Will you get the second covid 19 vaccine booster?

[LightBright]

I am not sure entirely, but leaning towards getting my 2nd booster, just not sure when. Is the government covering the cost still? If not, I am going on Medicare in June (already 65 just on my DH's insurance and he is retiring end of May.) So do not know if it makes a difference if I get it now with my regular insurance or better if Medicare pays?

DD said she is not getting a 2nd booster as she is still recovering from myocarditis from the 1st booster. She won't have her 2nd echocardiogram until May to see if everything has resolved, though she says the rapid heartbeats are not happening as often. The cardiologist said he is not sure what she should do and many of his colleagues are confused as well when it comes to booster shots.

I believe the government is covering the cost still. In various cities and counties they have free COVID vaccine clinics, some every weekend for example. Maybe see if your county has info on free clinics in your area. (I follow my county health department on Twitter to see what’s available and discussions of COVID topics.)

 

[Madam Bijoux]

I will definitely get one.

 

[missy]

Mixed Bag for Fourth Dose of Pfizer Vaccine vs Omicron​

— Real-world data show less infection and severity, but long-term benefit less clear​

by Molly Walker, Deputy Managing Editor, MedPage Today April 5, 2022

"

Rates of confirmed Omicron-related COVID infection and severe disease were lower after a fourth dose of the Pfizer-BioNTech vaccine, according to real-world data from Israel, although protection against confirmed infection seemed short-lived.

Among adults ages 60 and up, the adjusted rate of confirmed infection 4 weeks after the fourth dose was twice as low compared to those who received three doses (171 vs 340 cases per 100,000 person-days), reported Yair Goldberg, PhD, of Technion-Israel Institute of Technology in Haifa, and colleagues.



Moreover, the adjusted rate of severe illness after 4 weeks was three times lower in the four-dose group (1.6 vs 5.5 per 100,000 person-days), they wrote in the New England Journal of Medicine.

Adjusted rates of both infection and severe disease were both higher in a third "internal control" group, who received a fourth vaccine dose only 3 to 7 days earlier (308 and 3.6 cases per 100,000 person-days, respectively), they noted.

However, Goldberg and colleagues added that from week 5 onward, the rate ratio for confirmed infection began to decline, with the adjusted rate of infection 8 weeks after the fourth dose being "very similar to those in the control groups."

The authors concluded that a fourth dose provided "only short-term protection and a modest absolute benefit," for confirmed infection, but that it did increase protection against severe disease. They highlighted that "protection against severe illness did not appear to decrease by the sixth week after receipt of the fourth dose," but acknowledged that "More follow-up is needed in order to evaluate the protection of the fourth dose against severe illness over longer periods."



In January, Israeli authorities approved a fourth dose of Pfizer vaccine for adults ages 60 and up, high-risk populations, and healthcare workers, 4 months after a third dose, they noted. FDA recently authorized a second booster dose of Pfizer or Moderna vaccine for adults, ages 50 and up, and those with immunocompromising conditions, in part using real-world Israeli data as the basis for their decision.

Goldberg's group examined data on adults ages 60 and older who received three doses of Pfizer at least 4 months prior to the end of the study. The study period was defined as January 10 to March 2 for confirmed infection, and until February 18 for severe disease. The four-dose group completed their fourth dose at least 8 days prior to infection or severe COVID, they said.

Overall, 1,252,331 adults were included in the study, with 623,355 receiving four doses of vaccine and 628,976 not receiving four doses of vaccine. The aggregated four-dose group and internal control group had more person-days over age 80 (about 25% apiece vs 16.2%).



At 4 weeks, the adjusted rate of confirmed infection in the four-dose group was lower by a factor of 2.0 (95% CI 1.9-2.1) versus the three-dose group and lower by a factor of 1.8 (95% CI 1.7-1.9) versus the internal control group.

For severe disease at 4 weeks, the adjusted rate differences were 3.9 fewer cases per 100,000 person-days (95% CI 3.4-4.5) versus the three-dose group and 2.1 fewer cases per 100,000 person-days (95% CI 1.4-3.0) versus the internal control group.

Limitations to the data include unmeasured confounders, such as behavioral differences between adults who chose to receive the fourth dose and those who did not. Pre-existing conditions could have affected risk for severe disease, and the authors added they did not adjust for those as this information is not available in the national database. Different COVID treatment may have also affected the results, they noted.

