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

BACKGROUND: The role of serologic testing for SARS-CoV-2 has evolved during the pandemic as seroprevalence in global populations has increased. 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 updated best practice guidance related to SARS-CoV-2 serologic testing. This guideline is an update to the fourth in a series of rapid, frequently updated COVID-19 guidelines developed by IDSA. OBJECTIVE: To develop evidence-based recommendations and identify unmet research needs pertaining to the use of anti-SARS-CoV-2 antibody tests for diagnosis, decisions related to vaccination and administration of monoclonal antibodies or convalescent plasma in immunocompromised patients, and identification of a serologic correlate of immunity. METHODS: A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists and experts in systematic literature reviewed, 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 recommends against serologic testing to diagnose SARS-CoV-2 infection in the first two weeks after symptom onset (strong recommendations, low certainty of evidence). Serologic testing should not be used to provide evidence of COVID-19 in symptomatic patients with a high clinical suspicion and repeatedly negative nucleic acid amplification test results (strong recommendation, very low certainty of evidence). Serologic testing may assist with the diagnosis of multisystem inflammatory syndrome in children (strong recommendation, very low certainty of evidence). To seek evidence for prior SARS-CoV-2 infection, the panel suggests testing for IgG, IgG/IgM, or total antibodies to nucleocapsid protein three to five weeks after symptom onset (conditional recommendation, low certainty of evidence). In individuals with previous SARS-CoV-2 infection or vaccination, we suggest against routine serologic testing given no demonstrated benefit to improving patient outcomes (conditional recommendation, very low certainty of evidence.) The panel acknowledges further that a negative spike antibody test may be a useful metric to identify immunocompromised patients who are candidates for immune therapy. CONCLUSIONS: The high seroprevalence of antibodies against SARS-CoV-2 worldwide limits the utility of detecting anti-SARS CoV-2 antibody. The certainty of available evidence supporting the use of serology for diagnosis was graded as very low to low. Future studies should use serologic assays calibrated to a common reference standard.

The Infectious Diseases Society of America Guidelines on the Diagnosis of Coronavirus Disease 2019 (COVID-19): Molecular Diagnostic Testing.

Accurate molecular diagnostic tests are necessary for confirming a diagnosis of coronavirus disease 2019 (COVID-19) and for identifying asymptomatic carriage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The number of available SARS-CoV-2 nucleic acid detection tests continues to increase as does the COVID-19 diagnostic literature. Thus, the Infectious Diseases Society of America (IDSA) developed 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 nuances of test result interpretation in a variety of practice settings, and highlight important unmet research needs related to COVID-19 diagnostic testing. 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. The panel agreed on 12 diagnostic recommendations. Access to accurate SARS-CoV-2 nucleic acid testing is critical for patient care, hospital infection prevention, and the public health response to COVID-19 infection. Information on the clinical performance of available tests continues to grow, but the quality of evidence of the current literature to support this updated molecular diagnostic guideline remains 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 suggested for asymptomatic individuals with known or suspected contact with a COVID-19 case when the results will impact isolation/quarantine/personal protective equipment (PPE) usage decisions. Evidence in support of rapid testing and testing of upper respiratory specimens other than nasopharyngeal swabs, which offer logistical advantages, is sufficient to warrant conditional recommendations in favor of these approaches.

Utilizing Ceftazidime/Avibactam Therapeutic Drug Monitoring in the Treatment of Neurosurgical Meningitis Caused by Difficult-to-Treat Resistant Pseudomonas aeruginosa and KPC-Producing Enterobacterales.

