17 May History of pandemics and T cell immunity

Sun, 05/17/2020 - 20:26
  1. A nice overview how epidemics always disproportionally target socially and economically disfavored groups harder


  1. A very interesting paper on T cell responses in convalescent (healed) COVID patients :
  • Epitope pools detect CD4+ and CD8+ T cells in 100 and 70% of convalescent COVID patients
  • T cell responses are focused not only on spike but also on M, N and other ORFs
  • T cell reactivity to SARS-CoV-2 epitopes is also detected in non-SARS-CoV-2 exposed individuals (but exposed to other Coronaviruses.  
  • The IgG anti receptor binding domain (RBDdiscriminates best between COVID and non-COVID (Fig 1 p. 28)
  • With regard to T cell responses, the best discrimination is “activation induced markers” (OX40 CD137) expression upon  spike peptides stimulation of CD4 T cells (Fig 2A), but NOT the IFN-g production (Fig 2E). 
  • The CD8 T cell responses are weaker and less discriminatory than CD4 T cell responses.

One could suggest: OK then look for those epitopes that are specific for SARS-CoV-2 (and not cross-reactive with other Coronaviruses.  Maybe but you need to take into account that those epitopes should also be presented by a variety of HLA molecules.


  1. An hypothesis on  immune pathogenesis.  The new insight is that maybe COVID is not an acute, but rather subacute and that the immune pathogenesis could be different in the early and the later phase.  A typical acute pathology like complicated flu develops within days after infection and is characterized by a genuine “cytokine storm” (see Fig 3A), whereas in a typical chronic viral infection, such as HIV or hepatitis B/C, “immune activation and exhaustion” is dominant (Fig 3B).  For COVID both aspects could be present either early or later.  Hence, immune modulation should be careful, depending on what mechanism predominates: see Fig 4.   Hence, we need to follow up various immune parameters in patients with different profiles to understand what happens.


  1.  An example of such an approach, based on mRNA in blood in 3 patients is the topic of the last paper. The older, more severe patient showed a “cytokine storm” AFTER his “respiratory nadir.  Only IL-1 preceded it. Remarkably also, he cleared the virus much EARLIER than in the 2 mild cases, suggesting that he activated his “anti-viral” T cells earlier.  

As the authors admit, these are very limited data and preferentially they should be completed with data on genuine T cell responses, preferentially also from the mucosal site (e.g. broncho-alveolar), because, as is the case in other respiratory infection (e.g. TB), what you see in the periphery may be the “mirror image” of what is happening at the site of the infection….