The Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Antigen Testing.

BACKGROUND: Immunoassays designed to detect SARS-CoV-2 protein antigens (Ag) are commonly used to diagnose COVID-19. The most widely used tests are lateral flow assays that generate results in approximately 15 minutes for diagnosis at the point-of-care. Higher throughput, laboratory-based SARS-CoV-2 Ag assays have also been developed. The number of commercially available SARS-CoV-2 Ag detection tests has increased rapidly, as has the COVID-19 diagnostic literature. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the literature and develop best practice guidance related to SARS-CoV-2 Ag testing. This guideline is an update to the third in a series of frequently updated COVID-19 diagnostic guidelines developed by the IDSA. OBJECTIVE: The IDSA's goal was to develop evidence-based recommendations or suggestions that assist clinicians, clinical laboratories, patients, public health authorities, administrators and policymakers in decisions related to the optimal use of SARS-CoV-2 Ag tests in both medical and non-medical settings. METHODS: A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists and experts in systematic literature review identified and prioritized clinical questions related to the use of SARS-CoV-2 Ag tests. A review of relevant, peer-reviewed published literature was conducted through April 1, 2022. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. RESULTS: The panel made ten diagnostic recommendations. These recommendations address Ag testing in symptomatic and asymptomatic individuals and assess single versus repeat testing strategies. CONCLUSIONS: U.S. Food and Drug Administration (FDA) SARS-CoV-2 Ag tests with Emergency Use Authorization (EUA) have high specificity and low to moderate sensitivity compared to nucleic acid amplification testing (NAAT). Ag test sensitivity is dependent on the presence or absence of symptoms, and in symptomatic patients, on timing of testing after symptom onset. In contrast, Ag tests have high specificity, and, in most cases, positive Ag results can be acted upon without confirmation. Results of point-of-care testing are comparable to those of laboratory-based testing, and observed or unobserved self-collection of specimens for testing yields similar results. Modeling suggests that repeat Ag testing increases sensitivity compared to testing once, but no empirical data were available to inform this question. Based on these observations, rapid RT-PCR or laboratory-based NAAT remains the testing method of choice for diagnosing SARS-CoV-2 infection. However, when timely molecular testing is not readily available or is logistically infeasible, Ag testing helps identify individuals with SARS-CoV-2 infection. Data were insufficient to make a recommendation about the utility of Ag testing to guide release of patients with COVID-19 from isolation. The overall quality of available evidence supporting use of Ag testing was graded as very low to moderate.

Traumatic Proximal Femoral Fractures during COVID-19 Pandemic in the US: An ACS NSQIP® Analysis.

In order to determine the impact of COVID-19 on the treatment and outcomes in patients with proximal femoral fracture's (PFF), we analyzed a national US sample. This is a retrospective review of American College of Surgery's (ACS) National Surgical Quality Improvement Program (NSQIP) for patients with proximal femoral fractures. A total of 26,830 and 26,300 patients sustaining PFF and undergoing surgical treatment were sampled during 2019 and 2020, respectively. On multivariable logistic regression, patients were less likely to have 'presence of non-healing wound' (p < 0.001), functional status 'independent' (p = 0.012), undergo surgical procedures of 'hemiarthroplasty'(p = 0.002) and 'ORIF IT, Peritroch, Subtroch with plates and screws' (p < 0.001) and to be 'alive at 30-days post-op' (p = 0.001) in 2020 as compared to 2019. Patients were more likely to have a case status 'emergent', 'loss of ≥10% body weight', discharge destination of 'home' (p < 0.001 for each) or 'leaving against medical advice' (p = 0.026), postoperative 'acute renal failure (ARF)' (p = 0.011), 'myocardial infarction (MI)' (p = 0.006), 'pulmonary embolism (PE)' (p = 0.047), and 'deep venous thrombosis (DVT)' (p = 0.049) in 2020 as compared to 2019. Patients sustaining PFF and undergoing surgical treatment during pandemic year 2020 differed significantly in preoperative characteristics and 30-day postoperative complications when compared to patients from the previous year.

Automated conflict resolution for patients with multiple morbidity being treated using more than one set of single condition clinical guidance: A case study.

