Vaccine effectiveness of two-dose BNT162b2 against symptomatic and severe COVID-19 among adolescents in Brazil and Scotland over time: a test-negative…

Introduction

The pandemic impulse generated due to the infectious agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in millions of infections and around six million deaths globally.1,2 As late as May 9, 2022, there were 755,415 cases reported and 9103 deaths in KSA at the hand of SARS-CoV-2.2 Vaccination is regarded the at most survivor from the pandemic. However, keeping with the data collected as late as May 4, 2022, 11,562,157,794 inoculations are reported to be administered worldwide.3 The earliest COVID-19 vaccine manufactured and approved was Pfizer-BioNTech/BNT162b2 which has the goal to hold off the pandemic. The experimental studies were completed in a short duration and were given Food and Drug Administration (FDA) approval just after a few months following its I or II clinical trials that were held in May 2020. The EUA (emergency use authorization) for this vaccine was granted in the last month of the year 2020. It received 23 August 2021 the full FDA approval, after passing all safety and efficacy requirements.4 Three approved companies whose doses are presently available in Saudi Arabia include Pfizer-BioNTech/BNT162b2, Moderna, and Oxford/AstraZeneca COVID19 vaccines.5,6 Among the currently approved COVID-19 vaccines, Pfizer-BioNTech/BNT162b2 and Moderna mRNA-1273 are based on mRNA technology.710

With the detection of novel viral variants, like Omicron, Delta, and Coronavirus Mu variant, there is a worry that the decline in immunity over time will diminish the potency; therefore, the third dose called booster may be required to boost immunity in fighting against new strains.8 After getting FDA approval, the CDC (Centre for Disease Control and Prevention) recommended a third dose for all aged 65 and above, and later the eligibility was expanded to other groups. The WHO-World Health Organization is also emphasizing an additional dose of the vaccine, to emphasize vaccine efforts to decrease the death rates and turn down the severity of disease, to protect the general maintenance of health.11 In Saudi Arabia, an additional dose was suggested for all who crossed the age of 16 and had completed their 2 doses. The Ministry of Health (MOH) Saudi Arabia created cognizance of the third dose booster dose through a campaign called Maintain Your Level with Booster Shot so as to achieve maximum immunity in the community.5

Vaccine hesitancy (VH), the biggest challenge to overcome and managing the pandemic, is elucidated as refusal or delaying its acceptance despite its availability.12 A research in the Kingdom of Saudi Arabia (KSA) has reported that the driving factor in hesitancy in accepting the inoculations of the vaccine was the concern over its efficacy and safety. It was revealed in a review that the inclined awareness about safe vaccines and being honest in reporting adverse effects could help in tackling the delay faced in vaccine acceptance and improving the uptake of immunization.13

Several studies from various other areas of the world reported fewer side effects after administrating the first or second dose, such as pain at the site of injection, swelling, tenderness, redness, warmth, itch, and swollen armpit glands, headache, fever, fatigue, night sweats, chills and shivering, joint pain, muscle pain, nausea, vomiting, and loss of appetite.1419 Despite the reality that the clinical studies assured the vaccine was safe and effective, it had limitations, such as a few participants recruited in the clinical studies and a healthier than real-world sample. This may neglect some less frequent deleterious effects that may happen. The vaccine developed in a short span and using new technology triggered a worry among people regarding its safety. Post-marketing evaluation is necessary to increase the public confidence in the vaccine and motivate them to accept the vaccine.10,2023

Keeping the limitations of clinical studies in mind, further epidemiological studies are important to evaluate the short-term COVID-19 side effects and to increase public trust in the safety and efficacy of the vaccine. Health professionals are recruited in the present study with the hope that the unwanted effects being reported by health practitioners will be accurate in comparison to the non-health professionals. Therefore, this research objective is to identify the short-duration side effects after receiving the Pfizer-BioNTech/BNT162b2 COVID-19 vaccine in health practitioners in the Eastern Province of the Kingdom of Saudi Arabia.

A descriptive cross-sectional study, conducted in the Eastern Province of Saudi Arabia, used a self-administered online survey to look for adverse reactions reported by healthcare workers (HCWs) who have received the booster dose of Pfizer-BioNTech/BNT162b2 vaccine. All vaccinated respondents who had taken their booster dose of Pfizer-BioNTech/BNT162b2 vaccine were requested for online surveys wherever the respondents stayed requested to selfreport some mildtomoderate indications that they developed post-vaccination. The target people of the current study HCWs (aged 18 to more than 55 years) were working in the Eastern Province, Saudi Arabia. The entitled respondents were to have taken their booster dose of the COVID19 vaccine prior to participating and filling in the survey questionnaire. Clinical (physicians, nurses, medical technicians, and pharmacists) and nonclinical (administrative and medical record professionals, and nonmedical technicians) HCWs serving at private and public hospitals in Eastern Province during the study time were the target populations of the current study. Respondents who had not taken booster doses as well as not HCWs were excluded from the study. The survey team identified the respondents (HCWs) from their professional and personal contact. Information was collected about those who were entitled and eager to participate in the survey. We followed STROBE guidelines for cross-sectional studies.24

In this study, we calculated the minimum sample size according to Lwanga and Lemeshow.25 Due to the absence of previous data on post-vaccination side-effects of COVID-19 booster dose among HCWs in Saudi Arabia, the <0.50 presumed quantity was used,26 through a 5% margin of error and 95% confidence level. A total of 384 participants were deemed necessary for this study based on the minimum number. However, as this study was based on an online survey disseminated via social media, it was decided to decrease the sampling bias in our method. We increased it to include 577 participants, which is near about 1.5-fold of the required size. During the study period, 580 eligible respondents participated in the study.

An appraisal of literature, including PubMed, Google Scholar, and other databases, was conducted with the goal of identifying short-term and potential sideeffects that might occur after the Pfizer-BioNTech/BNT162b2 vaccination. The questionnaire was designed using Google Forms and was written in English and Arabic. The final versions were reviewed by four different experts in the field to check for face and content validity. It was initially distributed to a pilot sample consisting of 10 participants to check for any technical misunderstandings or contraindications. The final data analysis did not include the pilot survey response. The survey was made as short in length as possible. It was clarified that the information would be used only for medical research purposes, as the participants were not identified and had the right to withdraw at any stage. An online survey using choice randomization displays answer options at random to the participants to avoid selection bias. Multiple sections were included in the questionnaire. A brief description of the purpose of the study is contained in the first section, along with contact details for the investigators, and an agreement for participants to consent to participate. The second section of the questionnaire was designed for the purpose of gathering general information about the respondents comprising age, sex, educational qualification, occupation, chronic diseases such as hypertension, diabetes mellitus, asthma, and others, in addition to whether they had, previous infection history with SARS-CoV-2 infection. The third section of the study focused on the COVID-19 vaccine, specifically sideeffects experienced after Pfizer-BioNTechs/BNT162b2 COVID-19 vaccine, their timing, and duration. Participants were able to leave the box unchecked if no symptoms were reported. There is a subsection with a list of the most frequently sideeffects reported in other studies,21,2729 redness at the site of the injection, pain at the site of the injection, body pain, fatigue, other, fever, chills, delayed menstruation, headaches, skin rashes, swelling at the site of the injection, nausea, and vomiting. Moreover, a section was provided for reporting other possible unpublished sideeffects. The study participants may have experienced. Further-more, participants were asked to report visits to doctors and any hospitalizations after vaccination, as well as any medications taken after vaccination. The target group for this study are HCWs working in the Eastern Province of Saudi Arabia. The survey team identified the respondents for the survey. The surveys link was disseminated to the respondents via WhatsApp, SMS, or e-mail and in individual to set a meeting. Survey/data collection has been performed from 7 March 2022 to 20 April 2022. Since all participants were asked to conduct the survey, members of the survey team identified and verified the responses of those who did not participate. Survey responses were provided by eligible participants based on their willingness to participate in the research.

