Analysis of pathogen detection results of upper respiratory tract specimens from fever clinic patients

Objective: To explore the pathogen composition and distribution characteristics of pathogens in respiratory samples from patients with fever of unknown origin. Methods: A total of 96 respiratory samples of patients with unknown cause fever with respiratory symptoms were collected from four hospitals above grade II in Shijiazhuang area (Hebei Provincial Hospital of Traditional Chinese Medicine, Luancheng District People's Hospital, Luquan District People's Hospital, Shenze County Hospital) from January to April 2020, and multiplex-fluorescent polymerase chain reaction(PCR)was used to detect influenza A virus, influenza B virus, enterovirus, parainfluenza virus I/II/III/IV, respiratory adenovirus, human metapneumovirus, respiratory syncytial virus, human rhinovirus, human bocavirus, COVID-19, Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila, Pseudomonas aeruginosa, Streptococcus pneumoniae, Klebsiella pneumoniae, Group A streptococcus, Haemophilus influenzae, Staphylococcus aureus nucleic acid detection, the results were analyzed for chi-square. Results: A total of 8 pathogens were detected in the upper respiratory tract samples of 96 fever patients, including 1 kind of virus, 6 kinds of bacterias, and Mycoplasma pneumoniae. There were 12 viruses including influenza virus and parainfluenza virus, Legionella pneumophila and Chlamydia pneumoniae were not detected. The pathogen detection rates in descending order were Streptococcus pneumoniae (58/96, 60.42%), Haemophilus influenzae(38/96, 39.58%), Klebsiella pneumoniae (14/96, 14.58%), Staphylococcus aureus (10/96, 10.42%), Mycoplasma pneumoniae (8/96, 8.33%), Pseudomonas aeruginosa (6/96, 6.25%), Group A streptococcus (4/96, 4.17%) and human rhinovirus (2/96, 2.08%). The proportions of single-pathogen infection and multi-pathogen mixed infection in fever clinic patients were similar, 41.67% (40/96) and 45.83% (44/96), respectively, and 12.50% (12/96)of the cases had no pathogens detected. The infection rate of Mycoplasma pneumoniae in female patients with fever (21.43%) was higher than that in male patients with fever (2.94%) (P < 0.05). There was no statistical difference between the distribution of of other pathogens and gender and age(P > 0.05). Conclusions: The upper respiratory tract pathogens were mainly bacterial infections, and occasional human rhinovirus and Mycoplasma pneumonia infections. In clinical diagnosis and treatment, comprehensive consideration should be given to the pathogen detection.

Differences in nosocomial infections in patients on VV-ECMO for COVID-19 and influenza

Objectives: In COVID-19 associated acute respiratory distress syndrome (ARDS) requiring VV-ECMO, ventilator-associated-pneumonia (VAP), pulmonary aspergillosis and viral reactivations are observed frequently, but there is only little knowledge on incidence, onset and causative pathogens. This study analyzes frequency of VAP, pulmonary aspergillus infections, and viral reactivations in a large cohort of patients with ARDS treated with VV-ECMO due to either COVID-19 or Influenza. Method(s): Retrospective analysis of all consecutively patients at the University Hospital Regensburg requiring VVECMO due to COVID-19 (March 2020 and May 2022) or Influenza (May 2012 and December 2022). VAP was diagnosed according to current guidelines. Pulmonary Aspergillosis met criteria of probable COVID-associated Aspergillosis according to current guidelines. Result(s): 147 patients (age (median [IQR]) 55.3 [48.7 - 61.7], SOFA at VV-ECMO initiation 9 [8 - 12], 23 [14 - 38] days on VV-ECMO) suffering from COVID-19 and 72 influenza patients (age 55.3 [46 - 61.3], SOFA at VV-ECMO initiation 13 [10 - 15], 16 [10 - 23] days on VV-ECMO) were included in the analysis. Pulmonary superinfections were more frequent in COVID-19 than in influenza (VAP: 61% vs. 39%, pulmonary Aspergillosis: 33% vs. 22%, CMV reactivation: 19% vs. 4%, HSV reactivation: 49% vs. 26%.) The first episode of VAP in COVID-19 and Influenza was detected 2 days [1 - 15] after and 1 day (-3 - 22) before ECMO initiation, respectively. First VAP-episode in COVID-19 were mainly caused by Klebsiella spp. (29%,), Staphylococcus aureus (27%) and E. coli (11%). Further VAP-episodes (30% in COVID-19) and relapses of VAP were mainly caused by Klebsiella spp. (53%, 64%, respectively). In Influenza, VAP was mainly caused by Staphylococcus aureus (28%) and Streptococcus pneumoniae(28%), further VAP episodes were not observed. Conclusion(s): Superinfections were common in patients treated with VV-ECMO and occur more frequently in COVID-19 ARDS compared to Influenza. VAP occurs early and may significantly contribute to the need of VV-ECMO. Therefore, a meticulous routine microbiologic workup is advisable. The observed differences in the spectrum of secondary infectious agents in COVID19 compared to Influenza are not understood yet.