BACKGROUND: The number of people in the UK with two or more conditions continues to grow and their clinical management is complicated by the reliance on guidance focused on a single condition. This leaves individual clinicians responsible for collating disparate information from patient management systems and care recommendations to manually manage the contradictions that exist in the simultaneous treatment of various conditions. METHODS/DESIGN: We have devised a modelling language based on BPMN that allows us to create computer interpretable representations of single condition guidance and incorporate patient data to detect the points of conflict between multiple conditions based on their transformation to logical constraints. This has been used to develop a prototype clinical decision support tool that we can use to highlight the causes of conflict between them in three main areas: medication, lifestyle and well-being, and appointment bookings. RESULTS: The prototype tool was used to discern contradictions in the care recommendations of chronic obstructive pulmonary disease and osteoarthritis. These were presented to a panel of clinicians who confirmed that the tool produced clinically relevant alerts that can advise clinicians of the presence of conflicts between guidelines relating to both clashes in medication or lifestyle advice. CONCLUSIONS: The need for supporting general practitioners in their treatment of patients remains and this proof of concept has demonstrated that by converting this guidance into computer-interpretable pathways we can use constraint solvers to readily identify clinically relevant points of conflict between critical elements of the pathway.

The Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Antigen Testing.

BACKGROUND: Immunoassays designed to detect SARS-CoV-2 protein antigens are now commercially available. The most widely used tests are rapid lateral flow assays that generate results in approximately 15 minutes for diagnosis at the point-of-care. Higher throughput, laboratory-based SARS-CoV-2 antigen (Ag) assays have also been developed. The overall accuracy of SARS-CoV-2 Ag tests, however, is not well defined. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the literature and develop best practice guidance related to SARS-CoV-2 Ag testing. This guideline is the third in a series of rapid, frequently updated COVID-19 diagnostic guidelines developed by IDSA. OBJECTIVE: IDSA's goal was to develop evidence-based recommendations or suggestions that assist clinicians, clinical laboratories, patients, public health authorities, administrators and policymakers in decisions related to the optimal use of SARS-CoV-2 Ag tests in both medical and non-medical settings. METHODS: A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists and experts in systematic literature review identified and prioritized clinical questions related to the use of SARS-CoV-2 Ag tests. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. RESULTS: The panel agreed on five diagnostic recommendations. These recommendations address antigen testing in symptomatic and asymptomatic individuals as well as assess single versus repeat testing strategies. CONCLUSIONS: Data on the clinical performance of U.S. Food and Drug Administration SARS-CoV-2 Ag tests with Emergency Use Authorization is mostly limited to single, one-time testing versus standard nucleic acid amplification testing (NAAT) as the reference standard. Rapid Ag tests have high specificity and low to modest sensitivity compared to reference NAAT methods. Antigen test sensitivity is heavily dependent on viral load, with differences observed between symptomatic compared to asymptomatic individuals and the time of testing post onset of symptoms. Based on these observations, rapid RT-PCR or laboratory-based NAAT remain the diagnostic methods of choice for diagnosing SARS-CoV-2 infection. However, when molecular testing is not readily available or is logistically infeasible, Ag testing can help identify some individuals with SARS-CoV-2 infection. The overall quality of available evidence supporting use of Ag testing was graded as very low to moderate.

Evaluation of the aerosol generating potential of endoscopic dacryocystorhinostomy.

PURPOSE: The COVID-19 pandemic gave rise to renewed concerns of the transmission risks posed by surgeries on sites of high viral colonization such as the nasopharynx. Endoscopic dacryocystorhinostomy (DCR) involves the creation of a new tear duct from the lacrimal sac to the nasal cavity. The purpose of this project is to determine if endoscopic DCR is an aerosol generating procedure (AGP). METHODS: An optical particle sizer (OPS) was used to intraoperatively quantify aerosol concentrations during four cases of endoscopic DCR. The OPS sampled the air once every 60 seconds throughout the operations. The time of important operative steps were documented and correlated with OPS readings. Particle concentrations during each major surgical step were compared to baseline readings by the Mann Whitney U Test. RESULTS: There were statistically significant increases in median particle concentrations during laryngeal mask airway intubations for both particles 0.3 to 5.0 µm and >5.0 µm (P < .001 and P = .023, respectively). Median particle concentrations during nasolacrimal duct probing, middle meatal debridement, drilling, balloon insertion, tube insertion, and Posisef insertion were not statistically different from baseline. CONCLUSIONS: Endoscopic DCR in itself does not appear to be an AGP. It is, however, associated with other aerosol generating events such as laryngeal mask intubation, and thus requires appropriate personal protective equipment. Cautious interpretation of the results is encouraged given the limitations of OPS. LEVEL OF EVIDENCE: 4.

Quantifying SARS-CoV-2 viral load: current status and future prospects.

