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Coronavirus updates October 2021

missy

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October 26, 2021

Good morning. Covid cases have been falling in every region of the U.S., offering hope.

A Covid update​

It is time for one of The Morning’s occasional updates on the state of the pandemic. Today’s is focused on the U.S. and organized around three main points.​

1. Covid’s retreat continues​

The number of new daily Covid-19 cases has plunged 57 percent since peaking on Sept. 1. Almost as encouraging as the magnitude of the decline is its breadth: Cases have been declining in every region.​
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Data as of Oct. 24. Charts show a 7-day daily averageSource: New York Times database​
Forecasting Covid’s future is extremely difficult, as we all should know by now, and it’s certainly possible that cases will rise again in the coming weeks. But the geographic breadth of the decline does offer reason for optimism.​
Past Covid increases have generally started in one part of the country — like the South this past summer or the New York region in early 2020 — and then gone national. Today, there is no regional surge that seems to have the makings of a nationwide surge.​
Yes, there are some local hot spots, as has almost always been the case since the pandemic began. (You can look up your county.) Several of the hot spots are in northern parts of the country, like Alaska, Idaho, Montana, North Dakota and a few counties near the Canadian border in New Hampshire and Vermont. This pattern has led to some speculation that the onset of cold weather is causing the increases by moving more activity indoors — and that the entire country will soon experience a rise in caseloads.​
That does not seem to be the most likely scenario, however. In most colder regions, including both Canada and the densely populated parts of the northern U.S., cases are still falling. The biggest problem for Alaska and the Mountain West is probably not the weather; it’s the vaccine skepticism. Idaho is the nation’s least vaccinated state, and several other Western states are only slightly ahead of it.​
The C.D.C. tracks a range of Covid forecasting models. On average, the models predict that new daily cases in the U.S. will fall roughly another 20 percentover the next three weeks.​
The bottom line: There is no reason to expect another Covid surge anytime soon, but surges don’t always announce themselves in advance.​

2. Severity looks stable​

When the Delta variant began spreading this summer, many people worried that it was both much more contagious than earlier versions of the virus and much more severe. Only one of those two fears seems to be true.​
Delta is clearly more contagious, which is the main reason that every metric of the pandemic — cases, hospitalizations and deaths — soared this summer. But a typical Covid case during the Delta wave was about as severe as a typical case during the earlier stages of the pandemic. During the wave in late 2020 and early this year, about 1.2 percent of positive cases led to death; during the Delta wave, the share was 1.1 percent.​
Scientific studies trying to answer the severity question more precisely have come to conflicting conclusions. Some have found Delta to be more severe than other versions of the virus, and others have found that it is not. Until the research becomes clearer, the best guess may be that Delta is modestly more severe, which could explain why hospitalizations and death rates have held steady even as vaccination rates have risen.​
“Delta may be a little more serious, but not materially so,” Dr. Robert Wachter, chair of the department of medicine at the University of California, San Francisco, told me.​
This pattern can influence how you think about your day-to-day activities. If you are vaccinated (and boosted, if eligible) and you were comfortable socializing indoors and without a mask last spring, you can probably feel comfortable doing so again, now or soon. Wachter adds: “Some older people or those with medical conditions may want to be sure that everybody else indoors with them is vaccinated before removing their mask.”​

3. The U.S. is underperforming​

Despite all the encouraging news, one shadow still hangs over the U.S.: The pandemic does not need to be nearly as bad it is.​
About 1,500 Americans have died of Covid every day over the past week. For older age groups, the virus remains a leading cause of death. And the main reason is that millions of Americans have chosen to remain unvaccinated. Many of them are older and have underlying medical conditions, leaving them vulnerable to severe versions of Covid.​
For older people, the effects of vaccination are profound. In late August, near the height of the Delta wave, 24 out of every 10,000 unvaccinated Americans 65 and above were hospitalized with Covid symptoms, according to the C.D.C.Among fully vaccinated Americans 65 and above, the number was 1.5 per 10,000.​
Even so, many Americans are saying no to a shot. Among affluent countries, the U.S. is one of the least vaccinated, trailing Canada, Australia, Japan, South Korea, Britain, France, Germany, Italy and others. Less vaccination means more death:​
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Data as of Oct. 24Source: Our World in Data​
(These Times maps show the vaccination rates for each country.)​
The low vaccination rate in the U.S. is another consequence of our polarized politics and our high levels of socioeconomic inequality. Only 67 percent of American adults without a four-year college degree have received a shot, compared with 82 percent of college graduates, according to the most recent Kaiser Family Foundation poll. And only 58 percent of self-identified Republicans are vaccinated, compared with 90 percent of Democrats.​
It’s a triumph of misinformation. Offered a lifesaving drug to counteract a highly contagious virus, many Americans are instead choosing to take their chances.​
 

missy

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Infectious Disease>COVID-19 Vaccine

Pfizer Vax for Young Kids Passes the Test Among FDA Staff​

— No new safety concerns, but benefits may vary depending on COVID incidence​

by Molly Walker, Deputy Managing Editor, MedPage Today October 25, 2021


FDA ADCOMM Pfizer-BioNTech COVID-19 vaccine for children ages 5-11 over a photo of a man drawing from a vial of this vaccine.

Pfizer-BioNTech's COVID-19 vaccine produced an immune response and was safe and effective in young children, but its benefits may be largely dependent on severity of the COVID outbreak, according to FDA briefing documents released late Friday.
The FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) will meet on Tuesday for the third time this month to discuss COVID-19 vaccines, this time to see if the benefits outweigh the risks among children ages 5-11 years.

