Another set of results on the 4th dose of Pfizer or Moderna in Israel
  Efficacy of a Fourth Dose of Covid-19 mRNA Vaccine against Omicron

Small study (154 got Pfizer, 120 got Moderna).  All had 3 doses of Pfizer previously.  Study lasted to 3 weeks post vaccination.  Comparison of infections from 1 week to 3 weeks post vaccination.  Study & control individuals were supposed to have weekly PCR tests.   (This was during the very high infection rate period of January 2022)

Quote:Overall, 25.0% of the participants in the control group were infected with the omicron variant, as compared with 18.3% of the participants in the BNT162b2 group and 20.7% of those in the mRNA-1273 group. Vaccine efficacy against any SARS-CoV-2 infection was 30%

Most infected health care workers reported negligible symptoms, both in the control group and the intervention groups. However, most of the infected participants were potentially infectious, with relatively high viral loads 

At-home COVID-19 Test Instructions Frequently Misinterpreted

Quote:Participants [of an online survey] were randomly assigned to receive 1 of 3 different instructions [for at-home COVID test]: the FDA-authorized instructions, the intervention instructions, or no instructions.

Participants responded to 4 different risk scenarios, ranging from high probability of infection defined by symptoms or close contact with someone testing positive for COVID-19 to low likelihood of infection with no symptoms and no contact.

But when the self-test was negative despite a high probability of infection, 33% of the group that received the FDA’s instructions misinterpreted the test result to mean they did not need to quarantine, compared with 14% of the intervention group and 24% of the group that received no instructions.

A study came out on Tuesday that claims the protection of the 4th dose of Pfizer against infection wanes by the 8th week relative to those with 3 doses.  (But also shows an increase in protection against severe illness, but no sign of decrease over time of the study).

  https://www.nejm.org/doi/full/10.1056/NEJMoa2201570

The description of their study looked good, but there's something that doesn't add up to me.


Table 2 is the basis for claim for decreasing protection over time.  It shows a rate ration of confirmed infections of the 4-dose group in various weeks versus the 3-dose and internal control groups.  The rate ratio for the 7 separate weeks are  1.5, 2.1, 2.0, 1.7, 1.5, 1.2, 1.1 vs 3-dose  (similar numbers vs internal control group, with highest ratio of 1.9).



Yet in Table 1, where they compare the aggregat4ed 4-dose groups (all weeks) vs 3 dose and internal control groups, the number of infections in the 4-dose group was 177/100K days,

3-dose group: 361/100K days, Internal control group: 388/100K days.

So the risk ratio for the aggregate groups is 361/177 = 2.04 for  3-dose vs 4-dose, and 388/177 = 2.19 for internal control group vs 4-dose.


I don't understand that aggregated number vs their individual weeks.  How can the maximum for the internal control group be 1.9 when viewed weekly, but 2.19 when aggregated?



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Separate from that technical detail, were there systematic errors that invalidate their purported results of the decrease in effectiveness?

They do note that the risk of infection varied over time for the general population.  "Because incidences of both confirmed infection and severe illness increased rapidly during January 2022, the risk of exposure at the beginning of the study period was lower than at the end of the study period."  

Their study ran from early January to early March.   Their statement seems to be flat out  backwards when compared to the chart of daily new cases in Israel at Worldometers.info. The new case graph shows 41,000 new cases on the first day of the study (Jan 10), peaking at nearly 84,000 on day 14, dropping to 10,000 on the last day (Mar 2) of the study.  Indeed, it appears that the risk of infection in the general population was highest for those risk days when week 2 was early in the study and much less for those when week 8 was at the end of the study.  For those who got their 4th dose late in the study, their week 2 had much less chance of exposure than for those who got their 4th dose early in the study.   The paper gives no direct indication of how many people got their doses early versus late, but it probably can be estimated by using their risk days for each of the weeks.

There is also the effect of when individuals got COVID.  If a person got COVID in an early week, I expect they were excluded from later weeks.   If someone had a (relatively) riskier life style, they would more likely show up in the early infections.  Those remaining at 8 weeks would include the people that may be leading more secluded or otherwise cautious lifestyles.  I saw no discussion about any changes in lifestyles (perhaps due to addition or removal of government restrictions, or perhaps due to holidays or other reasons people may be exposed more or less than at other times) over the course of the study.

The details of the selection of the 3-dose group and the internal control group were not made clear.  For the 3-dose group, there is no event date to judge their weeks by.  Was it the same 3-dose group every week?   While "week N" for the study group was based on their date of vaccination, was the "week N" for the 3-dose group based on the week of the study?  Likewise, for the Internal Control Group, was the "week N" based on the week of the study?

