Housing and respiratory health: Exposures, health effects and interventions

Housing quality and affordability are well established as social determinants of health through direct and indirect mechanisms. Respiratory illnesses related to housing are nearly all the result of housing disrepair that allows intrusion into the home of environmental agents that are directly or indirectly associated with disease. Structural deficiencies such as leaks, cracks in the foundation or holes in the home's exterior can facilitate the presence of mould, which is causally linked to the development of asthma and is associated with exacerbation of asthma symptoms in children and adults. Indoor cleanliness can also contribute to the presence of mice and cockroaches. Proper ventilation can improve air quality, reducing exposure to PM, VOCs and infectious respiratory agents. Disparities in exposure to the housing conditions associated with respiratory disease are readily apparent across socioeconomic lines. Low-income families are less likely to be able to afford the costs of maintaining a home, which prevents them from making repairs that could improve respiratory health.Copyright © ERS 2023.

Respiratory syncytial virus: desperately seeking solutions

Respiratory syncytial virus (RSV) infection remains a major public health problem, especially in younger children and the elderly. But several monoclonal antibodies, antivirals and vaccines, either recently launched or in development, offer new hope for RSV prevention and treatment.Copyright © 2023 Wiley Interface Ltd.

Etiological structure of acute respiratory viral infections in children hospitalized in 2015-2018

Acute respiratory viral infections (ARVI) play an important role in morbidity formation among children. At the same time, studies about the ARVI etiological structure are not enough. The article presents the results of structure analyses of ARVI in children with severe and moderate degrees of disease hospitalized in the children's clinical hospital of Novosibirsk for the period 2015-2018. This research aimed to analyze the morbidity of acute respiratory viral infections with the estimation of a causal virus in children admitted to the hospital for the period 2015-2018. Material and methods. In this study, 1137 children aged between 0 and 15 years were examined. In order to determine the etiological factor in children with damage of the upper or lower respiratory tract, by using the method of RT-PCR (AmpliSensARVI-screen-FL test systems (InterLabService, Russia), mucus from the nose and throat was examined for the presence of genetic material of viruses that cause ARVI (influenza A and B viruses, parainfluenza viruses of types 1-4, respiratory syncytial virus, metapneumovirus, four types of human coronavirus, rhinovirus, adenovirus, and bocavirus). Results. The research found that the most frequently detected pathogens are respiratory syncytial virus (23.52%), influenza A and B viruses (19.73%) and rhinovirus (19.21%). Observe the dynamics some fluctuations in the detection of mentioned viral agents and increasing of mixed infections were detected. In addition, the importance of respiratory and gastrointestinal tract combined lesions, particularly for infants and preschool - age children has been noted. Conclusion. The distribution of respiratory viruses in children with severe ARVI who required hospitalization was assessed. It was shown the significance of the respiratory syncytial infection virus, influenza virus and rhinovirus in the etiological structure of hospitalized children of different ages that damage not only the respiratory tract, but also to the gastrointestinal tract. This is an important factor in optimizing the diagnosis, treatment and prevention of viral infections in children.Copyright © Infectious Diseases: News, Opinions, Training 2021.

Value of Biofire Filmarray pneumonia panel in evaluating secondary infection in critically ill patients with Coronavirus disease 2019.