Data for only those who had taken a booster dose of the Pfizer-BioNTech/BNT162b2 vaccine, respondents adherence with the inclusion and exclusion criteria and submitted a complete questionnaire. Of 577 participants, 74 (12.82%) individuals were excluded due to incomplete survey. Thirteen (2.25%) participants received the Moderna COVID-19 vaccine and were excluded from this study. In total, 490 (84.92%) respondents were included in the final analysis.

For conducting this study, we obtained ethical approval from the standing ethical review committee at Mohammed Al-Mana College for Medical Sciences (Reference number: SR/RP/80). We obtained the consent of all study participants before participation in the study. The study omitted responses with no informed consent, incomplete responses, those who failed to take a booster dose, respondents other than HCWs and those who taken a COVID-19 vaccine booster dose other than the Pfizer-BioNTech/BNT162b2 vaccine.

Statistical analysis was conducted using the data spread from Google Forms (Mountain View, California, USA) and Microsoft Excel (Version 2016), and then exported into Statistical Package for Social Sciences (SPSS) version 26.0 (IBM, Inc., Armonk, NY, USA). To depict the distribution of categorical variables, we used descriptive statistics such as occurrence, percentage, and mean standard deviation (SD), and to represent quantitative variables, we used median (interquartile range, IQR), respectively. ShapiroWilk tests were performed before the analysis to determine the normality of all quantitative variables. We cast off Pearsons chi-square (2) for examining the connotation amongst COVID-19 post-vaccination sideeffects and the independent variables (demographics and background features). MannWhitney U-tests and KruskalWallis tests were used to evaluate the number of COVID-19 post-vaccination adverse effects reported by the respondents as an ordinal dependent variable corresponding to the independent variables.

Additionally, a multivariate logistic regression investigation was conducted to determine the factors related to a complaint about sideeffects subsequent to administration of the PfizerBioNTech/BNT162b2 COVID-19 vaccine, which was coded as a replica reliant on variable (yes = 1 and no = 0). A multivariate ordinal logistic regression exploration was conducted to determine whether certain factors are associated with sideeffects following vaccination. A multivariate logistic regression model was created based on all variables that were associated with p 0.25 in univariate investigations.30 Odds ratios were calculated and intervals of confidence were calculated for all analyses. P-values were amended for multiple evaluations using the consecutive Bonferroni method (Bonferroni-Holm). Statistical significance was defined as p-values less than 0.05.31

Table 1 shows the general demographic characteristics of 490 vaccinated HCWs with the Booster dose of Pfizer-BioNTech/BNT162b2 vaccine participated in the study.

Table 1 General Demographic and Health Characteristics of the Participants (n = 490)

The mean SD age of the contributors was 33.836.91; more than half (56.74%, n = 278) of them were females, and 43.26% were males. Nurses were accounted for the majority of HCW group at 25.51% (n = 125), followed by Pharmacist (Medical) (18.37%, n = 90). Among all the HCW 29.18% (n = 143) have experienced between 1 and 2 years. Participants who had been previously diagnosed with COVID19 made up 32.86% (n = 161), most of whom were females (56.52%, 91/161). Only 8.37% (n = 41) of participants had reported suffering from a chronic disease.

As a result of this study, 81.84% (401/490) of the HCWs who took part described at least one post-vaccination side effect of COVID-19. There were 3 (14) reported side effects (median (IQR). Amongst the 401 HCWs who experienced postvaccination sideeffects of COVID19, Figure 1 displays that body pain (89%) and pain at the site of injection (88.73%) were the utmost frequent reported sideeffects, followed-by headache (28.68%), joint or bone pain (27.18%), muscle pain (26.43%), nausea or vomiting (21.2%), fever (18.95%), skin rashes (10.22%). On the other hand, the smallest often reported unwanted effects were redness at the site of injection (8.23), chills (7.98%), fatigue (7.73%), and swelling at the site of injection. However, 11.93% of the female respondents also reported delayed menstruation.

Figure 1 The frequency of COVID19 vaccine sideeffects reported among the participants (n = 401).

Participants who developed COVID-19 post-vaccination side effects were grouped according to their gender (Table 2). The results displayed that female HCWs had a meaningfully higher occurrence of side-effects of body pain (90.12% vs 87.34%; 2 = 18.37; p<0.001), pain at the site of the injection (89.30% vs 87.97%; 2 = 17.08; p = 0.001), swelling at the site of the injection (5.35% vs 2.53%; 2 = 4.76; p = 0.03), headache (89.30% vs27.85%; 2 = 6.33; p = 0.01), muscle pain (28.40% vs 23.42%; 2 = 9.66; p<0.001) and skin rashes (11.11% vs 8.86%; 2 = 6.33; p = 0.01) compared to male HCWs. On the other hand, the male HCWs had an ominously higher frequency of wholebody pain/fatigue (67.8%, 61/90) related to their female peers (50.0%, 80/160) (2 = 4.12; p = 0.04). Nonetheless, these significant differences were not retained when the BonferroniHolm adjustment was applied.

Table 2 Distribution of COVID19 Vaccine Sideeffects Reported Among the Healthcare Worker Participants According to Gender (n = 401)

In Table 3, we explore how COVID-19 vaccine side effects are associated with participant demographics and health background characteristics. HCWs developed side-effects at comparable frequencies (p = 0.001) among females (87.41%, 243/278) and males (74.52%, 158/221). There was substantial variance in the frequency of sideeffects consistent with participants age (<0.001) except >55 years age group. Interestingly, medical HCWs had a significantly lower frequency of unwanted effects than nonmedical HCWs (61.67% vs 80.73%; p = 0.001). Similarly, more than 5 years of experience significant side-effects (86.08%; p = 0.04) compared to another experience group of HCWs. There is no significant relationship between the history of comorbidities of COVID19 infection and side-effects experienced with the booster dose of vaccination. After BonferroniHolm correction, only two variables, sex, and occupation (medical) displayed a substantial link with the reporting of sideeffects.

Table 3 Associations of the Reported COVID19 Vaccine Sideeffects with the Participants Background Characteristics (n = 490)

In Table 4, we display the changes in the number of COVID-19 post-vaccination adverse effects stated by the deliberate HCWs according to self-governing variables. Medical HCWs have far fewer side effects (median = 4; IQR = 2, 3) as compared to nonmedical HCWs (median = 1; IQR = 1, 2) (U = 4148; p = 0.05) based on the MannWhitney U-test. Nevertheless, the KruskalWallis test did not show any significant differences in the number of side effects between age groups (H = 2; p = 0.36). As well, there were no significant differences in the number of side effects across variables (p > 0.05).

Table 4 Number of Sideeffects Reported by the Participants Following the Booster Dose of COVID19 Vaccine According to the Participants Background Characteristics (n = 401)

In Table 5, we present the results of multivariate logistic regression analysis for the factors accompanying reporting side-effects following the booster dose of the COVID19 vaccine among the HCWs. All variables that displayed relations with p 0.25 in the univariate analysis are available in Table 3. HosmerLemeshow test, cast-off for the inferential goodness-of-fit test, indicated the model fitted the data well (2 = 13.584; p = 0.317). The results revealed that a history of chronic diseases had a 0.44fold increased risk of side-effects compared to no history of chronic diseases health care workers (adjusted odds ratio (aOR) = 0.44; 95% CI = 0.224, 0.880), and a significant association of occupation with side-effects was also 1.61-fold increased risk compared to nonmedical ((aOR) = 1.61; 95% CI = 1.037, 2.513). Though, the substantial connotation of the year of experience with side-effects was not maintained in the multivariate analysis (p = 0.418).

