scholarly journals An algorithmic approach to the use of rapid molecular diagnostics for SARS-CoV-2, influenza viruses, and other respiratory pathogens during an unprecedented respiratory season

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S130-S130
Author(s):  
A S Maris ◽  
L Tao ◽  
C W Stratton ◽  
R M Humphries ◽  
J E Schmitz

Abstract Introduction/Objective The COVID-19 pandemic exacerbated deficiencies of testing personnel, reagents, supplies and disposables, instruments, and automation in many clinical laboratories. Upon entering respiratory season, a strategy was warranted to optimize laboratory resources when supplies were already limited and expected respiratory season test volume was unknown. An algorithm was devised to prioritize test ordering and TAT based on patient clinical scenario. Methods/Case Report The institutional respiratory season SARS-CoV-2 algorithm was constructed by a multidisciplinary team including infectious disease, infection prevention, laboratory, and IT/LIS leadership. CDC guidance on influenza testing was incorporated. Antigen-based testing was discontinued; only molecular amplification- based platforms with FDA EUA were utilized. Platforms had a range of TAT (20 minutes to 8 hours) and included fully- automated high throughput, rapid random access, point-of-care, and CDC SARS-CoV-2 assays. Test bundles included SARS-CoV-2 (monoplex), or SARS-CoV-2 + fluA&B (triplex), or SARS-CoV-2 + respiratory pathogen panel (multiplex RPP; includes 22 targets, including flu A&B). Results (if a Case Study enter NA) Key factors in the algorithm included whether the patient was outpatient or inpatient, hospital employee or not, symptomatic or not, immunocompetent or immunocompromised, and whether a concurrent order for other respiratory pathogens was included or not. Clinician responses for these factors determined the type of swab collected (wet swab in VTM or dry swab) and how quickly the TAT was indicated for a given patient using a colored-dot sticker system. Priority TAT in decreasing order was symptomatic inpatients, asymptomatic pre- procedure patients, asymptomatic admissions, symptomatic employees, and symptomatic outpatients. Conclusion An algorithm for respiratory pathogen testing during an unprecedented respiratory season prioritizes result TAT to an individual patient’s clinical situation while maximizing laboratory stewardship by eliminating redundant influenza testing and requiring ‘all upfront’ orders to avoid add-on orders that require ‘dumpster diving’ for samples. Limitations include inherent differences in sensitivity, LOD, and specificity when multiple different platforms are utilized to detect the same analytes.

2021 ◽  
Author(s):  
Gibran Horemheb-Rubio ◽  
Ralf Eggeling ◽  
Norbert Schmeisser ◽  
Nico Pfeifer ◽  
Thomas Lengauer ◽  
...  

Abstract Background: Lower respiratory tract infections are among the main causes of death. Although there are many respiratory viruses, diagnostic efforts are focused mainly on influenza. The Respiratory Viruses Network (RespVir) collects infection data, primarily from German university hospitals, for a high diversity of infections by respiratory pathogens. In this study, we computationally analysed a subset of the RespVir database, covering 217,150 samples tested for 17 different viral pathogens in the time span from 2010 to 2019. Methods: We calculated the prevalence of 17 respiratory viruses, analysed their seasonality patterns using information-theoretic measures and agglomerative clustering, and analysed their propensity for dual infection using a new metric dubbed average coinfection exclusion score (ACES). Results: After initial data pre-processing, we retained 206,814 samples, corresponding to 1,408,657 performed tests. We found that Influenza viruses were reported for less than half of all infections and that they exhibited the highest degree of seasonality Coinfections of viruses are frequent, the most prevalent coinfection was rhinovirus/bocavirus and most of the virus pairs had a positive ACES indicating a tendency to exclude each other regarding infection. Conclusions: The analysis of respiratory viruses dynamics in monoinfection and coinfection contributes to the prevention, diagnostic, treatment, and development of new therapeutics. Data obtained from multiplex testing is fundamental for this analysis and should be prioritized over single pathogen testing.