Introduction: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged as a novel viral agent that quickly spread worldwide. SARS-CoV-2 is responsible for the human coronavirus disease 2019 (COVID-19) which has claimed hundreds of thousands of lives and had an immeasurable toll on the economy. Currently, most clinical cases are identified by qualitative molecular testing. However, the need for quantitative assessment is gaining traction.Areas covered: In this review, the current state and future perspective of SARS-CoV-2 viral load quantification is presented.Expert opinion: Viral load quantification is a critical measure that informs clinicians of treatment response, actionable viral load levels, and guidance on patient management. Additionally, for pathogens with epidemiological consequences, viral load can provide information to guide infection control measures and policies. While qualitative detection is sufficient to identify cases and initiate containment and mitigation measures in the vast majority of COVID-19 cases, in certain situations, SARS-CoV-2 quantification is needed to assess viral load trending. However, there are obstacles to quantification, including variability in respiratory specimen collection and the lack of commutable reference material. At the same time, the need for quantification for clinical and epidemiological management is growing, especially concerning individuals with prolonged RNA shedding.

A Novel Negative Pressure, Face-Mounted Antechamber to Minimize Aerosolization of Particles During Endoscopic Skull Base Surgery.

BACKGROUND: The COVID-19 pandemic has revealed deficiencies in the adequacy of personal protective equipment (PPE) for healthcare workers. Endoscopic endonasal skull base surgery is thought to be among the highest-risk aerosol-generating procedures for surgeons and operating room personnel. OBJECTIVE: To validate the efficacy and clinical feasibility of a novel surgical device. METHODS: A low-cost, modifiable, and easily producible negative pressure, face-mounted antechamber was developed utilizing 3D printing and silicone molding. Efficacy was evaluated using an optical particle sizer to quantify aerosols generated during both cadaver and intraoperative human use with high-speed drilling. RESULTS: Particle counts in the cadaver showed that drilling led to a 2.49-fold increase in particles 0.3 to 5 µm (P = .001) and that the chamber was effective at reducing particles to levels not significantly different than baseline. In humans, drilling led to a 37-fold increase in particles 0.3 to 5 µm (P < .001), and the chamber was effective at reducing particles to a level not significantly different than baseline. Use of the antechamber in 6 complex cases did not interfere with the ability to perform surgery. Patients did not report any facial discomfort after surgery related to antechamber use. CONCLUSION: The use of a negative pressure facial antechamber can effectively reduce aerosolization from endoscopic drilling without disturbing the flow of the operation. The antechamber, in conjunction with appropriate PPE, will be useful during the COVID-19 pandemic, as well as during flu season and any future viral outbreaks.

Early experience with universal preprocedural testing for SARS-CoV-2 in a relatively low-prevalence area.

We implemented universal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing of patients undergoing surgical procedures as a means to conserve personal protective equipment (PPE). The rate of asymptomatic coronavirus disease 2019 (COVID-19) was <0.5%, which suggests that early local public health interventions were successful. Although our protocol was resource intensive, it prevented exposures to healthcare team members.

The Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Molecular Diagnostic Testing.

BACKGROUND: Accurate molecular diagnostic tests are necessary for confirming a diagnosis of coronavirus disease 2019 (COVID-19). Direct detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids in respiratory tract specimens informs patient, healthcare institution and public health level decision-making. The numbers of available SARS-CoV-2 nucleic acid detection tests are rapidly increasing, as is the COVID-19 diagnostic literature. Thus, the Infectious Diseases Society of America (IDSA) recognized a significant need for frequently updated systematic reviews of the literature to inform evidence-based best practice guidance. OBJECTIVE: The IDSA's goal was to develop an evidence-based diagnostic guideline to assist clinicians, clinical laboratorians, patients and policymakers in decisions related to the optimal use of SARS-CoV-2 nucleic acid amplification tests. In addition, we provide a conceptual framework for understanding molecular diagnostic test performance, discuss the nuance of test result interpretation in a variety of practice settings and highlight important unmet research needs in the COVID-19 diagnostic testing space. METHODS: IDSA convened a multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review to identify and prioritize clinical questions and outcomes related to the use of SARS-CoV-2 molecular diagnostics. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. RESULTS: The panel agreed on 17 diagnostic recommendations. CONCLUSIONS: Universal access to accurate SARS-CoV-2 nucleic acid testing is critical for patient care, hospital infection prevention and the public response to the COVID-19 pandemic. Information on the clinical performance of available tests is rapidly emerging, but the quality of evidence of the current literature is considered moderate to very low. Recognizing these limitations, the IDSA panel weighed available diagnostic evidence and recommends nucleic acid testing for all symptomatic individuals suspected of having COVID-19. In addition, testing is recommended for asymptomatic individuals with known or suspected contact with a COVID-19 case. Testing asymptomatic individuals without known exposure is suggested when the results will impact isolation/quarantine/personal protective equipment (PPE) usage decisions, dictate eligibility for surgery, or inform solid organ or hematopoietic stem cell transplantation timing. Ultimately, prioritization of testing will depend on institutional-specific resources and the needs of different patient populations.