A two-dose regimen of 10 μg apiece, administered 21 days apart, met immunobridging success criteria, FDA staff said. The agency analyzed data from topline results released in September that found increases in neutralizing antibody geometric mean titers among children ages 5-11 versus individuals ages 16-25, as well as comparable seroresponse rates among the two groups versus baseline.
Adverse events (AEs) were similar to other populations, with no cases of myocarditis or pericarditis, anaphylaxis or deaths among ages 5-11, and this was after data from an additional 1,590 vaccine recipients and 788 participants from the phase II/III trial (called cohort 2). This was per the agency's request "to allow for more robust assessment of serious adverse events and other adverse events of interest," FDA staff said.
The manufacturer even included a descriptive efficacy analysis, which made headlines on Friday morning, that found 90.7% vaccine efficacy (VE; 95% CI 67.4-98.3%), with three COVID cases in the vaccine group and 16 in placebo. None of the cases met the criteria for severe COVID.

Interestingly, FDA staff conducted a benefit/risk assessment using several models of both VE and COVID incidence. They found that while "numbers of clinically significant COVID-19-related outcomes prevented would clearly outweigh the numbers of vaccine-associated excess myocarditis cases over a range of assumptions for COVID-19 incidence," the strength of benefits were varied.
Data was primarily from phase II/III of the phase I/II/III study C4591007, which had 3,109 participants who received vaccine and 1,528 who received placebo. It was made up of two cohorts: Cohort 1, with 1,444 in the vaccine group and 714 in the placebo group, each with at least 2 months of follow-up safety data, and cohort 2, who had a median of 2.4 weeks of follow-up data at the time of data cutoff on October 8.
FDA staff noted, "data verification is in process, but not yet finished at the time this briefing book was completed."

The study is ongoing, with 70% of the participants from the U.S. They were a mean age of 8 years, 51-53% were boys, and nearly 80% were white. About 12% had obesity, and 21% had comorbidities putting them at risk of severe COVID-19.

About 20% of participants in the descriptive efficacy analysis who acquired COVID-19 had comorbidities, and most infections occurred during July-August 2021.
Examining reactogenicity, the most common AE was fatigue (39%), followed by headache (28%) and muscle pain (12%). Most systemic AEs were mild or moderate, and resolved 1-2 days after onset, FDA staff noted.
The most common unsolicited AE was lymphadenopathy, reported in 13 vaccine participants and one placebo participant, and more vaccine recipients reported hypersensitivity-related AEs, such as rash and dermatitis.
For the benefit/risk assessment, the FDA conducted a series of models that measured symptomatic COVID-19 cases, hospitalizations, ICU admissions, and death compared to excess myocarditis/pericarditis cases, hospitalizations, ICU admissions, and death.
They found that the benefits were highest among kids ages 5-11 in the scenarios using the Delta-surge peak incidence, high VE, and higher COVID death rate, and lowest in scenarios with the lowest incidence.
In this scenario, "the model predicts more excess hospitalizations due to vaccine-related myocarditis/pericarditis compared to prevented hospitalizations due to COVID-19," FDA staff wrote. "However, in consideration of the different clinical implications of hospitalization for COVID-19 versus hospitalization for vaccine-associated myocarditis/pericarditis [...] the overall benefits of the vaccine may still outweigh the risks under this lowest incidence scenario."
They also pointed out that they used a "conservative assumption" for myocarditis risk, namely healthcare claims from adolescents ages 12-17, and if the risk is lower among younger children, "the benefit-risk balance would be more favorable."
 

missy

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Sharing an email update from one of our physicians.
She does quarterly updates.

"

COVID UPDATE


I hesitate to say it, but I think the constant fear of worrying what’s next with Covid can finally settle down a little bit. I know that I, for one, have been living with a constant “what fresh hell is this” mentality. OK, we got the vaccine but some people are not taking it. Now there is a new variant that is 60% more infectious and causes more severe disease. Now kids are going back to school before there is a vaccine available for them. Now we are going into our first cold/flu season during full in-person school.