2020 ◽  
Author(s):  
Natalie C. Marshall ◽  
Ruwandi M. Kariyawasam ◽  
Nathan Zelyas ◽  
Mathew A. Diggle

Abstract Background: SARS-CoV-2 infection can present with a broad clinical differential that includes many other respiratory viruses; therefore, accurate tests are crucial to distinguish true COVID-19 cases from pathogens that do not require urgent public health interventions. Co-circulation of other respiratory viruses is largely unknown during the COVID-19 pandemic but would inform strategies to rapidly and accurately test patients with respiratory symptoms.Methods: This study retrospectively examined 298,415 respiratory specimens collected from symptomatic patients for SARS-CoV-2 testing in the three months since COVID-19 was initially documented in the province of Alberta, Canada. By focusing on 52,285 specimens that were also tested with the Luminex Respiratory Pathogen Panel for 17 other pathogens, this study examines the prevalence of 18 potentially co-circulating pathogens and their relative rates in prior years versus since COVID-19 emerged, including four endemic coronaviruses. Results: SARS-CoV-2 was identified in 2.2% of specimens. Parallel broad multiplex testing detected additional pathogens in only 3.4% of these specimens: significantly less than in SARS-CoV-2-negative specimens (p < 0.0001), suggesting very low rates of SARS-CoV-2 co-infection. Furthermore, the overall co-infection rate was significantly lower among specimens with SARS-CoV-2 detected (p < 0.0001). Finally, less than 0.005% of all specimens tested positive for both SARS-CoV-2 and any of the four endemic coronaviruses tested, strongly suggesting neither co-infection nor cross-reactivity between these coronaviruses. Conclusions: Broad respiratory pathogen testing rarely detected additional pathogens in SARS-CoV-2-positive specimens. While helpful to understand co-circulation of respiratory viruses causing similar symptoms as COVID-19, ultimately these broad tests were resource-intensive and inflexible in a time when clinical laboratories face unprecedented demand for respiratory virus testing, with further increases expected during influenza season. A transition from broad, multiplex tests toward streamlined diagnostic algorithms targeting respiratory pathogens of public health concern could simultaneously reduce the overall burden on clinical laboratories while prioritizing testing of pathogens of public health importance. This is particularly valuable with ongoing strains on testing resources, exacerbated during influenza seasons.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Natalie C. Marshall ◽  
Ruwandi M. Kariyawasam ◽  
Nathan Zelyas ◽  
Jamil N. Kanji ◽  
Mathew A. Diggle

Abstract Background SARS-CoV-2 infection can present with a broad clinical differential that includes many other respiratory viruses; therefore, accurate tests are crucial to distinguish true COVID-19 cases from pathogens that do not require urgent public health interventions. Co-circulation of other respiratory viruses is largely unknown during the COVID-19 pandemic but would inform strategies to rapidly and accurately test patients with respiratory symptoms. Methods This study retrospectively examined 298,415 respiratory specimens collected from symptomatic patients for SARS-CoV-2 testing in the three months since COVID-19 was initially documented in the province of Alberta, Canada (March-May, 2020). By focusing on 52,285 specimens that were also tested with the Luminex Respiratory Pathogen Panel for 17 other pathogens, this study examines the prevalence of 18 potentially co-circulating pathogens and their relative rates in prior years versus since COVID-19 emerged, including four endemic coronaviruses. Results SARS-CoV-2 was identified in 2.2% of all specimens. Parallel broad multiplex testing detected additional pathogens in only 3.4% of these SARS-CoV-2-positive specimens: significantly less than in SARS-CoV-2-negative specimens (p < 0.0001), suggesting very low rates of SARS-CoV-2 co-infection. Furthermore, the overall co-infection rate was significantly lower among specimens with SARS-CoV-2 detected (p < 0.0001). Finally, less than 0.005% of all specimens tested positive for both SARS-CoV-2 and any of the four endemic coronaviruses tested, strongly suggesting neither co-infection nor cross-reactivity between these coronaviruses. Conclusions Broad respiratory pathogen testing rarely detected additional pathogens in SARS-CoV-2-positive specimens. While helpful to understand co-circulation of respiratory viruses causing similar symptoms as COVID-19, ultimately these broad tests were resource-intensive and inflexible in a time when clinical laboratories face unprecedented demand for respiratory virus testing, with further increases expected during influenza season. A transition from broad, multiplex tests toward streamlined diagnostic algorithms targeting respiratory pathogens of public health concern could simultaneously reduce the overall burden on clinical laboratories while prioritizing testing of pathogens of public health importance. This is particularly valuable with ongoing strains on testing resources, exacerbated during influenza seasons.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
K. H. Chan ◽  
K. K. W. To ◽  
P. T. W. Li ◽  
T. L. Wong ◽  
R. Zhang ◽  
...  

