Post-COVID mRNA-vaccine IgG4 shift: worrisome?

COVID-19 vaccines play a key role in ending the pandemic. Unraveling the immunological phenomena involved in offering protective immunity is the cornerstone of achieving such success. This perspective evaluates the possible mechanisms and implications of IgG4 production in response to mRNA-based COVID-19 vaccines.

Emergency Department Co-testing for Human Immunodeficiency Virus When Testing for Gonorrhea and Chlamydia: A Readily Available, Missed Opportunity for Targeted HIV Testing in Emergency Departments.

OBJECTIVES: Conducting human immunodeficiency virus (HIV) testing in emergency departments (EDs) can be an effective approach to testing and reaching populations at highest risk of contracting HIV. METHODS: All gonorrhea and chlamydia (G/C) and HIV tests ordered in the Cleveland Clinic Health System's 14 EDs were included in the analysis. Data were collected from electronic health records. Descriptive statistics, with medians and means, were computed. RESULTS: From January 1, 2019, to December 31, 2021, we reviewed ED visits for the purpose of sexually transmitted infection (STI) screening, with an emphasis on G/C screening. In October 2019, both HIV rapid testing and G/C testing began across all 14 Cleveland Clinic EDs. The overall rate of co-testing for HIV when obtaining a G/C test for STI evaluation increased overall to around 30% for our health system EDs, with some individual EDs approaching 60%. CONCLUSIONS: The approach the Cleveland Clinic implemented is an effective way to test for HIV in the ED. Local health departments and stakeholders in HIV communities should support and collaborate with EDs in their jurisdictions to accelerate HIV testing initiatives by using an HIV plus G/C co-testing metric.

Outcomes After Positive Syphilis Screening.

BACKGROUND: Syphilis screening during pregnancy helps prevent congenital syphilis. The harms associated with false positive (FP) screens and whether screening leads to correct treatments has not been well determined. METHODS: The population included mothers and infants from 75 056 pregnancies. Using laboratory-based criteria we classified initial positive syphilis screens as FP or true positive (TP) and calculated false discovery rates. For mothers and infants we determined treatments, clinical characteristics, and syphilis classifications. RESULTS: There were 221 positive screens: 183 FP and 38 TP. The false discovery rate was 0.83 (95% confidence interval [CI], 0.78-0.88). False discovery rates were similar for traditional 0.83 [95% CI, 0.72-0.94] and reverse algorithms 0.83 (95% CI, 0.77-0.88), and for syphilis Immunoglobin (Ig) G 0.79 (95% CI, 0.71-0.86) and total 0.90 (95% CI, 0.82-0.97) assays. FP screens led to treatment in 2 women and 1 infant. Two high-risk women were not rescreened at delivery and were diagnosed after hospital discharge; 1 infant developed congenital syphilis. Among 15 TP women with new syphilis, the diagnosis was before the late third trimester in 14 (93%). In one-half of these women, there was concern for reinfection, treatment failure, inadequate treatment or follow-up care, or late treatment, and their infants did not achieve an optimal syphilis classification. CONCLUSIONS: Syphilis screening identifies maternal syphilis, but limitations include FP screens, which occasionally lead to unnecessary treatment, inconsistent risk-based rescreening, and among TP mothers failure to optimize care to prevent birth of infants at higher risk for congenital syphilis.

Cotesting for Human Immunodeficiency Virus and Sexually Transmitted Infections in the Emergency Department.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) and US Preventive Services Task Force (USPSTF) guidelines recommend screening for human immunodeficiency virus (HIV) in patients aged 15 to 65 years, as well as those at increased risk. Patients screened in the emergency department (ED) for gonorrhea (GC) and/or chlamydia represent an increased-risk population. Our aim was to assess compliance with CDC and USPSTF guidelines for HIV testing in a national sample of EDs. METHODS: We examined data from the 2010 to 2018 Nationwide Emergency Department Sample, which can be used to create national estimates of ED care to query tests for GC, chlamydia, HIV, and syphilis testing. Weighted proportions and 95% confidence intervals (CIs) were reported, and Rao-Scott χ 2 tests were used. RESULTS: We identified 13,443,831 (weighted n = 3,094,214) high-risk encounters in which GC/chlamydia testing was performed. HIV screening was performed in 3.9% (95% CI, 3.4-4.3) of such visits, and syphilis testing was performed in 2.9% (95% CI, 2.7-3.2). Only 1.5% of patients with increased risk encounters received both HIV and syphilis cotesting. CONCLUSIONS: Despite CDC and USPSTF recommendations for HIV and syphilis screening in patients undergoing STI evaluation, only a small proportion of patients are being tested. Further studies exploring the barriers to HIV screening in patients undergoing STI assessment in the ED may help inform future projects aimed at increasing guidance compliance.