"

 

[missy]

"

Original antigenic sin: Are boosters a threat?​

Katelyn Jetelina

Many are trying to decide whether to get another booster. In order to make this decision, benefits must be weighed with risks. More than 11.3 billiondoses of COVID19 vaccines have been distributed, so we are well aware that the vast majority of side effects are mild. Are there any other risks to getting another booster, like “original antigenic sin” (OAS)?
There has been considerable chatter among the public about OAS. From what I can tell, attention was sparked after an op-ed was published in the NYT before Omicron. A few clinicians, including Paul Offit, said:

“It’s (...) possible that repeatedly “training” the immune system to fight the original virus could reduce the effectiveness of a variant-specific booster. This phenomenon, called “original antigenic sin,” has been observed with influenza and human papillomavirus vaccines. In other words, for those not in immediate need of a boost, there may be a significant advantage to waiting until a booster more closely aligned with circulating variants becomes available; boosting on the original antigen could be counterproductive.”

OAS is one of the most complicated and misunderstood parts of an already complex immune system. I partnered with Edward Nirenberg to “translate” the science:

• What is OAS?
• What is the science saying about OAS for SARS-CoV-2?
• Is OAS a risk that should be weighed for a fourth booster?

Disclaimer: This post was incredibly difficult to write. My hardest since the pandemic began. It’s a very complex topic that even PhD immunologists get mixed up (and I’m an epidemiologist). This makes “translating” the topic even more difficult. I hope I don’t lose you. But if I do, just go to the “bottom line” section. Buckle up.

Original antigenic sin (OAS)​

When we come in contact with a virus or get a vaccine for the first time, our immune system develops a repertoire of tools. One of those tools is B-cells, which are antibody factories. Each B-cell makes a single antibody shape, and they can pump out huge quantities of antibodies if needed. If you come in contact with another variant, B-cells can evolve and modify the antibodies they create for a new variant. This is just like factories that can modify their product on the line.
The immune system wants to clear a threat in the fastest way possible. Responses based on memory (as opposed to modifying the antibodies) work fastest, so B-cells get to work pumping out antibodies of shapes they’ve seen before. This is called “imprinting.” Imprinting in and of itself is neither good nor bad. It simply reflects that a person's first exposure to a virus can have a noticeable effect on their later responses to variants of that same virus.
Original antigenic sin (OAS) is a special type of imprinting. In OAS, prior memory can interfere and even prevent you from generating antibodies against new variants. How this occurs is not well understood.
But we do know that OAS occurs with some other viruses, like the flu. For example, the first flu infection you get as a child has been shown to impact the way you react to flu variants later in life. While it could induce a less than optimal response, it can also be good and provide a more robust response. The figure below displays this phenomenon nicely.
Say a 2 year old is infected with the flu with A-D shapes on the virus. So, that child makes antibodies with A-D shapes. But then, at 5 years old, they are exposed to another variant with shapes A, C, E, and F. Because of the first exposure, only antibodies for shapes A and C respond. Even though there are only two shapes recognized, they provide a much stronger response than originally. Then, say at 20 years old, that same person is exposed to a virus with shapes A, D, E, and G. Because of the very first exposure (at 2 years old), antibodies A and D are recalled to fend off the infection; antibodies against E and G do not get made.

​

Figure 11.34 from Murphy K, Weaver C. Janeway’s Immunobiology. 9th ed. Boca Raton, FL: CRC Press; 2016
During the 1918 flu pandemic, we also saw very worrisome epidemiological signs of OAS. Those who were previously infected by the Russian flu (i.e. a different type of swine flu) did significantly worse during the pandemic than those not previously infected by the Russian flu.
Because we’ve seen OAS with other viruses, it’s theoretically possible with SARS-CoV-2. And scientific studies are now coming through.

What is the science saying?​

The best way to analyze OAS is to look at someone who has never been exposed to SARS-CoV-2 (including through vaccination) and infect them with Omicron. Then, compare their immune response to someone who has been vaccinated and gets a breakthrough case. To my knowledge, this type of study has not been conducted. So we have to rely on proxy studies and assess OAS indirectly. So far, results are mixed.
On one hand, there is some evidence of OAS with SARS-CoV-2:

• One scientific group found that exposure to coronaviruses (like the common cold) before the pandemic may impact our response to SARS-CoV-2. It’s important to note that there were significant internal inconsistencies with this study though.
• Another group found that monkeys with a Beta-specific or Omicron-specific booster had no extra protection compared to a regular formula booster. This was surprising because Omicron has 32 changes on its spike protein compared to the original virus. So, one would hypothesize that a vaccine with an updated spike protein would provide some sort of additional protection. OAS may explain why it’s not working. Importantly, there could be alternative explanations of why this is happening, too. For example, there may have not been enough follow-up time or Omicron or Beta may simply not be as good at driving the immune response.

Then there’s science showing OAS only with infection and not vaccination:

• One study found that SARS-CoV-2 infections caused B-cells to recall past coronavirus infection (like common cold) memory. But vaccines did not. This could be because of location: COVID19 is inhaled—as opposed to vaccines, which are introduced in the muscle—causing less affinity.