And yet: The vaccination rate in NYC is over 70%. The vaccine rate for the zip code 112.. is 72%. Compared to my home state of Alabama, where there is a 40% vaccination rate, these numbers are great. When we read the news about Delta tearing through the country, it is in areas where vaccination rates are low. Delta now accounts for 97% of American Covid cases; unless a major new variant appears, the way life is now is the way it will be for the foreseeable future. There is a new variant, Delta Plus, on the horizon, but it is only slightly different from Delta, with an increase in transmissibility of about 10% (no data yet on whether it is a more severe infection).
The current vaccines are effective in all known variants. Experts say that the virus would need to mutate quite a lot to evade the effectiveness of vaccines that are available now. The return to school/work did increase the Covid case number in the U.S. to about 1,500 a day for the 7 day average from the lowest summer numbers of 200 a day for the 7 day average. But the case numbers are holding steady at that rate, with no exponential increase. Ongoing safety protocols and contact management seem to be doing their jobs. And vaccines for younger kids are just on the horizon. Vaccine breakthrough infections are happening, but these infections almost universally lead to only minor symptoms.
Covid numbers for one week in NYC
335 per 100,000 cases were in unvaccinated individuals.
23 per 100,000 of unvaccinated people were hospitalized.
3 per 100,000 of unvaccinated people died.
VS
68 per 100,000 cases were in vaccinated individuals.
3 per 100.000 of these people were hospitalized.
0 per 100.000 of vaccinated people died.
COVID TESTING
Covid testing is available here at Gifford Family Practice! I can do rapid testing and PCR testing. The PCR test I use is through Quest diagnostics and takes 2-3 days for results.
I looked into getting the rapid PCR test with results in 8 hours, like they do at CareCube, but it was cost prohibitive. The machine and initial supplies are about $7,000 and the test kits are $1,000 per 24. I will keep my eye out for cheaper alternatives.
Post Covid Syndrome
Yesterday, I attended a 2 hour seminar on caring for patients with Post Covid Syndrome presented by the New York State Commissioner of Health, Dr. Zucker. I definitely feel more prepared to help my patients who might be suffering from Long Covid. I will continue to educate myself as more research comes to light.
COVID VACCINE UPDATE
Boosters
Boosters abound!
Pfizer boosters are recommended 6 months after the original series for:
Everyone 65+
18+ with underlying conditions
18+ with occupational risk
Pfizer boosters are full-dose and do not differ from the first two vaccines in the series.
Moderna boosters are recommended 6 months after the original series for:
Everyone 65+
18+ with underlying conditions
18+ with occupational risk
Moderna booster shots are ½ the dose of the original two vaccines in the series.
Johnson and Johnson boosters are recommended 2 months after the original shot for:
Everyone who received a Johnson and Johnson vaccine.

Patients can choose to have another Johnson and Johnson vaccine as a booster or either of the mRNA vaccines (Pfizer or Moderna) as a booster. Getting Pfizer or Moderna as a booster is my strong recommendation, as this boosts immunity significantly more than getting another Johnson and Johnson vaccine. The current data show that a Moderna booster increases antibodies 76-fold. A Pfizer booster increases antibodies 35-fold. Another Johnson and Johnson increases antibodies only 4-fold. Antibodies are not the full story when it comes to vaccine efficacy for this particular virus. Therefore, this does not translate directly into how effective the different boosters are at preventing disease. This is also why neither the FDA nor the CDC recommend checking covid antibodies levels to determine vaccine efficacy.
There is no concrete data on antibody responses of other mix-and-match vaccine combos. Patients can feel free to get whichever booster they want. The only strong recommendation I have is to boost Johnson and Johnson with Moderna or Pfizer.
The current vaccines are preventing hospitalization and death in low-risk people, even without a booster. If you are not one of the people for whom boosters are recommended, rest assured that you do not need one at this time. That recommendation might change as more information is gathered and analyzed or with waning immunity over the passage of time.
All individuals are considered fully vaccinated from a “vaccine pass” standpoint after the initial series. There is no requirement for boosters at this time.
COVID VACCINES FOR AGES 5-11
Can you hear it? That’s the sound of a million parents breathing a sigh of relief. Covid vaccines for kids are (almost) here.
The committee meets on Nov 3 to make a formal determination, but everyone expects the Pfizer pediatric formulation to be approved at that time. As you may recall, I was unable to provide adult Pfizer vaccines because they come in lots of 1,000 that must be kept at ultra-cold temperatures. Pfizer for kids comes in lots of 100 and has different storage regulations. They can be kept refrigerated for up to 10 weeks and I will most likely be able to provide them. I have already pre-booked my doses!
I have been on the precipice of receiving doses of Covid vaccines before, however, only to have hopes dashed. When I have the vaccines sitting securely in my fridge, I will send out a Portal Broadcast. My plan is to clear my schedule during after-school times for a couple of weeks, reserving those times only for pediatric Covid and flu shots, in order to vaccinate as many kids as possible as quickly as possible. That way our little ones will be fully protected come winter break!
In the unfortunate event that I do not receive any vaccine supply, I will contact you with information on where you can get it for your children. If you have not heard from me and you have an opportunity to vaccinate elsewhere, please take it.
Learn from my experience! When vaccines for adults first came out, a good number of my patients got Covid between taking the first dose and the second dose. Your children will not be immune until 2 weeks after the second dose. Even if they are first in line for the vaccine, they will NOT be immune by Thanksgiving. Continue to take all normal precautions until it has been 2 weeks after the 2nd dose.

Masks
I have been so delighted to see so many of you wearing my favorite mask, the Air Queen. I want to make it more clear that even though it is marketed as an N95 equivalent it is only 94% as effective as an N95. It should not be used in high-risk situations as a replacement for an N95 or KN95. I use it as a super effective comfortable everyday mask. I continue to wear a FIT-tested medical N95 at the office with patients with respiratory illness. I wear a KN95 when I have to be in an indoor space for prolonged periods with folks of unknown vaccine status like the grocery store.
I have also found a very effective pediatric mask that my child loves: Dr. Puri.
XXXXX FAMILY PRACTICE OPERATIONAL NEWS
Almost all appointments are now done indoors. I still see patients outdoors for Covid testing and for respiratory illness appointments. Please let me know in advance by email if you have any respiratory symptoms so that I may prepare the outdoor space.
If you do not let me know in advance then you will just have to deal with an unswept floor, possibly dusty chairs and mosquitos (yes, still!)
When you arrive for your appointment, whether indoors or outdoors, please ring the doorbell so that I know you have arrived. Rest assured that I disinfect all surfaces, including the doorbell, after seeing someone who is sick.
I am now using the waiting room as a consultation space — the part of the visit that used to happen in my office — so the waiting room is not available to patients who arrive early. If you arrive early and it is raining, you can ring the bell and I will let you wait in the courtyard, where you’ll be protected under the tent.
I wish all of my wonderful patients a safe and lovely Halloween. I have already seen a number of Covid-safe candy-delivering devices go up on stoops. I was so impressed by how creative people were last year. One house delivered candy by drone! Another had a pulley system. Another used a fishing pole. I went old-school and just tossed candy from my stairs, Mardi Gras-style.
However you celebrate, have a great time!