Evaluation of Microbiological Culture and Antibiogram of the Patient with Corneal Ulcer due to Exposure Keratitis in the Intensive Care Unit in Sina Farshchian Hospital (2019-2020)

Background: Since patients admitted to the intensive care unit have a compromised im-mune system and are more prone to infection than other patients, timely diagnosis and treatment of corneal ulcers among this group of patients can prevent vision loss. Therefore, it is necessary to treat eye infections and corneal ulcers promptly and economize prohibitive costs. Objective(s): Appropriate treatment with the most effective antibiotic before the answer is available to prevent corneal ulcer complications and blindness. Method(s): This study was conducted from November 2019 to November 2020 and after approval by the ethics committee of Hamedan University of Medical Sciences with the code of ethics: IR.UMSHA.REC.1398.716. First, the corneal secretions of 121 patients admitted to the intensive care unit of Sina Hospital are prepared by an ophthalmologist (after anesthetizing the cornea with tetra-caine drops and sterile swabs) and culture in four growth mediums (blood agar, chocolate agar, thio-glycolate, and EMB). Microbial cultures are examined after 48 hours and a fungal culture is examined one week later. Disc diffusions are placed in positive microbial cultures. Antibiotic susceptibility or resistance of the antibiogram was recorded. Other demographic data, including patients' age and sex, are extracted from ICU files. Also, test results and patient identifications are recorded in a checklist designed for this purpose. Result(s): Of all the antibiotics used against common bacteria, vancomycin (84%), colistin (80.43%), cefazolin (80%), and levofloxacin (60%) had the highest sensitivity and gentamicin (93.75%), ceftazidime (86.42%) Erythromycin (85%) had the highest resistance against isolated bacteria. Conclusion(s): The data obtained from this study showed that the most common microorganisms in the age group under the age of 30 years were Acinetobacter Baumannii, in the group of 30-60 years old was Klebsiella pneumonia, and age group over 61 years old was Staphylococcus aureus, and the most sensitive antibiotics in the age group under 30 years were vancomycin and levofloxacin and the age group30-60 were colistin and vancomycin and in the age group over 61 years were vancomycin and cefazolin.Copyright © 2023 Bentham Science Publishers.

Primary immunodeficiency associated with a SAMD9L mutation

Background: SAMD9L is a tumor suppressor involved in regulating the proliferation and maturation of cells, particularly those derived from the bone marrow, and appears to play an important role in cerebellar function. It can be activated in hematopoietic stem cells by type I and type II interferons. It has been hypothesized to act as a critical antiviral gatekeeper regulating interferon dependent demand driven hematopoiesis. Gain of function mutations can present with an immunodeficiency due to transient severe cytopenias during viral infection. Case presentation: We report a 3-year-old boy born full term with a history of severe thrombocytopenia requiring transfusions, developmental delay, ataxia, seizure disorder, and recurrent severe respiratory viral infections. His infectious history was significant for respiratory syncytial virus with shock requiring extracorporeal membrane oxygenation complicated by cerebral infarction and a group A streptococcus empyema, osteomyelitis requiring a left below the knee amputation, and infections with rhinovirus, COVID-19, and parainfluenza requiring hospitalizations for respiratory support. Initial immunologic evaluation was done during his hospitalization for parainfluenza. His full T cell subsets was significant for lymphopenia across all cell lines with CD3 934/microL, CD4 653/microL, CD8 227/microL, CD19 76/microL, and CD1656 61/microL. His mitogen stimulation assay to phytohemagglutinin and pokeweed was normal. Immunoglobulin panel showed a mildly decreased IgM of 25 mg/dL, but normal IgA and IgG. Vaccine titers demonstrated protective titers to 12/22 pneumococcus serotypes, varicella, diphtheria, mumps, rubella, and rubeola. Repeat full T cell subsets 6 weeks later revealed marked improvement in lymphocyte counts with CD3 3083/microL, CD4 2101/microL, CD8 839/microL, CD19 225/microL, and CD1656/microL. A primary immunodeficiency genetic panel was ordered and positive for a heterozygous SAMD9L c.1549T>C (p.Trp517Arg) mutation classified as a variant of unknown significance. Discussion(s): This patient's history of severe viral infections, ataxia, thrombocytopenia, and severe transient lymphopenia during infection is suggestive of a SAM9DL gain of function mutation. Protein modeling done by the laboratory suggests this missense mutation would affect protein structure. The mutation found has been observed in individuals with thrombocytopenia. This case highlights the importance of immunophenotyping both during acute illness and once recovered.Copyright © 2023 Elsevier Inc.