On the other hand, there is evidence that OAS is not a concern for SARS-CoV-2 among humans.

• An interesting study found OAS occurred in mice but not children. Specifically, scientists infected mice with the common cold and they were unable to make antibodies against SARS-CoV-2. On the other hand, scientists found that children with a history of this common cold were able to make SARS-CoV-2 antibodies.
• Most recently a team from BioNTech evaluated 3 vaccine doses+infection compared to 2 doses+infection. They found that those with the 3 doses+infection had a higher number of neutralizing antibodies and created Omicron-specific B-cell memory. This suggests an “expanded imprint”—prior memory did not interfere with generating antibodies against new variants. Importantly, though, some level of imprinting was still present, as the majority of memory B cells were those from the original vaccine.
• Data from a group of individuals in Stanford and Mongolia found that many COVID19 vaccines (not just mRNA) had extremely broad responses—significantly more so than those elicited by infection from specific variants, suggesting that the immune system has more paths of protection for new variants of concern.
• A French group tracked the antibody response against SARS-CoV-2 over time in humans. They found that while initially B-cells recalled cold coronaviruses, they were successively replaced with SARS-CoV-2-specific antibodies. This, again, argues against a substantial role for OAS.

Can another booster make OAS worse?​

It’s plausible that repeated boosting may make it harder to respond to future variants. Theoretically, repeated exposure to an older variant formula may drive our immune system to concentrate too much on old features and not on new features. But despite some truly surprising evolutionary leaps of the virus (like Omicron) we have not seen any convincing evidence of OAS among humans, which is great news.
In the event that OAS does prove to be a concern, there are tactics that vaccinology can take to work around it. For example, we are testing universal vaccines against SARS-CoV-2 and are fortunately seeing early promising results. Furthermore, flu scientists have found a way to boost immunity by targeting other areas of the virus. In a phase I study, scientists tested this strategy and OAS was not a problem for more than 1 year later.

Bottom line​

After two years of vaccines and the virus significantly mutating, there is no definitive evidence of OAS in humans being an important concern for COVID-19.
Without knowing the future, decisions must continuously weigh benefits with risks we know right now. Evidence from Israel shows meaningful benefit of a fourth mRNA dose (or second booster) against severe disease among older adults. We need to be responsive to the needs of our immune systems to protect us from this virus. The reality is, for someone who needs a booster, the theoretical concern of OAS is not a strong enough reason to not get it.

Bottom bottom line​

If you’re eligible, go get your booster.
Love, YLE and Edward Nirenberg

"

 

[whitewave]

I just received my second Pfizer booster yesterday and I have no side effects, not even localized soreness or swelling at injection site.

 

[SparklieBug]

DH is, as I write, at an appointment for his second Moderna booster. Due to his chronic autoimmune condition, the advice was for him to receive a second booster.

I do not plan to have a second booster unless there's some catastrophic variant that has a specific booster developed for it.

 

[Daisys and Diamonds]

I wish everyone would just wear their masks. I don't understand why it's such a big hardship. The reason we are still in this mess IMO is because people are crying their rights are being trampled on...it's a sad commentary about humans in general. IMO.

Wear a mask, save a grandma (or yourself)

Here today 16 & 17 years olds are now eligible for the (1st) booster

 

[missy]

Third booster might be necessary in the fall.

Third Booster May Be Needed This Fall

Because COVID-19 booster protection falls after 4 months, a third booster shot may be needed this fall for those who are newly eligible for a second.

www.medscape.com

"
People now eligible for a second COVID-19 booster may need a third one by this fall, NJ Advance Media reported.

CDC Director Rochelle Walensky, MD, told the outlet that because booster protection falls after 4 months, a third booster shot may be needed this fall for those who are newly eligible for a second.

"We don't know exactly what that looks like, but we do want to make sure that people are aware of that because if they're only going to get one boost, that may be the one to get," she said. "It may not be the same booster as we have right now."


The FDA and CDC last week signed off on a second COVID-19 booster for people 50 and older and all adults with certain health conditions.


"This is especially important for those 65 and older and those 50 and older with underlying medical conditions that increase their risk for severe disease from COVID-19, as they are the most likely to benefit from receiving an additional booster dose at this time," Walensky said.

An FDA advisory committee will meet Wednesday with members of the CDC and the National Institutes of Health to discuss the potential fall booster."

 

[missy]

Wear a mask, save a grandma (or yourself)

Here today 16 & 17 years olds are now eligible for the (1st) booster

I never stopped wearing masks. Greg and I are the only ones in this state (it feels like lol) who are still wearing masks indoors grocery shopping etc.