Table 5 Multivariate Analysis of Factors Associated with Reporting of Sideeffects Following COVID19 Vaccine Among the Participants (n = 401)

Moreover, Table 6 provides the multivariate ordinal logistic regression analysis results for the factors prompting the number of COVID-19 vaccine side-effects described by the studied health care workers. Table 4 presents a univariate analysis that showed differences with a probability of p 0.21; all variables that showed a difference were included in the model. The model had a good fit and was statistically significant (2 = 19.254, p < 0.001). In the current study, the rate of stated side-effects was meaningfully predisposed by HCW gender and history of COVID-19 infection. The results indicated that holding other variables unchanged, a history of COVID-19 infection was fewer expected to report a greater number of side-effects than no history of COVID-19 infection (aOR = 17.410; 95% CI = 0.575, 1.974; p < 0.001). Likewise, female respondents were less likely to report a greater number of side-effects than male contributors (aOR = 5.164; 95% CI = 0.116, 1.576; p = 0.023).

Table 6 Results of Ordinal Logistic Regression for the Factors Associated with the Number of Reported Sideeffects Following the COVID19 Vaccine (n = 401)

Period and controlling of the described COVID19 vaccine sideeffects among the health care workers who developed COVID19 post-booster dose vaccination sideeffects, 77.81% (312/401) of the testified sideeffects happened on the day of getting the vaccine (Day 0). In contrast, 16.21% and 5.49% of the stated sideeffects happened on Day 1 and Day 2 post-vaccination (the second and third postvaccination days of booster dose), correspondingly. However, only 0.50% HCWs reported side effects appeared after day 2 of a post-booster dose of vaccination. The period of informed sideeffects was 12 days for 58.35% (n = 234) and 35 days for 25.94% (n = 104), while the sideeffects lasted for more than 5 days for only 7.73% (n = 31) of the subcategory of members who reported unwanted effects. Furthermore, 3.0% (n = 12) of those who experienced sideeffects go to a doctor, and medicine for a post-booster dose of vaccination sideeffects was taken by 83.79% (n = 336). Only 1.5% HCWs (n=6) were admitted to the hospital for less than 24 hours; however, only 0.50% (n = 2) were admitted to the hospital for 2436 hours (Table 7).

Table 7 The Onset, Duration, and Management of COVID19 Vaccine Sideeffects Were Reported Among the Participants in the Study (n = 401)

Presenting transparently the possible side effects post-vaccine administration is an approach to keeping trust in the vaccines and maximizing the benefits of vaccines safely. Subsequently, populations fears against vaccines could be dissipated. In this context, the current research sheds light on the prevalence of Side-Effects related to mRNA-based COVID-19 Vaccine booster dose among HCWs in the Eastern Province of Saudi Arabia.

The outcomes of the current study revealed a high incidence of side effects among the respondents where 81.84% of them have stated the minimum of one side-effect post-COVID-19 vaccine booster dose. This is consistent with data from other studies examining the safety of booster dose.32 However, compared to a previous study for first and second doses in which short-term sideeffects of Pfizer-BioNTech/BNT162b2 in individuals age span between 18 and 70 years old were investigated, fewer overall sideeffects (40%, n = 208) were recorded.33

Our findings show that body pain (89%) and injection site pain (88.73%) were typically indicated sideeffects by the HCW respondents, similar to the data publicized by Phase 3 clinical trial with the Pfizer-BioNTech/BNT162b2 vaccine revealed that pain at the injected site was the prevalent complication (7183%). However, in contrast to findings of the stated clinical trial where fatigue was the second reported side-effects (3447%), our data show fatigue was among the least frequently reported side effects (7.73%).34 We found higher values for delayed menstruation indicated by female participants (11.93%) than those reported by Edelman et al in the USA (4.3%).35

Our results corroborate with previous studies where a genderrelated variance in describing adverse events after numerous vaccines. It was detected a vigorous inflammatory and immune responses to vaccines in females as opposed to males, which could elaborate the genderbased variances response toward vaccinations.36 Additionally, behavioral, genetic, and hormonal elements could trigger the divergence in adverse events after vaccination between genders.37,38

Remarkably, the contemporary paper revealed that medical profession participants showed an important connotation with the reporting of sideeffects, which concurs well with the findings of a study done by Darraj et al in Saudi Arabia.39 Medical HCWs were more likely than nonmedical HCWs to detail a higher figure of side effects. These could be related to the medical and scientific background of medical HCWs about vaccine safety, which would improve their capacity to recognize and distinguish manifestations.39

Contrary to several earlier reports indicating that people with prior exposure to COVID-19 infection detailed more side effects, our results do not seem to confirm their observation.20,34,40 In fact, no significant relations with history of COVID19 infection and side effects experienced with the booster dose of vaccination were noted in our study. However, a noteworthy link between increased reporting side effects and participants having a history of chronic diseases was noted and also confirms previous findings in Germany.41

In this study, 77.81% of the reported sideeffects happened on vaccination day (0 day), which is in agreement with the results stated in other comparable studies.33,42 In the present investigation around 83.79% of the respondents were on medications (chiefly analgesics) to lessen the side effects. Analgesics are commonly used by Saudi Arabians both currently working in healthcare and those not in healthcare to ease the COVID-19 vaccines side effects.43 Moreover, just 3% of the respondents necessitated seeing a physician owing to sideeffects from the vaccines, and only 2% of the respondents were hospitalized. This will fully endorse the vaccines safety.

As a result of the present study, we can add more social confidence related to the safety of the COVID-19 Pfizer-BioNTech/ BNT162b2 vaccine, allowing to speed vaccination coverage. The transparent reporting of side effects by health care workers is especially central for accepting vaccinations for the general public. This is because people are more likely to be vaccinated when directed by a healthcare professional.44

However, our study is not without limitations. First, a self-administered online survey was used to assemble the data, which could result in a reporting bias and quite a small sample size. We chose an online study because we wanted to guarantee participants safety, due to the COVID-19 pandemic, SARS-CoV-2 viruses, and the recommendation to continue social distancing as a precaution measure in Saudi Arabia. In addition, conducting community-based surveys would be difficult during this pandemic. Thus, we collected our data online through a self-reported survey, and it was distributed based on the authors networks. Another limitation of the current study is that it observed the vaccines short-term side-effects (from day 0). Vaccine effects on our cohort are still unknown in both the short- and long-term. Likewise, side effects subsequent to the booster dose of the vaccine were investigated, whereas the side-effects post the first and second dose of the vaccine were not studied. Additionally, the participants were only Pfizer-BioNTech/BNT162b2 recipients. Therefore, more multicentred investigations with bigger sample sizes are necessary to confirm the different COVID-19 vaccines safety profiles permitted in the country as well as, forthcoming studies to assess other rare events such as thromboembolic profiles and myocarditis and to confirm the immunogenicity of the booster doses are also important.45

The current research comes up with relevant information regarding the side effects that can occur post-COVID-19 vaccine administration amongst HCW in the Eastern Province of Saudi Arabia. The outcomes indicated that most respondents had body pain and site injection pain, whereas fatigue is among the least reported side-effects post-booster dose. The female respondents also report delayed menstruation, but it would be necessary to collect extensive data from a large number of vaccinated populations to assess any significant association between delayed menstruation and the COVID-19 vaccine. Additionally, occupations related to healthcare were highly connected with more reporting of sideeffects. Self-medication practice to alleviate side-effects due to the vaccination is clearly manifested in the. Overall, the outcomes pointed to entirely tolerable mild to moderate reported COVID19 postbooster dose vaccination sideeffects. Consequently, the existing studys findings reinforce the vaccines safety and offer main standard facts to rise healthcare workers and the general communitys awareness of the predictable sideeffects subsequent COVID19 vaccines. This could convince the reluctant, refusal persons and pessimists to receive the booster dose COVID19 vaccine.

There is no funding to report.

The authors have no conflicts of interest to declare in this work.

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The low number of children under 5 receiving the COVID-19 vaccine on Long Island has pediatricians worried kids will not be protected in time for school and another possible wave in the fall.

Just 4,727 children inthe age group in Nassau and Suffolk counties have received a first dose of the vaccine, according to state data. That's3.1% of the eligible population.

I'm a little surprised and a little disappointed, said Dr. Eve Meltzer Krief of Huntington Village Pediatrics. Most people just don't understand that in the last wave, they were the ones that were hospitalized more than any other pediatric age group. Most people just really think that COVID doesn't affect young children and that couldn't be farther from the truth.

