29 January 2023 Episode 312 Clinical consequences of COVID and news on vaccines

Sun, 01/29/2023 - 15:42

Dear colleagues,

This short episode will  be arranged in two paragraphs: clinical findings on long-term effects of acute COVID and some  news about vaccines.

With many thanks to colleagues who shared some of this material (Patrick Smits; Pierre Van Damme…).


First a reminder: Episode 312-0 = COVID highlights during first 2 years by the Royal Society of Medicine  

Par 1 New clinical findings on long term effects of COVID

Ep 312-1: Edlows JAMA Network Pediatrics: Overall 6 % neurodevelopmental problems at 1 year in babies from positive mothers versus 3 % if the mother had not been infected.  More risk if infection during third trimester.

It is a retrospective study in 7700 babies that needs confirmation.  

Ep 312-2:  Falko Tesch medRxiv 26 Jan 2023:  42% increased risk of new-onset autoimmune diseases after acute SARS-CoV-2 in Germany



Table 2  shows a long list of auto-immune diseases with increased incidence after COVID, ranging from Hashimoto’s thyroiditis to rheumatoid arthritis.  The highest RR is for Wegener > Behcet > Guillain-Barré > sarcoidosis > thrombocytopenia purpura > arteritis temporalis …

People with severe COVID have a clearly elevated risk on auto-immunity.



Ep 312-3: Mizrak Barak BMJ Jan 2023: Long COVID in a large Israeli cohort (with test-negative controls)

Main findings:

  • Patients with mild covid-19 had an increased risk for a small number of health outcomes, most of which resolved within a year from diagnosis




  • Children (below 11) had fewer outcomes, which mostly resolved in the late period, highest risk in mid-age group; sex had a minor effect on risk of outcomes.


  • Findings remained consistent across SARSCoV-2 variants: between March 2020-Oct 2021 (WT to Delta, omicron not included)


  • Breakthrough infections (after vaccination): lower risk for dyspnoea and similar risk for other outcomes was observed in vaccinated patients with BTI  compared with unvaccinated patients


Ep 312-4: Lucie Bernard-Raichon Nat Med Nov 2022:  Severe COVID causes gut microbiome dysbiosis and secondary systemic infections, because of epithelial damage and bacterial translocation  

It is a complex paper that shows a decrease of diversity, with overgrowth of the family of Akkermansiaceae  (= mucin-degrading bacteria) both in experimentally infected mice and hospitalized patients.

There is an associated increase  of mucin-producing Globlet cells and a decrease of Paneth cells, which produce anti-microbial and anti-viral factors such as lysozyme.

In patients, microorganisms from the dysbiotic gut microbiome translocate into the blood with dangerous systemic infections of drug-resistant microbes , plausibly due to a combination of the immunocompromising effects of the viral infection and antibiotic-driven depletion of commensal gut microbes with loss of gut barrier integrity.

These findings are reminiscent of AIDS patients, chemotherapy for cancer and inflammatory bowel disease

Ep 312-5: Hannah Davis Nat Rev Microbiol Jan 2023: Long-COVID findings, mechanisms, recommendations

Long COVID symptoms and the impacts on numerous organs with differing pathology.

The presentation of pathologies is often overlapping, which can exacerbate management challenges.




MCAS, mast cell activation syndrome;

ME/CFS, myalgic encephalomyelitis/chronic fatigue syndrome;

POTS, postural orthostatic tachycardia syndrome.


Hypothesized mechanisms of long COVID pathogenesis




EBV, Epstein–Barr virus; HHV-6, human herpesvirus 6



Par 2 News on vaccines


Reassuring news for children with MISC: COVID-19 vaccine for children after MIS-C appears safe


Remember Ep 310-2 and -3: some common features between MISC and post RNA vaccine myocarditis: similar inflammatory markers, but also high circulating levels of Spike protein.


Ep 312-6: Matthew D. Elias JAMA Open Pediatrics Jan 2023


In 385 patients with a history of MIS-C, 48.1% were vaccinated for COVID-19: “normal” proportion with mild side effects, but none experienced serious adverse reactions, including a diagnosis of myocarditis or MIS-C recurrence.





Reassuring news about stroke after Pfizer vaccine in 65+


Ep 312-6: Carol Goh CY SAGE Journal June 2022: A probable case of vaccine-induced thrombotic thrombocytopenia in a 76 year old after Pfizer mRNA  (Sorry only abstract, I have no access to full paper)


Ep 312-7:  Reuters 18 Jan 2023: EU drug regulator has not seen signal of possible Pfizer COVID shot stroke link


To be followed up  (but clearly very rare).


Perspectives on COVID vaccines:


Ep 312-8/-9:  FDA advice to simplify vaccination against SARS-CoV-2 in the future = based on Influenza model.



Hence, adaptation of vaccine composition once per year, because:

  • Everybody has baseline immunity by vaccination and/or infection.
  • Booster protects little against infection with the latest omicron variants but strongly against severe disease (see Ep 307, 310, 311).
  • Consistent messaging is needed, because “booster fatigue”, in general population.


However, many questions need to be addressed:

  • Include Wild-type, along with new variant or leave WT out (because risk on imprinting and immune deviation)?  
  • Which vaccine format for booster: only mRNA (because most evidence), also protein-based?
  • Route: intranasal vaccine?
  • What clinical evidence is needed to approve adapted vaccine?
  • ….     


Still much to be learned….


Best wishes,