Intrafamilial Exposure to SARS-CoV-2 Induces Cellular Immune Response without Seroconversion

Abstract

Background. In the background of the current COVID-19 pandemic, serological tests are being used to assess past infection and immunity against SARS-CoV-2. This knowledge is paramount to determine the transmission dynamics of SARS-CoV-2 through the post pandemic period. Several individuals belonging to households with an index COVID-19 patient, reported symptoms of COVID-19 but discrepant serology results. Methods. Here we investigated the humoral and cellular immune responses against SARS-CoV-2 in seven families, including nine index patients and eight contacts, who had evidence of serological discordances within the households. Ten unexposed healthy donors were enrolled as controls. Results. All index patients recovered from a mild COVID-19. They all developed anti-SARS-CoV-2 antibodies and a significant T cell response detectable up to 69 days after symptom onset. Six of the eight contacts reported COVID-19 symptoms within 1 to 7 days after the index patients but all were SARS-CoV-2 seronegative. Six out of eight contacts developed a SARS-CoV-2-specific T cell response against structural and/or accessory proteins that lasts up to 80 days post symptom onset suggesting a past SARS-CoV-2 infection. Conclusion. Exposure to SARS-CoV-2 can induce virus-specific T cell responses without seroconversion. T cell responses may be more sensitive indicators of SARS-Co-V-2 exposure than antibodies. Our results indicate that epidemiological data relying only on the detection of SARS-CoV-2 antibodies may lead to a substantial underestimation of prior exposure to the virus

Immune responses to SARS-CoV-2 in children of parents with symptomatic COVID-19

“…Investigating immune responses to SARS-CoV-2 across all age groups is key to understanding disease susceptibility, severity determinants, and vaccine candidates. Detailed investigations of immune responses during SARS-CoV-2 infection have been reported in adults [10][11][12] , with exposure to SARS-CoV-2 causing speci c T cell responses without seroconversion 13 . Data on immune responses in children exposed to SARS-CoV-2 are limited.…”

Mapping the SARS-CoV-2 spike glycoprotein-derived peptidome presented by HLA class II on dendritic cells

“…Notably, the four seasonal common cold-causing human coronaviruses and the zoonotic Middle East respiratory syndrome (MERS) and SARS coronaviruses typically elicit poorly-sustained nAb responses, putatively enabling subsequent re-infection 6 . However, somewhat more durable T cell responses are induced, which in animal models can prevent development of severe disease on challenge, providing a rationale for vaccine-mediated induction of T cell as well as nAb responses 7,8,9,10 .…”

A Lymph Node Targeted Amphiphile Vaccine Induces Potent Cellular and Humoral Immunity to SARS-CoV-2

“…Isotype analysis yielded similar observations to those made in young healthy mice, with AMP-CpG driving more Th1, IgG2bc-dominant responses compared with soluble CpG or alum, which yielded more balanced or Th1, IgG1-biased profiles ( Figure 9D-G SARS-CoV-2 neutralizing antibody responses to infection are temporary, declining quickly after recovery 16 . In addition, recent studies have shown that a subset of patients recover from COVID-19 with SARS-CoV-2 specific T cells but not neutralizing antibodies 8,9,10 , indicating a potentially important role for T cells as a mechanism of disease prevention or mitigation. Indeed, in mouse models, CD8 + and CD4 + T cells were necessary for protective immunity against SARS and MERS infections 42,43 .…”

“…An optimal SARS-CoV-2 vaccine should generate potent T cell immunity alongside neutralizing antibody responses. Patient recovery from SARS-CoV-2 infection without mechanical ventilation is significantly associated with elevated T cell levels 4,5,6,7 , and T cell responses without humoral responses have proven sufficient for COVID-19 resolution 8,9,10 . Conversely, death has been associated with reduced T cell numbers in COVID-19 11 , with lymphocyte subset analyses implicating deficiency in both CD3 + CD4 + and CD3 + CD8 + T cells 4 .…”