Objective To explore the application value of Biofire Filmarry pneumonia panel (PN) in detection of secondary and concomitant pathogen among critically ill patients with coronavirus disease 2019(COVID-19). Methods We consecutively included and analyzed the clinical data of critically ill patients with COVID-19 transferred to the ICU from February to April 2020 in the Sino-French Campus of Wuhan Tongji Hospital. Samples of Bronchoalveolar lavage fluid obtained by bedside bronchoscopy were sent for Biofire Filmarray PN and standard culture concomitantly. We compared the results of two methods and evaluated their concordance. Results In total, 21 critically ill patients with COVID-19 were included and 54 samples were tested, including 33 (61.1%) Biofire Filmarray PN tests (21 patients) and 21 (38.9%) standard cultures (14 patients), in which 19 pairs (38 samples) underwent both tests simultaneously. In Biofire Filmarray PN group, the turnaround time was about 1 hour. There were 74 positive results in 32 samples (97.0%) from 20 patients, including 29 cases(39.2%) of Acinetobacter baumannii complex, 21 cases (28.4%) of Pseudomonas aeruginosa, 16 cases (21.6%)of Klebsiella pneumoniae, 5 cases (6.8%) of Escherichia coli, 1 case (1.4%)each of Enterobacter cloacae, Haemophilus influenzae, and respiratory syncytial virus. In the standard culture group, the turnaround time was about 3 days. 19 positive results returned in 16 (76.2%) samples from 11 patients, including 8 cases (42.1%) of Pseudomonas aeruginosa, 6 cases (31.6%) of Acinetobacter baumannii, 4 cases (21.1%) of Stenotrophomonas malt and 1 case (5.3%) of Myxobacterium. Among the 19 pairs of "back-to-back" specimens, 15 pairs were concordant, and the agreement ratio was 78.9%. Conclusions Acinetobacter baumannii and Pseudomonas aeruginosa may be the common pathogens of secondary or concomitant infection in critically ill patients with COVID-19. Biofire Filmarray PN is a rapid diagnostic test and has application value in such patients;its sensitivity and accuracy require further investigation with larger sample sizes.Copyright © 2021, Peking Union Medical College Hospital. All rights reserved.

Host Expression Profiling From Diagnostic Coronavirus Disease 2019 Swabs Associates Upper Respiratory Tract Immune Responses With Radiologic Lung Pathology and Clinical Severity.

Background: COVID-19 presents with a breadth of symptomatology including a spectrum of clinical severity requiring intensive care unit (ICU) admission. We investigated the mucosal host gene response at the time of gold standard COVID-19 diagnosis using clinical surplus RNA from upper respiratory tract swabs. Methods: Host response was evaluated by RNA-sequencing, and transcriptomic profiles of 44 unvaccinated patients including outpatients and in-patients with varying levels of oxygen supplementation were included. Additionally, chest X-rays were reviewed and scored for patients in each group. Results: Host transcriptomics revealed significant changes in the immune and inflammatory response. Patients destined for the ICU were distinguished by the significant upregulation of immune response pathways and inflammatory chemokines, including cxcl2 which has been linked to monocyte subsets associated with COVID-19 related lung damage. In order to temporally associate gene expression profiles in the upper respiratory tract at diagnosis of COVID-19 with lower respiratory tract sequalae, we correlated our findings with chest radiography scoring, showing nasopharygeal or mid-turbinate sampling can be a relevant surrogate for downstream COVID-19 pneumonia/ICU severity. Conclusions: This study demonstrates the potential and relevance for ongoing study of the mucosal site of infection of SARS-CoV-2 using a single sampling that remains standard of care in hospital settings. We highlight also the archival value of high quality clinical surplus specimens, especially with rapidly evolving COVID-19 variants and changing public health/vaccination measures.

Ventilator-associated lower respiratory tract infections: Etiology and diagnosis.

Objective. To review a literature published over the past 5 years and our own data on the etiology of lower respiratory tract infections (LRTI), antimicrobial resistance and its relationships between sepsis and choice of appropriate antibiotic therapy. Materials and methods. National Nosocomial Infections Surveillance (NNIS) criteria were used to diagnose LRTI. A review of the articles regarding LRTI from the Russian and international English language journals published over 6 years was performed. Identification of microorganisms was performed by culture over the period of 2003-2013;since 2014, MALDI-TOF MS method was used for this purpose. Results. Despite the ongoing policy to limit the use of antimicrobial therapy in the ICUs, there is an increase in carbapenemase-producing isolates in the ICUs from 2.2% (2018) to 11.7% (2020, 9 months). Along with the trend to increase in carbapenemase-producing pathogens causing LRTI, their variability is also increasing. In particular, it applies to strains producing carbapenemases OXA-48 or combination of OXA- 48 with KPC;with the trend to combined production of carbapenemase beginning at 2019. Conclusions. Carbapenemase producers are becoming more widespread in the ICU settings, including the lower respiratory tract in mechanically ventilated patients. Practitioners didn't get used to associate VAP with the Sepsis-3 criteria. The changes in etiology include the increased rate of carbapenem-resistant Enterobacterales and non-fermenting Gram-negative bacteria, primarily Acinetobacter spp., in Russia. It's due to improved quality of respiratory support and increased consumption of carbapenems, tigecycline and polymyxins. Significant increase of OXA-48-producing pathogens is likely to be associated with a poor compliance with temporary guidelines on COVID-19 with regard to antibiotic therapy.Copyright © 2021, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