Post-adenoviral-based vaccines Guillain-Barre Syndrome: A proposed mechanism.

Despite great public health advances achieved by COVID-19 vaccines, rare side effects may impact the public acceptance. Guillain-Barre Syndrome has increasingly been reported with adenoviral-based vaccines. This perspective proposes a possible mechanism underlying this rare but clinically significant side effect thereby providing insights for improving our current vaccines against COVID-19.

COVID-19 during Pregnancy and Postpartum.

Coronavirus Disease 2019 (COVID-19) triggered by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection has been declared a pandemic by the World Health Organization (WHO) on March 11, 2020. Oxidative stress and its related metabolic syndromes are potential risk factors in the susceptibility to, and severity of COVID-19. In concert with the earliest reports of COVID-19, obstetricians started to diagnose and treat SARS-CoV-2 infections during pregnancy ("COVID-19-Pregnancy"). High metabolic demand to sustain normal fetal development increases the burden of oxidative stress in pregnancy. Intracellular redox changes intertwined with acute phase responses at the maternal-fetal interface could amplify during pregnancy. Interestingly, mother-to-fetus transmission of SARS-CoV-2 has not been detected in most of the COVID-19-Pregnancy cases. This relative absence of vertical transmission may be related to the presence of lactoferrin in the placenta, amniotic fluid, and lacteal secretions. However, the cytokine-storm induced during COVID-19-Pregnancy may cause severe inflammatory damage to the fetus, and if uncontrolled, may later result in autism spectrum-like disorders and brain development abnormalities in neonates. Considering this serious health threat to child growth and development, the prevention of COVID-19 during pregnancy should be considered a high priority. This review summarizes the intricate virulence factors of COVID-19 and elucidate its pathobiological spectrum during pregnancy and postpartum periods with a focus on the putative and complex roles of endogenous and exogenous lactoferrin in conferring immunological advantage to the host.

The antinuclear antibody HEp-2 indirect immunofluorescence assay: a survey of laboratory performance, pattern recognition and interpretation.

BACKGROUND: To evaluate the interpretation and reporting of antinuclear antibodies (ANA) by indirect immunofluorescence assay (IFA) using HEp-2 substrates based on common practice and guidance by the International Consensus on ANA patterns (ICAP). METHOD: Participants included two groups [16 clinical laboratories (CL) and 8 in vitro diagnostic manufacturers (IVD)] recruited via an email sent to the Association of Medical Laboratory Immunologists (AMLI) membership. Twelve (n = 12) pre-qualified specimens were distributed to participants for testing, interpretation and reporting HEp-2 IFA. Results obtained were analyzed for accuracy with the intended and consensus response for three main categorical patterns (nuclear, cytoplasmic and mitotic), common patterns and ICAP report nomenclatures. The distributions of antibody titers of specimens were also compared. RESULTS: Laboratories differed in the categorical patterns reported; 8 reporting all patterns, 3 reporting only nuclear patterns and 5 reporting nuclear patterns with various combinations of other patterns. For all participants, accuracy with the intended response for the categorical nuclear pattern was excellent at 99% [95% confidence interval (CI): 97-100%] compared to 78% [95% CI 67-88%] for the cytoplasmic, and 93% [95% CI 86%-100%] for mitotic patterns. The accuracy was 13% greater for the common nomenclature [87%, 95% CI 82-90%] compared to the ICAP nomenclature [74%, 95% CI 68-79%] for all participants. Participants reporting all three main categories demonstrated better performances compared to those reporting 2 or less categorical patterns. The average accuracies varied between participant groups, however, with the lowest and most variable performances for cytoplasmic pattern specimens. The reported titers for all specimens varied, with the least variability for nuclear patterns and most titer variability associated with cytoplasmic patterns. CONCLUSIONS: Our study demonstrated significant accuracy for all participants in identifying the categorical nuclear staining as well as traditional pattern assignments for nuclear patterns. However, there was less consistency in reporting cytoplasmic and mitotic patterns, with implications for assigning competencies and training for clinical laboratory personnel.

Highlights of the 33rd annual scientific meeting of the Association of Medical Laboratory Immunologists (AMLI).