 

[missy]

Interesting JAMA article FYI

"

Protection by a Fourth Dose of BNT162b2 against Omicron in Israel​

List of authors.

• Yinon M. Bar-On, M.Sc.,
• Yair Goldberg, Ph.D.,
• Micha Mandel, Ph.D.,
• Omri Bodenheimer, M.Sc.,
• Ofra Amir, Ph.D.,
• Laurence Freedman, Ph.D.,
• Sharon Alroy-Preis, M.D.,
• Nachman Ash, M.D.,
• Amit Huppert, Ph.D.,
• and Ron Milo, Ph.D.
• 
  

  Abstract​

  BACKGROUND​

  On January 2, 2022, Israel began administering a fourth dose of BNT162b2 vaccine to persons 60 years of age or older. Data are needed regarding the effect of the fourth dose on rates of confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and of severe coronavirus disease 2019 (Covid-19).
  

  METHODS​

  Using the Israeli Ministry of Health database, we extracted data on 1,252,331 persons who were 60 years of age or older and eligible for the fourth dose during a period in which the B.1.1.529 (omicron) variant of SARS-CoV-2 was predominant (January 10 through March 2, 2022). We estimated the rate of confirmed infection and severe Covid-19 as a function of time starting at 8 days after receipt of a fourth dose (four-dose groups) as compared with that among persons who had received only three doses (three-dose group) and among persons who had received a fourth dose 3 to 7 days earlier (internal control group). For the estimation of rates, we used quasi-Poisson regression with adjustment for age, sex, demographic group, and calendar day.
  

  RESULTS​

  The number of cases of severe Covid-19 per 100,000 person-days (unadjusted rate) was 1.5 in the aggregated four-dose groups, 3.9 in the three-dose group, and 4.2 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of severe Covid-19 in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 3.5 (95% confidence interval [CI], 2.7 to 4.6) and was lower than that in the internal control group by a factor of 2.3 (95% CI, 1.7 to 3.3). Protection against severe illness did not wane during the 6 weeks after receipt of the fourth dose. The number of cases of confirmed infection per 100,000 person-days (unadjusted rate) was 177 in the aggregated four-dose groups, 361 in the three-dose group, and 388 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of confirmed infection in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 2.0 (95% CI, 1.9 to 2.1) and was lower than that in the internal control group by a factor of 1.8 (95% CI, 1.7 to 1.9). However, this protection waned in later weeks.
  

  CONCLUSIONS​

  Rates of confirmed SARS-CoV-2 infection and severe Covid-19 were lower after a fourth dose of BNT162b2 vaccine than after only three doses. Protection against confirmed infection appeared short-lived, whereas protection against severe illness did not wane during the study period.
  During late December 2021, with the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (omicron) variant, the prevalence of confirmed infection rose sharply in Israel. Some of the contributing factors were increased immune evasion by the variant1 and the passage of more than 4 months since most adults had received their third vaccine dose. In an effort to address the challenges presented by the omicron variant and to reduce the load on the health care system, on January 2, 2022, Israeli authorities approved the administration of a fourth dose of the BNT162b2 vaccine (Pfizer–BioNTech) to persons who were 60 years of age or older, as well as to high-risk populations and health care workers, if more than 4 months had passed since receipt of their third dose. The real-world effectiveness of the fourth dose against confirmed infection and severe illness remains unclear. In this study, we used data from the Israeli Ministry of Health national database to study the relative effectiveness of the fourth dose as compared with only three doses against confirmed infection and severe illness among older persons in the Israeli population.
  

  Methods​

  STUDY POPULATION​

  For this analysis, we included persons who, on January 1, 2022, were 60 years of age or older and had received three doses of BNT162b2 at least 4 months before the end of the study period (March 2). We excluded the following persons from the analysis: those who had died before the beginning of the study period (January 10); those for whom no information regarding their age or sex was available; those who had had a confirmed SARS-CoV-2 infection before the beginning of the study, determined with the use of either a polymerase-chain-reaction (PCR) assay or a state-regulated rapid antigen test; those who had received a third dose before its approval for all older residents (i.e., before July 30, 2021); those who had been abroad for the entire study period (January 10 to March 2; persons were considered to be abroad 10 days before traveling until 10 days after their return to Israel); and those who had received a vaccine dose of a type other than BNT162b2.
  For persons who met the inclusion criteria, we extracted information on March 4, 2022, regarding SARS-CoV-2 infection (confirmed either by state-regulated rapid antigen test or by PCR) and severe Covid-19 (defined with the use of the National Institutes of Health definition2 as a resting respiratory rate of >30 breaths per minute, an oxygen saturation of <94% while breathing ambient air, or a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of <300) during the 14 days after confirmation of infection. During the study period, infections were overwhelmingly dominated by the omicron variant.3 We also extracted data regarding vaccination (dates and brands of first, second, third, and fourth doses) and demographic variables such as age, sex, and demographic group (general Jewish, Arab, or ultra-Orthodox Jewish), as determined by the person’s statistical area of residence (similar to a census block4).​