"
 

missy

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Summing up most people can safely get MRNA vaccines even if they have lots of allergies.

"
Original Investigation
Allergy
October 26, 2021

Association of Self-reported High-Risk Allergy History With Allergy Symptoms After COVID-19 Vaccination​

Lily Li, MD1,2; Lacey B. Robinson, MD, MPH2,3,8; Rajesh Patel, MD, MPH2,4; et alAdam B. Landman, MD2,5; Xiaoqing Fu, MS3,8; Erica S. Shenoy, MD, PhD2,6; Dean M. Hashimoto, MD2,7; Aleena Banerji, MD2,3; Paige G. Wickner, MD, MPH1,2; Upeka Samarakoon, MS, PhD, MPH3,8; Christian M. Mancini, BS3,8; Yuqing Zhang, Dsc2,3,8; Kimberly G. Blumenthal, MD, MSc2,3,8
Author Affiliations Article Information
JAMA Netw Open. 2021;4(10):e2131034. doi:10.1001/jamanetworkopen.2021.31034


Key Points
Question What is the association between self-reported history of high-risk allergy and allergic reactions after messenger RNA (mRNA) COVID-19 vaccination?
Findings In this cohort study of 52 998 health care employees, self-reported high-risk allergy history was associated with an increased risk of self-reported allergic reactions after mRNA COVID-19 vaccination. Most of the reported allergy symptoms, however, did not impede the completion of the 2-dose vaccine protocol.
Meaning
This finding suggests that the mRNA COVID-19 vaccines are safe to receive for eligible individuals.
Abstract
Importance
Allergic history in individuals with confirmed anaphylaxis to a messenger RNA (mRNA) COVID-19 vaccine is common. However, the risk factors for allergy symptoms after receiving the vaccine are unknown.
Objective To assess the association between self-reported history of high-risk allergy and self-reported allergic reactions after mRNA COVID-19 vaccination of health care employees.
Design, Setting, and Participants This cohort study obtained demographic, medical, and vaccine administration data of employees of Mass General Brigham from the institutional electronic health record. Employees who received at least 1 dose of an mRNA COVID-19 vaccine between December 14, 2020, and February 1, 2021, and who completed at least 1 postvaccination symptom survey in the 3 days after vaccination were included.
Exposures Self-reported history of high-risk allergy, defined as a previous severe allergic reaction to a vaccine, an injectable medication, or other allergen.
Main Outcomes and Measures The primary outcome was 1 or more self-reported allergic reactions in the first 3 days after dose 1 or dose 2 of an mRNA COVID-19 vaccine. Multivariable log binomial regression was used to assess the association between allergic reactions and high-risk allergy status.
Results A total of 52 998 health care employees (mean [SD] age, 42 [14] years; 38 167 women [72.0%]) were included in the cohort, of whom 51 706 (97.6%) received 2 doses of an mRNA COVID-19 vaccine and 474 (0.9%) reported a history of high-risk allergy. Individuals with vs without a history of high-risk allergy reported more allergic reactions after receiving dose 1 or 2 of the vaccine (11.6% [n = 55] vs 4.7% [n = 2461]). In the adjusted model, a history of high-risk allergy was associated with an increased risk of allergic reactions (adjusted relative risk [aRR], 2.46; 95% CI, 1.92-3.16), with risk being highest for hives (aRR, 3.81; 95% CI, 2.33-6.22) and angioedema (aRR, 4.36; 95% CI, 2.52-7.54).
Conclusions and Relevance This cohort study found that self-reported history of high-risk allergy was associated with an increased risk of self-reported allergic reactions within 3 days of mRNA COVID-19 vaccination. However, reported allergy symptoms did not impede the completion of the 2-dose vaccine protocol among a cohort of eligible health care employees, supporting the overall safety of mRNA COVID-19 vaccine.