On June 18, the Centers for Disease Control and Prevention released its recommendation that all children 6 months through 4years of age receive a COVID-19 vaccine. That opened up the vaccine to almost 20 million additional children across the country, the agency said.

WHAT TO KNOW

The Moderna vaccine is a two-shot regimen administered one month apart. The Pfizer-BioNTech COVD-19 vaccine is a three-shot course for children in the youngest age group. The first two doses are given three weeks apart with the third at least 8 weeks after the second dose.

That time lag could explain some of the lower numbers for fully vaccinated children on Long Island, 733 eligible children ages 4 and younger have been fully vaccinated against COVID-19, according to the state Health Department.

Across the country, vaccinations of children under 5 have lagged behind other age groups.

About 2.8% of children under the age of 5 in the United States, or about 544,000,had received at least one COVID-19 vaccine dose as of July 20, according to the Kaiser Family Foundation.

When KFF compared it with the same point in the earlier rollout of vaccines for children between the ages of 5 and 11, 5.3 million or 18% of children in that age group had received their first dose.

In New York, children younger than 5 have the lowest vaccination rates of all age groups, statistics show.

Less than 1% of kids four and younger, or 9,139, have been fully vaccinated, according to the state Health Department. More than 53,000 or about 4.7% of the eligible 1.1 million population has received at least one shot.

Surveys have shown many parents are reluctant to have children in this youngest age group vaccinated citing myriad reasons. Some said they wanted to wait several months while others point to figuresshowing children are less likely to becomeseverely ill from COVID-19 than adults.

The CDC said that while most children with COVID-19 might have mild symptoms or no symptoms at all, theycan still become very ill and even die from the virus.

Dr. Matthew Harris, medical director of Northwell Healths vaccine program and a pediatric emergency medicine specialist, said there has been an increase in positive COVID-19 cases, including children in this youngest age group.

It really is absolutely important that pediatricians and family doctors continue to encourage vaccination for all their patients against COVID-19 and take every opportunity to counsel patients and parents about the benefits, said Harris, a father of three who had his own infant son vaccinated in June.

Harris pointed out trends in the pandemic have shown upticks in COVID-19 vaccinations tend to follow increases in cases and hospitalizations.

At that point, however, parents may have missed the ball, he said.

Meltzer Krief, who sits on the executive council of the Long Island-Brooklyn/Queens chapter of the American Academy of Pediatrics, said parents of young children under 5 might mistakenly think their child does not need to be vaccinated if they dont attend preschool or day care.

Parents have to realize, unless they live in a bubble, they could bring it home to their young children, she said. And those who are going to be in day care and preschool, where masks aren't required, that is where youre going to be seeing a lot of transmission happening, particularly this new variant that really wasn't circulating in the spring they're going to be sitting in classrooms, not really with any protection, transmitting this potentially very serious disease to each other.

Both Pfizer and Moderna are working on bivalent boosters: vaccines made up of both the old formula and a new one that targets the Omicron BA.4 and BA.5 subvariants of the coronavirus.

But cases are high now. There are about 124,000 new cases reported each day -- far from the levels reported during the Omicron surge, but nearing peak case rates from the Delta wave -- and cases are more undercounted than ever.

Some experts wonder whether the Omicron-specific boosters will come in time to make a difference and if they will actually offer more protection than the current shots.

A prediction game

The current shots are based on the original strain of the virus and offered nearly full protection, even from infection, early on. With new variants in circulation, the vaccines still are good at keeping people out of the hospital, but most scientists think people need a vaccine that offers more protection.

Dr. Michael Chang, a pediatric infectious disease specialist at Memorial Hermann Health System in Houston, thinks vaccines with an Omicron component will be helpful -- within limits.

"I just wish that the timing had been sooner so that we could actually be dealing with the kind of BA.5 surge that we have right now," he said.

With the highly contagious BA.5 subvariant now dominant, the goal of minimizing the number of infections is "kind of lost," but the new vaccines should help keep hospitalizations and deaths down, Chang said.

"I do think, anytime you can introduce additional strains or variants into a vaccine, the human body's immune response tends to be a little bit broader and more durable and potentially longer-lasting," he said.

Dr. Edward Michelson, chair of the Department of Emergency Medicine at Texas Tech University Health Sciences Center in El Paso, is seeing many patients again, even those who had Omicron earlier in the year.

"Omicron is not protecting people even a few months after they got sick with it. These subvariants are getting them again, much to my surprise," Michelson said. "The good news is, most of the patients don't need hospitalization."

'A new vaccine could really pay dividends'

While scientists are still trying to determine exactly how well the new vaccines will protect people, Lessler said, the model assumes that the reformulated vaccine would have about 80% efficacy against infection with the currently circulating strains. But that depends on how many people actually get an updated booster.

"Absent any real new variants, that kind of efficacy would be enough to really tamp down the current circulation if we have a broad uptake of the vaccines," Lessler said. "A new vaccine could really pay dividends, particularly if we can get it to a broad swath of the population."

Ideally, public health campaigns could be built to encourage people to get a flu vaccine and a Covid-19 vaccine at the same time, he said.

Lessler presented an earlier version of the model to the FDA's independent vaccine advisers, who voted in June to recommend that the vaccine makers include BA.4 and BA.5 in the fall booster. They said that including an Omicron element would offer more protection.

"While it's impossible for anyone to predict which variants will be circulating at the time, the goal as I see it is to add the subvariants that are most likely to give us that broad spectrum of antibodies that will hopefully prevent serious disease, which is really what we're trying to do," said Dr. Archana Chatterjee, dean of the Chicago Medical School at Rosalind Franklin University of Medicine and Science and a member of the FDA's Vaccines and Related Biological Products Advisory Committee.

Europe's approach

"Our program continues to focus on all variants of concern and we remain committed to the public health needs as defined by regulators, Europe and elsewhere," a spokesperson for Pfizer told CNN in an email.

In the United States, a vaccine updated for BA.4/5 got the go-ahead for fall.

Dr. Larry Corey, a vaccine development expert and professor of medicine and infectious disease division at Fred Hutchinson Cancer Research Center in Seattle, said the data makes a strong case for the addition. Research on infections shows that the BA.4 and BA.5 subvariants seem to induce stronger immune response than BA.1 and BA.2.

"We don't have the data yet. Certainly, we will know by the end of August," Corey said.

As with so much during the pandemic, scientists are making educated guesses and figuring things out as they go.

"We'll start sleeping better in a month, see whether it does well in animals, and we'll feel we made the right decision when we boost a bunch of people with the BA.4/BA.5 variants," Corey said.

A virus that breaks all the rules

Even as the virus changes, there is only so much vaccine makers can do, says University of Michigan epidemiologist Arnold Monto, who has served as acting chair of the FDA's vaccine advisory panel.

"Basically, we can only use those viruses that we know about," Monto said.

Omicron was a big change from previous variants, he said, and most evolutionary virologists don't think there will be such a big leap again. Rather, the changes will probably be along the Omicron lines.

But then again, "this has been a tricky virus. It has broken all the rules."

Regardless, Monto is confident that adding the BA.4/BA.5 element to the new vaccines will help.

"While we know that the latest viruses that we are encountering that will go into the vaccine probably are not going to the be the viruses in the coming fall and winter, the answer is not to chase them but to try and catch up and broaden them," he said.

In other words, vaccine makers will want to have a wide a distribution of immunity in the population. That's why they'll continue to include the original strain as well as Omicron.

It seems possible that we'll be facing different variants in the fall, but Dr. Eric Rubin, an adjunct professor of immunology and infectious disease at Harvard T.H. Chan School of Public Health, said there is a "very reasonable argument" that having some diversity in the immune response is still a good thing.

"For me, the most important thing we can measure right now is the breadth of immunity and not try to guess which strain is going to be there. That's probably more important than trying to guess what comes up in the fall," said Rubin, who is also on the FDA's vaccine advisory committee but was not a part of the Omicron booster discussion.

