than toward meropenem and imipenem. An increased rate of non-susceptibility toward levofloxacin was observed in southern Taiwan (15.1%) and elderly patients (≥65 years; 11.4%). Most isolates were susceptible to vancomycin and linezolid. CONCLUSION: Empirical treatment with ceftriaxone monotherapy for pneumococcal meningitis should be carefully monitored owing to its high non-susceptibility rate. The susceptibility rates of most isolates to penicillin (used for treating non-meningitis pneumococcal diseases), carbapenems (ertapenem and doripenem), respiratory quinolones (moxifloxacin and levofloxacin), vancomycin, and linezolid suggested the potential of these antibiotics in treating pneumococcal diseases in Taiwan.

Clinical manifestation and disease progression in COVID-19 infection.

Coronavirus disease 2019 (COVID-19) is mainly an infectious disease of the respiratory system transmitted through air droplets, and pulmonary symptoms constitute main presentations of this disease. However, COVID-19 demonstrates a clinically diverse manifestation ranging from asymptomatic presentation to critically illness with severe pneumonia, acute respiratory distress syndrome, respiratory failure, or multiple organ failure. Accumulating evidences demonstrated that COVID-19 has extrapulmonary involvement, including neurological, smelling sensation, cardiovascular, digestive, hepatobiliary, renal, endocrinologic, dermatologic system, and others. Over a third of COVID-19 patients manifest a wide range of neurological symptoms involving the central/peripheral nervous system. Underlying cardiovascular comorbidities were associated with detrimental outcomes, meanwhile the occurrence of cardiovascular complications correlate to poor survival. Gastrointestinal symptoms frequently occur and have been associated with a longer period of illness. Impaired hepatic functions were associated with the severity of the disease. Higher rate of acute kidney injury was reported in critically ill patients with COVID-19. Endocrinologic presentations of COVID-19 include exacerbating hyperglycemia, euglycemic ketosis, and diabetic ketoacidosis. The most common cutaneous manifestation was acro-cutaneous (pernio or chilblain-like) lesions, and other skin lesions consist of maculopapular rash, vesicular lesions, livedoid/necrotic lesions, exanthematous rashes, and petechiae. This review article summarized the general clinical signs and symptoms, radiologic features, and disease manifestation with progression in patients with COVID-19.

The precaution strategy toward the COVID-19 pandemic in the operating room of a tertiary hospital in Taiwan.

BACKGROUND: The pandemic of SARS-CoV-2 (COVID-19), which began in December 2019, spread mostly from person to person through respiratory droplets. A recommendation was issued to postpone all elective surgical practices. However, some confirmed or suspected COVID-19 patients required life-saving emergent surgeries. METHODS: To facilitate emergent surgical interventions for these patients, we have reviewed the current literature and established an algorithm of precautions to be taken by operating room team members during the COVID-19 pandemic. RESULTS: The initial algorithm of preparation for surgical intervention during the COVID-19 pandemic was relatively simple. However, the abrupt increase of confirmed COVID-19 cases due to returned overseas travelers since mid-March 2020 disrupted the routine hospital clinical service. Due to the large number of febrile patients, the algorithm was therefore revised according to travel history, occupation, contact and cluster history (TOCC), unexplained fever/symptoms, and emergent/nonemergent surgery. TOCC (+) patients presenting with otherwise unexplained fever/symptoms would be regarded as belonging to the fifth category of "severe special infectious pneumonia." If the patient requires emergent surgery to relieve the non-life-threatening disorders, two times of negative COVID-19 tests are necessary before the operation is approved. For life-threatening situations without two negative results of COVID-19 tests, the operation schedule should be approved by the Chairman of Surgery Management Committee. CONCLUSION: The application of a clear and integrated algorithm for operating room team members aids in effective personal protective equipment facilitation to keep both healthcare providers and patients safe as well as to prevent hospital-based transmission of COVID-19.

The clinical manifestations and interval changes of reverse-transcriptase quantitative polymerase chain reactions among different specimens of coronavirus disease 2019 patients.

BACKGROUND: Since December 2019, a number of cases and deaths due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have been reported worldwide. In spite of clinical manifestations similar to the SARS-CoV epidemic in 2003, affected organs and severity are yet to be defined. Moreover, viral load alterations and viral shielding among different specimens remained scarce. Therefore, clarifying clinical presentations and correlations among viral loads, disease severity, and viral shielding of SARS-CoV-2 infection is crucial in the disease prevention. METHODS: The clinical courses of SARS-CoV-2 cases were presented through Gantt charts. Laboratory examinations and reverse-transcriptase quantitative polymerase chain reactions (RT-qPCR) among different specimens were tested periodically. Cycle thresholds (CT) were recorded and presented as viral loads. RESULTS: From March 2020 to April 2020, 4 SARS-CoV-2 cases were presented, of which, cases 1 and 2 manifested the symptoms severer than cases 3 and 4, along with higher serum lactate dehydrogenase levels and graded for lymphocytopenia. Case 4 initially exhibited anosmia but recovered within a short period. Curves of the CT of all the cases, except case 2, concaved upward after prescribing hydroxychloroquine (HCQ) and azithromycin. Except for case 4, the CT in most stool specimens remained undetectable; however, none of the cases presented gastrointestinal symptoms. Surprisingly, the CT values of the saliva specimens were inconsistent with those of the nasopharyngeal swabs and sputum. CONCLUSION: SARS-CoV-2 manifests various symptoms. Sudden onset of central nervous system symptoms should be considered. The timing of HCQ and azithromycin administration might be a key factor in the viral load reduction. Positive prediction values of RT-qPCR of different specimens should be tested carefully to prevent false-negative results.

Highlight of severe acute respiratory syndrome coronavirus-2 vaccine development against COVID-19 pandemic.

The pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has brought an unprecedented impact upon the global economy and public health. Although the SARS-CoV-2 virology has been gradually investigated, measures to combat this new threat in public health are still absent. To date, no certificated drug or vaccine has been developed for the treatment or prevention of coronavirus disease Extensive researches and international coordination has been conducted to rapidly develop novel vaccines against SARS-CoV-2 pandemic. Several major breakthroughs have been made through the identification of the genetic sequence and structural/non-structural proteins of SARS-CoV-2, which enabled the development of RNA-, DNA-based vaccines, subunit vaccines, and attenuated viral vaccines. In this review article, we present an overview of the recent advances of SARS-CoV-2 vaccines and the challenges that may be encountered in the development process, highlighting the advantages and disadvantages of these approaches that may help in effectively countering COVID-19.

Rapid establishment of a COVID-19 biobank in NHRI by National Biobank Consortium of Taiwan.

By the request of the Minister of Health and Welfare, NHRI Biobank was assigned to establish a COVID-19 biobank in early Feb, 2020 to collect COVID-19 patients' blood samples for Taiwan researchers and industries in an emergent way. It was set up in less than 3 weeks and quickly opened for application. By August 5, 2020, this COVID-19 biobank has collected 165 blood samples of 110 patients from more than 10 hospitals across north, middle and south part of Taiwan, including both COVID-19 (+) and (-) pneumonia patients. This biobank can provide applicants with biosamples, such as serum, DNA and RNA, and also the clinical and genomic data, so as to accelerate the COVID-19 treatment and prevention research in Taiwan. This COID-19 biobank already received 15 applications. It has become the most important research resource for the COVID-19 pandemic in Taiwan, including new screening reagents, disease mechanism, the variable human responses and epidemic preventions. Since it is publicly available for both academic and industrial applicants.