28 Nov 2021 Episode 194: Urgent interventions needed in primary school children: systematic testing, effective non-pharmacological interventions and expeditious vaccination

Sun, 11/28/2021 - 16:02

Dear colleagues,

The title of this Episode is not “neutral”. It is a call for action, because I’m very concerned about the present policy with regard to children, especially those in primary schools.  While it is very evident now that they have a very prominent role in  the present “wave” which profoundly threatens our health system, the latest decisions by our various governments seem to simply deny this obvious fact, choosing instead to essentially turn a blind eye to what happens in the schools.

It is evident to everybody (also non-medics with common sense) that

  • It is too late to take action when already 3 children in a class are SARS-CoV-2 positive (especially when there is no systematic screening in place).
  • The non-pharmacological interventions to limit viral transmission are largely insufficient: CO2 meters and good ventilation are not universally applied and masking of primary school children remains a taboo.
  • Although the Pfizer vaccine has been approved now by CDC and EMA as safe and efficacious for primary school children, “vaccine hesitancy” remains widespread, even amongst the education and medical communities.     

In the present Episode, I summarize some recent and relevant literature (mostly of the last month, including a lot of preprints) in an unbiased way in order to make your own judgment.  First some clinical aspects, followed by a few papers and recommendations on testing and mitigation strategies and finally what we know about antibodies and vaccination.

Clinical aspects

Ep 194-1: Ayed medRxiv 14 Nov:  Approximately 10% of infants born to mothers with SARS-CoV-2 infections during pregnancy showed developmental delays.  As could be expected:

  • The risk of developmental delays was higher in those whose mothers had SARS-CoV-2 infections during the first (P=0.039) and second trimesters (P=0.001)
  • Infants born at <31 weeks gestation were more prone to developmental delays than those born at >31 weeks gestation (10% versus 0.8%; P=0.002).

 

Ep 194-2: Delahoy MMWR Trends of severe COVID in children of 14 stated USA.

  • Among 3,116 hospitalized children and adolescents during March 1, 2020–June 19, 2021: 827 (26.5%) were admitted to ICU, 190 (6.1%) required IMV, and 21 (0.7%) died.  
  • June-July 2021 164 hospital admissions with 38 (23 %) to ICU, 16 (10 %) IMV and 3 (2%) died.

Conclusion of the authors: Preventive measures to reduce transmission and severe outcomes in children and adolescents are critical, including vaccination, universal masking in schools, and masking by persons aged ≥2 years in other indoor public spaces and child care centers.

 

Ep 194-3: Schober in medRxiv: Risk factors in 403 hospitalized children (median age 3.8 yrs) for severe disease that occurred in 102 (33%).  

  • 50 % showed a least one comorbidity (thus also 50 % without co-morbidities).
  • Multiple comorbidities, obesity, neurological disorder, anemia, and/or hemoglobinopathy, shortness of breath, bacterial and/or viral coinfections, chest imaging compatible with COVID-19, neutrophilia, and MIS-C diagnosis were independent risk factors for severity.
  • The risk profile and presence of comorbidities differed between pediatric age groups, but age itself was not associated with severe outcomes.    

 

Ep 194-4: Edward medRxiv Oct 2021: Influence of variants on disease severity in children < 18 yrs in Chicago

Compared to non-VOC COVID-19 infections, the gamma VOC, but not the alpha or delta

VOCs, was associated with increased severity.

Ep 194-5: Lorthe medRxiv Nov 2021: Analysis of an Alpha outbreak in a primary school in Switzerland.

Involved 20 children 4 to 6 years from 4 classes, 2 teachers and a total of 4 household members.

Infection attack rates were between 11.8 and 62.0% among pupils from the 4 classes, 22.2% among teachers and 0% among non-teaching staff.

Secondary attack rate among household members was 15.4%.

Symptoms reported by 63% of infected  children, 100% of teachers and 50% of household members.  

