2 June 2021 Episode 143 More on children, vaccines and Indian variant

Dear colleagues,

Ep 143-1 : NEJM Good news on efficacy and safety of Pfizer vaccine in > 1000 children (12-15 yrs) in USA:

• No serious side effects.
• Efficacy > 7 days after 2nd dose: 100 % (0 in vaccine versus 16 in placebo
• Efficacy after 1st dose: 75 % (3 in vaccine versus 12 in placebo)
• Efficacy based on confirmed symptomatic COVID (respiratory symptoms).

Ep 143-2: Abu-Raddad J Trav Med: Fine analysis of Pfizer efficacy against South-African variant in Qatar:

As expected, efficacy against any symptom was negligible within 2 weeks after 1st dose, but increased to 65% against B.117 (now renamed alpha) and to 46 % to B. 1.315 (now beta).  It reached maximum 2 weeks after 2nd dose of 89.5 % against alpha and 75 % against beta.

Efficacy against severe, critical or fatal disease started in the second week after 1st dose (26 %), increased to 73 % in third week after the 1st dose and > 97 % 2 weeks after 2nd dose, irrespective of the variant.

Ep 143-3: Khoury in Nature models published clinical efficacy and in vitro neutralization data in the various vaccine trials.  The  known order of efficacy with mRNA and S protein vaccines on top, followed by Adeno (J&J > AZ) and inactivated vaccines rather at the bottom clearly correlates with in vitro neutralization.  (Data restricted to epidemics with “WT” D614G virus).

They deduce that one needs 20 % neut as compared to mean convalescent titers to enjoy 50 % protection against infection and only 3 %  for 50 % protection against severe disease.

Based on the observed waning of neut Ab over time (estimated half-life about 100 days), it is evident that one will need a boost after a different time, depending on the initial strength of the vaccine (level of neut induced) and that the boost needs to come faster if more infectious variants arise.

All very logical, but….

two limitations:

• Based on comparison with convalescent plasma, which was not standardized across trials.
• Only circulating antibodies are considered and not memory B cells (or T cells). 

Ep 143-4, -5 and -6:   Provide arguments of long term memory B cells after natural SARS-CoV-2 infection (investigated at 7 months p.i.) and after mRNA vaccination (investigated up to 7 weeks after second dose).  While S-antibody titers may tend to decrease in the serum and circulating B cells, producing anti-S may even disappear, the lymph nodes still contain low but measurable memory B cells. 

The caveat is that in the first study (om memory after infection 143-4) only mild cases of relatively young patients (mean age 49) were included.  It remains to be seen if this “positive news” also applies to (very) old people, who survived severe disease.

It is also confirmed that previously SARS-CoV-2 infection, enhances the neut antibody titers by vaccination very strongly, including against the alpha (British) and beta (S-A) variants.

Ep 143-7 and -8: Data from UK on vaccine protection against “Indian variant” B.1.617.2 (delta):

• NHS reduced protection by vaccine against delta after 1st dose, but maintained protection after 2 doses
• More in depth analysis, comparing AZ and Pfizer for Indian vs British variant :
  • After 1st dose: similar reduction in protection for both vaccines, but more pronounced for Indian (only 33 %) vs British (51 %).
  • After 2nd dose: Pfizer 93 % protection against British and 88 % against Indian, while AZ only 66 % against British and 60 % against Indian.  While confidence intervals overlap for Indian versus British, Pfizer clearly outperforms AZ.

Ep 143-9: Mercier gives a nice overview of Multisystem Inflammatory Syndrome in Children in France.  It is of course a rare condition, but nevertheless, look at Fig 2: while the overall COVID hospitalizations were counted in the tens of thousands, dozens of MIS-C follow the COVID waves. A few hundreds of French children aged 2-16 have been critically ill with MIS-C.

Ep 143-10: Gill and Schellekens (from World Bank) argue that COVID-19 mortality is NOT more prevalent in high income countries (HIC with ageing populations), as generally accepted, but that developing countries (DC) take the largest share.  The  discrepancy between the accepted impression and the grim reality is due to underreporting and lack of care in DC.  Fig 7 p. 8 summarizes : reported cases are almost equal in HIC and DCs, but the burden of the world’s estimated excess mortality due to COVID is 86 % in DC and only 14 % in HIC. 

The presumptions and calculations to calculate this “real” excess mortality are however not explicated and in part B a discussion is presented, which does not really resolve the question….

CONCLUSIONS

1. Children are vulnerable to serious COVID, but can effectively be protected with Pfizer
2. Although serum neutralizing antibodies and S-specific peripheral blood B cells after infection and vaccination may decline, the memory B cells in lymph nodes may be long-lived.
3. Astra-Zeneca protects less than Pfizer, especially against the Indian variant
4. Excess mortality due to COVID may be more pronounced in developing countries than previously thought.  

Best wishes,

Guido