Use of Economic Evaluation of Vaccines: The Experience in Colombia, 2000 to 2021

Objectives: To describe the use of economic evaluation to update the antigens dispensed by the Colombian Expanded Program on Immunization (EPI) from 2000 and 2021. Method(s): a review of economic evaluation of vaccines (EEV) studies conducted by the Expanded Program of Immunization in Colombia between 2000 and 2021. A literature search was carried out in different databases complemented with information obtained from different stakeholders who participated in the updating process. Result(s): In 2000, sponsored by the Pan-American Health Office of the World Health Organization (PAHO/WHO), was conducted the cost-effectiveness analysis of vaccination against Hemophilus influenzae type b was the first economic evaluation of vaccines (EEV) conducted ever in Colombia. Between 2005 and 2007, 4 EEV (Rotavirus, Heptavalent Pneumococcus, Influenza and Hepatitis A) were carried out in order to inform the decision process at local level in Bogota DC, the Colombian capital. Between 2007 and 2010, the Ministry of Health sponsored 8 EEV (Rotavirus, 7- and 10-valent pneumococcus, Influenza, Hepatitis A, chickenpox, tetanus in men, and HPV) which were used to decide about the introduction of new vaccines at national level. Subsequently, with the support of PAHO's PROVAC initiative, Colombia went from having 6 EPI vaccines in the 1990s, to 21 EPI vaccines that currently protect against 29 diseases, not including the vaccines used against COVID-19 which Colombia have been using since March 2021. Conclusion(s): Colombia has been one of the middle-income countries with the highest number of vaccines included in its EPI in the last 20 years and the use of the EEV has been essential for decision-making.Copyright © 2023

Impact of COVID-19 pandemic on blood culture practices and bacteremia epidemiology.

The COVID-19 pandemic has strongly impacted healthcare settings. We assess changes in blood culture practices and results during the COVID-19 era. All blood culture vials processed between January 1, 2017, and December 31, 2020, by 3 clinical laboratories were included. A baseline period from January 1, 2017 to December 31, 2019, was compared to the year 2020. COVID-19 "waves" were defined as follows: "wave 1" from March 16 to May 10, 2020, and "wave 2" from October 29 to December 14, 2020. A mean of 143.5 and 158.6 vials per day were processed in 2019 and 2020 respectively. Up to 300 and 220 vials per day were processed during waves 1 and 2. Among positive vials, a higher rate of contaminant was noticed during wave 1 (55.9% vs 45.0%; P < 0.0001) and interwave (46.0% vs 38.6%; P < 0.0001) in comparison to previous years. The prevalence of contaminants returned to the baseline level during wave 2. Streptococcus pneumonia prevalence fell in 2020 in comparison to the baseline (0.4% vs 1.4%; P < 0.0001). The COVID-19 pandemic was associated with an increase in the number of blood culture vials processed, the rate of contaminants, and a fall in the number of pneumococcal bloodstream infections.

Changes in the Incidence of Invasive Pneumococcal Disease in Calgary, Canada, during the SARS-CoV-2 Pandemic 2020-2022.

We describe the impact of non-pharmaceutical interventions (NPIs) during the COVID-19 pandemic on invasive pneumococcal disease (IPD) in Calgary. IPD declined significantly worldwide during 2020 and 2021. This may be due to the reduced transmission of and decrease in circulating viruses that often co-infect with the opportunistic pneumococcus. Pneumococcus has not been shown to frequently co-infect or cause secondary infection with SARS-CoV-2. We examined and compared incidence rates in Calgary per quarter in the pre-vaccine, post-vaccine, 2020 and 2021 (pandemic) and 2022 (late pandemic) eras. We also conducted a time series analysis from 2000-2022 allowing for change in trend at introduction of vaccines and for initiation of NPIs during the COVID-19 pandemic. Incidence declined in 2020/2021 but by the end of 2022 had begun to rapidly recover to near pre-vaccine rates. This recovery may be related to the high rates of viral activity in the winter of 2022 along with childhood vaccines being delayed during the pandemic. However, a large proportion of the IPD caused in the last quarter of 2022 was serotype 4, which has caused outbreaks in the homeless population of Calgary in the past. Further surveillance will be important to understand IPD incidence trends in the post-pandemic landscape.