Is Office Laryngoscopy an Aerosol-Generating Procedure?

OBJECTIVES/HYPOTHESIS: The aims of this work were 1) to investigate whether office laryngoscopy is an aerosol-generating procedure with an optical particle sizer (OPS) during clinical simulation on healthy volunteers, and 2) to critically discuss methods for assessment of aerosolizing potentials in invasive interventions. STUDY DESIGN: Prospective quantification of aerosol and droplet generation during clinical simulation of rigid and flexible laryngoscopy. METHODS: Two healthy volunteers were recruited to undergo both flexible and rigid laryngoscopy. An OPS was used to quantify aerosols and droplets generated for four positive controls relative to ambient particles (speech, breathing, /e/ phonation, and /ae/ phonation) and for five test interventions relative to breathing and phonation (flexible laryngoscopy, flexible laryngoscopy with humming, flexible laryngoscopy with /e/ phonation, rigid laryngoscopy, and rigid laryngoscopy with /ae/ phonation). Particle counts in mean diameter size range from 0.3 to >10 µm were measured with OPS placed at 12 cm from the subject's nose/mouth. RESULTS: None of the laryngoscopy interventions (n = 10 each) generated aerosols above that produced by breathing or phonation. Breathing (n = 40, 1-3 µm, P = .016) and /ae/ phonation (n = 10, 1-3 µm, P = .022; 3-5 µm. P = .083; >5 µm, P = .012) were statistically significant producers of aerosols and droplets. Neither speech nor /e/ phonation (n = 10 each) were associated with statistically significant aerosols and droplet generation. CONCLUSIONS: Using OPS to detect droplets and aerosols, we found that office laryngoscopy is likely not an aerosol-generating procedure. Despite its prior use in otolaryngological literature, an OPS has intrinsic limitations. Our study should be complemented with more sophisticated methods of droplet distribution measurement. LEVEL OF EVIDENCE: 3 Laryngoscope, 130:2637-2642, 2020.

Environmental and Aerosolized Severe Acute Respiratory Syndrome Coronavirus 2 Among Hospitalized Coronavirus Disease 2019 Patients.

During April and May 2020, we studied 20 patients hospitalized with coronavirus disease 2019 (COVID-19), their hospital rooms (fomites and aerosols), and their close contacts for molecular and culture evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Among >400 samples, we found molecular evidence of virus in most sample types, especially the nasopharyngeal (NP), saliva, and fecal samples, but the prevalence of molecular positivity among fomites and aerosols was low. The agreement between NP swab and saliva positivity was high (89.5%; κ = 0.79). Two NP swabs collected from patients on days 1 and 7 post-symptom onset had evidence of infectious virus (2 passages over 14 days in Vero E6 cells). In summary, the low molecular prevalence and lack of viable SARS-CoV-2 virus in fomites and air samples implied low nosocomial risk of SARS-CoV-2 transmission through inanimate objects or aerosols.

Implementation of a Pooled Surveillance Testing Program for Asymptomatic SARS-CoV-2 Infections on a College Campus - Duke University, Durham, North Carolina, August 2-October 11, 2020.

On university campuses and in similar congregate environments, surveillance testing of asymptomatic persons is a critical strategy (1,2) for preventing transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). All students at Duke University, a private research university in Durham, North Carolina, signed the Duke Compact (3), agreeing to observe mandatory masking, social distancing, and participation in entry and surveillance testing. The university implemented a five-to-one pooled testing program for SARS-CoV-2 using a quantitative, in-house, laboratory-developed, real-time reverse transcription-polymerase chain reaction (RT-PCR) test (4,5). Pooling of specimens to enable large-scale testing while minimizing use of reagents was pioneered during the human immunodeficiency virus pandemic (6). A similar methodology was adapted for Duke University's asymptomatic testing program. The baseline SARS-CoV-2 testing plan was to distribute tests geospatially and temporally across on- and off-campus student populations. By September 20, 2020, asymptomatic testing was scaled up to testing targets, which include testing for residential undergraduates twice weekly, off-campus undergraduates one to two times per week, and graduate students approximately once weekly. In addition, in response to newly identified positive test results, testing was focused in locations or within cohorts where data suggested an increased risk for transmission. Scale-up over 4 weeks entailed redeploying staff members to prepare 15 campus testing sites for specimen collection, developing information management tools, and repurposing laboratory automation to establish an asymptomatic surveillance system. During August 2-October 11, 68,913 specimens from 10,265 graduate and undergraduate students were tested. Eighty-four specimens were positive for SARS-CoV-2, and 51% were among persons with no symptoms. Testing as a result of contact tracing identified 27.4% of infections. A combination of risk-reduction strategies and frequent surveillance testing likely contributed to a prolonged period of low transmission on campus. These findings highlight the importance of combined testing and contact tracing strategies beyond symptomatic testing, in association with other preventive measures. Pooled testing balances resource availability with supply-chain disruptions, high throughput with high sensitivity, and rapid turnaround with an acceptable workload.

Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19:Serologic Testing.

BACKGROUND: The availability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serologic testing has rapidly increased. Current assays use a variety of technologies, measure different classes of immunoglobulin or immunoglobulin combinations and detect antibodies directed against different portions of the virus. The overall accuracy of these tests, however, has not been well-defined. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the coronavirus disease 2019 (COVID-19) serology literature and construct best practice guidance related to SARS-CoV-2 serologic testing. This guideline is the fourth in a series of rapid, frequently updated COVID-19 guidelines developed by IDSA. OBJECTIVE: IDSA's goal was to develop evidence-based recommendations that assist clinicians, clinical laboratories, patients and policymakers in decisions related to the optimal use of SARS-CoV-2 serologic tests in a variety of settings. We also highlight important unmet research needs pertaining to the use of anti-SARS-CoV-2 antibody tests for diagnosis, public health surveillance, vaccine development and the selection of convalescent plasma donors. METHODS: A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists and experts in systematic literature review identified and prioritized clinical questions related to the use of SARS-CoV-2 serologic tests. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. RESULTS: The panel agreed on eight diagnostic recommendations. CONCLUSIONS: Information on the clinical performance and utility of SARS-CoV-2 serologic tests are rapidly emerging. Based on available evidence, detection of anti-SARS-CoV-2 antibodies may be useful for confirming the presence of current or past infection in selected situations. The panel identified three potential indications for serologic testing including: 1) evaluation of patients with a high clinical suspicion for COVID-19 when molecular diagnostic testing is negative and at least two weeks have passed since symptom onset; 2) assessment of multisystem inflammatory syndrome in children; and 3) for conducting serosurveillance studies. The certainty of available evidence supporting the use of serology for either diagnosis or epidemiology was, however, graded as very low to moderate.

Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19.

BACKGROUND: Accurate molecular diagnostic tests are necessary for confirming a diagnosis of coronavirus disease 2019 (COVID-19). Direct detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids in respiratory tract specimens informs patient, healthcare institution and public health level decision-making. The numbers of available SARS-CoV-2 nucleic acid detection tests are rapidly increasing, as is the COVID-19 diagnostic literature. Thus, the Infectious Diseases Society of America (IDSA) recognized a significant need for frequently updated systematic reviews of the literature to inform evidence-based best practice guidance. OBJECTIVE: The IDSA's goal was to develop an evidence-based diagnostic guideline to assists clinicians, clinical laboratorians, patients and policymakers in decisions related to the optimal use of SARS-CoV-2 nucleic acid amplification tests. In addition, we provide a conceptual framework for understanding molecular diagnostic test performance, discuss the nuance of test result interpretation in a variety of practice settings, and highlight important unmet research needs in the COVID-19 diagnostic testing space. METHODS: IDSA convened a multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review to identify and prioritize clinical questions and outcomes related to the use of SARS-CoV-2 molecular diagnostics. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. RESULTS: The panel agreed on 15 diagnostic recommendations. CONCLUSIONS: Universal access to accurate SARS-CoV-2 nucleic acid testing is critical for patient care, hospital infection prevention and the public response to the COVID-19 pandemic. Information on the clinical performance of available tests is rapidly emerging, but the quality of evidence of the current literature is considered low to very low. Recognizing these limitations, the IDSA panel weighed available diagnostic evidence and recommends nucleic acid testing for all symptomatic individuals suspected of having COVID-19. In addition, testing is recommended for asymptomatic individuals with known or suspected contact with a COVID-19 case. Testing asymptomatic individuals without known exposure is suggested when the results will impact isolation/quarantine/personal protective equipment (PPE) usage decisions, dictate eligibility for surgery, or inform administration of immunosuppressive therapy. Ultimately, prioritization of testing will depend on institutional-specific resources and the needs of different patient populations.