Intrafamilial Exposure to SARS-CoV-2 Induces Cellular Immune Response without Seroconversion
clinical diagnostics immunology/immunity
Authors:Gallais et al.
Journal/ Pre-Print:medRxiv
Tags: Clinical, Diagnostics, Immunology/Immunity
Research Highlights
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Exposure of individuals to SARS-CoV-2 positive patients could lead to the development of COVID-19 symptoms and SARS-CoV-2 specific T cell responses, in the absence of seroconversion.
Summary
Nine SARS-CoV-2-infected patients from seven families developed mild COVID-19 symptoms, SARS-CoV-2 specific T cell responses and seroconversion for anti-viral immunoglobulin. Of the eight household members who were exposed to the infected individuals, six reported COVID-19-like symptoms yet did not produce an antibody response according to three distinct antibody tests. Six of the eight exposed individuals did however produce SARS-CoV-2 specific T cell responses against viral structural and accessory proteins. Even though the study is limited in sample size, it shows SARS-CoV-2 specific T cell responses in the absence of seroconversion. The authors argue that reliance on serological testing would lead to an underestimation of COVID-19 prevalence, although the incidence of this phenomenon is not yet established. It would be also of interest to understand how the absence of seroconversion impacts long-term protection from reinfection.
Impact for SARS-CoV2/COVID19 research efforts
Understand the immune response to SARS-CoV2/COVID19
Develop diagnostic tools for SARS-CoV2/COVID19
Study Type
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In vitro study
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Patient Case study
Strengths and limitations of the paper
Novelty: Gallais et al. described the absence of SARS-CoV-2 specific humoral responses, despite the development of mild symptoms and specific T cell responses. Possible underestimation of COVID-19 prevalence if epidemiological data is based on antibody titres.
Standing in the field: A strength in this study is the use of three commercial serological assays for S and N-specific immunoglobulin. The discrepancy between humoral and cellular responses is confirmed in a recent larger cohort (https://www.biorxiv.org/content/10.1101/2020.06.29.174888v1) where interestingly healthy donors and exposed relatives were twice as likely to have virus-specific memory T cell responses than antibody responses.
Appropriate statistics:No statistics used
Viral model used: SARS-CoV-2 PCR-confirmed infected patients and exposed relatives from March 2020 in Strasbourg, France. T cell responses against common coronavirus (HCoV-299E and HCoV-OC43) peptides was also assessed.
Translatability: Virus-specific T cell responses may be a more sensitive measure of SARS-CoV-2 infection than serological assays.
Main limitations:
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Small sample size and no grouped statistics, although the patient information is well described. It is not clear if the index patients or contacts have pre-existing conditions or medications.
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The enrolment strategy for these patients is unclear. If these households were selected for their discrepancies in seroconversion after SARS-CoV-2 exposure, what was the total number of households available for enrolment? This is important to understand the frequency of the absence of seroconversion.