Evolution is trying to find its own path, however, and the virus will do whatever works for it as opposed to us. Down the line, he hopes we'll have even better vaccines that will prevent not just severe disease but infections as well.

"I don't think a perpetual game of catchup is going to work forever. We need to think about new approaches," Rubin said.

But he emphasized that more people should get vaccinated and boosted in order to keep cases, hospitalizations and deaths down.

Some people should still get boosted now

The FDA is still encouraging adults 50 and older and those with compromised immune systems to get a second booster now, with the current formula. That would leave enough of an interval for them to get an updated booster in the fall.

Once boosters are updated for the fall, the FDA said, people who get boosted now "may consider getting one." Scientists say it will be important to get this updated version.

"The current vaccines do a pretty great job at keeping people out of hospitals," Rubin said. "I don't really want to dismiss what we've got there. Of course, we always want better."

Late one afternoon last October, Dr. Shelley Odronic sat in her office and, just as she had thousands of times before, slid a rectangular glass slide onto her microscope.

A pathologist who works in rural Ohio, Odronic leaned forward to examine tissue from the placenta of a woman who had recently given birth. She increased the magnification on the microscope. Never had she seen so many tiny, congealed reservoirs of blood or such severe inflammation of the tissue, a sign the placenta had been fighting an infection.

Right away, I knew it wasnt compatible with life, Odronic said.

She asked her secretary to print out the patients chart. In dark letters were the words fetal demise. A stillbirth, the death of a fetus at 20 weeks or more of pregnancy. But that didnt solve the mystery. Odronic had examined many placentas from pregnancies that ended in stillbirth. None looked like this withered and scarred.

Odronic kept reading. No chronic medical conditions. Good prenatal care. Then, buried in the middle of the report, she spotted something. Seven days before the stillbirth, the mother had tested positive for COVID-19. Odronic wondered if the virus could explain the damage to the placenta. In the world of placenta pathology, a new affliction is unusual, especially one so dramatic in presentation and so devastating in effect.

Her mind traveled to Dr. Amy Heerema-McKenney, a pathologist at Cleveland Clinic and an expert on the placenta, who had trained Odronic during residency. Odronic went to sleep that night with a pit in her stomach and a plan to call her former teacher in the morning.

Heerema-McKenney was in her office when the phone rang. As she listened, she knew that what Odronic was describing was what she and her colleagues had observed repeatedly over the past several months: a patient positive for the coronavirus, a placenta destroyed by COVID-19, a baby stillborn.

Their next discovery was equally stunning. None of the stillbirths they studied involved a pregnant person who had been fully vaccinated. The doctors checked with colleagues across the country and around the world. The fatal pattern held.

Unvaccinated women who contracted COVID-19 during pregnancy were at a higher risk of stillbirths. They also were more likely to be admitted to the intensive care unit, give birth prematurely or die. Yet their greatest protection the COVID-19 vaccine sat largely untouched, buried under doubt, polluted by disinformation.

Pharmaceutical companies and government officials failed to ensure that pregnant people were included in the early development of the COVID-19 vaccine, a calamitous decision made amid the urgency of a rapidly spreading pandemic. That decision left pregnant people with little research to rely on when making a critical decision on how best to keep the babies growing inside of them safe.

At the same time that research was excluding pregnant people from vaccine trials, a full-scale assault on vaccination was unfolding online. Taking advantage of the lack of data, conspiracy theorists, anti-vaxxers and even some medical professionals spread false claims about the vaccines safety in pregnancy, leading many pregnant people to delay or refuse the vaccine. Even now, with numerous studies unequivocally announcing the safety of the vaccine for pregnant people, some doctors have failed to communicate the dangers of COVID-19 to pregnant people or the vaccines role in mitigating it.

The Centers for Disease Control and Prevention contributed to the confusion with vague early messaging about whether pregnant people should get vaccinated. While Americans lined up at pharmacies and stalked vaccine websites in hopes of securing a shot last year, pregnant people had some of the lowest vaccination rates among adults, with only 35% fully vaccinated by last November. Meanwhile, many Americans were already moving on to their boosters after federal officials that month expanded eligibility for the additional shots to anyone 18 or older. And much of the country was beginning to return to pre-pandemic life. The Sunday after Thanksgiving, for instance, set the record for the busiest day of air travel since March 2020.

November also marked a key moment in the understanding of COVID-19s impact on stillbirths. A CDC study looking at 1.2 million births in the first 18 months of the pandemic found that more than 8,000 pregnancies ended in stillbirths, including more than 270 of them in patients with a documented COVID-19 diagnosis at the time of delivery.

Although stillbirths were rare overall, babies were dying. The risk of a stillbirth nearly doubled for those who had COVID-19 during pregnancy compared with those who didnt. And during the spread of the delta variant, that risk was four times higher.

Indeed, doctors discovered that some stillbirths resulted from COVID-19 directly infiltrating the placenta, a condition they named SARS-CoV-2 placentitis. Cases were found even in people whose COVID-19 symptoms were mild or nonexistent. In some cases, however, placentas were discarded with medical waste without being tested for COVID-19, and parents never learned what led to their babys stillbirth.

COVID-19 also led to stillbirths among pregnant people who became exceedingly ill after contracting the virus. It damaged their lungs and clotted their blood, putting their babies in such severe distress that they were born before they could take their first breath.

These are pregnancies that should not have ended, Heerema-McKenney said.

She and others had tried to alert the CDC as well as maternal and state health organizations to their findings, but she said they either didnt get a response or were told they needed to collect more data and publish studies. Pathologists are experts in disease diagnosis, dealing with death and illness from the safe distance of their labs. Convincing obstetricians who met with patients daily or doctors who were making policy recommendations was a challenge.

I tried to sound the alarm. We tried so hard to get people to listen, Heerema-McKenney said. It was a really frustrating place to be as pathologists doing these autopsies, looking at these placentas and saying, God, no, not another case.

Around the same time Heerema-McKenney was examining the damaged placentas, Ginger Munro was on life support in a hospital 250 miles away in another part of Ohio.

She and her husband, Kendal, had been trying to have a child for five years. They hadnt expected that shed get pregnant in the middle of a pandemic. But when her pregnancy test came back positive in the spring of 2021, she rushed to post a picture of it in an online pregnancy group. Is it just me or can you see the 2 lines?? she asked.

The pandemic had already brought much change to their lives. Ginger, who lives in the small town of Washington Court House in southwest Ohio, quit her job as assistant nutrition director with the countys Commission on Aging. She stationed hand sanitizer throughout her house and in her car, and she only went grocery shopping early in the morning. If she noticed someone in an aisle, she skipped it.

I knew the virus was real, she said, but I was terrified to take the vaccine.

Ginger worried that the vaccines development had been rushed, and she hadnt seen any data showing it was safe for pregnant people. At this point, the CDC had not explicitly recommended the vaccine during pregnancy. Ginger already worried she was tempting fate by getting pregnant at 40; she said she didnt want to risk endangering her baby by taking the vaccine.

Besides, if it was really important, her doctor would have mentioned it, and, she said, she would have followed his advice. But, she said, he never did. Her family hadnt gotten vaccinated either. In a mostly rural county where less than half of the residents were vaccinated, they were hardly alone.

Her doctor declined to comment through a spokesperson at the hospital system where he works; the spokesperson said the hospital couldnt disseminate information about the vaccine to pregnant patients before it was recommended.

Gingers pregnancy progressed without complications. She and Kendal shared the news of a new baby with Gingers two daughters from a previous marriage. At their kitchen table, near a sign that read eat cake for breakfast, Sophia, then 14, covered her mouth with both hands while Hailee, then 18, simply beamed.

At a backyard gender reveal three months later, Gingers growing belly resembled a basketball against her tiny frame. She leaned in to kiss her husband, her long, dark hair falling onto her shoulders. Red confetti rained down on the deck.

Kendal, an aircraft maintenance and avionics manager at an airport two counties away, worked through the pandemic. In the summer, when they realized his cough was actually COVID-19, it was too late. Ginger was sick.