Ah....  That may explain their claims, in a negative manner.  If week 8 of either control group was the last week of February, then the number of infections was low, and the number of infections were high in week 2.  But the study group for week 2 includes some (who had early vaccinations) when the infection rate of the population was high plus some (who had late vaccinations) when the infection rate of the population was low.   If there were NO reduction in infections due to the fourth dose, the results would still show an improvement of study group for week 2 versus control group for week 2.

https://www.fda.gov/news-events/press-an...-older-and

Quote:The agency amended the emergency use authorizations as follows: 

• A second booster dose of the Pfizer-BioNTech COVID-19 Vaccine or Moderna COVID-19 Vaccine may be administered to individuals 50 years of age and older at least 4 months after receipt of a first booster dose of any authorized or approved COVID-19 vaccine.
  
• A second booster dose of the Pfizer-BioNTech COVID-19 Vaccine may be administered to individuals 12 years of age and older with certain kinds of immunocompromise at least 4 months after receipt of a first booster dose of any authorized or approved COVID-19 vaccine. These are people who have undergone solid organ transplantation, or who are living with conditions that are considered to have an equivalent level of immunocompromise.
  
• A second booster dose of the Moderna COVID-19 Vaccine may be administered at least 4 months after the first booster dose of any authorized or approved COVID-19 vaccine to individuals 18 years of age and older with the same certain kinds of immunocompromise.
  

Moderna has announced their results of their trial on young children.

Quote:Moderna Announces its COVID-19 Vaccine Phase 2/3 Study in Children 6 Months to Under 6 Years Has Successfully Met Its Primary Endpoint 

• Two 25 μg doses of mRNA-1273 in participants 6 months to under 6 years met primary endpoint with robust neutralizing antibody titers similar to adults mRNA-1273 was generally well tolerated in this age group
  
• Although not a primary endpoint, statistically significant vaccine efficacy was observed during the Omicron wave that was consistent with the lower two-dose effectiveness against Omicron seen in adults
  
• Moderna is moving forward with global regulatory submissions for mRNA-1273 for primary vaccination of children 6 months to under 6 years of age
  
• Additionally, Moderna has initiated a submission to the FDA for emergency use authorization of mRNA-1273 in children 6 to under 12 years of age; mRNA-1273 is approved for use in this age group in Europe, Canada and Australia
  

Quote:In both age groups [6 months to 2 years; 2 years to 6 years], two doses of 25 µg provided similar immunogenicity to the 100 µg two-dose primary series in adults ages 18 to 25 years, meeting the non-inferiority criteria and immunobridging[1], and indicating that the benefit of mRNA-1273 conferred to adults ages 18 to 25 are also conferred to children and infants as young as 6 months. SARS-Cov-2-neutralizing antibody geometric mean ratio (GMR) comparing the response in children 6 months to under 2 years to the response in young adults from the Phase 3 COVE study was 1.3 (95% Cl: 1.1, 1.5) and was 1.0 (95% Cl: 0.9, 1.2) for the 2 to under 6 years age group. This also predicts protection from COVID-19 and severe COVID-19 disease down to 6 months of age.

The Omicron SARS-CoV-2 variant predominated in the U.S. during the KidCOVE study in these younger age groups. The secondary endpoint of vaccine efficacy confirms statistically significant, but lower efficacy against COVID-19 infection as expected during the Omicron wave and consistent with adult observational data. Using the Phase 3 COVE study COVID-19 definition, vaccine efficacy in children 6 months to 2 years was 43.7% and vaccine efficacy was 37.5% in the 2 to under 6 years age group. In this case, statistically significant is defined as a lower bound on the 95% confidence interval which is greater than 0. The majority of cases were mild, and no severe COVID-19 disease was observed in either age group. The absence of any severe disease, hospitalization or death in the study precludes the assessment of vaccine efficacy against these endpoints.

One of my neighbors said they had just gotten a second booster. (Two MRNA shots, then booster, and now another booster)

I'm 4.5 months since my booster, and I'm starting to wonder if it is getting time to try to get another booster.  That is, I'm concerned that my protection from the MRNA  shots has waned, and I'm at risk of getting COVID if exposed.   I'm at elevated risk if I do get COVID.

The CDC has no recommendation for a "second booster".   What they do have is that for moderately or severely immunocompromised individuals, their recommendation is a 3-shot first series, followed by a booster.

I have seen one of the MRNA companies indicate they were getting ready to apply for approval for a 2nd booster.

So, I'm going to look for data indicating level of immunity at 5 months out from a 3rd shot, and the benefits of that immunity against Omicron (BA.2)
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BA.2 continues to grow and decrease the older Omicron variants.  The CDC no longer shows any Delta or  Other (ie, 100% Omicron's 3 variants).  It seems to be dominant in the NE US and least widespread in the center of the US.