Introduction
The messenger RNA (mRNA) COVID-19 vaccines from Pfizer-BioNTech and Moderna received emergency use authorization from the US Food and Drug Administration in December 2020 for prevention of severe COVID-19. Within days of the authorization, several reports of severe allergic reactions to the mRNA COVID-19 vaccines emerged, generating widespread concern regarding vaccine safety and creating a barrier to public health mass vaccination efforts.1 Currently, the only contraindications for receipt of the mRNA COVID-19 vaccines are a known history of a severe or an immediate allergic reaction to any vaccine component, which includes the excipient polyethylene glycol (PEG), and an allergic reaction to a previous dose of an mRNA vaccine.2,3
Since December 2020, the rate of allergy symptoms that have been reported after mRNA COVID-19 vaccination has been approximately 2%,4 and the incidence of anaphylaxis has been estimated as 0.025 to 2.47 cases per 10 000 vaccinations.4-9 Among individuals with confirmed anaphylaxis to mRNA COVID-19 vaccines, about one-third reported a history of anaphylaxis.4,7 National and international guidelines on mRNA COVID-19 vaccination have varied and included mixed messages for individuals with a history of anaphylaxis.10-12 In the US, the Centers for Disease Control and Prevention (CDC), national task forces, and health care institutions developed prescreening tools to risk-stratify individuals according to a clinical assessment of their high-risk allergy history, including a severe allergic reaction to an injectable medication, vaccine, PEG, or anaphylaxis from any other cause.13-15 However, these recommendations were based solely on expert opinion, and whether high-risk allergy is associated with allergy symptoms after mRNA COVID-19 vaccination is unknown.
Identification of risk factors for allergy symptoms after COVID-19 vaccination will guide safe vaccination practices for individuals at the highest risk and inform strategies that target vaccine hesitancy that is associated with allergy concerns. In this cohort study, we aimed to assess the association between self-reported history of high-risk allergy and self-reported allergic reactions after mRNA COVID-19 vaccination in a large prospective cohort of health care employees.
Methods
Study Population and Data Sources
Mass General Brigham (formerly Partners HealthCare System) is an integrated health care system comprising 16 health care institutions in northeastern US and is the largest employer in Massachusetts with approximately 87 000 employees. We prospectively studied Mass General Brigham employees who received at least 1 dose of an mRNA COVID-19 vaccine and completed at least 1 postvaccination symptom survey assessment. This study was approved by the Mass General Brigham Institutional Review Board, which granted a waiver of informed consent because the study was secondary observational research. We followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.16 The study period was from December 14, 2020, to February 1, 2021, and follow-up was conducted through March 1, 2021.
The Mass General Brigham institutional vaccination procedures and voluntary reporting of allergy symptoms after vaccination have been previously described in a study of allergic reaction and anaphylaxis incidence after mRNA dose 1 (which occurred from December 16, 2020, to February 12, 2021).4 Briefly, the prevaccination allergy risk assessment was performed through a screening questionnaire (eMethods in the Supplement) that was completed by the employees either online or by telephone or in person (with assistance from a hospital staff member) for those without computer or smartphone access. Completion of the prevaccination questionnaire was required of all employees, who were asked to attest that their answers were truthful.
Employees were directed via email or a hyperlink on an existing custom COVID-19 symptom-check application17 to record and report their own postvaccination symptoms daily for 3 days after vaccination using a web-based survey (REDCap; Vanderbilt University) (eMethods in the Supplement). For employees without computer or smartphone access, symptom checks were conducted by hospital staff by telephone call or text message. Survey completion was defined as full completion of at least 1 of the 3 postvaccine symptom surveys after receiving either dose of the 2-dose vaccine series. Overall, the symptom check response rate was 88% (85% for male and 89% for female employees).
Exposure
Exposure status (history of high-risk allergy) was ascertained before the initial vaccine administration from each employee’s completed screening questionnaire (eMethods in the Supplement). Employees who reported no history of a severe allergic reaction received an mRNA COVID-19 vaccine with a standard 15-minute observation period. Individuals who reported any history of a severe allergic reaction to an injectable medication, vaccine, or other allergen (eg, food, venom, drug, or latex) were considered to be at higher risk and eligible for an mRNA COVID-19 vaccine with a 30-minute observation period, per CDC guidelines.18 Those with a self-reported history of an immediate or a severe allergic reaction to a component of the vaccine (eg, PEG or polysorbate) required evaluation with a Mass General Brigham allergist before vaccine eligibility, although ultimately few employees were found ineligible for the vaccines.13
Outcomes
The primary outcome was 1 or more self-reported allergy symptoms in the first 3 days after either dose 1 or dose 2 of an mRNA COVID-19 vaccine. Reportable allergy symptoms included itching or rash (other than at the injection site), hives, angioedema (swollen lips, tongue, eyes, or face), and respiratory symptoms (wheezing, chest tightness, or shortness of breath) (eMethods in the Supplement).
The secondary outcome was self-reported severe allergy symptoms to the mRNA COVID-19 vaccine. These symptoms included (1) hives, itching, or rash other than at the injection site, and (2) either respiratory symptoms, angioedema, or both in the first 3 days after vaccination. For employees whose symptoms were considered severe, we identified the frequency with which they were evaluated by an allergy specialist at Mass General Brigham and whether the specialist determined that the symptoms were consistent with a true allergic response.
Covariates
We obtained employee demographic data, including age, sex, and race and ethnicity (which were self-reported by employees), from the Mass General Brigham electronic health record (EHR). Race was categorized as Asian, Black, White, other (ie, American Indian, Native Hawaiian, or individuals who identified as belonging to 2 or more race categories), or unknown, whereas ethnicity was categorized as Hispanic, non-Hispanic, or unknown. Employee role was categorized as clinical (eg, health care practitioner, pharmacist, dietitian, or physical therapist), administrative (eg, human resources or marketing), support services (eg, environmental services or food services), or other (eg, sales). Among clinical staff, health care practitioners were defined as medical doctors, registered nurses, and physician assistants. Comorbidities were identified by the presence of at least 1 International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis code19-23in the 12 months before vaccination. We calculated Charlson comorbidity index score (range: 0-16, with higher scores indicating a more severe condition).24,25 Vaccine administration data, including manufacturer and Mass General Brigham satellite site, were obtained from the EHR.
Statistical Analysis