Having trouble reaching her doctor, she went to two different emergency rooms. One, she said, declined to treat her with monoclonal antibodies, which research had shown can be an effective treatment for pregnant people with COVID-19. The other, which described her in medical records as an exceedingly pleasant individual admitted with symptomatic COVID-19 pneumonia, transferred her about an hour away to the University of Cincinnati Medical Center. There, records show, she was admitted with acute respiratory distress syndrome due to COVID-19.

The University of Cincinnati doctor asked Ginger and Kendal who was on FaceTime because of the hospitals COVID-19 protocols about fetal priority. Ginger made her wishes clear: Save the baby, their baby, the baby they had tried so hard to have. Kendal, who was worried about both his wife and their unborn child, said he went along with Ginger in that moment.

You were so scared, Kendal wrote in a notebook that night. We told each other over and over how much we loved each other.

They hung up so the doctors could insert a breathing tube. Before they could begin, Kendal called back three more times just to hear her voice.

Doctors put Ginger on ECMO, a form of life support reserved for the sickest patients. Kendal, Hailee, Sophia and Gingers mother and sister were later allowed in the hospital two at a time, and they prayed at her bedside nearly every night. Ginger was sedated, her face swollen and obscured by tubing, her cheeks flattened by the crush of the ventilator straps, her wrists tied down so she wouldnt accidentally pull out her breathing tube.

Her family took solace in knowing the babys heartbeat was steady and her ultrasounds were normal. The doctors gave Ginger medication to help the babys lungs mature in case she was born early. After more than 30 days on ECMO, doctors took Ginger off the machine only to put her back on the next morning. She was the first patient in the hospitals history to be placed on ECMO twice.

The plan, records show, was to deliver at 28 weeks. But the day after Ginger was put back on life support, Kendal got the call telling him the baby was on her way. As doctors prepared for the delivery in Gingers intensive care room, the family camped out in the waiting room, jittery from excitement and vending machine snacks. They talked about baby names and future family outings. They pulled the waiting room chairs together to form makeshift beds and covered themselves with blankets they brought from home.

They dont know if they actually fell asleep before a nurse burst through the doors screaming at them to follow. Shes coming! Shes coming! They didnt make it far before they were blocked by doctors and nurses, some huddled over an incubator in the middle of the hall and the rest crowded around Ginger.

Hailee tried to peer over the sea of blue scrubs to catch the first glimpse of her little sister. She smiled beneath her black mask. Shell be OK, she said to herself.

But after a few minutes of trying to revive the baby, a doctor told Kendal it was time. Kendal nodded, asked for a chair and collapsed as he tried to process his daughters death.

Then another wave of grief washed over him. Someone would have to tell Ginger.

Gingers medical records describe a baby born at 27 weeks without signs of life after an uncomplicated delivery. Her placenta had separated from the wall of the uterus, the risk of which studies have shown increases with COVID-19.

When Ginger woke up, she looked down at her sunken belly and realized she had given birth. She assumed her daughter was in the newborn intensive care unit. Ginger was barely able to speak around the tube in her trachea, but after a few days in which no one brought the baby to her, she couldnt wait any longer. Ginger turned to her mother and sister and mouthed the words, Wheres the baby?

The room fell silent. They called Kendal, who rushed to the hospital. He told her what had happened. He described their daughters dark hair and her long fingers and toes, just like her mothers.

Ginger, who had always loved the sweet smell of a newborns breath, whispered to her husband.

Did you smell her breath?

She wasnt breathing, he said.

In the hurried quest for a safe and effective COVID-19 vaccine, pharmaceutical companies and government officials did not include pregnant people in their initial plans. Its a failure that continues to reverberate.

They absolutely should have been included in COVID vaccine trials from the beginning, said Kathryn Schubert, president and CEO of the Society for Womens Health Research, a Washington, D.C.-based nonprofit that advocates for the inclusion of women in research and clinical trials.

Researchers and advocates have spent more than four decades trying to dismantle the belief that its unsafe or unethical for pregnant women to participate in clinical trials. A couple years ago, it seemed like they had finally prevailed.

Shortly before leaving office, President Barack Obama signed into law the 21st Century Cures Act, which established the Task Force on Research Specific to Pregnant Women and Lactating Women. The group found longstanding obstacles, including liability concerns, to including pregnant and lactating people in clinical research. It concluded that recommending halting medication or forgoing treatment while pregnant may actually endanger the health of the mother and her fetus more than the treatment itself.

The need for everything from asthma to depression medication doesnt stop when a person gets pregnant, and when a catastrophic event such as a pandemic hits, experts said, pregnancy should not preclude someone from receiving life-saving treatment.

Around the same time, researchers discovered that the Zika virus, which was mainly transmitted through mosquitoes, could pass from a pregnant person to their fetus and cause severe birth deformities. A second group of experts joined together to develop separate guidance on including pregnant people in the research, development and deployment of pandemic vaccines.

Both groups pushed to remove pregnant women from a list of vulnerable populations that required additional review before being allowed to participate in research. Instead of proving that pregnant women should be included, manufacturers would need to provide compelling evidence for why they shouldnt.

In 2018, the federal task force issued recommendations calling for including pregnant and breastfeeding people in biomedical research, and the Department of Health and Human Services adopted some of the guidance. But a gap remained between what the task force and others insisted was needed and what was actually happening.

We were frustrated because COVID-19 provided an opportunity to implement the recommendations of the task force, said Dr. Diana Bianchi, the director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the chair of the task force.

In February 2021, Bianchi and her colleagues published an article lamenting the exclusion of those who were pregnant or breastfeeding from the initial COVID-19 vaccine clinical trials. Pregnant and lactating persons should not be protected from participating in research, but rather should be protected through research, they wrote.

Ruth Faden, the founder of the Johns Hopkins Berman Institute of Bioethics, helped lead the group that issued the guidance after Zika. She and others urged manufacturers to include pregnant people in the development of the COVID-19 vaccine as part of Operation Warp Speed, the federal program that provided billions of taxpayer dollars to pharmaceutical companies to speed up vaccine production.

There is a playbook in place so that when the U.S. launches Operation Warp Speed, it should be pretty obvious what should be done, she said. Its not like no one knows how to do this, either ethically or technically.

Nevertheless, it doesnt happen, Faden added. Once again, pregnant people are left behind.

A spokesperson for Pfizer said the company followed guidance from the Food and Drug Administration. Although pregnant people were not included in the initial vaccine clinical trials, Pfizer tested its vaccine on pregnant rats and did not identify any safety concerns. The company subsequently launched a clinical trial with pregnant women but halted it because at that point the vaccine had already been recommended for pregnant people.

Similarly, Moderna also studied its vaccine on pregnant animals, but the company said it made the decision to prioritize the study of the safety and efficacy of the vaccine in adults who werent pregnant. It called that approach consistent with the precedent to study new vaccines in pregnant women only after demonstration of favorable benefit and risk in healthy adults.

In response to questions from ProPublica, Johnson & Johnson referred a reporter to its website, which didnt address the relevant issues.

Some government officials, including several from the Food and Drug Administration, said they support having pregnant women take part in clinical studies of vaccines for emerging infectious disease, including COVID-19. A spokesperson for the National Institute of Allergy and Infectious Diseases, which is part of the National Institutes of Health, said the agency did not dictate the protocol development for the trials and said that responsibility lies with the companies.

The failure to include pregnant people early on in COVID-19 vaccine trials was, at least in part, a casualty of the tremendous urgency to respond to an intense public threat and develop the vaccine as quickly as possible, Faden said. But multiple groups had published road maps on how to ethically include pregnant people without slowing down that process.

I cant tell you how many pregnant people might not have died or how many stillbirths might not have occurred if the playbook had been followed, she said, but Im willing to bet it was a significant chunk that would have been prevented if there had been a full-throated, evidence-based recommendation for COVID-19 vaccines in pregnancy almost simultaneous to when it was available for the rest of the adult population.