Viral Identification Using Multiplex Polymerase Chain Reaction Testing Does Not Reduce Antibiotic Prescribing in Paediatric Intensive Care Units.

PCR tests for viral identification, performed on nasopharyngeal secretions, have experienced a major boom in the last few years. Their use is very frequent, but their indications are still not well defined, especially in Paediatric Intensive Care Units (PICU). These tests are used for the microbiological diagnosis of lower respiratory infections but can be used in other situations. The aim of the study was to investigate the effect of viral identification on antibiotic therapy management. We conducted a single-centre retrospective study from 1 October 2017 to 31 December 2019. This study included all consecutive FilmArray® Respiratory Panel tests performed in patients hospitalised in a PICU. Patients were identified using the microbiology laboratory prospective database and data were extracted from the medical record. 544 tests corresponding to 408 patients were included. The main reasons for testing were pneumonia (34%) and bronchiolitis (24%). In 70% of cases, at least one virus was identified, with Human Rhinovirus (56%) and Respiratory Syncytial Virus (28%) being the two predominant. Bacterial co-infection was present in 25% of cases. Viral identification was not associated with reduced antibiotic therapy. On multivariate analysis, antibiotic management was significantly associated with clinical gravity, CRP value or radiology findings regardless of virus identification. Viral identification has an epidemiological value, but antibiotic prescription relies on other factors.

Automated cough detection in COVID-19 and nonCOVID-19 pneumonia using machine learning-based technology

Background: Viral and bacterial pneumonia are characterized by exaggerated inflammation, dyspnea, and cough. We investigated cough evolution in hospitalized patients with COVID-19 and non-COVID-19 pneumonia using a novel, automated cough count detector. Material(s) and Method(s): In this observational cohort study, we used an automated, machine learning-based, contact-free, near real-time, smartphone-enabled cough counter to quantify cough in 46 patients with pneumonia in a non-ICU setting. Cough frequencies were correlated to clinical and laboratory markers of pneumonia disease activity. Result(s): We observed steady declines of cough frequencies during hospital stay in both COVID-19 and non-COVID19 pneumonia. Cough frequencies were associated with the degree of oxygenation/ oxygen supplementation (ROX index, FiO2, SpO2, breathing rate) as well as markers of inflammation (ferritin, CRP, LDH, body temperature) (Figure 1). No association with markers of multi-systemic disease (ASAT, ALAT, D-dimer) was found. Conclusion(s): Mobile technology leverages cough detection and allows for unobtrusive, long-term monitoring of patients in aerosol isolation. Results from this study suggest that cough frequency represents a surrogate marker of pneumonia disease activity. Future studies are warranted to assess cough frequency as a clinically actionable digital biomarker for lower respiratory tract infections.

Protein Energy Wasting and Clinical Outcomes of Children with Ckd2-5d- a Prospective Longitudinal Study

