17 July T and B cells herd immunity and immunotherapy

1. Comment on pre-existing T cell immunity (Nature Reviews)

SARS-CoV-2 pre-existing T cell immune reactivity to some COVID-19 peptides exists to 20-50 % in the general population.

It is hypothesized, but not yet proven, that this might be due to “memory” immunity to circulating common cold coronaviruses.

This might have implications for COVID-19 disease severity, herd immunity and vaccine development, which theoretically could either be promoted or hampered by “cross-protection” (see H1N1 Influenza) or “original antigen enhancement “ (see Dengue).

Implication: research on pre-existing T cell immunity can help to understand heterogeneity in disease expression, response to vaccination etc. is  

2. Herd Immunity:

• Based on the R0 of 2.5, the most conservative estimate is that you need 60 % of the population to have acquired immunity by infection or vaccination with SARS-CoV-2 to prevent a new epidemic.
• There is, however, heterogeneity in susceptibility (based on crowding, behavior and genetic factors, but probably also pre-existing cross-reacting T cells).
• Heterogeneity lowers the threshold for herd immunity, bc the original estimates are based on the spread in the most susceptible individuals.  The next waves will have to reach the less susceptibles and therefore the spread slows down…. However, the estimates on what level of immunity you need vary widely.

3. Living review on treatment with convalescent plasma: see summary in attachment.  Full paper see https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013600.pub2/full

As you can seen despite over 5000 patients having received convalescent plasma, there is no conclusion possible: only 1 randomized trial with no clear result.  Many non-controlled trials, with no clear results. Many trials are underway, but, quite cynically, they will only provide trustworthy results if a fullblown “second wave” will hit us….

Hence the repeated sentence in the review: We are very uncertain whether convalescent plasma has any effect….

4. Kinetic analysis of viral load and antibody responses in mild versus severe COVID ( Wang JCI)

• Severe patients show viral shedding in various tissues for many weeks, while in mild patients, it is restricted to respiratory tract and only a few weeks.
• Mild patients very low IgM responses, but similar IgG responses.   
• Neutralizing Ab higher in severe patients
• No cross-reacting Ab to common coronaviruses induced (in contrast with cross-reacting T cells!), but Ab cross-reactivity with SARS, without cross-neutralization.

Associated comment plea for the use of convalescent plasma before day 10 (i.e. before the patient mounts Ab himself): could protect from widespread tissue inflammation, as observed in severe cases (and reflected by viral load and IgM response  

5. First report on disappearance of neutralizing Ab in a mild COVID patient within 3 months.  Also no SARS-CoV-2 circulating B cells left.  Nevertheless, this does not necessarily imply loss of B (and T) cell memory, which could still be protective upon re-encounter with SARS-CoV-2

6. There are several very recent encouraging (peer reviewed) papers in Nature, Cell etc on generation of potent human neutralizing antibodies from patient B cells that could be used as immunotherapy in stead of less reliable convalescent plasma.  The papers contain a lot of nice figures, but files are very big.  So, I just add the summaries. If you cannot access the files, I can send you the pdf separately.

Best wishes,

Guido