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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335191

ABSTRACT

ABSTRACT Clinical diagnoses rely on a wide variety of laboratory tests and imaging studies, interpreted alongside physical examination and documentation of symptoms and patient history. However, the tools of diagnosis make little use of the immune system’s internal record of specific disease exposures encoded by the antigen-specific receptors of memory B cells and T cells. We have combined extensive receptor sequence datasets with three different machine learning representations of the contents of immune repertoires to develop an interpretive framework, MAchine Learning for Immunological Diagnosis (Mal-ID) , that screens for multiple illnesses simultaneously. This approach can already reliably distinguish a wide range of disease states, including specific acute or chronic infections, and autoimmune or immunodeficiency disorders, and could contribute to identifying new infectious diseases as they emerge. Importantly, many features of the model of immune receptor sequences are human-interpretable. They independently recapitulate known biology of the responses to infection by SARS-CoV-2 or HIV, and reveal common features of autoreactive immune receptor repertoires, indicating that machine learning on immune repertoires can yield new immunological knowledge.

2.
J Clin Immunol ; 42(2): 253-265, 2022 02.
Article in English | MEDLINE | ID: covidwho-1565436

ABSTRACT

Patients with primary antibody deficiency are at risk for severe and in many cases for prolonged COVID-19. Convalescent plasma treatment of immunocompromised individuals could be an option especially in countries with limited access to monoclonal antibody therapies. While studies in immunocompetent COVID19 patients have demonstrated only a limited benefit, evidence for the safety, timing, and effectiveness of this treatment in antibody-deficient patients is lacking. Here, we describe 16 cases with primary antibody deficiency treated with convalescent plasma in four medical centers. In our cohort, treatment was associated with a reduction in viral load and improvement of clinical symptoms, even when applied over a week after onset of infection. There were no relevant side effects besides a short-term fever reaction in one patient. Longitudinal full-genome sequencing revealed the emergence of mutations in the viral genome, potentially conferring an antibody escape in one patient with persistent viral RNA shedding upon plasma treatment. However, he resolved the infection after a second course of plasma treatment. Thus, our data suggest a therapeutic benefit of convalescent plasma treatment in patients with primary antibody deficiency even months after infection. While it appears to be safe, PCR follow-up for SARS-CoV-2 is advisable and early re-treatment might be considered in patients with persistent viral shedding.


Subject(s)
COVID-19/immunology , COVID-19/therapy , Plasma/immunology , Primary Immunodeficiency Diseases/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Child , Female , Humans , Immunization, Passive/methods , Male , Middle Aged , Virus Shedding/immunology , Young Adult
3.
Clin Immunol ; 230: 108803, 2021 09.
Article in English | MEDLINE | ID: covidwho-1322033

ABSTRACT

To better understand COVID-19 infection in patients receiving biologic and immunomodulatory therapies, we evaluated prevalence and outcomes for symptomatic cases of COVID-19 at a large therapeutic infusion center in New York City during the height of the pandemic. 2074 patients received treatment with biologic infusions at our center between March and May 2020, and 34 patients developed symptomatic COVID-19 infection, for an overall low rate of 1.64%. The majority of infections and deaths were in a small subset of patients with a primary immunodeficiency. Patients with inflammatory or autoimmune conditions requiring biologic therapies tended to have mild cases. Higher inflammatory responses were observed in patients who died.


Subject(s)
Ambulatory Care Facilities , Autoimmune Diseases/therapy , Biological Factors/administration & dosage , COVID-19/epidemiology , SARS-CoV-2 , Biomarkers , COVID-19/complications , COVID-19/mortality , Comorbidity , Female , Humans , Incidence , Inflammation/metabolism , Male , Middle Aged , New York City/epidemiology , Prevalence
7.
Nat Med ; 26(7): 1033-1036, 2020 07.
Article in English | MEDLINE | ID: covidwho-244499

ABSTRACT

Here, we describe a serological enzyme-linked immunosorbent assay for the screening and identification of human SARS-CoV-2 seroconverters. This assay does not require the handling of infectious virus, can be adjusted to detect different antibody types in serum and plasma and is amenable to scaling. Serological assays are of critical importance to help define previous exposure to SARS-CoV-2 in populations, identify highly reactive human donors for convalescent plasma therapy and investigate correlates of protection.


Subject(s)
Betacoronavirus/immunology , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Coronavirus Infections/immunology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/immunology , Seroconversion , Adult , Betacoronavirus/pathogenicity , COVID-19 , COVID-19 Testing , Case-Control Studies , Coronavirus Infections/blood , Coronavirus Infections/therapy , Coronavirus Infections/virology , Electrophoresis, Polyacrylamide Gel , Enzyme-Linked Immunosorbent Assay , Humans , Immunization, Passive , Longitudinal Studies , Middle Aged , Neutralization Tests , Pandemics , Pneumonia, Viral/therapy , Pneumonia, Viral/virology , SARS-CoV-2 , Young Adult
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