Background: Central nervous system (CNS) infections caused by Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales and difficult-to-treat resistant (DTR) Pseudomonas aeruginosa represent a formidable clinical challenge. Antimicrobial regimens that efficiently penetrate the cerebrospinal fluid (CSF) and achieve sufficient concentrations associated with microbiologic and clinical cure are limited. We evaluated therapy with ceftazidime-avibactam (CAZ-AVI) in order to guide precise dosing in the treatment of CNS infections. Methods: Therapeutic drug monitoring (TDM) was performed in 3 patients with health care-associated ventriculitis and meningitis (HAVM) using CAZ-AVI 2.5 g infused intravenously every 8 hours as standard and extended infusion. Simultaneous CSF and plasma samples were obtained throughout the dosing interval in each patient. Concentrations of CAZ and AVI were determined by liquid chromatography/mass spectrometry. Results: Bacterial identification revealed KPC-producing Klebsiella pneumoniae (KPC-Kp), DTR Pseudomonas aeruginosa, and KPC-producing Enterobacter cloacae (KPC-Ent.c). All isolates were resistant to carbapenems. The minimum inhibitory concentrations (MICs) of CAZ-AVI were 0.25/4, 4/4, and 0.25/4 µg/mL, respectively. CAZ and AVI concentrations were determined in CSF samples ranging from 29.0 to 15.0 µg/mL (CAZ component) and 4.20 to 0.92 µg/mL (AVI component), respectively. AVI achieved concentrations ≥1 µg/mL in 11 out of 12 CSF samples collected throughout the dosing interval. Clinical and microbiologic cure were attained in all patients. Conclusions: Postinfusion concentrations of CAZ-AVI were measured in plasma and CSF samples obtained from 3 patients with complicated CNS infections caused by antimicrobial-resistant isolates. The measured concentrations revealed that standard CAZ and AVI exposures sufficiently attained values correlating to 50% fT > MIC, which are associated with efficient bacterial killing.

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.

Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19.

BACKGROUND: There are many pharmacologic therapies that are being used or considered for treatment of coronavirus disease 2019 (COVID-19), with rapidly changing efficacy and safety evidence from trials. OBJECTIVE: Develop evidence-based, rapid, living guidelines intended to support patients, clinicians, and other healthcare professionals in their decisions about treatment and management of patients with COVID-19. METHODS: In March 2020, the Infectious Diseases Society of America (IDSA) formed a multidisciplinary guideline panel of infectious disease clinicians, pharmacists, and methodologists with varied areas of expertise to regularly review the evidence and make recommendations about the treatment and management of persons with COVID-19. The process used a living guideline approach and followed a rapid recommendation development checklist. The panel prioritized questions and outcomes. A systematic review of the peer-reviewed and grey literature was conducted at regular intervals. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations. RESULTS: Based on the most recent search conducted on May 31, 2022, the IDSA guideline panel has made 30 recommendations for the treatment and management of the following groups/populations: pre- and post-exposure prophylaxis, ambulatory with mild-to-moderate disease, hospitalized with mild-to-moderate, severe but not critical, and critical disease. As these are living guidelines, the most recent recommendations can be found online at: https://idsociety.org/COVID19guidelines. CONCLUSIONS: At the inception of its work, the panel has expressed the overarching goal that patients be recruited into ongoing trials. Since then, many trials were done which provided much needed evidence for COVID-19 therapies. There still remain many unanswered questions as the pandemic evolved which we hope future trials can answer.

Diagnostic approach and update on encephalitis.

PURPOSE OF REVIEW: The present article gives an update and outlines the fundamental principles of clinical reasoning and a diagnostic approach to a patient suspected to have acute encephalitis. RECENT FINDINGS: Encephalitis remains to be associated with significant mortality and neurological morbidity. Unfortunately, the etiologic diagnosis remains elusive for the majority of the patients with encephalitis preventing targeted therapies. Clinicians could utilize clues such as duration of symptoms, exposure history, cerebrospinal fluid profile, neuroimaging findings and locations, and entertain certain opportunistic infections in immunosuppressed individuals. A comprehensive diagnostic for the most common viral and autoimmune etiologies should be systematically done and prompt empiric antiviral therapy should be started. Evaluation and therapy for autoimmune etiologies should be done for patients with a negative viral work up. Brain biopsy and metagenomic sequencing should be considered for patients with unknown etiologies that are clinically worsening. SUMMARY: Encephalitis remains with unacceptable mortality and morbidity with the most common etiologies being idiopathic. A comprehensive diagnostic work up and prompt antiviral and autoimmune therapies are of paramount importance to improve the outcomes of this devastating disease.

Pharmacologic Treatment and Management of Coronavirus Disease 2019.

Over the last 2 years, there has been gradual and sustained progress toward our understanding of pharmacotherapy for coronavirus disease 2019 (COVID-19) as a result of large- and small-scale randomized controlled trials. Numerous new and repurposed treatments have been evaluated; some have demonstrated benefit in clinically important outcomes like mortality and hospitalization, and optimism for oral antiviral treatments is growing. Given the rapidly evolving landscape of COVID-19 treatments, frontline clinicians should use treatment and management guidelines to guide their approach to each patient, with the individual's severity and location of illness in mind to appreciate the nuances in clinical evidence.

Lessons Learned from Coronavirus Disease 2019 (COVID-19) Therapies: Critical Perspectives From the Infectious Diseases Society of America (IDSA) COVID-19 Treatment Guideline Panel.