Sewage data is suggesting that we *may* be seeing the start of wider infections.  In the SF Bay Area, the rate of virus in sewage has bounced around a bit in different jurisdictions, but no widespread trend.   The CDC shows more sewage sites increasing dramatically in virus than decreasing dramatically, but the total sites decreasing some is more than the total sites increasing some.
The Biobot site shows a very slight increase overall.

I went to a basketball game this weekend and calculated that statistically that there would be about 2 people in the infectious stage in the audience, at least or the first game.  (Btw, I was disappointed at how many people (the vast majority near where I was) were not wearing masks.)  I wore my N95, arrived & left when there weren't crowds, and stayed at least 10' from other people.  With 2 days between games, I figured maybe 4 for the second game.

It's been a month since anyone's felt a need to post anything.  That's good news (but also could be a sign of burnout).

The CDC is finally showing wastewater surveillance numbers.
https://covid.cdc.gov/covid-data-tracker...rveillance

The data is unequally collected in the US.  It is most densely collected in OH, WI, IL, KS, NY, NC, CO.  A number of states have zero or one sites collecting data.

While 61% of the sites have levels reduced by 10% or more, 33% have levels increased by 10% or more.  9% have gone up by a factor of 10 or more (possibly because they were 0 before and are now 1??)

The number of samples with detection has gone down over the last two weeks.
They don't say anything about variant detection in wastewater.
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For herd immunity, the seroprevalence numbers is a good way to look at things.
  https://covid.cdc.gov/covid-data-tracker...prevalence

Of blood donors (ie, a select population that is surely not representative of the entire population), 94.7% have antibodies (infection or vaccination).

Separately, the percentage of people that have had COVID is 43.3%, based on antibodies.
The estimate is that 9.8% of the population got their first case of COVID between Dec. 26 and Jan. 29.


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There have been a number of interesting papers that have come out recently about the effects of COVID.
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In variants, the CDC indicates 0.0% Delta.  Of the 3 Omicron variants, B.1.1.529 (15%) was being slowly supplanted by BA.1.1 (74%) but now BA.2 (12%) is starting to grow, depressing BA.1.1.

The FDA group that decides about vaccines is due to meet on Feb. 15 to discuss Pfizer's proposed vaccines for those 6-months old to 5 years old.  From what I see, the approval is not a slam dunk.  If approved, the US is intending to get 10M doses of the vaccine to those that would administer shots (pharmacies, etc.) by Monday, Feb. 21.  (Pharmacies can only give doses to 4+.  Younger children will have to get it from a pediatrician.)

Quote: Just over 20% of kids aged 5-11 are vaccinated, while 55% of children 12-17 are vaccinated, according to the CDC.

The NIH has a dashboard that shows seroprevalence in the US over time.  I wish they subdivided it by geographic regions.

The data only goes to the end of November (before the incredible Omicron surge).  If I understand their data, roughly 30% of the population showed evidence of having had COVID-19 before Omicron.  Obviously that number has jumped significantly.  I wouldn't be surprised if it were at 60%.

The question in my mind is, how many people are still (or again) very vulnerable to Delta & Omicron.  The current unmasking of America makes it trecherous for those of us who have been diligent, or lucky, enough to have avoided COVID-19.  Yes, we can continue to wear our masks, but others who may be shedding virus profusely, won't be.  Take your mask off to get a sip of water and you may just inhale a single droplet from an infected person that isn't wearing a mask.



In the news is very concerning report about cardiovascular disease, over a year after having recovered.

Quote:COVID-19 boosted the risk of all 20 cardiovascular ailments studied, including heart attacks, arrhythmias, strokes, transient ischemic attacks, heart failure, inflammatory heart disease, cardiac arrest, pulmonary embolism, and deep vein thrombosis.

For example, veterans who had had COVID-19 faced a 72% higher risk of heart failure after 12 months than those in a control group who didn’t test positive. That translated to nearly 12 more infected people per 1000 developing heart failure than those in a control group. Overall, the investigators found 45 more infected people per 1000 developed any of the 20 conditions than did uninfected controls.  

Quote:The risks were evident regardless of age, race, sex and other cardiovascular risk factors, including obesity, hypertension, diabetes, chronic kidney disease and hyperlipidemia; they were also evident in people without any cardiovascular disease before exposure to COVID-19, providing evidence that these risks might manifest even in people at low risk of cardiovascular disease. 

The MIT Technology Review has a longish article on the Wuhan "Bat Lady" and the lab.  The author, who has worked in bio labs, had good access to Shi Zhengli, the lab, and the various people investigating or theorizing about the possibility of a lab leak.  There's nothing surprising in the article, but a lot of good background information and a view of the personal side of Shi Zhengli.