This study evaluated a new multiplex kit, Luminex NxTAG Respiratory Pathogen Panel, for respiratory pathogens and compared it with xTAG RVP Fast v2 and FilmArray Respiratory Panel using nasopharyngeal aspirate specimens and culture isolates of different swine/avian-origin influenza A subtypes (H2N2, H5N1, H7N9, H5N6, and H9N2). NxTAG RPP gave sensitivity of 95.2%, specificity of 99.6%, PPV of 93.5%, and NPV of 99.7%. NxTAG RPP, xTAG RVP, and FilmArray RP had highly concordant performance among each other for the detection of respiratory pathogens. The mean analytic sensitivity (TCID50/ml) of NxTAG RPP, xTAG RVP, and FilmArray RP for detection of swine/avian-origin influenza A subtype isolates was 0.7, 41.8, and 0.8, respectively. All three multiplex assays correctly typed and genotyped the influenza viruses, except for NxTAG RRP that could not distinguish H3N2 from H3N2v. Further investigation should be performed if H3N2v is suspected to be the cause of disease. Sensitive and specific laboratory diagnosis of all influenza A viruses subtypes is especially essential in certain epidemic regions, such as Southeast Asia. The results of this study should help clinical laboratory professionals to be aware of the different performances of commercially available molecular multiplex RT-PCR assays that are commonly adopted in many clinical diagnostic laboratories.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Van-Thuan Hoang ◽  
Saliha Ali-Salem ◽  
Khadidja Belhouchat ◽  
Mohammed Meftah ◽  
Doudou Sow ◽  
...  

AbstractRespiratory tract infections (RTIs) are common among Hajj pilgrims, but risk factors for RTIs and respiratory pathogen acquisition during the Hajj are not clearly identified. Based on previous studies, most frequent pathogens acquired by Hajj pilgrims were investigated: rhinovirus, human coronaviruses, influenza viruses, Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae and Haemophilus influenzae. 485 pilgrims were included. 82.1% presented with RTIs. Respiratory chronic diseases were associated with cough, Influenza-like illness (ILI) and the acquisition of H. influenzae. Vaccination against invasive pneumococcal diseases (IPD) and influenza was associated with a decrease in the acquisition of S. pneumoniae and prevalence of ILI (aRR = 0.53, 95%CI [0.39–0.73] and aRR = 0.69, 95%CI [0.52–0.92] respectively). Individuals carrying rhinovirus and H. influenzae-S. pneumoniae together were respectively twice and five times more likely to have respiratory symptoms. Individual with H. influenzae-K. pneumoniae carriage were twice (p = 0.04) as likely to develop a cough. The use of disposable handkerchiefs was associated with a decrease in the acquisition of S. aureus (aRR = 0.75, 95%CI [0.57–0.97]). Results could be used to identify pilgrims at increased risk of RTIs and acquisition of respiratory pathogens. Results also confirm the effectiveness of influenza and IPD vaccinations in reducing ILI symptoms and acquisition of S. pneumoniae carriage respectively.


Author(s):  
Maria K. Smatti ◽  
Hamad E. Al-Romaihi ◽  
Hebah A. Al-Khatib ◽  
Peter V. Coyle ◽  
Asmaa A Al Thani ◽  
...  

Background: Acute respiratory infections (ARIs) lead to high rates of mortality and morbidity among children. However, studies on the etiology of respiratory infections among children in Qatar and surrounding countries are still limited. Objectives: To describe the prevalence and seasonality of RSV, influenza, and other respiratory pathogens among children in Qatar. Methods: We retrospectively collected data of 33,404 patients <15 years old presented with Influenza-like illness (ILI) from 2012 to 2017. All samples were tested for influenza viruses, while 30,946 were tested for a complete panel of 21 respiratory pathogens. Results: At least one respiratory pathogen was detected in 26,138 (78%) of patients. Together, human rhinoviruses (HRV), respiratory syncytial virus (RSV), and influenza viruses comprised nearly two-thirds of all ILI cases, detected in 24%, 19.7%, and 18.5%, respectively. A detection rate of 5-10% was recorded for adenovirus, human parainfluenza viruses (HPIVs), bocavirus (HboV), and human coronaviruses (HCoVs). Other pathogens such as human metapneumovirus (HMPV), enteroviruses, mycoplasma pneumonia, and parechovirus had prevalence rates below 5%. ILI positive cases were detected throughout the year. RSV, influenza, HMPV exhibited strong seasonal activity in the winter, while HRV was primarily active during low RSV and influenza activity. The burden of RSV exceeds that of influenza among young age groups (<5 years), affecting 17-30% of ILI cases. Prevalence of influenza, on the other hand, correlated positively with age, ranging from 23% to 32% in age groups above five years. Further, male patients had higher rates of HRV (26%) and adenovirus (9%), whereas females showed a higher prevalence of influenza (22%), and RSV (20%) infections. Conclusion: This comprehensive report provides insights into the etiology of ILI among children in Qatar, which represents the Gulf region. Our results reinforce the significance of active surveillance of respiratory pathogens to improve infection prevention and control strategies, particularly among children.