  STUDY DESIGN​

  The study period started on January 10, 2022, and ended on March 2, 2022, for confirmed infection and ended on February 18, 2022, for severe illness. The starting date was set to 7 days after the start of the vaccination campaign (January 3, 2022) so that at least the first four-dose group (days 8 to 14 after vaccination) would be represented throughout the study period (Fig. S1 in the Supplementary Appendix, available with the full text of this article at NEJM.org). The end dates were chosen to minimize the effects of missing outcome data due to delays in reporting PCR or antigen test results and to allow time for the development of severe illness.
  The design of the study was similar to that of a previous study in which we assessed the protection conferred by the third vaccine dose as compared with the second dose.5 We calculated the total number of person-days at risk and the incidence of confirmed infection and of severe Covid-19 during the study period defined for each outcome. For persons who received the fourth dose, treatment groups were defined according to the number of weeks that had passed since receiving that dose, starting from the second week (8 to 14 days after vaccination). These four-dose groups were compared with two control groups. The first control group included persons who were eligible for a fourth dose but had not yet received it (three-dose group). Because persons who received the fourth dose might have differed from those who had not according to unmeasured confounding variables, a second control group was defined as persons who had received a fourth dose 3 to 7 days earlier (internal control group). This control group included the same persons as the four-dose groups, but during a period in which the fourth dose was not expected to affect the rate of confirmed infection or severe illness. The membership in these groups was dynamic, and participants contributed risk days to different study groups on different calendar days, depending on their vaccination status.​

  OVERSIGHT​

  The study was approved by the institutional review board of the Sheba Medical Center. All the authors contributed to the conceptualization of the study, critically reviewed the results, approved the final version of the manuscript, and made the decision to submit the manuscript for publication. The authors vouch for the accuracy and completeness of the data in this report. The Israeli Ministry of Health and Pfizer have a data-sharing agreement, but only the final results of this study were shared.​

  STATISTICAL ANALYSIS​

  Using quasi-Poisson regression, we estimated the rates of confirmed infection and severe Covid-19 per 100,000 person-days for each study group (included as factors in the model), with adjustment for the following demographic variables: age group (60 to 69 years, 70 to 79 years, or ≥80 years), sex, and demographic group (general Jewish, Arab, or ultra-Orthodox Jewish). 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. Moreover, the fraction of the population in each study group changed throughout the study period (Fig. S1). Therefore, we included calendar date as an additional covariate to account for changing exposure risk.6 The end of the study period for severe Covid-19 was set to 14 days before the date of data retrieval (March 4), allowing at least 14 days of follow-up time for the development of severe illness. To ensure the same follow-up time for severe Covid-19 in all persons, we considered only cases of severe illness that developed within 14 days after confirmation of infection. The date used for counting events of severe Covid-19 was defined as the date of the test confirming the infection that subsequently led to the severe illness.
  Persons who received four doses were assigned to groups according to the numbers of weeks that had passed since receipt of the fourth dose; for each outcome, we estimated the incidence rate in each of these four-dose groups and in the two control groups. We calculated two rate ratios for each treatment group and each outcome: first, the ratio of the rate in the three-dose group to that in each four-dose group; and second, the ratio of the rate in the internal control group to that in each four-dose group. Note that the higher this rate ratio is, the greater the protection conferred by the fourth dose of vaccine. In addition, adjusted rate differences per 100,000 person-days during the study period were estimated with a method similar to that used in our previous analysis.7 Confidence intervals were calculated by exponentiating the 95% confidence intervals for the regression coefficients, without adjustment for multiplicity. Thus, the confidence intervals should not be used to infer differences between study groups.
  To check for possible biases, we performed several sensitivity analyses. First, we estimated the rate ratios for confirmed infection using an alternative statistical method that relied on matching (similar to that used by Dagan et al.8), as described in detail in the Supplementary Appendix; this approach could not be applied to the analysis of severe Covid-19 because of the small case numbers. Second, we examined the results of using data on infections confirmed only by PCR testing and excluding data on those confirmed by state-regulated antigen testing. Third, we repeated the analyses with data from the general Jewish population only. Fourth, we analyzed the data while accounting for the exposure risk over time in each person’s area of residence. Fifth, we analyzed the data while accounting for the time of vaccination since the third dose. Further details of the sensitivity analyses are provided in the Supplementary Appendix.​

  Results​

  STUDY POPULATION​

  Figure 1.

  

  Study Population.Table 1.