We described the characteristics of employees according to their history of high-risk allergy. Categorical variables were compared using a χ2 test, and continuous variables were compared using an unpaired, 2-tailed t-test or Wilcoxon rank sum test, as indicated.
We estimated the risk of allergic reactions after vaccination by high-risk allergy status and examined their association using log binomial regression. In the multivariable regression model, we adjusted for demographic factors, medical comorbidities, and vaccine manufacturer as well as present adjusted relative risk (aRR) with its 95% CI as the measure of effect. Allergic comorbidities from diagnostic codes were not included in the model, as they likely represent the exposure of interest (high-risk allergy).26 To establish whether the association between high-risk allergy status and risk of allergic reactions after vaccination was modified by other risk factors, we examined the association of high-risk allergy status within the strata of sex, age (<55 years vs ≥55 years), race (Black, White, or other), and vaccine manufacturer. We tested for a modification of the association by including an interaction term (between high-risk allergy status and each risk factor) in the multivariate regression model.
All analyses were performed using SAS, version 9.4 (SAS Institute). Two-sided P < .05 was considered to be statistically significant.
Results
A total of 52 998 Mass General Brigham employees were included in the cohort. This cohort had a mean (SD) age of 42 (14) years and was composed of 38 167 women (72.0%) and 14 831 men (28.0%). Of these employees, 51 706 (97.6%) completed the full 2-dose vaccine series and 474 (0.9%) reported a history of high-risk allergy (Figure). Baseline characteristics according to high-risk allergy status are presented in Table 1. The percentages of women (80.8% [383 of 474] vs 71.9% [37 784 of 52 524]) and Black individuals (9.5% [45 of 474] vs 4.8% [2521 of 52 524]) were higher among those with a history of high-risk allergy vs those without. In total, 47 327 employees (89.3%) had at least 1 previous encounter in the EHR before vaccination. Individuals with a history of high-risk allergy compared with those without were older (46 years vs 42 years) and had more atopic disease (16.7% vs 8.7%; P < .001) and a higher prevalence of anxiety (28.9% vs 23.9%; P = .01), hypertension (14.6% vs 10.9%; P = .01), and malignant neoplasm (4.0% vs 2.4%; P = .03). Distributions of vaccine manufacturer, vaccination site, and employee role also differed by high-risk allergy status.
Among the 474 employees who reported a history of high-risk allergy, a past reaction to an idiopathic or known allergen (eg, food, venom, drug, or latex,) was common (n = 221 [46.6%]). A total of 217 employees (45.8%) reported a previous severe allergic reaction to an injectable medication or vaccine. Only 9 individuals (1.9%) had a history of a severe allergic reaction to PEG or PEG-containing products (eg, Miralax and injectable steroid), and 8 of these individuals were evaluated by a Mass General Brigham allergist before vaccine administration.27
There were 2516 of 52 998 employees (4.7%) who reported 1 or more allergy symptoms in the 3 days after receiving either dose of an mRNA vaccine (Table 2). Individuals with vs without a history of high-risk allergy reported more allergic reactions (11.6% [n = 55] vs 4.7% [n = 2461]). Mild symptoms, such as rash or itching (other than at the injection site), were the most commonly reported reaction in the cohort (1422 of 52 998 [2.7%]), followed by respiratory symptoms (687 of 52 998 [1.3%]), hives (476 of 52 998 [0.9%]), and angioedema (342 of 52 998 [0.6%]). High-risk allergy history was associated with an increased risk of allergic reactions (RR, 2.48; 95% CI, 1.93-3.18). Adjustment of other potential confounders did not change the association materially (aRR, 2.46; 95% CI, 1.92-3.16). In the adjusted analyses, a history of high-risk allergy was associated with an increased risk of hives (aRR, 3.81; 95% CI, 2.33-6.22) and angioedema (aRR, 4.36; 95% CI, 2.52-7.54) after either dose, although risks were consistently higher after dose 1.
The relative associations of high-risk allergy with risk of allergic reactions were consistent across strata of other risk factors, including sex, age, race, and vaccine manufacturer (Table 3). Older age (RR, 1.00; 95% CI, 0.99-1.00), Black race (RR, 1.69; 95% CI, 1.47-1.95), higher Charlson comorbidity index score (RR, 1.04; 95% CI, 1.01-1.06), and receipt of Moderna (vs Pfizer-BioNTech) vaccine (RR, 1.49; 95% CI, 1.37-1.63) were associated with an increased risk of allergic reactions after an mRNA COVID-19 vaccination, whereas male (vs female) sex was associated with decreased risk (RR, 0.66; 95% CI, 0.60-0.73) (eTable 1 in the Supplement).
Self-reported severe allergic reactions in the 3 days after COVID-19 vaccination were uncommon (140 of 52 998 [0.3%]). Of the 140 individuals who reported severe allergy symptoms after either vaccine dose, 6 (4.3%) had a history of high-risk allergy. Manual validation identified that of 65 individuals with severe reactions and who were seen by a Mass General Brigham allergist or immunologist, 41 (63.1%) had a confirmed allergic reaction. Those with reactions that were deemed nonallergic had symptoms, such as dizziness, fever, chills, tachycardia, and headache. The risk of self-reported severe allergic reactions in the 3 days after vaccination was 1.3% among employees with a high-risk allergy history and 0.3% among those without such a history. High-risk allergy history was associated with an increased risk of severe allergic reactions after mRNA COVID-19 vaccination (RR, 4.96 [95% CI, 2.20-11.19]; aRR, 5.20 [95% CI, 2.30-11.75]).
To assess whether potential misclassification of self-reported allergy symptoms after vaccination may affect these findings, we evaluated the association of high-risk allergy with the risk of allergic reactions after vaccination among clinical health care practitioners. The effect size estimates for health care practitioners were slightly higher than those for the general employee cohort, particularly after dose 1 (eTable 2 in the Supplement). In an adjusted model, a history of high-risk allergy was associated with an increased risk of allergic reactions (aRR, 2.93; 95% CI, 1.82-4.73), with the highest relative risk for hives (aRR, 7.39; 95% CI, 3.33-16.40) and angioedema (aRR, 4.76; 95% CI, 1.53-14.82).
Discussion
In this large prospective study of health care employees in the US, 97.6% of the cohort successfully completed the recommended 2-dose mRNA COVID-19 vaccine series. We found that a self-reported history of high-risk allergy was associated with a 2.5-fold higher risk for self-reported allergic reactions in the 3 days after vaccination and an approximately 4-fold higher risk of hives and angioedema specifically. Although reporting of severe allergic reactions to an mRNA COVID-19 vaccine was rare (0.3%), those with a history of high-risk allergy were at a nearly 5-fold increased risk of these reactions, and such reactions were verified by specialists in most individuals who sought clinical care for their symptoms within the Mass General Brigham system. These identified associations were not sensitive to covariate adjustment and persisted across subgroups that were stratified by these factors.