Epidemiology of Respiratory Infections during the COVID-19 Pandemic.

To face the COVID-19 outbreak, a wide range of non-pharmaceutical interventions (NPIs) aimed at limiting the spread of the virus in communities, such as mask-wearing, hand hygiene, social distancing, travel restrictions, and school closures, were introduced in most countries. Thereafter, a significant reduction of new asymptomatic and symptomatic COVID-19 cases occurred, although there were differences between countries according to the type and duration of the NPIs. In addition, the COVID-19 pandemic has been accompanied by significant variations in the global incidence of diseases due to the most common non-SARS-CoV-2 respiratory viruses and some bacteria. In this narrative review, the epidemiology of the most common non-SARS-CoV-2 respiratory infections during the COVID-19 pandemic is detailed. Moreover, factors that could have had a role in modifying the traditional circulation of respiratory pathogens are discussed. A literature analysis shows that NPIs were the most important cause of the general reduction in the incidence of influenza and respiratory syncytial virus infection in the first year of the pandemic, although the different sensitivity of each virus to NPIs, the type and duration of measures used, as well as the interference among viruses may have played a role in modulating viral circulation. Reasons for the increase in the incidences of Streptococcus pneumoniae and group A Streptococcus infections seem strictly linked to immunity debt and the role played by NPIs in reducing viral infections and limiting bacterial superimposed infections. These results highlight the importance of NPIs during pandemics, the need to monitor the circulation of infectious agents that cause diseases similar to those caused by pandemic agents, and the need to make efforts to improve coverage with available vaccines.

["When it rains, it pours" - de novo diagnosed multiple myeloma with invasive Streptococcus pneumoniae infection in severe COVID-19 complicated with cytokine storm]. / "A baj nem jár egyedül" ­ de novo diagnosztizált myeloma multiplex invazív Streptococcus pneumoniae fertozéssel citokinviharral szövodött COVID­19-ben.

With the appearance of SARS-CoV-2, the range of infections, considered the most common cause of death for people with multiple myeloma, has expanded. Although the omicron variant (PANGO B.1.1.529) of SARS-CoV-2, that dominates the world at the time of manuscript writing, is less likely to cause fatal infection in immunocompetent patients compared to the delta variant (PANGO B.1.617.2), its transmissibility did not decrease. The likelihood of a severe or critical course of COVID-19 in patients with multiple myeloma is increased by the humoral and cellular immunosuppression caused by the malignancy itself, its targeted hematological treatment, and other comorbidities associated with the disease (e.g., chronic kidney failure). Antiviral therapies, monoclonal antibody preparations used as pre- or post-exposure prophylaxis, and possibly convalescent plasma therapy, started as early as possible might prevent the clinical progression of COVID-19. While the incidence of community-acquired co-infections accompanying COVID-19 in the average population is not exceptionally high, in people with multiple myeloma, Streptococcus pneumoniae infection that follows respiratory viral diseases is approximately 150 times more likely to cause invasive disease. As a result of modern oncohematological treatment, multiple myeloma has now become a chronic disease accompanied by relapses, and those affected should be immunized against the above two pathogens. In our manuscript, we describe the case of an adult patient with severe COVID-19 complicated by cytokine storm and invasive Streptococcus pneumoniae infection who was diagnosed with de novo multiple myeloma during hospital care, and, finally, we briefly review the related literature data. Orv Hetil. 2023; 164(20): 763-769.

Pneumococcal Disease: Global Disease Prevention Strategies with a Focus on the Challenges in Iraq.

Pneumococcal disease is a global public health concern that significantly contributes to clinical disease burden and economic burden. Patients frequently afflicted are young children and older adults, as well as the immunocompromised population. Immunization is the most effective public health strategy to combat pneumococcal disease and several vaccine formulations have been developed in this regard. Although vaccines have had a significant global impact in reducing pneumococcal disease, there are several barriers to its success in Iraq. The war and conflict situation, increasing economic crises and poverty, poor vaccine accessibility in the public sector, and high vaccine costs are a few of the major obstacles that impede a successful immunization program. The last reported third dose pneumococcal conjugate vaccine coverage for Iraq was 37% in 2019, which is expected to reduce even further owing to the COVID-19 pandemic. Thus, strategies and policies to improve pneumococcal vaccine availability and coverage need to be strengthened to achieve maximum benefits of immunization. In the current review, we provide an overview of the existing knowledge on pneumococcal disease-prevention strategies across the globe. The main aim of this manuscript is to discuss the current status and challenges of pneumococcal vaccination in Iraq as well as the strategies to prevent pneumococcal infections.