  

  Demographic and Clinical Characteristics of the Persons in the Study Groups.
  A total of 1,252,331 persons met the criteria for inclusion in the study (Figure 1). The total number of events and person-days at risk in each of the study groups, along with the distribution of covariates used in the analysis, are shown in Table 1, which provides statistics aggregated across weeks since receipt of the fourth dose from the second week onward. The information for each treatment group according to the week since receipt of the fourth dose is provided in Table S1. Overall, the distributions of covariates in the aggregated treatment groups are similar to those in the internal control group. As compared with the three-dose group, the aggregated four-dose groups and the internal control group included more person-days over the age of 80 years (24.9% and 25.1%, respectively, vs. 16.2%) and more person-days from the general Jewish population (94.2% and 93.7% vs. 84.4%). Those in the three-dose group had a larger number of risk days than did those in the aggregated four-dose groups (31.0 million person-days vs. 23.9 million person-days) but had more confirmed infections (111,780 vs. 42,325) and more severe cases (1210 vs. 355).​

  PROTECTION CONFERRED BY THE FOURTH DOSE​

  As shown in Table 1, the unadjusted rate of confirmed infection was 177 cases per 100,000 person-days in the aggregated four-dose groups, 361 cases per 100,000 person-days in the three-dose group, and 388 cases per 100,000 person-days in the internal control group. The unadjusted rate of severe Covid-19 was 1.5 cases per 100,000 person-days in the aggregated four-dose groups, 3.9 cases per 100,000 person-days in the three-dose group, and 4.2 cases per 100,000 person-days in the internal control group.
  Table 2.

  

  Results of the Quasi-Poisson Regression Analysis of Confirmed SARS-CoV-2 Infection.Table 3.

  

  Results of the Quasi-Poisson Regression Analysis of Severe Covid-19.Figure 2.

  

  Adjusted Rate Ratios for Confirmed Infection and Severe Illness.
  The results of the quasi-Poisson regression analysis are summarized in Table 2 for confirmed infection and in Table 3 for severe illness. Figure 2 provides a graphical representation of the results for both confirmed infection and severe illness.
  The adjusted rate of confirmed infection was lower in the four-dose groups than in the two control groups. The adjusted rate among persons in the fourth week (22 to 28 days) after receipt of the fourth dose was lower by a factor of 2.0 (95% confidence interval [CI], 1.9 to 2.1) than that in the three-dose group and was lower by a factor of 1.8 (95% CI, 1.7 to 1.9) than that in the internal control group. The adjusted rate of confirmed infection (after rounding) in the fourth week after the fourth dose was 171 cases per 100,000 person-days (95% CI, 165 to 177), as compared with 340 cases per 100,000 person-days (95% CI, 337 to 343) in the three-dose group and 308 cases per 100,000 person-days (95% CI, 299 to 317) in the internal control group (Table S2). In the analysis of adjusted rate differences, the group in the fourth week after the fourth dose had 170 fewer confirmed infections per 100,000 person-days (95% CI, 162 to 176) than the three-dose group, and 137 fewer confirmed infections per 100,000 person-days (95% CI, 125 to 14 than the internal control group. From the fifth week (29 to 35 days) onward, the rate ratio for confirmed infection started to decline. The adjusted rate of infection in the eighth week after the fourth dose was very similar to those in the control groups; the rate ratio for the three-dose group as compared with the four-dose group was 1.1 (95% CI, 1.0 to 1.2), and the rate ratio for the internal control group as compared with the four-dose group was only 1.0 (95% CI, 0.9 to 1.1).
  The rate ratios comparing the control groups with the four-dose groups were larger and longer-lasting for severe Covid-19. For persons in the fourth week after receipt of the fourth dose, the adjusted rate of severe illness was lower by a factor of 3.5 (95% CI, 2.7 to 4.6) than that in the three-dose group and was lower by a factor of 2.3 (95% CI, 1.7 to 3.3) than that in the internal control group. The adjusted rate of severe Covid-19 (after rounding) in the fourth week after the fourth dose was 1.6 cases per 100,000 person-days (95% CI, 1.2 to 2.0), as compared with 5.5 cases per 100,000 person-days (95% CI, 5.2 to 5.9) in the three-dose group and 3.6 cases per 100,000 person-days (95% CI, 3.0 to 4.5) in the internal control group (Table S2). The adjusted rate differences were 3.9 fewer cases per 100,000 person-days (95% CI, 3.4 to 4.5) and 2.1 fewer cases per 100,000 person-days (95% CI, 1.4 to 3.0) than the three-dose group and the internal control group, respectively. Severe illness continued to occur at lower rates in the four-dose groups than in the control groups in later weeks after receipt of the fourth dose, and no signs of waning were evident by the sixth week after receipt of the fourth dose (Figure 2).​