Author(s):  
Katharine Uhteg ◽  
Adannaya Amadi ◽  
Michael Forman ◽  
Heba H Mostafa

Abstract Background Our understanding of the co-circulation of infrequently targeted respiratory pathogens and their contribution to symptoms during the COVID-19 pandemic is currently limited. This research aims at 1) understanding the epidemiology of respiratory pathogens since the start of the pandemic, 2) assessing the contribution of non-SARS-CoV-2/influenza/RSV respiratory pathogens to symptoms, and 3) evaluating coinfection rates in SARS-CoV-2 positive patients, both vaccinated and unvaccinated. Methods Retrospective analysis of respiratory pathogens identified by the Johns Hopkins Diagnostic Laboratory between December 2019 and October 2021 was performed. In addition, we assessed the contribution of respiratory pathogens other than SARS-CoV-2 to symptomatic disease by re-testing two cohorts of specimens that were 1) collected from symptomatic patients and 2) received limited respiratory pathogen testing. The first cohort was patients tested negative by the standard of care SARS-CoV-2/influenza/RSV testing. The second was a cohort of SARS-CoV-2 positive symptomatic fully COVID-19 immunized and unimmunized patients. Results Between December 2019 and October 2021, a total of 11,806, 62,829, and 579,666 specimens were tested for an extended respiratory panel, influenza/RSV/with or without SARS-CoV-2 panel, or SARS-CoV-2, respectively. Positivity rates of different targets differed between different months and were impacted by the COVID-19 pandemic. The SARS-CoV-2 negative cohort had 8.5% positivity for other respiratory pathogens that included primarily enterovirus/rhinovirus (5.8%). In the SARS-CoV-2 positive cohort, no other respiratory pathogens were detected. Conclusions The COVID-19 pandemic impacted the circulation of certain respiratory pathogens. Other respiratory viral pathogens were associated with symptomatic infections; however, coinfections with SARS-CoV-2 were highly uncommon.


2019 ◽  
Author(s):  
Van-Thuan Hoang ◽  
Thi-Loi Dao ◽  
Tran Duc Anh Ly ◽  
Khadidja Belhouchat ◽  
Kamel Larbi Chaht ◽  
...  

AbstractRespiratory tract infections are frequent among Hajj pilgrims. We conducted this study to describe the dynamics of the acquisition of respiratory pathogens, their potential interactions and risk factors for possible lower respiratory tract infection symptoms (LRTI) among French pilgrims during the 2018 Hajj. Pilgrims from Marseille who were participating in the Hajj were recruited. Each participant underwent four successive systematic nasopharyngeal swabs before and during their stay in Saudi Arabia. Carriage of the main respiratory pathogens was assessed by PCR. 121 pilgrims were included and 93.4% reported respiratory symptoms during the study period. Polymicrobial carriage was observed in 73.8% samples. The acquisition of rhinovirus, coronaviruses and Staphylococcus aureus occurred soon after arrival in Saudi Arabia and rates decreased gradually after days 5 and 6. In contrast, Streptococcus pneumoniae and Klebsiella pneumoniae carriage increased progressively until the end of the stay in Saudi Arabia. Haemophilus influenzae and Moraxella catarrhalis carriage increased starting around days 12 and 13, following an initial clearance. Influenza viruses were rarely isolated. We observed an independent positive mutual association between S. aureus and rhinovirus carriage and between H. influenzae and M. catarrhalis carriage. Dual carriage of H. influenzae and M. catarrhalis was strongly associated with S. pneumoniae carriage (OR = 6.22, 95%CI [2.04-19.01]). Finally, our model showed that M. catarrhalis carriage was negatively associated with K. pneumoniae carriage. Chronic respiratory disease was associated with symptoms of LRTI. K. pneumoniae, M. catarrhalis-S. aureus and H. influenzae-rhinovirus dual carriage was associated with LRTI symptoms. Our data suggest that RTIs at the Hajj are a result of complex interactions between a number of respiratory viruses and bacteria.Author summaryDespite the recommendation to take individual preventive measures to prevent respiratory tract infections, these infections remain common among Hajj pilgrims. Respiratory pathogens acquired during the Hajj are usually studied individually, although in their natural environment they often compete or coexist with multiple microbial species. A better understanding of polymicrobial interactions in the nasopharynx among Hajj pilgrims is important. Our study describes the dynamics of the acquisition of respiratory pathogens and their potential interactions among pilgrims during the Hajj. We found that polymicrobial carriage was observed in most individuals and that some pathogens associated positively while other did not. Some pathogen associations correlated with symptoms of lower respiratory tract infections.