Despite the challenges of the pandemic, there has been substantial progress with coronavirus disease 2019 (COVID-19) therapies. Pivotal COVID-19 trials like SOLIDARITY, RECOVERY, and ACCT-1 were rapidly conducted and data disseminated to support effective therapies. However, critical shortcomings remain on trial conduct, dissemination and interpretation of study results, and regulatory guidance in pandemic settings. The lessons that we learned have implications for both the current pandemic and future emerging infectious diseases. There is a need for establishing and standardizing clinical meaningful outcomes in therapeutic trials and for targeting defined populations and phenotypes that will most benefit from specific therapies. Standardized processes should be established for rapid and critical data review and dissemination to ensure scientific integrity. Clarity around the evidence standards needed for issuance of both emergency use authorization (EUA) and biologic license application (BLA) should be established and an infrastructure for executing rapid trials in epidemic settings maintained.

Therapeutic Emergency Use Authorizations (EUAs) During Pandemics: Double-edged Swords.

Given the urgent need for treatments during the coronavirus disease 2019 pandemic, the US Food and Drug Administration issued emergency use authorizations (EUAs) for multiple therapies. In several instances, however, these EUAs were issued before sufficient evidence of a given therapy's efficacy and safety were available, potentially promoting ineffective or even harmful therapies and undermining the generation of definitive evidence. We describe the strengths and weaknesses of the different therapeutic EUAs issued during this pandemic. We also contrast them to the vaccine EUAs and suggest a framework and criteria for an evidence-based, trustworthy, and publicly transparent therapeutic EUA process for future pandemics.

Infectious Diseases Society of America Guidelines on Infection Prevention for Healthcare Personnel Caring for Patients with Suspected or Known COVID-19.

BACKGROUND: Since its emergence in late 2019, SARS-CoV-2 continues to pose a risk to healthcare personnel (HCP) and patients in healthcare settings. Although all clinical interactions likely carry some risk of transmission, human actions like coughing and care activities like aerosol-generating procedures likely have a higher risk of transmission. The rapid emergence and global spread of SARS-CoV-2 continues to create significant challenges in healthcare facilities, particularly with shortages of personal protective equipment (PPE) used by HCP. Evidence-based recommendations for what PPE to use in conventional, contingency, and crisis standards of care continue to be needed. Where evidence is lacking, the development of specific research questions can help direct funders and investigators. OBJECTIVE: Develop evidence-based rapid guidelines intended to support HCP in their decisions about infection prevention when caring for patients with suspected or known COVID-19. METHODS: IDSA formed a multidisciplinary guideline panel including frontline clinicians, infectious disease specialists, experts in infection control, and guideline methodologists with representation from the disciplines of public health, medical microbiology, pediatrics, critical care medicine and gastroenterology. The process followed a rapid recommendation checklist. The panel prioritized questions and outcomes. Then a systematic review of the peer-reviewed and grey literature was conducted. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations. RESULTS: The IDSA guideline panel agreed on eight recommendations, including two updated recommendations and one new recommendation added since the first version of the guideline. Narrative summaries of other interventions undergoing evaluations are also included. CONCLUSIONS: Using a combination of direct and indirect evidence, the panel was able to provide recommendations for eight specific questions on the use of PPE for HCP providing care for patients with suspected or known COVID-19. Where evidence was lacking, attempts were made to provide potential avenues for investigation. There remain significant gaps in the understanding of the transmission dynamics of SARS-CoV-2 and PPE recommendations may need to be modified in response to new evidence. These recommendations should serve as a minimum for PPE use in healthcare facilities and do not preclude decisions based on local risk assessments or requirements of local health jurisdictions or other regulatory bodies.

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.

Severe covid-19 pneumonia: pathogenesis and clinical management.

Severe covid-19 pneumonia has posed critical challenges for the research and medical communities. Older age, male sex, and comorbidities increase the risk for severe disease. For people hospitalized with covid-19, 15-30% will go on to develop covid-19 associated acute respiratory distress syndrome (CARDS). Autopsy studies of patients who died of severe SARS CoV-2 infection reveal presence of diffuse alveolar damage consistent with ARDS but with a higher thrombus burden in pulmonary capillaries. When used appropriately, high flow nasal cannula (HFNC) may allow CARDS patients to avoid intubation, and does not increase risk for disease transmission. During invasive mechanical ventilation, low tidal volume ventilation and positive end expiratory pressure (PEEP) titration to optimize oxygenation are recommended. Dexamethasone treatment improves mortality for the treatment of severe and critical covid-19, while remdesivir may have modest benefit in time to recovery in patients with severe disease but shows no statistically significant benefit in mortality or other clinical outcomes. Covid-19 survivors, especially patients with ARDS, are at high risk for long term physical and mental impairments, and an interdisciplinary approach is essential for critical illness recovery.