Introduction: Protein energy wasting (PEW) is an established entity in adults with CKD but is not well studied in children. The burden of PEW has been observed to be higher in Indian children with CKD compared to the chronic kidney disease in children (CKiD) cohort. The impact of PEW on outcomes needs to be addressed in these children with CKD. This prospective longitudinal study was undertaken in children with CKD 2-5D to assess the association of PEW with clinical outcomes of infection related hospital admissions (IRHA). Method(s): Children (age 2-18 years) with CKD 2-5D, from a tertiary care center were recruited for PEW assessment from January 2017 following ethical committee approval and informed consent. Children with evidence of infection in the last month and those on dialysis for less than a month were excluded. Demographic characteristics and clinical outcomes of hospital admissions were recorded till June 2022. Based on the CKiD study, PEW was diagnosed and categorized using 5 criteria: 1. Muscle mass (Mid arm muscle circumference);2. Body mass (body mass index);3. Biochemical parameters (serum cholesterol, serum albumin, serum transferrin, and C-reactive protein);4: Appetite and 5. Short stature. PEW was further categorized as mild (> 2 criteria), standard (> 3 criteria), and modified (> 3 criteria with short stature). Infections that needed hospitalization included viral hemorrhagic fever, COVID-19 infection, sepsis, urinary tract infection, lower respiratory tract infection, peritonitis, and catheter-related blood stream infection. Result(s): Among 136 children (45 on dialysis, mean age 122 + 46 months, 70% males) 72 (53%) had PEW. The proportions of those with mild, standard, and modified PEW were 8%, 13%, and 32% respectively. Over a mean follow-up of 38 + 21 months, 104 (76%) children required hospital admissions of which 69% were due to infections. Death was noted in 2%, and 12% got transplanted. The proportion of children needing hospital admissions was significantly higher in those with PEW compared to those without PEW (85% vs 66% respectively, p=0.011). IRHA was observed in 68% of children with PEW compared to 36% without PEW (p<0.001). The proportion of IRHA in those with dialysis with or without PEW ((87% vs 50%, p=0.001) was significantly higher compared to those with CKD 2-5 (54% vs 32%, p= 0.03). In the overall cohort, the proportion of IRHA was significantly higher with modified PEW compared to other PEW categories (p<0.001), [modified: 74.4%, standard: 58.0%, mild: 59%, no PEW: 36%]. On multivariable analysis, by adjusting for age, gender, etiology of CKD, and dialysis, the presence of PEW and dialysis status were independent factors associated with IRHA [Adjusted OR 3.58 (1.62,7.89), p=0.002] and [OR 3.29 (1.4,7.75), p=0.006, respectively]. Similarly, the presence of inflammation was independently associated with IRHA [OR 3.93 (1.49, 10.3), p=0.002]. Figure 1 shows the risk factors associated with IRHA based on PEW categories and inflammation status. [Formula presented] Conclusion(s): In children with CKD 2-5D, the presence of PEW and inflammation were significantly associated with IRHA. Children with modified PEW had nearly 5 times more risk of developing IRHA, reinforcing the importance of growth as a unique parameter of PEW in these children. No conflict of interestCopyright © 2023

The impact of passive smoking in infancy on respiratory morbidity during covid-19 pandemic: a birth-cohort study

Objective: To evaluate the role of passive smoking (PS) on the incidence of wheezing and overall respiratory morbidity in infants born during the first peak of the coronavirus (COVID-19) pandemic, compared to infants born during the preceding year. Method(s): We used data collected in our recently published retrospective birth cohort study of 588 infants, 294 in each group, born in February-March 2020 (COVID-19 group) compared to a control group born in February-March 2019 (pre-COVID-19 group), at one year of age, using parental, telephone questionnaires. The primary outcome of wheezing/bronchodilator were similarly decreased, in PS and in non-PS (NPS)1. We further, conducted a post-hoc subgroup analysis of the respiratory outcomes: recurrent wheezing, emergency-room (ER) visits, pneumonia and admissions due to lower-respiratory-tract-infections (LRTI), to account for PS exposure. Atopy, daycare attendance, breastmilk, cesarean-section, siblings and gestational age were included in logistic regression models. Result(s): Demographic, perinatal, and atopic characteristics were similar between the groups. In NPS, secondary outcomes, including wheezing (OR 0.43, 95%CI 0.24-0.76), LRTI admissions (OR 0.1, 95%CI 0.01-0.89), recurrent wheezing (OR 0.28, 95%CI 0.11-0.7), ER admissions (OR 0.32, 95%CI 0.13-0.8) and pneumonia (OR 0.16, 95%CI 0.04-0.57) showed significant decreases during the COVID-19 first year pandemic. However, in PS, we did not observe these decreases in the respiratory morbidities. Conclusion(s): This study uncovers the overwhelming hazard of PS in abolishing the effect of the first year of COVID19 pandemic lock-downs, on infant's major respiratory morbidities.