By the time the CDC specifically recommended the vaccine for pregnant people, in August 2021, the damage had been done.

A dizzying and vague series of advisories led to confusion and delayed vaccinations. When the COVID-19 vaccines were first made available in December 2020, the CDC said health care workers and residents of long-term care facilities should be prioritized, but the shots were not explicitly recommended for pregnant people. Instead, the agency said on its webpage for vaccines and pregnancy that pregnant health care workers may choose to be vaccinated. In explaining that decision, the CDC said that experts had considered how mRNA vaccines, which do not contain the live virus, work. They concluded that the vaccines are unlikely to pose a risk for people who are pregnant.

However, the CDC added, the potential risks of mRNA vaccines to the pregnant person and her fetus are unknown because these vaccines have not been studied in pregnant women.

In January, the World Health Organization recommended against pregnant people getting the vaccine unless they faced increased risk, such as complicating comorbidities or exposure to the virus due to a job in health care, but the agency later reversed course.

A few months later, in March 2021, the CDC continued its lukewarm messaging that pregnant people may choose to be vaccinated. The agency listed some points for pregnant people to consider discussing with their health care providers, starting with how likely they are to be exposed to COVID-19.

After a promising study showed that the vaccine was safe for pregnant people, CDC Director Dr. Rochelle Walensky said at a White House briefing in late April that the CDC was recommending the vaccine for them. But the CDC did not update its website to reflect her comments and said the agencys guidance had not changed: Pregnant people may choose to be vaccinated.

Once again, pregnant people were put in the precarious position of receiving ambiguous and inconsistent recommendations. In May 2021, the CDC reiterated that pregnant people faced an increased risk of getting severely ill from COVID-19, but the language surrounding the vaccine If you are pregnant, you can receive a COVID-19 vaccine was noncommittal.

A CDC spokesperson, responding to questions from ProPublica, said in an email that pregnant people were part of the first recommendations in December 2020 that encouraged people 16 and older to get vaccinated. At that time, data about the safety and efficacy of the vaccine during pregnancy was limited because pregnant people had been excluded from pre-authorization clinical trials, so the CDC included additional supporting language for pregnant people, saying they were eligible and could choose to receive the vaccine. The agency said its recommendations were based on available evidence and evolved throughout the pandemic.

Before making changes to its guidance, the CDC had its team of scientists review available data to ensure that there was an abundance of evidence.

For each update to the statement of risks during pregnancy, multiple types of studies and the strength of evidence for each were reviewed, another CDC spokesperson said. These reviews of the evidence were accompanied with discussions among subject matter experts both internally and externally with clinical partners for an ultimate determination of risk.

Dr. Cynthia Gyamfi-Bannerman, a perinatologist and chair of the department of obstetrics, gynecology and reproductive sciences at the University of California, San Diego School of Medicine, shared the daunting task of making vaccine recommendations for pregnant people as part of COVID-19 task forces for two leading organizations, The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine.

In the beginning, she said, the only pregnancy-specific data they had came from a few dozen participants who were inadvertently included after becoming pregnant during the clinical trials and from some pregnant animal data.

It played out in real time in the COVID pandemic because we see the effects of not including pregnant people in these trials, Gyamfi-Bannerman said. We couldnt make a strong recommendation, so pregnant people were hesitant. I think that directly led to fewer people using the vaccine than we would have wanted.

At the end of June 2021, the CDC added a general update to its website to reflect the dangers of the delta variant tearing across much of the country. Getting vaccinated prevents severe illness, hospitalizations, and death, it wrote. Unvaccinated people should get vaccinated and continue masking until they are fully vaccinated.

But it wasnt until Aug. 11, eight months after the first vaccine was administered, that the CDC issued its formal recommendation that pregnant and breastfeeding people get vaccinated.

The vaccines are safe and effective, Walensky said in a statement at the time, and it has never been more urgent to increase vaccinations as we face the highly transmissible Delta variant and see severe outcomes from COVID-19 among unvaccinated pregnant people.

August would prove to be the deadliest month for COVID-19-related deaths of pregnant people. The CDC issued an emergency call the next month strongly recommending the vaccine to pregnant people, noting that approximately 97% of pregnant people hospitalized with COVID-19 were unvaccinated. The dangers to symptomatic pregnant people included a 70% increased risk of death, and their developing babies could face a host of perils, including stillbirths.

Researchers have yet to determine exactly why some pregnant people with COVID-19, vaccinated and unvaccinated alike, deliver stillborn babies, while others do not. Attempts to answer that question have been hindered, in part, by incomplete data. The CDCs statistics on COVID-19-related fetal and maternal deaths are undercounts. The CDC has data on less than 73,000 birth outcomes following a mothers confirmed COVID-19 diagnosis in 2020 and 2021, of which 579 were pregnancy losses.

That information was sent in by fewer than three dozen health departments, and those estimates dont include states like Mississippi, which in September reported 72 COVID-19-related stillbirths since the start of the pandemic, nearly double what the state would have expected, according to data from the Mississippi State Department of Health. Preliminary state data shows total stillbirths increased there in 2020 then dipped in 2021, but were still higher than pre-pandemic numbers.

A separate CDC database shows more than 220,000 COVID-19 cases and at least 305 deaths among pregnant people.

CDC recognizes that pregnant people faced challenging decisions about how to best protect themselves in the setting of uncertainty related to both the infection and the COVID-19 vaccine, a CDC spokesperson said, adding, COVID-19 vaccination remains one of the best ways to protect yourself and your family from serious illness from COVID-19.

Heartbroken and determined, Jaime Butcher has emerged as an unofficial ambassador for the vaccine, posting in online pregnancy and stillbirth forums about the risks of being pregnant and unvaccinated.

No one, she said, told her of the risks. Doctors, the CDC and health officials, she continued, arent doing enough to inform people. Even now, well into the pandemics third year, the message still isnt getting through.

I kept seeing it happening more and more to women and it wasnt talked about, she said. They just say, Oh, get the vaccine, which is great, but they dont talk about what getting the virus can do to pregnant women.

As a wedding planner, Butcher was surrounded by love. She found it with her husband, then in the daughter growing in her belly, who they named Emily after Butchers grandmother.

Butcher suffered five miscarriages before, she said, she opened an email from an in-vitro fertilization clinic confirming her pregnancy in the summer of 2020. She screamed, and her husband rushed to wrap her in a hug.

They waited until she was five months along to announce her pregnancy at Thanksgiving. The next day, Black Friday, they bought a high chair, a tummy time mat and pink onesies.

They were taking precautions, Butcher said, especially since the vaccine wasnt yet available to her or her husband. But a week later, she woke up with a runny nose, though she didnt think much of it. Still, she went to the hospital to make sure everything was OK. An ultrasound came back normal.

When her daughters kicking slowed the next morning, she called her doctors office again. They told her to eat something sweet to get the baby moving. She tried everything she could find: orange juice, Cheerios, Twix, graham crackers, peanut butter and jelly. Nothing worked.

A few hours later, Butcher drove herself to the hospital, where she followed her daughters heartbeat on the screen. Steady. Then slow. Then still.

She delivered at 23 weeks. Butcher didnt know she had COVID-19 until they tested her at the hospital. A lab report later revealed extensive damage to the placenta.

I was in shock. I was in shock that I lost my daughter, in shock that I had COVID, Butcher said. She should be alive, but its because of COVID that I lost her.

A week later, she parked in front of Kohls to return the high chair, the clothes still on tiny hangers and the stroller her mom gave her. As she made her way to the register, she saw a baby in an identical stroller. The tears stung all the way down her cheeks.

You see what you want right in front of you, she said, and its like, My baby should be here. This shouldnt have happened.

Even before the pandemic, almost a quarter of all stillbirths may have been preventable. The stillbirth crisis has simmered silently in the U.S., claiming the lives of more than 20,000 babies annually. But parents often suffer alone, overwhelmed by grief and guilt.

