18 April Perspective second part

Sun, 04/19/2020 - 11:53

Dear colleagues,

Sorry to be absent for a few days: I had to prepare for the course on COVID I’m teaching tomorrow.

Here I’m back with a discussion on possible scenarios for the post-pandemic peak, based on a recent paper in Science by Kissler and Lipsitch.  Fig 3 p. 12 shows different scenarios: from recurrence each year if immunity after infection is short-lived (40 weeks), biennial recurrence (immunity 100 weeks) or even extinction (immunity for life). There is also a “rebound scenario”: apparent extinction and reappearance in 2024.

Clearly, to judge the value of these scenarios, you should look at the basic presumptions:

  1. Seasonality: this has clearly been shown for the “old” alfa (229E, NL63, and beta (OC43, HKU1) coronaviruses (see Dominguez J Gen Virol paper fig 1 p 3).  It has been suggested for SARS-CoV-1, because it appeared in Nov 2002 and disappeared in July 2003.  But it remains to be seen for SARS-CoV-2.
  2. Cross-neutralization between betacoronaviruses.  It has been shown indeed that sera from SARS-CoV-1 subjects can cross-neutralize OC43 in vitro (see Chan J Infect Table 2 p. 135), but I cannot find literature that the reverse would be true.  There is this interesting story of an outbreak of OC43 in an elderly facility (British Columbia 2006), with 8 % mortality, that was first suspected to be SARS, but then proven OC43.  They show cross-reactivity of serum Ab towards epitopes in N (Table 4 p 6), but provide no data on cross-neutralization.
  3. The seasonality of the common alfa and beta CoV suggests that there is no long-lived immunity and this has been proven experimentally for the alfa CoV 229E (see Reed 1984 and Callow 1990), also because of viral evolution.  Unfortunately, I could not find similar experiment for the beta’s.
  4. There is evidence of long-lived immunity in SARS-CoV-1 patients. As you can see in Mo Respirology 2006, neutralizing IgG antibodies persist for > 700 days, but there is a decay of > 2.5 log 10 ! In view of similarity between both SARS-CoV’s, one could hope that SARS-CoV-2 will induce rather long-lived in vitro neutralizing antibodies too, but it remains to be seen what the in vivo protective value is of these neutralizing antibodies.    
  5. Kissler and Lipsitch also briefly elaborate on the possibility that “too much social distancing”, followed by relaxation of those measures,  would paradoxically increase the next wave of COVID-19, because not enough herd immunity is  induced.  This presumption is based on a retrospective analysis of the Spanish Flu “ in which the size of the autumn 1919 peak was inversely related to that of the subsequent winter, after interventions were no longer in place”.  I’m not sure with what level of confidence one can perform such “historical retrospective epidemiology”, but maybe some of you have experience with it?     


As far as understand Kissler anf Lipsitch’ conclusions, their cautious position is that in the absence of a very effective vaccine or treatment, we will have to find an equilibrium between intermittent “physical distance”, “track and isolate” and maintaining a high level or even increasing the critical care capacities.  Maybe they do not want to take too much of a “political” position in the very heated debate between Trump and his critics? Anyhow, let’s keep out of that wasp nest and see what we can do to get our own countries out of the present lockdown, as safely as possible.

My personal very “down to earth” research agenda would be: we need more insight on the predictive value of neutralization assays and whether there is important cross-neutralization (not just cross-reactivity) between the beta-Coronaviruses OC43, HKU1 and SARS-CoV-2.   But, I’m out of active service, as you know.  So, it’s up to you, guys.

As a desert, an long interview in French with Luc Montagner that a colleague sent me yesterday:


So, in follow-up of a retracted paper by scientist from India, Montagner now claims that SARS-CoV-2 is NOT a natural virus, but that it has been constructed in a lab, presumable as an experimental vaccine against HIV, because it contains HIV sequences

Don’t ask me whether this is true: I don’t have the capability to investigate it, but I guess there are people amongst you who could check the published sequences and verify whether there is enough homology with HIV to suspect such a monstrous manipulation?    Anyhow, I’m sure various experienced groups (e.g. in Los Alamos) will enlighten us in the coming days…..

In the meantime: please stay cool and take care