Better COVID-19 outcomes in children with good asthma control

Background: The role of pediatric asthma in susceptibility to COVID-19 is poorly defined. The aim of our study was to assess possible risk factors for severe COVID-19 in children with asthma. Method(s): In our observational study, we systematically assessed the occurrence of COVID-19 in children with asthma <18 years in a six-month period prior to their regular outpatient visit in our asthma clinic from December 1, 2020 to March 31, 2021, by using a predefined questionnaire. We compared characteristics of patients presenting with signs of SARS-CoV-2 upper (URTI) or lower respiratory tract infection (LRTI), focusing on factors that could be associated with severity of COVID-19, such as asthma phenotype, treatment with inhaled corticosteroids (ICS), asthma severity and the degree of asthma control assessed by the Asthma Control Test at the outpatient visit. Result(s): Out of 210 screened patients, 27% (57/210) reported exposure to COVID-19. Forty-two children were symptomatic after the exposure. In the symptomatic group, 64% (27/42) reported symptoms of URTI and 36% (15/42) of LRTI. We observed poorer asthma control in patients with LRTI compared to URTI (80% vs 7%, p <0.001). Moreover, patients with LRTI were older (14.6+/-3.2 years vs 12.0+/-4.1 years, p=.042), more frequently girls (60% vs 26%, p=.029), with a non-allergic asthma phenotype (43% vs 13%, p=.020). Regular ICS use and asthma severity were not associated with COVID-19 presentation in these children. However, patients on regular ICS had better asthma control (p=.026). Conclusion(s): The results of our study suggest that good asthma control, treatment adherence optimization and allergic asthma phenotype enable better COVID-19 outcomes in children with asthma.

Acute Lower Respiratory Tract Disease (aLRTD)is a complex clinical syndrome causing significant disease burden in a prospective cohort study

Background: Acute Lower Respiratory Tract Disease (aLRTD) includes pneumonia, non-pneumonic lower respiratory tract infection (NP-LRTI), heart failure (HF) and chronic respiratory disease exacerbation (CRDE). COVID19 has affected aLRTD disease burden. Few studies estimate total aLRTD burden, and subgroup distribution may have changed. Aim(s): To describe the frequency of individual aLRTD components and determine the impact of COVID19 on aLRTD disease. Method(s): A prospective cohort study of all adults >=18y admitted to either acute care hospital in Bristol, UK, from Aug 20-Jul 21. Patients were included if presenting with signs/symptoms or a clinical/radiological diagnosis of aLRTD. Result(s): 9243 aLRTD hospitalisations occurred: 5161 pneumonia, 2636 NP-LRTI, 1990 HF, 4144 CRDE, and 198 undifferentiated aLRTD cases. Overlap was common (Fig1): 31% HF and 83% CRDE events occurred in association with pneumonia or NP-LRTI. Hospitalisation rates corresponded with COVID-19 incidence over time. 41% hospitalisations were associated with positive SARS-CoV-2 test. Non-COVID19 aLRTD hospitalisations showed less variation over time. Discussion(s): aLRTD is a complex matrix with significant overlap between CRDE, HF and pneumonia/NP-LRTI. COVID19 disease in hospitalised adults was a large component of total aLRTD during this pandemic year;however, non-COVID19 aLRTD caused considerable disease burden.

Clinical characteristics and molecular epidemiology of human metapneumovirus in children with acute lower respiratory tract infections in China, 2017 to 2019: A multicentre prospective observational study.