Severe allergic reactions to vaccines are rare, with a reported incidence of 1.31 to 7.91 cases per million vaccine doses.9,28 However, a recent study of 429 highly allergic individuals who received the Pfizer-BioNTech vaccine under medical observation identified a much higher rate of minor allergic reactions (1.4%) and anaphylaxis (0.7%).29 Past vaccine reactions have largely been attributed to excipients rather than to vaccine active ingredients.13,30 The cohort in the present study included 217 employees with a history of a severe allergic reaction to an injectable medication or a vaccine and 9 employees with a history of severe allergic reaction to PEG. By reported history alone, many of these individuals may have been ineligible for an mRNA COVID-19 vaccine, according to many international guidelines. However, following the CDC guidelines, with allergist consultation, risk stratification, and shared decision-making, all employees were able to complete the 2-dose vaccine series.27 For the rare individuals with a history of severe allergic reactions to PEG, consultation with an allergist or immunologist is recommended because the mRNA vaccine may not be an absolute contraindication for such individuals.
Lessons may also be learned from previous restrictions of vaccine based on excipient allergy. For example, concerns were raised regarding the safety of administering egg-containing immunizations to individuals with an egg allergy during the H1N1 influenza A pandemic from 2009 to 2010 and played a role in global vaccine hesitancy. A large body of evidence subsequently emerged that indicated inactivated influenza vaccine to be safe for those with an egg allergy, and current national and international guidelines now recommend the administration of influenza vaccine to individuals with an egg allergy of any severity.31 Future studies involving diverse populations are needed to help address ongoing questions regarding the safety of mRNA COVID-19 vaccines in individuals with suspected or confirmed PEG allergy. Moreover, the emergence of allergy symptoms on first exposure, as was more commonly observed in this study, is atypical for IgE-mediated reactions,1 and an investigation of other mechanisms (eg, non-IgE-mediated mast cell activation or complement activation) underlying these reactions is warranted.
Of individuals with allergist-confirmed severe allergic reactions to mRNA COVID-19 vaccine to date, roughly one-third reported a history of anaphylaxis and most were women.4,7 Cutaneous findings about Moderna arm, a delayed-onset localized skin reaction, have been described largely in female patients.32 In a study of more than 400 dermatological reactions after COVID-19 vaccination, 90% of participants were women in an international dermatology registry.33 Similarly, we found female sex to be an independent factor in self-reported allergic reactions after mRNA COVID-19 vaccination in an adjusted multivariable model. This prospective study design vastly reduces the impact of reporter bias that is observed in case series and registry studies. Further studies are needed to better understand the risk factors, including sex, for allergic reactions after receipt of an mRNA COVID-19 vaccine. A multicenter, phase 2 randomized clinical trial is currently being conducted to assess COVID-19 vaccination reactions in individuals with a history of high-risk allergy and control participants with no atopic history.34
Assessment of allergy symptoms after vaccination was based on self-reported reactions. Of the 175 possible severe allergic reactions in a CDC report, 86 (49%) were ultimately deemed nonanaphylactic allergic reactions.7 The true incidence of postvaccination allergic reactions may therefore be lower than that reported in this study. Given the scale of the national mass vaccination efforts and the volume of employees who were vaccinated in a short time frame, manual review of all reported allergy symptoms was not feasible. However, allergic reactions were validated in more than 60% of those who reported severe reactions and who had a specialist visit, and in a subgroup analysis of clinical professionals with medical knowledge and training, allowing for high-quality self-reported health data,35 we observed a stronger association between high-risk allergy and risk of allergy symptoms after vaccination, suggesting less random misclassification of the outcome. Although additional prospective studies are needed to further examine the risk factors for confirmed allergic reactions after COVID-19 vaccination, perceived (ie, self-reported) allergy symptoms are also critical to study because of their equivalent association with public perception and vaccine hesitancy.
Recent data indicated that, even for individuals who reported immediate and potentially allergic reactions after the first dose of an mRNA COVID-19 vaccine, the second dose can be safely administered.36 Similarly, in this cohort, few individuals did not complete the 2-dose vaccine regimen, raising the possibility that not all first-dose reactions are truly allergic or may occur through non–IgE-mediated mechanisms. Reasons for incomplete vaccination vary and may include ineligibility for dose 2 after an allergy evaluation, scheduling factors, or other personal reasons for vaccine hesitancy. Future work directed at better understanding the reasons for delaying or not completing COVID-19 vaccination is warranted.
Strengths and Limitations
This study has some strengths. First, it included a large sample size; used comprehensive, prospectively collected data on allergy history (given that reporting was a requirement for vaccine eligibility); and captured more than 88% of the entire Mass General Brigham employee population with postvaccination symptom surveys. Second, we performed subgroup analyses of clinical health care practitioners and manual EHR reviews for employees who met the definition of experiencing a severe allergic reaction.
This study also has some limitations. First, the cohort consisted only of health care employees in the northeastern US, and thus the study findings may not be generalizable to health care employees in other parts of the country or to international populations.37 However, given the thousands of individuals who were included in this study, the findings remain informative and highly relevant as mRNA booster vaccinations begin. Second, comorbidity information may be incomplete for some individuals because they may have medical practitioners outside of the Mass General Brigham system and therefore their medical history may not be fully recorded in the EHR. However, this problem is inherent in the use of EHR data for clinical research; before comorbidity ascertainment, we identified that more than 89% of employees had at least 1 encounter that allowed for the near-complete capture of comorbidity data in the year before COVID-19 vaccination. Moreover, because self-reporting a history of high-risk allergy was required for vaccine eligibility and scheduling, per institutional protocols, exposure data were complete for all study participants. Third, adjustment for potential confounders in the multivariable models did not substantially change the effect size estimates, suggesting that any residual confounding is unlikely to jeopardize the internal validity of the findings.
Conclusions
This cohort study found that a self-reported history of high-risk allergy was associated with an increased risk of self-reported allergic reactions after mRNA COVID-19 vaccination, but most of the reported allergy symptoms did not impede the completion of the 2-dose mRNA COVID-19 vaccine series. Risks were higher after dose 1, and the reactions with the highest risk were hives and angioedema. Severe allergic reactions were rare. This study not only highlighted that high-risk allergy history was associated with allergy symptoms after COVID-19 vaccination but also supported the overall safety of mRNA vaccines in all eligible individuals.
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missy

