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Authors:Gallais et al. 

Journal/ Pre-Print:medRxiv 

Tags: Clinical, Diagnostics, Immunology/Immunity 

Research Highlights

  1. 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. 


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 aunderestimation 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  

  • In vitro study 

  • 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 ( 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:  

  • 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.   

  • 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.