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.

Acute Symptomatic Seizures in Critically Ill Patients with COVID-19: Is There an Association?

BACKGROUND: The coronavirus disease of 2019 (COVID-19) emerged as a global pandemic. Historically, the group of human coronaviruses can also affect the central nervous system leading to neurological symptoms; however, the causative mechanisms of the neurological manifestations of COVID-19 disease are not well known. Seizures have not been directly reported as a part of COVID-19 outside of patients with previously known brain injury or epilepsy. We report two cases of acute symptomatic seizures, in non-epileptic patients, associated with severe COVID-19 disease. CASE PRESENTATIONS: Two advanced-age, non-epileptic, male patients presented to our northeast Ohio-based health system with concern for infection in Mid-March 2020. Both had a history of lung disease and during their hospitalization tested positive for SARS-CoV-2. They developed acute encephalopathy days into their hospitalization with clinical and electrographic seizures. Resolution of seizures was achieved with levetiracetam. DISCUSSION: Patients with COVID-19 disease are at an elevated risk for seizures, and the mechanism of these seizures is likely multifactorial. Clinical (motor) seizures may not be readily detected in this population due to the expansive utilization of sedatives and paralytics for respiratory optimization strategies. Many of these patients are also not electrographically monitored for seizures due to limited resources, multifactorial risk for acute encephalopathy, and the risk of cross-contamination. Previously, several neurological symptoms were seen in patients with more advanced COVID-19 disease, and these were thought to be secondary to multi-system organ failure and/or disseminated intravascular coagulopathy-related brain injury. However, these patients may also have an advanced breakdown of the blood-brain barrier precipitated by pro-inflammatory cytokine reactions. The neurotropic effect and neuroinvasiveness of SARS-Coronavirus-2 have not been directly established. CONCLUSIONS: Acute symptomatic seizures are possible in patients with COVID-19 disease. These seizures are likely multifactorial in origin, including cortical irritation due to blood-brain barrier breakdown, precipitated by the cytokine reaction as a part of the viral infection. Patients with clinical signs of seizures or otherwise unexplained encephalopathy may benefit from electroencephalography monitoring and/or empiric anti-epileptic therapy. Further studies are needed to elucidate the risk of seizures and benefit of monitoring in this population.

Cerebrovascular complications and vasculopathy in patients with herpes simplex virus central nervous system infection.

OBJECTIVE: Herpes simplex viruses (HSV) are neurotropic and known to cause central nervous system (CNS) infections. We aimed to describe the clinical and imaging features of cerebrovascular complications in patients with HSV CNS infections. METHODS: We reviewed records of patients with HSV infections by querying acyclovir use in a clinical registry of parenteral anti-infective therapy at a tertiary medical center from January 2010 until September 2018. One patient who met the inclusion criteria is subsequently added. Diagnostic criteria for HSV CNS infection were intrathecal presence of viral DNA with clinical signs of CNS involvement. RESULTS: Of 36 patients who met the criteria for HSV CNS infections, cerebrovascular complications occurred in 6 patients (17%). Two patients with HSV-1 encephalitis had cerebrovascular complications (1 ischemic stroke, 1 intraparenchymal hemorrhage). Four patients had HSV-2 infection without encephalitis had cerebrovascular complications (3 ischemic strokes, 1 cerebral vein thrombosis). All 3 patients with ischemic strokes without encephalitis had pattern of vasculitis on vessel imaging on MRI with segmental narrowing and vessel wall irregularities of large intracranial arteries with circumferential wall enhancement. CONCLUSION: Cerebrovascular complications of HSV can occur with encephalitis or as isolated events with vasculitis.

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.

Neurologic complications of COVID-19.

Patients with COVID-19 have a fairly high risk of neurologic complications, including encephalopathy, stroke, central nervous system infection, seizures, and neuromuscular diseases. Many report losing their senses of smell and taste, and many survivors report lingering neurocognitive impairment. The diagnosis and treatment of these complications does not differ from that in other patients, although sophisticated testing may not be readily available for a patient in intensive care and respiratory isolation. Clinicians should therefore be alert to these complications.