The early immune response after SARS-Cov-2 infection

Location : webinar Speaker : Guy Gorochov (CIMI-paris)

IgA dominates the early neutralizing antibody response to SARS-CoV-2

We thought that IgA responses might be particularly important to study in patients with COVID-19, given the mucosal route of entry taken by the virus. We tested 145 patients by cytofluorometry, serology (using a new photonic ring resonance platform) and neutralisation tests, in collaboration with the Pasteur Institute.
Surprisingly, we observed that the cellular and humoral responses to SARS-Cov-2 are mainly IgA-based initially. A very important blood recirculation of IgA-secreting plasmablasts, probably of pulmonary origin, generally precedes the IgG response, but also the IgM response. Finally, we show for the first time that, when induced, purified IgA is a much more potent neutralising agent of SARS-Cov-2 than IgG.
Overall, IgA appears to be not only the best early serological marker of COVID-19, but also an important antiviral effector that future vaccine approaches may consider attempting to elicit specifically.

A dichotomous cytokine response differentially associated with COVID-19 severity and mortality

We recently helped to show that type I interferon (IFN) responses are defective in a significant proportion of COVID-19 patients (Zhang et al. & Bastard et al. Science, 24 September), typically in those suffering from a pro-inflammatory cytokine storm. However, in the Science articles, an important dimension is missing, as not all patients suffer from this defective response to type 1 IFN.
We now present a two-dimensional picture of the cytokine response of COVID-19. Using a systematic unsupervised bioinformatics approach to analyse 12 cytokines together, we document for the first time a dichotomous cytokine response. While some patients, typically with critical respiratory severity, indeed have high levels of IL-6, IL-8 and TNF-α and low type I IFN responses, other patients, typically with moderate respiratory severity, have low levels of pro-inflammatory cytokines and rather high levels of IFN. Furthermore, we show that it is the exacerbated IFN response that is associated with mortality in these patients. Protective associations with other cytokines are also observed.

The heterogeneous cytokine response that we demonstrate may explain why therapies targeting a particular cytokine have so far met with rather mixed success. We believe that our results not only contribute significantly to a better understanding of the pathophysiology of COVID-19, but will also have an impact on clinical practice towards a more personalised therapeutic approach based on cytokine profiling, as physicians are in fact faced with at least two types of ‘cytokine storms’ with opposite characteristics.

Team involved :

Gorochov Guy