Serological tests detected 8 seroconversions unidentified by SARS CoV-2 virological tests

 

Table on p. 20 shows that in total 20 out of 113 pupils and 2 out of 9 teachers were SARS-CoV-2 positive.  Obviously this was in an ideal situation, where repeated testing was done and everybody was aware of what was going on, with a variant that was far less infectious than the present one.

Question: Is the present testing strategy in Belgian schools sufficient?

Ep 194-6: Siegel in MMWR shows the trends of hospitalization amongst children in the US between Aug 2020 and 2021.  Clearly, all age groups are affected (Fig) and there is a clear inverse correlation with the overall degree of vaccination in the various states (Table).

Ep 194-7: Thelwall (medRxiv Nov 2021) found that in England during the period April 2020 and March 2021 household with 3 generations contributed little to COVID clusters.

Mitigating Strategies

Ep 194-8: Report by ECDC July 2021. Some messages:

  • Children equally susceptible as adults and can transmit
  • They will become increasing proportion of the epidemic
  • Increased preparedness, including non-pharmacological interventions and testing contacts

Ep 194-9: Practical questions and answers.  Strikingly, there is reservation to apply masking in children of less than 12 years old.

Ep 194-10: Very elaborated strategy proposed by CDC with key messages:

  • Vaccination is the leading public health prevention strategy, also for children
  • CDC recommends universal indoor masking by all students (age 2 and older), staff, teachers, and visitors to K-12* schools, regardless of vaccination status
  • Screening testing should be offered once per week to all students and staff, not fully vaccinated (see Table)
  • Ventilation is also worked out in detail (see page 9)
  • Physical distancing, handwashing and respiratory etiquette,
  • Staying home when sick and getting tested, contact  tracing in combination with quarantine and isolation, and cleaning and disinfection are also important layers of prevention to keep schools safe.

* The K-12 refers to the combination of primary and secondary education that children receive from kindergarten until 12th grade, starting at ages 4-6 and continuing through ages 17-19.

                                                                                                                                                       

 

Antibodies

Antibody responses after infection

Ep 194-11: Messiah in medRxiv on durability of antibody responses after natural infection in children in Texas.  The main finding is that over 95 % of the children who had anti-nucleoprotein Ab (as evidence of past SARS-CoV-2 infection) retained these Ab over a 6 months period.  The authors conclude that “infection-induced antibodies persist and thus may 105 provide some protection against future infection for at least half a year”   

However, protection is rather associated with anti-Spike Ab (which were not reported) and it is also not mentioned whether the titer of Ab remained stable or declined. Also, no antigen- or PCR testing is reported.

Ep 194-12: Zhai in medRxiv on association of SARS-CoV-2 antibody with age of convalescent outpatients.  

Serum antibody concentration was positively associated with microneutralization activity and participant age, suggesting that young adult outpatients (< 30 years old) did not generate as robust antibody memory, compared with older adults

Remarkable however: neither participant sex, the timing of blood sampling following the onset of illness, nor the number of SARS-CoV-2 spike protein specific B cells correlated with serum antibody concentration.

Passive immunity

Ep 194-13: Esteve-Palau on vaccination of lactating mothers with Pfizer:

  • Vaccination is safe during breastfeeding and transmits antibodies into breast milk, but the levels in milk are much lower than in serum: at peak (= 4 weeks after 2nd dose) 1,700 U/ml in serum versus 50 U/ml in milk.
  • Levels decreased in parallel, but remained positive after 6 months.
  • There were 2 breakthrough infections in the mothers (ASY and mild).  The baby of the mildly symptomatic mother also showed some symptoms, but none of the babies were tested. Afterwards, Spike Ab levels increased.

 

Ep 194-14: Anti-Spike Ab in infant after vaccination or infection of mother during pregnancy:

  • Vaccinated mothers: 94% (58/62) of infants had detectable anti-S IgG at 2 months, and 60% (18/30) had detectable antibody at 6 months.
  • Only 8 % (1/12) of infants from infected mothers had detectable Ant-S IgG at 6 months.