  SENSITIVITY ANALYSES​

  The results of the matched analysis of confirmed infection were similar to the results obtained in the main analysis (Fig. S3). In addition, restricting the quasi-Poisson regression analysis to the general Jewish population, adding as a covariate the exposure risk over time in each individual’s area of residence, or adding as a covariate the time since administration of the third dose did not substantially change the results of the main analysis (Figs. S4 and S5).
  As described in the Supplementary Appendix, the testing policy in Israel was changed in early January 2022 (before the study period) for persons younger than 60 years of age. Even though the testing policy for the study population (persons ≥60 years of age) did not change, we tested the possible effect of the type of diagnostic test used to confirm infection by repeating the analysis counting only infections confirmed by positive PCR tests. This resulted in only very minor changes to the estimated level of protection conferred by the fourth dose (Figs. S4 and S5). In addition, we compared the testing rate and test type (PCR or antigen) among persons who received the fourth dose as compared with those who received only three doses and found the differences to be of limited extent (Fig. S2).​

  Discussion
  The omicron variant is genetically divergent from the ancestral SARS-CoV-2 strain for which the BNT162b2 vaccine was tailored. The results presented here indicate that as compared with three vaccine doses given at least 4 months earlier, a fourth dose provides added short-term protection against confirmed infections and severe illness caused by the omicron variant. The incidence rate for confirmed infection was lower by a factor of 2 and the rate of severe disease lower by a factor of 3 among persons in the fourth week after receiving the fourth dose than among eligible persons who did not receive the fourth dose.
  Comparing the rate ratio over time since the fourth dose (Figure 2) suggests that the protection against confirmed infection with the omicron variant reaches a maximum in the fourth week after vaccination, after which the rate ratio decreases to approximately 1.1 by the eighth week; these findings suggest that protection against confirmed infection wanes quickly. In contrast, protection against severe illness did not appear to decrease by the sixth week after receipt of the fourth dose. More follow-up is needed in order to evaluate the protection of the fourth dose against severe illness over longer periods.
  Although our analysis attempts to address biases such as confounding, some sources of bias may not have been measured or adequately controlled for — for example, behavioral differences between persons who received the fourth dose and those who did not. For severe illness, differences in the prevalence of coexisting conditions could potentially have affected the results; however, this information is not recorded in the national database, and therefore we did not adjust for such differences. Differences in coexisting conditions could also be associated with differential treatment with antiviral drugs such as ritonavir-boosted nirmatrelvir, which could have affected the results. To address some of these biases, we compared the rate of confirmed infection and severe illness within the group of people who received the fourth dose. Estimates of the rate ratio during the first days after vaccination could include the effect of transient biases (Fig. S6). These potential biases include the “healthy vaccinee” bias,9 in which people who feel ill tend not to get vaccinated in the following days, which leads to a lower number of confirmed infections and severe disease in the four-dose group during the first days after vaccination. Moreover, one would expect that detection bias due to behavioral changes, such as the tendency to perform fewer tests after vaccination, is more pronounced shortly after receipt of the dose.
  Thus, we compared the rates of confirmed infections and severe illness at different weeks after the fourth dose, from the second week onward, with the rates on days 3 to 7 after its receipt, a period during which the transient biases would have diminished but before the vaccine would be expected to have affected the rate of the outcomes of interest.6 The rate ratios obtained for confirmed infections were very similar to those obtained when comparing the treatment groups with the persons who did not receive a fourth dose. For severe illness, the rate ratios relative to the internal control group were lower than the rate ratios relative to the three-dose group. Even when the internal control group was the basis for comparison, the rate ratios for severe illness were still higher than those for confirmed infection and did not show signs of waning immunity.
  In addition, several sensitivity analyses were performed to assess the robustness of the results to further potential biases. First, we performed the analyses using data only from the general Jewish population, since the participants in that group are more common in the population that received the fourth dose. Second, we included in the model the risk of exposure in the person’s area of residence. The results of these analyses were similar to the results of the main analysis.
  Overall, these analyses provided evidence for the effectiveness of a fourth vaccine dose against severe illness caused by the omicron variant, as compared with a third dose administered more than 4 months earlier. For confirmed infection, a fourth dose appeared to provide only short-term protection and a modest absolute benefit. Several reports have indicated that the protection against hospital admission conferred by a third dose given more than 3 months earlier is substantially lower against the omicron variant than the protection of a fresh third dose against hospital admission for illness caused by the B.1.617.2 (delta) variant.1,10,11 In our study, a fourth dose appeared to increase the protection against severe illness relative to three doses that were administered more than 4 months earlier.​

  Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
  Mr. Bar-On, Dr. Goldberg, and Dr. Mandel and Drs. Huppert and Milo contributed equally to this article.
  This article was published on April 5, 2022, at NEJM.org.
  