Effects of pneumococcal conjugate vaccines on reducing the risk of respiratory disease associated with coronavirus infection.

Pneumococcal conjugate vaccines (PCVs) provide protection against vaccine-type pneumococcal disease in both children and adults. Growing evidence suggests that PCVs also reduce pneumonia and lower respiratory tract infections (LRTIs) more broadly, including protecting against viral-associated respiratory diseases. In this short narrative review, we highlight clinical studies investigating whether PCVs might have a role in reducing coronavirus disease, both those caused by endemic human coronaviruses (HCoVs) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). These studies include two randomized controlled trials assessing HCoV-associated pneumonia, one each in children and older adults, and two observational studies of PCV13 effectiveness against HCoV-associated LRTI and COVID-19 in adults. We discuss possible mechanisms for PCV protection including preventing viral pneumococcal co-infections and the possibility that pneumococci in the upper respiratory tract might modify the host immune response to SARS-CoV-2. Lastly, we identify knowledge gaps and further questions on the potential role of PCVs during the COVID-19 pandemic.

Rheumatologistadherence to Vaccine Recommendation in Patients with Immune-Mediated Inflammatory Diseases

Objectives: Backgroud: Patients with immune-mediated inflammatory diseases (IMID), have an increased risk of presenting infections, this arises from immunosuppression related to the disease and its treatments. Vaccination in patients with autoimmune diseases is highly recommended by various clinical practice guidelines(1). Studies in Latin America show low rates of adherence, both in patients vaccine application and doctor's recommendations. One study shows that the lack of vaccination in 43% of their patients was due to their rheumatologist not recommending it (2). This is an eye opener on the key role physicians play in the overall outcome. Objective(s): To determine the adherence rate rheumatologists have, when it comes to recommending their patients vaccinations, suggested by clinical practice guidelines. Method(s): A descriptive study was performed, with previous authorization by the research department of the Colombian rheumatology association (ASOREUMA). A survey was sent via email to all its members asking about general knowledge about the subject and percentages on recommendations in their daily practice. Result(s): The survey was sent to 214 rheumatologist members of ASOREUMA, 34 (16%) of whom responded. In clinical practice there is a universal knowledge on the vaccination requirements for patients with IMID, nevertheless just 38.2% of clinicians tell patients to vaccinate against influenza of the 80%-100% of patients they see. For pneumococcus its 26.5%, hepatitis B 20.6%, human papilloma virus 8.8%, herpes zoster 2.9%. When it comes to SARS CoV2 vaccines it's by far the most recommended with 79.4%, and most physicians consider its mechanism of action before prescribing it. In table 1 we are summarizing the primary results. Conclusion(s): Despite the fact that rheumatologists are widely aware of the indications for vaccination in patients with IMID, these recommendations are not transmitted to all patients, due to the limited care time for each patient;in addition to the fact that the vast majority consider that the health system does not allow quick and timely access to these services.

Bacterial Infectious Diseases in the Covid-19 Era

The outbreak of SARS-CoV-2 in December 2019 in China quickly spread to the rest of the world. By March 2020, the World Health Organization declared the COVID-19 pandemic, and several mitigation strategies were implemented worldwide, highlighting social distancing, quarantine and the use of face masks. Since then, many studies have reported the impact of these interventions on the occurrence of other infectious diseases, especially bacterial infectious diseases disseminated through airborne. Invasive infections with respiratory bacterial pathogens, such as Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Bordetella pertussis, Chlamydia pneumoniae and Mycoplasma pneumoniae have had a marked decline in several countries of the world. Low- and middle-income (LMIC) and high-income countries (HIC) were at different seasons of the year when COVID-19 started and interventions were implemented, but long-lasting consequences of seasonal differences are yet to be elucidated. In this session, we aim to describe the impact of COVID-19 and related intervention strategies in bacterial infectious diseases between LMIC and HIC;determine whether and how the onset of COVID-19 pandemic has changed the broader scenario of infectious diseases;and envision future and emerging infectious diseases in the post-pandemic world.Copyright © 2023

RAPID IDENTIFICATION OF ETIOLOGICAL AGENTS OF RESPIRATORY TRACT INFECTIONS DURING THE COVID-19 PANDEMIC USING THE MULTIPLEX-PCR METHOD.