 

Vaccination in children

 

Ep 194-15: Official statements from CDC and EMA that Pfizer vaccine (10 µg twice)  in children 5-11 is

  • Efficacious:  90 % prevention of symptomatic COVID: 3 in 1305 vaccinated versus 16 in 663 placebo children. No data on infections
  • Safe: similar side effects as in adolescents: mild or moderate and transient. No mentioning of myocarditis.    

 

Ep 194-16: Olson MMWR Oct 2021:  Effectiveness of Pfizer vaccine against COVID-19 hospitalization in adolescents.

  • VE against hospitalization was 93% (95% CI = 83%–97%) (Table 3), during the period when Delta was the predominant variant. Similar for 12-15 yrs and 16-18 yrs
  • Table 2: Of the 6 fully vaccinated hospitalized: none was critical;
  • Of the 173 non-vaccinated 77 admitted to ICU, 29 critical and 2 died.

 

Ep 194-17: Clifford: effect of AZ and Pfizer on transmission of breakthrough infection to household contacts in England

  • There is a 81% “secondary attack rate” for Delta in unvaccinated households.  
  • Vaccine effectiveness against acquisition of a Delta infection in the household setting  was however low; 14% and 24 % after full ChAdOx1 and BNT162b2 respectively.
  • Contacts older than 18 were slightly (1.2 X) more likely to acquire infection than children.  

 

Ep 194-18: Real world study on risk of Pfizer vaccination versus infection (in Israeli adults). Always compared with matched controls (not vaccinated or not infected)

 

After vaccination:

Myocarditis: 2.7 excess cases per 100,000

Lymph node swelling: 78 excess per 100,000

Herpes zoster: 16 excess per 100,000

Appendicitis: 5 excess per 100,000

 

After infection

Myocarditis: 11 excess cases per 100,000

Cardiac arrhythmias (a 3.8-fold increase  =  166 cases per100,000 infected patients),

Kidney damage (14.8-fold ; 125 excess  per 100,000),

Pericarditis (5.4-fold ; 11 excess per 100,000),

Pulmonary embolism (12.1-fold ; 62 excess per 100,000),

Deep vein thrombosis (3.8-fold ; 43 excess per 100,000),

Myocardial infarction (4.5-fold  25 excess cases per 100,000),

Stroke(2.1-fold increase; 14 excess per 100,000).

 

Ep 194-19: UK program on childhood influenza vaccination reduced influenza also in older adults.

 

Information captured by the Royal College of General Practitioners network showed that cumulative GP Influenza like Illness consultation rates in individuals aged 50–70 years were lower in pilot areas that vaccinated primary (children aged 4–11 years) and secondary (children aged 11–13 years) school children compared with non-pilot areas (consultation rate: 3.4 per 100 000 vs 17.4 per 100 000, respectively); similar results were also seen for swab positivity (% positive 7.7% vs 29.5%, respectively).

 

General conclusions:

 

From an academic point of view, one can argue that not all these observations are consistent and there is need for much more research in children to reach final conclusions, but we cannot wait till everything has been triple-checked to act.  It is very clear from the literature that this virus threatens their physical and mental health and that of their parents and grandparents.  Just “wait and see” (= the present policy) will not offer any solution, but looks more like “a recipe for disaster”.

 

An active policy to reduce the free circulation of the virus in schools is urgently needed:

  • Primary school children should have rapid access to vaccination, by preference via the well-organized school medicine or any other channel.
  • In the meantime, non-pharmacological interventions, including systematic testing, universal  masking and proper ventilation, as outlined in the CDC document (Ep 194-10), should immediately be implemented.

 

Today, it seems very likely, at least to me, that delaying these measures any longer will result either in a collapse of our health system and/or large-scale school closures and/or a general lockdown.

 

These are bold statements for a scholar, who follows everything “from a distance”, I admit. 

If you have good arguments against these conclusions, I would like to read them and, if you agree, share them within our small community (by your name or anonymously as you prefer).   

 

Take care.

 

Best wishes,

 

Guido

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