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The big test ahead​

For much of the past year, countries with access to vaccines have been making steady progress out of the pandemic, and more and more places are reopening. But they now face the biggest test yet: winter.
The latest Bloomberg Covid Resilience Ranking shows that vaccination-powered reopening is delivering dividends for an increasing group of countries, especially in Europe. The top ranks, with Ireland at No. 1, are now joined by the United Arab Emirates, Chile and Saudi Arabia, which made the top 15 by deploying similar strategies of granting the vaccinated more freedoms. Among places that have moved up in the October ranking, Japan, South Korea and New Zealand have seen vaccination rates rising rapidly and community mobility improving.
The growing drive to reopen is being aided by an improving Covid situation—monthly deaths in October are set to fall to an almost one-year low. But the onset of colder weather is bringing with it the threat of resurgences in the Northern Hemisphere, and the reopening of borders means any new variants will rapidly spread, particularly in less vaccinated places.
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A Covid-19 vaccination center sign opposite Westminster in London.
Photographer: Dan Kitwood/Getty Images Europe
Reopening also poses a challenge for former Covid-Zero jurisdictions like Singapore—healthcare systems and the population will need to get used to higher case and mortality numbers than before and that’s not an easy transition to make.
And even where it’s balmy year round, plans to return to the mass gatherings of pre-Covid times also carry risks. Saudi Arabia and the UAE, both highly vaccinated and now reopened, are expecting millions of visitors at major events starting this month, such as the Expo in Dubai. And among those countries that continue to rank lowest in Southeast Asia, Indonesia, Malaysia, Thailand, Vietnam and the Philippines have all announced or started on plans to reopen. This will test a region that’s been one of the hardest hit in the world even as their vaccination rates improve.
In Europe, where most people are back to relatively normal life, a worrying jump in cases as the weather cools is already being seen in places like the U.K and Latvia. Will its pioneering strategies of longer vaccine dose intervals and largely limiting quarantine-free entry to the inoculation hold up and continue to provide a path out of the pandemic? Stay tuned for November’s Ranking.—Stephanie Phang
 

Asscherhalo_lover

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My Harry (now 10 months old) has finally gotten a slot in the Moderna trial! We've been waiting since spring. He's set to go in Monday, FX he gets the real deal!
 

Austina

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I got a text from the NHS today inviting me to go for my booster :( Sadly I’m not old enough here in Tx to qualify yet, but hopefully it won’t be too much longer before they start boosting the under 65’s.
 

Lookinagain

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mellowyellowgirl

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Bahaha they confirmed today they are not letting the antivaccers out until we reach 95% double dose!!!! That is awesome all around, especially for the kids who can't be vaccinated yet.

Wooooohoooooo

They loosened another bunch of restrictions for us though. I love it! Means I can live my life freely and the chances of running into some festy person are lower.

It's also extremely fair because if you qualify for an exemption (they're introducing a system to stop exemption shopping and the harassment of doctors) you get the same freedoms as vaccinated people. So really you're only being punished if you're a non science believing whackjob.

I love Australia! We were a bit dumb cruising on the elimination strategy but now we're back to being sensible. Emails for boosters have been going around. They're planning for winter already!

 
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