Objective. Most respiratory infections have similar symptoms, so it is clinically difficult to determine their etiology. This study aimed to show the importance of molecular diagnostics in identifying the etiological agent of respiratory infections, especially during the coronavirus disease 2019 (COVID-19) pandemic. Methods. A total of 849 samples from patients hospitalized at the University Clinical Center Kragujevac (from January 1 to August 1, 2022) were examined using automated multiplex-polymerase chain reaction (PCR) tests. The BioFire-FilmArray-Respiratory Panel 2.1 test was used for 742 nasopharyngeal swabs [identification of 19 viruses (including SARS-CoV-2) and four bacteria], while the BioFire-FilmArray-Pneumonia Panel was used [identification of 18 bacteria and nine viruses] (BioMerieux, Marcy l'Etoile, France) for 107 tracheal aspirates. The tests were performed according to the manufacturer's instructions, and the results were available within an hour. Results. In 582 (78.4%) samples, the BioFire-FilmArray-Respiratory Panel 2.1 plus test identified at least one pathogen. The rhinovirus (20.6%), SARS-CoV-2 (17.7%), influenza A (17.5%), respiratory syncytial virus (12.4%), and parainfluenza 3 (10.1%) were the most common. Other viruses were found less frequently, and Bordetella parapertussis was detected in one sample. In 85 (79.4%) samples, the BioFire-FilmArray-Pneumonia Panel test identified at least one bacterium or virus. The most prevalent bacteria were Staphylococcus aureus (42.4%), Haemophilus influenzae (41.2%), Streptococcus pneumoniae (36.5%), Moraxella catarrhalis (22.3%), and Legionella pneumophila (2.4%). Among viruses, rhinovirus (36.5%), adenovirus (23.5%), influenza A (11.8%), and the genus Coronavirus (4.7%), were detected. Conclusion. Multiplex-PCR tests improved the implementation of therapeutic and epidemiological measures, preventing the spread of the COVID-19 infection and Legionnaires' disease.Copyright © 2022, Serbian Medical Society. All rights reserved.

Single center retrospective study on the distribution of pathogens in elderly patients with acute exacerbation of chronic obstructive pulmonary disease

Objective: To explore the distribution and correlation of pathogens in the elderly patients with AECOPD, so as to guide the rational use of antibiotics and hormones in clinic. Methods: A total of 111 patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) admitted to Nanjing First Hospital from January 2019 to January 2020 were retrospectively analyzed. The basic data such as eosinophil, neutrophil and lymphocyte count, the levels of C-reactive protein(CRP) and erythrocyte sedimentation rate (ESR)in blood routine examination were collected. Further, the pathogens were qualified by sputum fluorescence quantitative polymerase chain reaction, and the pathogens distribution was analyzed. Results: The level of ESR and the ratio of cardiovascular diseases showed significant differences between the pathogen-positive group and pathogen-negative group. In this study, the top five pathogens in AECOPD patients were EB virus (21.6%), Haemophilus influenzae (19.8%), Streptococcus pneumoniae (17.1%), herpes simplex virus(14.4%), influenza A virus(14.4%). The detection rate of influenza A virus was correlated with influenza B virus and Aspergillus (P < 0.05);The detection rate of respiratory syncytial virus was correlated with Candida, Moraxella catarrholis, Streptococcus pneumoniae and Haemophilus influenzae (P < 0.05);The detection rate of Escherichia coli was correlated with rhinovirus, adenovirus, Klebsiella pneumoniae and Acinetobacter baumannii (P < 0.05);The detection rate of Candida was correlated with that of Moraxella catarrholis and Pseudomonas aeruginosa(P<0.05);The detection rate of human coronavirus was correlated with Haemophilus influenzae, herpes simplex virus and Streptococcus pneumoniae(P < 0.05). Conclusions: AECOPD are mostly induced by different pathogens, especially mixed infection of bacteria and virus. It is helpful to guide the rational use of antibiotics by analyzing the etiological characteristics in the elderly patients with AECOPD.

Impact of Covid-19 and Host Factors on the Humoral Immune Repertoire in Treated Hiv

