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Microbiol Spectr ; 9(2): e0105921, 2021 10 31.
Article in English | MEDLINE | ID: covidwho-1495012


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and has since caused a global pandemic resulting in millions of cases and deaths. Diagnostic tools and serological assays are critical for controlling the outbreak, especially assays designed to quantitate neutralizing antibody levels, considered the best correlate of protection. As vaccines become increasingly available, it is important to identify reliable methods for measuring neutralizing antibody responses that correlate with authentic virus neutralization but can be performed outside biosafety level 3 (BSL3) laboratories. While many neutralizing assays using pseudotyped virus have been developed, there have been few studies comparing the different assays to each other as surrogates for authentic virus neutralization. Here, we characterized three enzyme-linked immunosorbent assays (ELISAs) and three pseudotyped vesicular stomatitis virus (VSV) neutralization assays and assessed their concordance with authentic virus neutralization. The most accurate assays for predicting authentic virus neutralization were luciferase- and secreted embryonic alkaline phosphatase (SEAP)-expressing pseudotyped virus neutralizations, followed by green fluorescent protein (GFP)-expressing pseudotyped virus neutralization, and then the ELISAs. IMPORTANCE The ongoing COVID-19 pandemic is caused by infection with severe acute respiratory syndrome virus 2 (SARS-CoV-2). Prior infection or vaccination can be detected by the presence of antibodies in the blood. Antibodies in the blood are also considered to be protective against future infections from the same virus. The "gold standard" assay for detecting protective antibodies against SARS-CoV-2 is neutralization of authentic SARS-CoV-2 virus. However, this assay can only be performed under highly restrictive biocontainment conditions. We therefore characterized six antibody-detecting assays for their correlation with authentic virus neutralization. The significance of our research is in outlining the advantages and disadvantages of the different assays and identifying the optimal surrogate assay for authentic virus neutralization. This will allow for more accurate assessments of protective immunity against SARS-CoV-2 following infection and vaccination.

Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Serological Testing/methods , COVID-19/diagnosis , Neutralization Tests/methods , SARS-CoV-2/immunology , Adult , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Male , Middle Aged , Protein Domains/immunology , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/immunology , Vesicular stomatitis Indiana virus/immunology , Vesicular stomatitis New Jersey virus/immunology
Curr Opin Hematol ; 28(6): 394-400, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1377996


PURPOSE OF REVIEW: To discuss the clinical experience of coronavirus disease 2019 (COVID-19) in hematopoietic cell transplant and chimeric antigen receptor T-cell therapy recipients over the past year and to identify key knowledge gaps for future research. RECENT FINDINGS: Immunocompromised individuals and those with chronic health conditions are especially susceptible to infections, which have had a disproportionate impact on health outcomes during the COVID-19 pandemic. Several studies have evaluated the clinical characteristics and outcomes of transplant and cellular therapy (TCT) recipients who developed COVID-19. Age, sex, comorbid conditions, and social determinants of health are important predictors of the risk of severe acute respiratory syndrome coronavirus 2 infection and of the eventual severity of the disease. Various treatment approaches have been investigated over the last year. The paradigm of management strategies continues to evolve as more experience is accumulated. SUMMARY: In this review, we summarize some important findings as they relate to the clinical characteristics of TCT recipients who develop COVID-19. We also discuss some treatment approaches that are currently recommended and opine on vaccination in this population.

COVID-19/epidemiology , Cell- and Tissue-Based Therapy/standards , Hematopoietic Stem Cell Transplantation/standards , Immunocompromised Host , Practice Guidelines as Topic/standards , Receptors, Chimeric Antigen/immunology , Transplant Recipients/statistics & numerical data , COVID-19/immunology , COVID-19/virology , Humans , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification
J Immunol Res ; 2020: 1372494, 2020.
Article in English | MEDLINE | ID: covidwho-820046


Type I interferons (IFN-I) are a group of related proteins that help regulate the activity of the immune system and play a key role in host defense against viral infections. Upon infection, the IFN-I are rapidly secreted and induce a wide range of effects that not only act upon innate immune cells but also modulate the adaptive immune system. While IFN-I and many IFN stimulated genes are well-known for their protective antiviral role, recent studies have associated them with potential pathogenic functions. In this review, we summarize the current knowledge regarding the complex effects of human IFN-I responses in respiratory as well as reemerging flavivirus infections of public health significance and the molecular mechanisms by which viral proteins antagonize the establishment of an antiviral host defense. Antiviral effects and immune modulation of IFN-stimulated genes is discussed in resisting and controlling pathogens. Understanding the mechanisms of these processes will be crucial in determining how viral replication can be effectively controlled and in developing safe and effective vaccines and novel therapeutic strategies.

Antiviral Agents/metabolism , Flavivirus/physiology , Interferon Type I/metabolism , Respiratory Tract Infections/immunology , Viral Vaccines/immunology , Virus Diseases/immunology , Animals , Humans , Immunity, Innate , Public Health , Vaccination , Virus Replication