  Author Affiliations
  From the Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot (Y.M.B.-O., R.M.), Technion–Israel Institute of Technology, Haifa (Y.G., O.A.), the Hebrew University of Jerusalem, (M.M.) and the Israel Ministry of Health (O.B., S.A.-P., N.A.), Jerusalem, the Bio-statistical and Bio-mathematical Unit, the Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Ramat Gan (L.F., A.H.), and the Faculty of Medicine, Tel Aviv University, Tel Aviv (A.H.) — all in Israel.
  Dr. Goldberg can be contacted at [email protected] or at the Faculty of Industrial Engineering and Management, Technion–Israel Institute of Technology, Technion City, Haifa 3200003, Israel.​

  Supplementary Material
  

  Supplementary Appendix	PDF	1046KB
  Disclosure Forms	PDF	221KB

  References (11)
  

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[siamese3]

@missy Thanks for posting all if the information!!

 

[missy]

@missy Thanks for posting all if the information!!

Thank you!

 

[Daisys and Diamonds]

I never stopped wearing masks. Greg and I are the only ones in this state (it feels like lol) who are still wearing masks indoors grocery shopping etc.

You are an inspiration
We still have to wear ours here and despite the zits i plan to keep wearing them

 

[SparklieBug]

I never stopped wearing masks. Greg and I are the only ones in this state (it feels like lol) who are still wearing masks indoors grocery shopping etc.

+1. Mask mandates are now finished, although businesses may still ask people to wear them. As of April 9, proof of vaccines will no longer be required, although some businesses may continue to request it.

We wear masks still, and I'm surprised how many others do, as well!

 

[MamaBee]

I wear masks every time I go into a store or have someone inside the house for repairs. I ask them to wear one too. My husband forgets to put his on so I have to follow him around to make sure he wears one. I even carry extra in my purse to make sure he has one. I think he forgets on purpose. He just doesn’t worry about getting Covid. I worry about what he does when I’m not with him.

 

[missy]

Food for thought.

"

Who really decides vaccine policy?​

When it comes to U.S. vaccination policy, who is in the driver’s seat? It’s up to officials at the Food and Drug Administration and the Centers for Disease Control and Prevention to authorize and lay out the standards for administering vaccines. But some experts have started to wonder aloudwhether vaccine makers have been framing the debate over whether and when to give more shots. “I feel like at some level, the companies kind of dictate the conversation,” said Paul Offit, a vaccine expert at the Children’s Hospital of Philadelphia, at a meeting of FDA advisers this week. “It shouldn’t come from them. It really has to come from us.” American culture is marked by epic rivalries between big corporations: McDonalds vs. Burger King. Coke vs. Pepsi. Ford vs. General Motors. Apple vs. Microsoft. But corporate sagas get more complicated when public health is on the line. Right now drugmakers Pfizer and Moderna are locked in a blow-for-blow battle over the market for messenger RNA shots. Both have to answer to their shareholders, and of late those shareholders haven’t been happy. Pfizer shares are off about 10% from a recent high in December, while Moderna shares have lost about two-thirds of their value since a peak in August. Each company has a lot riding on Covid-19 vaccines as a long-term franchise, but lots of open questions remain, and the data is thin. The battle for vaccine market share is part of a long history of American corporate rivalries, like between McDonald’s and Burger King. Photographer: Luke Sharrett/Bloomberg It’s as uncertain as ever just what the future of Covid shots might be. Europe is moving much more slowly to embrace boosters, even after an omicron wave that exposed how vulnerable society is to new variants. There, regulators have taken a more skeptical view of their utility. And in the U.S., the strain of a torrid cycle of shots over the past two years is starting to show. “The current situation where we are feeling compelled to boost every four months potentially is not sustainable,” said Mark Sawyer, a professor of pediatric infectious disease from the University of California in San Diego, who also serves on the FDA advisory panel. —Tim Annett "

 

[Lookinagain]

I'm still trying to decide if I want to get my second booster of Pfizer or get Moderna for the second booster. I wish I knew more about that.

 

[missy]

I'm still trying to decide if I want to get my second booster of Pfizer or get Moderna for the second booster. I wish I knew more about that.

If you got Pfizer for the first booster I would consider getting Moderna for the second. I posted articles explaining mixing mRNA vaccines might help boost immunity beyond what you might see when not combining.

 

[Lookinagain]

If you got Pfizer for the first booster I would consider getting Moderna for the second. I posted articles explaining mixing mRNA vaccines might help boost immunity beyond what you might see when not combining.

Yes, I thought you had but I want to go back and read them again. But I am definitely considering Moderna this time. Thank you for all the information you are posting.