Background: People with HIV (PWH) on antiretroviral therapy (ART) appear to be at higher risk for worse COVID-19 outcomes, but the underlying mechanisms-including effects of COVID-19 and host factors on the broader humoral immune repertoire-are poorly understood. Method(s): REPRIEVE enrolled a global cohort of ART-treated PWH ages 40-75. COVID+ was defined by positive receptor binding domain IgG or IgA from annual visits 5/2020-2/2021. Antibody isotype, subclass, and Fc receptor Luminex arrays to SARS-CoV-2, CMV, EBV, HSV, HIV, influenza, pneumococcus, and RSV were assessed. Report of COVID diagnosis (collected every 4 months) was defined as mild, moderate, or severe (asymptomatic if no clinical diagnosis but IgG/ IgA+). FDR-corrected regression was used to assess effects of 1) COVID+ on non- SARS-CoV-2 repertoire in full cohort and 2) host factors on non-SARS-CoV-2 and SARS-CoV-2 repertoire in COVID- and COVID+ cohorts, respectively, adjusted for age, sex, region, nadir CD4, and HIV VL at entry. Result(s): Of 2,464 unvaccinated participants, 283 (11%) were COVID+;260 (92%) were asymptomatic. Median age was 53, 35% were women, 50% had nadir CD4 < 200, median current CD4 was 649, and 97% had HIV VL < 400. In the full cohort, COVID+ was associated with higher CMV PP65 IgG3 and FcgammaRIIA (P< 0.05);COVID severity was not associated with the non-SARS-CoV-2 repertoire. Among COVID-, older age, female sex, and lower nadir CD4 were associated with higher EBV and CMV responses;IgG1 levels were higher in women for all non-SARS-CoV-2 antigens assessed (P< 0.05). Among COVID+, higher BMI was associated with amplified SARS-CoV-2 IgG, IgA, IgM, and FcgammaRIIA responses (P< 0.05). Lower nadir CD4 was associated with a SARSCoV- 2 repertoire shift toward IgM and FcgammaRIIB (P< 0.05). Age and sex were not associated with SARS-CoV-2-related repertoire changes in COVID+. Conclusion(s): Our analysis presents a comprehensive view of host factors associated with the humoral immune repertoire among a global cohort of ART-treated PWH. COVID's association with higher CMV responses may suggest increased susceptibility to or a consequence of persistent inflammation after infection. The striking amplification of SARS-CoV-2 responses with higher BMI suggests an excessive inflammatory response. Lower nadir CD4 was related to uncontrolled extra-follicular and inhibitory SARS-CoV-2 responses, which are unlikely to be protective. These findings may suggest mechanisms underlying factors associated with worse COVID-19 outcomes among PWH. (Figure Presented).

Co-infections and antimicrobial use in hospitalized patients with moderate-severe COVID-19

Introduction/Aim: Coinfection in COVID-19 has been reported internationally, however, data on prevalence and outcomes in Australia is lacking. This study aimed to determine the prevalence and microbiology of coinfections, associated antimicrobial use, and outcomes in hospitalised patients with moderate-severe COVID-19 admitted to the Sunshine Coast University Hospital (SCUH). Method(s): A retrospective observational cohort study of adult patients admitted to the SCUH from February to July 2022 with moderate-severe COVID-19 was conducted. Demographics, comorbidities, laboratory, microbiological and radiological results, antimicrobial use, and hospital length of stay were collected. All-cause 30-day mortality and ICU admission were also collected, and incidence rate ratios (IRR) were calculated. Result(s): Sixty-six patients (57% male;median age 78.3) were captured. 13 coinfections occurred in 11 (16.7%) patients. Microbiological testing was performed in 94% of patients;respiratory viral PCR in 78.8%, blood cultures in 69.7%, sputum cultures in 25.8%, urinary antigens in 13.6% and atypical serology in 12.1%. Bacterial pathogens were most prevalent (53.8% of coinfections), whilst viral and fungal infections accounted for 30.8% and 15.4%, respectively. The most common pathogens were Streptococcus pneumoniae, Pseudomonas aeruginosa and influenza A. Most patients (74.2%) received empirical antibiotic therapy (mean = 5.5 days), with similar rates of use between those with coinfection (66.7%) and those without (75.9%). Overall patient mortality was 10.6%, with coinfections demonstrating a higher 30-day mortality (IRR = 2.0). Coinfected patients were seven times more likely to experience ICU admission (IRR = 7.5) compared to patients without coinfections. Conclusion(s): The prevalence of confirmed coinfection in hospitalised patients with moderate-severe COVID 19 was low;however, antimicrobial use was high. Importantly, patients with coinfections were twice as likely to die, and seven times more likely to be admitted to ICU. This study indicates the importance of developing improved diagnostic tools to identify coinfection and to help guide appropriate antimicrobial use.

Pneumococcal carriage among high-risk adults in a country with nonmandatory pneumococcal vaccination during the coronavirus disease 2019 pandemic.