2016 ◽  
Vol 54 (12) ◽  
pp. 2950-2955 ◽  
Author(s):  
Daniel A. Green ◽  
Letiana Hitoaliaj ◽  
Brian Kotansky ◽  
Sheldon M. Campbell ◽  
David R. Peaper

Multiplex tests for respiratory tract infections include up to 20 targets for common pathogens, predominantly viruses. A specific therapeutic intervention is available for individuals testing positive for influenza viruses (oseltamivir), and it is potentially beneficial to identify non-influenza viruses to avoid unnecessary antibiotic use. We evaluated antimicrobial prescriptions following respiratory pathogen testing among outpatients at a large Veterans Administration (VA) medical center. Results of the FilmArray respiratory panel (BioFire, Salt Lake City, UT) from 15 December 2014 to 15 April 2015 were evaluated among 408 outpatients, and patient medical records were reviewed. Differences in antibiotic and oseltamivir prescription rates were analyzed. Among 408 patients tested in outpatient centers (emergency departments, urgent care clinics, and outpatient clinics), 295 (72.3%) were managed as outpatients. Among these 295 outpatients, 105 (35.6%) tested positive for influenza virus, 109 (36.9%) tested positive for a non-influenza virus pathogen, and 81 (27.5%) had no respiratory pathogen detected. Rates of oseltamivir and antibiotic prescriptions were significantly different among the three test groups (chi-squared values of 167.6 [ P < 0.0001] and 10.48 [ P = 0.005], respectively), but there was no significant difference in antibiotic prescription rates between the non-influenza virus pathogen group and those who tested negative (chi-square value, 0; P = 1.0). Among adult outpatients, testing positive for influenza virus was associated with receiving fewer antibiotic prescriptions, but no such effect was seen for those who tested positive for a non-influenza virus. These data suggest that testing for influenza viruses alone may be sufficient and more cost-effective than multiplex pathogen testing for outpatients.


2020 ◽  
Vol 5 (5) ◽  
pp. 897-907
Author(s):  
Abraham J Qavi ◽  
Allison McMullen ◽  
Carey-Ann D Burnham ◽  
Neil W Anderson

Abstract Background Upper respiratory tract infections are common, and the ability to accurately and rapidly diagnose the causative pathogen has important implications for patient management. Methods We evaluated the test-ordering practices for 2 commonly utilized nucleic acid amplification tests (NAATs) for the detection of respiratory pathogens: the Xpert Flu Assay for influenza A/B (Flu assay) and the Biofire FilmArray respiratory panel assay (RP assay), which detects 20 different targets. Our study examined repeat testing; that is, testing within 7 days from an initial test. Results Our study found that repeat testing is common for each of the individual assays: 3.0% of all Flu assays and 10.0% of all RP assays were repeat testing. Of repeat testing, 8/293 (2.7%) of repeat Flu assays and 75/1257 (6.0%) of RP assays resulted diagnostic gains, i.e., new detections. However, for the RP assay, these new detections were not always clinically actionable. The most frequently discrepant organisms were rhinovirus/enterovirus (28/102, 27.5%), followed by respiratory syncytial virus (12/102, 11.8%) and coronavirus OC43 (11/102, 10.8%). Furthermore, there were 3,336 instances in which a patient was tested using both a Flu assay and RP assay, of which only 44 (1.3%) had discrepant influenza results. Conclusions Our findings suggest opportunities exist to better guide ordering practices for respiratory pathogen testing, including limiting repeat testing, with the goal of optimization of clinical yield, and diagnostic stewardship.


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