Human metapneumovirus (HMPV) infection is one of the leading causes of hospitalization in young children with acute respiratory illness. In this study, we prospectively collected respiratory tract samples from children who were hospitalized with acute lower respiratory tract infection in six hospitals in China from 2017 to 2019. HMPV was detected in 145 out of 2733 samples (5.3%) from the hospitalized children. The majority of HMPV-positive children were under the age of two (67.6%), with a median age of one year. HMPV can independently cause acute lower respiratory tract infection in young children, while all patients showed mild clinical symptoms. Of all the co-infected patients, HMPV was most commonly detected with enterovirus (EV) or rhinovirus (RhV) (38.0%, followed by respiratory syncytial virus (RSV) (32.0%). The highest detection rate occurred from March to May in both northern and southern China. Out of 145 HMPV positive samples, 48 were successfully typed, of which 36 strains were subgrouped into subtypes A2c (75%), eight strains were included in subtype B1 (16.7%), and four strains were included in subtype B2 (8.3%). Moreover, 16 A2c strains contained 111-nucleotide duplications in the G gene. Twenty-seven complete HMPV genomes were successfully obtained, and 25 (92.6%) strains belonged to subtype A2c, whereas one strain was included in subgroup B1 and another was included in subgroup B2. A total of 277 mutations were observed in the complete genomes of 25 A2c strains. All results presented here improve our understanding of clinical characteristics and molecular epidemiology of HMPV infection in children.

The Biofire® Filmarray® Pneumonia Plus panel for management of lower respiratory tract infection in mechanically-ventilated patients in the COVID-19 era: a diagnostic and cost-benefit evaluation.

We assessed the diagnostic performance of the Biofire® Filmarray® Pneumonia Plus panel (FA-PP) compared to standard culture in Intensive Care Unit patients with suspected ventilator-associated lower respiratory tract infection in the COVID-19 era. We determined whether its implementation in routine diagnostic algorithms would be cost-beneficial from a hospital perspective. Of 163 specimens, 96 (59%) returned negative results with FA-PP and conventional culture, and 29 specimens (17.8%) were positive with both diagnostic methods and yielded concordant qualitative bacterial identification/isolation. Thirty-nine specimens (23.9%) gave discordant results (positive via FA-PP and negative via culture). Real-life adjustments of empirical antimicrobial therapy (EAT) after FA-PP results resulted in additional costs beyond EAT alone of 1868.7 €. Adequate EAT adjustments upon FA-PP results would have resulted in a saving of 6675.8 €. In conclusion, the data presented supports the potential utility of FA-PP for early EAT adjustment in patients with ventilator-associated lower respiratory tract infection.

An understanding of discordant SARS-CoV-2 test results: An examination of the data from a central Auckland laboratory

AIM: The diagnostic sensitivity of the SARS-CoV-2 real time reverse transcription polymerase chain reaction (RT-PCR) test has not been determined. This has led to a degree of uncertainty in the interpretation of results, particularly in patients tested repeatedly. The aim of this study was to explore the characteristics of patients who initially tested negative, and subsequently tested positive for SARS-CoV-2. METHOD(S): This retrospective observational study utilised data from the LabPlus Virology laboratory, Auckland City Hospital, to identify cases (hospital and community) with initial negative and subsequent positive SARS-CoV-2 RT-PCR results. Their clinical and laboratory characteristics were summarised. RESULT(S): From 1 February to 13 April a total of 20,089 samples were received for SARS-CoV-2 testing. Of 2,011 samples from patients with multiple tests, 25 samples were positive. Nine samples were from patients who initially tested negative then tested positive. Reasons for the initial negative test results, which were all from upper respiratory tract samples, included pre-symptomatic presentation or late presentation. All patients had significant risk factors and ongoing or evolving symptoms, which warranted repeat testing. CONCLUSION(S): Few patients had discordant test results for SARS-CoV-2 RT-PCR. For patients who have a significant risk factor and a negative test result, repeat testing should be performed. Copyright © 2020 New Zealand Medical Association. All rights reserved.