The annual meeting of the Association of Medical Laboratory Immunologists (AMLI) was convened virtually over the month of August. Prior to the emergence of the COVID-19 pandemic, AMLI's scientific committee had chosen the following topics as the focus of its 2020 meeting: Histocompatibility Testing and Transplant Immunology; Secondary Immunodeficiency and Immunotherapy Monitoring; ANA Update; and Emerging Infectious Diseases and New Algorithms for Testing. Given the central role of the discipline in the evaluation of the host response to infection, it was apt to add a separate session on antibody testing for SARS-CoV-2 infections to the original program. The current report provides an overview of the subjects discussed in the course of this meeting.

Home testing for COVID-19: Benefits and limitations.

The home test kits for detecting SARS-CoV-2 infection with Food and Drug Administration emergency use authorization primarily use either isothermal nucleic acid amplification or antigen detection, and each test has advantages and limitations in terms of sensitivity and specificity, cost, results reporting, and results turnaround time. In clinical studies, these tests provide accurate positive results in symptomatic individuals, although negative results are less accurate. There are also accuracy concerns for positive results in asymptomatic individuals. These factors have implications for their clinical interpretation and use.

Interlaboratory Agreement of Anti-Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Serologic Assays in the Expedited College of American Pathologists Proficiency Testing Program.

CONTEXT.­: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently emerged, currently pandemic virus, and the etiologic agent of coronavirus disease 2019 (COVID-19). Clinical testing for antibodies to SARS-CoV-2 has rapidly become widespread, but data regarding the interlaboratory performance of these serologic assays are limited. OBJECTIVE.­: To describe the development and initial results of the College of American Pathologists (CAP) SARS-CoV-2 Serology Survey. DESIGN.­: Members from the CAP Microbiology and Diagnostic Immunology and Flow Cytometry Committees formed a working group to support development of a new proficiency testing survey for anti-SARS-CoV-2 antibody assays. Supplemental questions in the survey assessed the state of SARS-CoV-2 serologic testing among participating laboratories as of July 2020. Results were analyzed for agreement by immunoglobulin (Ig) isotype tested, assay manufacturer, and methodology. RESULTS.­: A total of 4125 qualitative results were received from 1110 laboratories participating in the first survey. Qualitative agreement for assays measuring anti-SARS-CoV-2 total antibodies or IgG was greater than 90% for all 3 samples in the survey. Qualitative agreement for IgM and IgA for the negative sample was greater than 95%, but lacked consensus for the other 2 samples. CONCLUSIONS.­: These initial data suggest overall excellent agreement and comparable performance for most qualitative anti-SARS-CoV-2 IgG and total antibody assays across all participating clinical laboratories, regardless of specific target antigen or assay methodology.

Evaluation of a new Strongyloides ELISA IgG Test Kit.

BACKGROUND: Strongyloides stercoralis poses a significant clinical and public health challenge not only in endemic regions but also in non-endemic regions associated with travel. Ruling out this infection is essential in immuno-compromised hosts given the high probability of reactivation and mortality. METHODS: In this study we compared an ELISA based on two recombinant antigens in the United States with a highly sensitive and specific reference serological test. RESULTS & CONCLUSION: There was 100% agreement between the two methods. ELISA assays based on Strongyloides stercoralis recombinant antigens has the potential to improve specificity. Further studies are warranted.

Operational Usability Evaluation of the LIAISON® QuantiFERON®-TB Gold Plus Solution in a High Volume Laboratory Setting.

BACKGROUND: Screening for latent tuberculosis infection (LTBI) using interferon gamma release assays has become commonplace for a variety of reasons. Given the high test volume, automated platforms are highly desired. METHODS: To this end, we performed an operational usability study using a newly FDA-approved, fully automated, random-access platform. RESULTS & CONCLUSIONS: Our results showed that this platform can save time and labor and will be a potential useful addition to streamline LTBI screening. Studies to verify performance characteristics are warranted.

Congenital syphilis: Missed opportunities and the case for rescreening during pregnancy and at delivery.

Two infants treated for syphilis born to at risk mothers who screened negative at their first prenatal visit but were not rescreened at delivery are described. The first presented with classic, but unrecognized, features of congenital syphilis. In the second case, possible early maternal syphilis was diagnosed soon after delivery using the treponemal first reverse-screening algorithm. Although the child's physical exam was normal and the maternal rapid plasma reagin (RPR) negative, the child was treated for syphilis because maternal confirmatory treponemal tests suggested recent seroconversion. Given the re-emergence of congenital syphilis, our report aims to demonstrate the importance of rescreening women at increased risk and improve awareness of common manifestations of the syphilis disease in the newborn. For women at increased risk, repeat syphilis testing early in the third trimester and again at delivery in communities and populations with a high prevalence of syphilis is recommended.