7 May 2021 Episode 137 modeling of vaccination and responses in some immunosuppressed patients

Fri, 05/07/2021 - 18:31

 

Ep 137-1: Haghpanah EClinMed April 2021:  Effect of durability, timing and transmission-blocking capacity of a COVID vaccine on morbidity and mortality.

As can be expected, early and accelerated implementation of a vaccine that is less effective in transmission-blocking is more efficacious in reducing morbidity and mortality than later introduction of a more efficacious vaccine.

Therefore: non-pharmacological interventions should remain in place longer if the vaccine is less transmission-blocking or introduced late.

Clearly, this study is based on US situation. But anyhow, we are in a similar situation: we are introducing late and at least one of the vaccines used (AZ) has only 50 % infection blocking activity.

Ep 137-2: Moghadas PLOS Biology April 2021: Benefit of delaying the second dose of mRNA vaccines

This study is also modeling the US situation (with suboptimal vaccine roll-out) and is based on the published data of Moderna and Pfizer.

Moderna outperformed Pfizer-BioNTech for maximum benefits with a delayed second dose strategy (DSD).

For example, with 20% preexisting immunity and a daily vaccination rate of 30 doses per 10,000 people

  •  Moderna averted an additional 0.72 hospitalizations per 10,000 with a 12-week DSD strategy (Fig 3B).
  •  For Pfizer maximum benefit was achieved with a 9-week DSD which averted 0.44  hospitalizations

 

Conclusion: When racing against a burgeoning outbreak, prioritizing vaccine coverage with rapid distribution of the first dose would be critical to mitigating adverse outcomes and allow the healthcare system to also address non-COVID-19 medical needs of the population.

In the case of low incidence, it would still be important to accelerate vaccination with the first dose to protect the maximum number of individuals ahead of any outbreak surge.

 

Ep 137-3: Solforosi JEM Comparing one and two doses of J&J vaccine in aged non-human primates

  • A regimen of two moderate doses (5 X 1010) 8 weeks apart elicits clearly higher (10X) Neut Ab titers, compared to a single high dose (1011), while a shorter interval (4 weeks) resulted in intermediate levels. (Fig 1)
  • This regimen protects “aged” NHP (14-22 yrs old) almost perfectly against a challenge 13 weeks after first dose (both single high dose and two moderate dose vaccinations).  (Fig 4)
  • As expected the neut Ab were equally active against the British variant, but less against a single E484K mutant and much less against the South-African variant (Fig . 6). 
  • Remarkably: most of the samples from the one dose (7/12) failed to neutralize the South-African variants, while weak neut activity was present in all sera from the two dose regimen.   

 

Ep 137-4: Kupferschmidt and Vogel about the future of Adenovirus vaccines.

  • Reiterates the relative risks/benefit ratio of Astra-Zeneca, according to age and infection risk.
  • As could be expected, there is emerging evidence that not only J&J, but also the other adenovector vaccines (Sputnik and Cansino) show the vaccine-induced immune thrombotic thrombocytopenia.
  • Developing countries will be very reluctant to use the Adenovector vaccines, if they are no longer applied in the North.
  • Interesting reminder: there has been a similar situation with “Rotashield”, a vaccine that protects against severe rotavirus infection, but it was associated with rare occurrence of “intussusception”.  Not applying this vaccine in developing countries had caused thousands of preventable deaths in young infants….

 

Vaccine responses in some immunosuppressed populations

Ep 137-6: Ikizler in Kidney International provides a nice overview of studies in patients with terminal kidney disease.  What I take from it:

  • After natural infection in dialysis patients, antibodies tend to wane after 6 months, but not dramatically and there is evidence of robust T cell responses.
  • The induction of antibodies by (mRNA) vaccination in dialysis patients is delayed, but most seroconvert, although at clearly lower titers than healthy controls.    
  • In an Israeli study, some dialysis patients got infected 7 days after 2nd dose.
  • By contrast in kidney transplant patients, responses are much lower: only a minority (20-30 %) seroconverts.  Those patients are at increased risk for COVID complications.  Ep 137-5B and C)
  • Besides the kidney disease and drug induced immune suppression (Ep 137-5C), there are other “confounding factors”, such as advanced age and co-morbidities (diabetes, cardiovascular disease).  The effect of age is nicely illustrated in Ep 137-5 A and C))

 

Clearly,  these patients remain at increased risk after vaccination and should maintain some non-pharmacological measures to prevent infection (mask…). It is also advisable that their family members get vaccinated asap: ring-vaccination.

 

Ep 137-6: Similar observation in heart transplant patients (A) and in liver transplantation (B), although in these patients the percentage seroconverters was a bit higher than in renal transplants (here at 50 %).  

 

Ep 137-7: Cancers

 

  1. Herishanu (Blood): Chronic Lymphocytic Leukemia (CLL) : limited seroconversion:
  • 79 % in clinical remission after treatment.
  • 55.2% in treatment-naïve
  • 16% only in patients under treatment: especially the anti-CD20 antibody treatment, which depleted B cells.
  • Also effect of age and sex (females responded better).

 

  1. Mountzer (medRxiv) Various hematological cancers: CLL clearly has the worst response, while a higher proportion of patients with lymphoma’s and multiple myeloma’s do respond, irrespective of age, cancer therapy or IgG levels, hence linked to the B cell nature of the cancer in CLL.

 

  1. Leticia (Lancet) a smaller study, suggesting that the response to vaccination is better in solid cancers (as compared to hematological ones)

 

  1. Tougeron (Eur J Cancer) provides clear guidelines for vaccination in cancer patients.  Nevertheless, things are evolving quickly: this publication, accepted in March, still mentions pregnancy as a “contra-indication”….

 

 

Update on variants (kindly provided by colleague P Smits)

 

Nice overview:  https://myorthoevidence.com/Blog/Show/126?vgo_ee=s2oiXrKrkTakIjfIrnJ2PtE%2BkBUIVIipeuvLV6m8%2BDA%3D

Some details:

 

https://covariants.org/variants/S.L452R

https://covariants.org/variants/20C.S.484K

https://covariants.org/variants/20A.S.154K

https://covariants.org/variants/20A.S.478K

 

I’ll be back with some comments on the ground-breaking study by Zhang on integration of SARS-CoV-2 tomorrow.

 

Best wishes for now,

 

Guido  

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