Characterization of Inhaled Nitric Oxide (iNO) for the treatment of Viral Community Acquired Pneumonia (CAP)

Background. Nitric Oxide (NO) has been previously demonstrated to have antimicrobial, anti-inflammatory, and vasodilator properties. Extensive work has been done in the clinical setting to explore these properties with iNO administered intermittently at high concentrations of 150-250 ppm. While viral CAP has gained major attention with the emergence of COVID-19, treatment methods remain limited and are challenging to develop. The purpose of this study is to assess iNO treatment administered to hospitalized adults with viral CAP. Methods. This is a randomized, open label multi-center ongoing study. Study population includes subjects aged 18-80, hospitalized for vCAP including COVID-19. Following enrollment, subjects were randomized 1:1 to either iNO [150ppm for 40 minutes, 4 times daily, up to 7 days in addition to standard supportive treatment (SST)], or control [SST alone]. iNO was delivered by LungFitTM, an innovative NO generator under development (Beyond Air, NY, USA). Follow up period is 180 days. Study endpoints include safety and the time to reach a stable saturation of >=93%. In addition, different other clinical parameters are collected to profile the effect of iNO in this population. Results. Analyzing the Intent To Treat (ITT) population (n=35, [16 iNO and 19 control]), safety profile of iNO treatment observed so far, was found to be favorable with no treatment related Adverse Events (AEs). Faster clinical improvement was noted in the iNO treatment group, paralleling CRP improvement between baseline to end of treatment (mean 2.7 mg/dl comparing treatment group [n=8] to control group [n=7], data not final). Conclusion. These data suggest that intermittent treatment with 150ppm iNO is safe and well tolerated and may contribute to faster clinical improvement in viral CAP. Different laboratory parameters may shed some light and help to characterize this observed effect, supporting the further exploration of iNO for the treatment of viral lower respiratory tract infection, including COVID-19.

Weakening the waves: Impact of a syndrome-based antimicrobial stewardship intervention during COVID-19

Background. Lower respiratory tract infections (LRTIs) from SARS-CoV-2 are difficult to distinguish from other viral or bacterial etiologies. This has led to increased antimicrobial use (AU) during the pandemic and concerns for concomitant rise in antimicrobial resistance (AMR). It is crucial for antimicrobial stewardship (ASP) to develop strategies to mitigate excess AU and curve AMR. We leveraged a syndrome-based ASP intervention targeting LRTIs and the use of anti-Pseudomonal beta lactams (APBL) during the COVID-19 pandemic. Methods. We incorporated COVID-19 elements into a syndrome-based prospective audit and feedback (PAF) at an urban community hospital. Elements included EMR order sets (Figure 1) that discouraged routine AU for COVID-19 and PAF targeting LRTIs and COVID-19 therapies. Empiric selection discouraging APBL was incorporated during the first COVID-19 wave. Order sets and PAF were then modified to reflect novel COVID-19 therapeutics and AU was strongly discouraged in subsequent waves. Data on AU and AMR from 2018-2022 was reviewed. Figure 1. Electronic medical records COVID-19 antimicrobial order set Results. Average quarterly AU increased during the first pandemic year by 8.7%, from 359.5 to 391 days of therapy per 1000 patient days (DOT/1000), with peaks 22.5% above the pre-pandemic average during COVID-19 surges. AU increased each COVID-19 surge, with smaller peaks each subsequent wave. DOT/1000 declined 29% from the first wave to the Omicron wave. AU decreased the second year to 318, an 18.6% decrease from the first pandemic year. Ceftriaxone use increased during surges, reflecting our LRTI guidelines (Figure 2). Peaks declined each subsequent wave, from a peak of 239 in the first wave to 75 during Omicron, a 68% decrease. The average monthly DOT/1000 for APBL decreased from 73.51 to 63.21 (Figure 3). Incidence rate of ESBL and CRE initially rose and then declined (Figure 4). Figure 2. Antimicrobial use (DOT/1000) before and during the COVID-19 pandemic Figure 4. Antipseudomonal beta lactam use before and during the COVID-19 pandemic Figure 5. Incidence of multidrug resistance organisms before and during the COVID-19 pandemic Conclusion. ASP successfully incorporated COVID-19 elements and steered AU during the pandemic. Though total AU increased, APBL use declined and AU peaks decreased with each COVID-19 wave, reflecting adherence with ASP recommendations. AMR increased during the first year and subsequently declined. ASP can play a vital role guiding AU during respiratory pandemics.