BACKGROUND: Streptococcus pneumoniae carriage is a prerequisite for clinical infections and is used to make public health decisions on vaccine licensure. Pneumococcal carriage data among high-risk Thai adults are needed before national vaccine program introduction. The association between coronavirus disease 2019 (COVID-19) and pneumococcal carriage were also investigated. METHODS: During the COVID-19 pandemic, a multi-center cross-sectional study was conducted among high-risk Thai adults from September 2021 to November 2022. Pneumococcal carriage and serotypes were investigated using both conventional and molecular methods. Demographics and co-morbidities were determined for carriage while accounting for case clustering from various study sites. RESULTS: A total of 370 individuals were enrolled. The prevalence of pneumococcal carriage, as determined by the molecular method, was 30.8 % (95 % confidence interval (CI): 26.1-35.8), while after excluding non-typeable pneumococci from the oropharyngeal sample, the carriage prevalence was 20.8 % (95 % CI: 16.79-25.31). The serotype coverage rates by pneumococcal vaccine were 12.3 %, 13.1 %, and 16.4 % for PCV13, PCV15 or PCV20, and PPSV23, respectively, while the non-vaccine type was the majority (45.1 %). The most common serotype was 19B/C (35.5 %), followed by 6 A/B/C/D (10.7 %). The age group under 65 years was associated with a higher pneumococcal carriage rate than the age group 85 and older (odds ratio (OR): 5.01, 95 % CI: 1.75-14.36). There was no significant difference between SARS-CoV-2 and carriage status. CONCLUSIONS: The prevalence of pneumococcal carriage in Thais was high. The majority of serotypes were not covered by the vaccine. Further studies on the link between carriage serotypes and disease are required. The magnitude and serotype distribution of carriage were comparable in the SARS-CoV-2 positive and negative groups.

Randomized trial to evaluate the safety, tolerability, and immunogenicity of a booster (third dose) of BNT162b2 COVID-19 vaccine coadministered with 20-valent pneumococcal conjugate vaccine in adults ≥65 years old.

BACKGROUND: Older adults are at increased risk of adverse outcomes from pneumococcal disease and COVID-19. Vaccination is an established strategy for preventing both illnesses. This study evaluated the safety and immunogenicity of coadministration of the 20-valent pneumococcal conjugate vaccine (PCV20) and a booster (third dose) of BNT162b2 COVID-19 vaccine. METHODS: This phase 3, randomized, double-blind, multicentre study included 570 participants aged ≥65 years randomized 1:1:1 to PCV20 and BNT162b2 coadministered, or PCV20 or BNT162b2 only (administered with saline for blinding). Primary safety endpoints included local reactions, systemic events, adverse events (AEs) and serious AEs (SAEs). Secondary objectives were immunogenicity of PCV20 and BNT162b2 when administered together or separately. RESULTS: Coadministration of PCV20 and BNT162b2 was well tolerated. Local reactions and systemic events were generally mild-moderate; injection-site pain and fatigue were the most frequent local and systemic events, respectively. AE and SAE rates were low and similar across groups. No AEs led to discontinuation; no SAEs were considered vaccination-related. Robust immune responses were observed, with opsonophagocytic activity geometric mean fold rises (GMFRs; from baseline to 1 month) of 2.5-24.5 and 2.3-30.6 across PCV20 serotypes in Coadministration and PCV20-only groups, respectively. GMFRs for full-length S-binding IgG of 35.5 and 39.0, and for neutralizing titres against SARS-CoV-2-wild type virus of 58.8 and 65.4, were observed in the Coadministration and BNT162b2-only groups, respectively. CONCLUSIONS: Safety and immunogenicity of coadministered PCV20 and BNT162b2 were similar to those of PCV20 or BNT162b2 administered alone, suggesting that the 2 vaccines may be coadministered. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04887948.

An extraction-free one-step CRISPR-assisted detection platform and a potential Streptococcus pneumoniae at-home self-testing kit.

A rapid, accurate, easy-to-use nucleic acid detection technology is essential for disease diagnosis and control. Herein, we improved CRISPR-top (cluster regularly interspaced short palindromic repeats-mediated testing in one-pot) to develop Extraction-free one-step CRISPR-assistant detection (ExCad), a simple, rapid, accurate gene detection tool for unextracted colonies and samples. We established a pretreatment protocol to rapidly liquify sputum samples and release nucleic acids within 10 min. The ExCad results can be visualised by a real-time fluorescence reader or the naked eye under blue light. We developed an ExCad-Sp assay to detect Streptococcus pneumoniae from unextracted strains and specimens, and optimised the assay conditions. Assay feasibility was evaluated using sputum samples from 32 patients, and it achieved 92.9 % (13/14) sensitivity, 100 % (18/18) specificity, 100 % (13/13) positive predictive value, and 94.7 % (18/19) negative predictive value compared with bacteria culture. The ExCad-Sp assay has potential for developing an at-home self-testing kit for S. pneumoniae.