In a new study published on the preprint server medRxiv*, researchers describe failures of the French healthcare system as reflected by increased hospitalizations due to certain acute cardiovascular diseases in 2021, which was coincident with the coronavirus disease 2019 (COVID-19) pandemic.

Study:Change in incidence of cardiovascular diseases during the covid-19 pandemic and vaccination campaign: data from the nationwide French hospital discharge database. Image Credit: crystal light / Shutterstock.com

Throughout the world, cardiovascular diseases remain the leading cause of death among men and women. Although COVID-19 primarily affects the respiratory system, it is also associated with several non-pulmonary consequences, including effects on the cardiovascular system.

Although rare, COVID-19 vaccines have been associated with cardiovascular manifestations. For example, the Pfizer-BioNTech messenger ribonucleic acid (mRNA)-based COVID-19 BNT162b2 vaccine was found to induce myocarditis in some individuals, whereas vector-based vaccine caused thrombotic thrombocytopenia in rare instances.

In France, cardiovascular diseases were the second most common cause of hospitalization in 2019. After the initial detection of COVID-19 in January 2020, France faced a shortage of healthcare management services. Three lockdowns were subsequently implemented between March 2020 to May 2021 to reduce the transmission of COVID-19 and the burden on healthcare services.

The current retrospective cohort study analyzed variations in the incidence of cardiovascular diseases pre- and post-COVID-19 in France. This analysis also considered the ways in which COVID-19 vaccination may have altered incident case rates.

The French National Uniform Hospital Data Set Database (PMSI) provided data from 2019-2021, with 2019 considered as the reference year. COVID-19 vaccination data were acquired from the French Ministry of Solidarity and Healthcare web portal.

International Statistical Classification of Diseases and related health problems, 10th revision (ICD10) codes were used to identify cardiovascular pathologies, with a primary focus on inflammatory and thromboembolic processes. These diseases were divided into five categories, which included:

For each pathology, only cases that were hospitalized for the first time in two years between 2019 and 2021 were included.

A total of 919,514 patients were studied for ten pathologies. A significant decline in hospitalizations was observed for all pathological conditions preceding the first lockdown between March 2020 and April 2020.

During this period, the rate of angina pectoris and arterial thrombosis/embolism declined by more than 35%, whereas a decline of about 30% was observed for patients with DVT. MI, TIA, and myocarditis rates also declined by 20-23%, whereas the incidence of pericarditis- and stroke-related hospitalizations declined by 13% and 14%, respectively. PE hospitalizations declined by 4%.

Four pathological groups with similar temporal patterns were identified based on the case ratios between each year, case trend, and annual relative risk. These groups were defined as sustained decrease, attenuated decrease, partial rebound, and increase.

In group A, which was otherwise known as the sustained decrease group, the incidence and relative risk of hospitalizations significantly declined each year and overall. Angina pectoris and DVT cases were included in this group.

In group B, otherwise known as the attenuated decrease group, a significant decrease in hospitalizations was reported by 2020 and was followed by an unchanged rate of hospitalizations between 2020 and 2021. This group included TIA, stroke, other venous thromboses, and pericarditis cases.

In the partial rebound group C, a significant decrease in 2020 cases was followed by a significant increase in hospitalizations in 2021. MI, arterial embolism, and thrombosis hospitalizations were included in this group.

In the increasing group D, PE and myocarditis cases were associated with an increase in their relative risk for hospitalization and overall incidence. These changes were independent of 2019 to 2020 changes.

Further analysis revealed a progressive rise in myocarditis-related hospitalizations from May to August 2020, until ultimately declining between September and October 2021. Notably, myocarditis occurred more frequently in men between the ages of 10 and 19, as well as those between 20 and 29 years of age, in 2021 as compared to 2019.

Myocarditis, caseload per sex and age, per year.

Conversely, a more even distribution of excess cases was observed in terms of both the age and sex of PE patients. The most notable differences were observed in elderly patients, particularly females over 70 years of age.

Pulmonary embolism, caseload per sex and age, per year.

When vaccination data was considered for non-COVID-19-related hospitalizations, a significant increase in myocarditis hospitalizations was reported among men between 10-29 years of age in March 2020. A similar rise in myocarditis cases was reported between June and October 2021 in this age group, which corresponded to when they were eligible for their first dose of COVID-19 vaccines.

A similar trend was reported among women aged 70 years and older with PE and their first COVID-19 vaccine doses.

Except for PE and myocarditis, all other targeted cardiovascular pathologies were found to decline between January and October 2021 as compared to 2019. These declined admission rates reflect the significant number of patients throughout France who did not have access to hospital services at this point in the pandemic.

The subsequent rise in acute coronary atherothrombosis reported in 2021 may be a re-normalization of necessary hospital care after this period. These findings suggest that the healthcare system in France faced significant challenges in providing important cardiac care to patients in 2021, despite any lessons that they may have learned during the first year of the pandemic.

The rise in myocarditis cases may be attributed to limited access to cardiac care in hospitals, as well as adverse reactions to current COVID-19 vaccines. Similarly, the rise in PE cases also occurred simultaneously when certain patient groups were eligible for their first COVID-19 vaccine doses.

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Recently, my 1-year-old received her first dose of the COVID-19 vaccine. Ellie was a trooper, crying for only about 30 seconds after the nurse delivered the dose. She was bouncing around the house as soon as we got home.

I got my first dose while pregnant to protect Ellie and me, as the immunity I received transferred safely to her. I delivered a perfectly healthy baby, and Ellie had no reaction to the first dose she received.

Of course, my decisions to get us both vaccinated were made only after poring over data and consulting with my doctor.

As the senior adviser for the California Department of Public Healths vaccine task force, I am inundated with coronavirus infection trends, surrounded by research and data day-in and day-out. Ive learned that COVID-19 is one of the top five causes of child death. During last winters omicron surge, COVID-19 hospitalizations for kids ages 4 and under were five times higher than when the delta variant was circulating earlier and 1 in 5 kids hospitalized with the virus was admitted to the intensive care unit. My husband also works in health care, where he hears cases of patients in the ICU fighting for their lives.

These are all constant reminders of how COVID-19 continues to ravage families and why we need to continue to look out for one another.

Knowing these facts firsthand had made me anxious while pregnant and during Ellies infancy. As parents, we want to do everything we can to protect the proverbial lights of our lives. I felt helpless without a vaccine during Ellies delicate first year.

That concern for loved ones spills over into the home that we share with my parents. My mother takes care of Ellie while my husband and I work, and my dad is highly vulnerable to the most serious consequences of COVID-19. Years ago, he was diagnosed with lung cancer, and his surgical treatment left him with about 75% lung capacity.

Like other multigenerational households, weve taken extraordinary care to keep ourselves and one another protected against the virus masking, isolating if we dont feel well, limiting interactions with non-family members and receiving all eligible vaccine doses. We are extra careful to avoid places where the coronavirus might be circulating. Regrettably, our family has missed out on a lot of activities.

Thats why I was thrilled when vaccines for all family members finally became available. I was heartened to know that thousands of infants and toddlers as young as 6-months-old were part of robust clinical trials that demonstrated the vaccines safety and effectiveness for our youngest children.

I feel fortunate to live in a country that rigorously researches and tests vaccines before they are authorized by the Food and Drug Administration and endorsed by the Centers for Disease Control and Prevention and for Californias added layer of review through an independent panel in partnership with Washington, Oregon and Nevada that examines the data.

In fact, the COVID-19 vaccine is just one of many proven vaccinations helping to keep my toddler healthy by protecting her from infectious diseases like whooping cough, measles and influenza, among others.

Now that our whole family has been vaccinated, we have a newfound peace of mind knowing that weve done everything we can to keep one another healthy. My parents can freely embrace Ellie with less worry, and she can safely spend more time with others outside our household.

We are among the nearly 29 million Californians who have been vaccinated against COVID-19. Nearly 67% of the states children ages 12 to 17 and more than 36% of those 5 to 11 have received doses of these safe and effective vaccines. This is good news, as research has shown that the vaccine protects children against the worst outcomes of COVID-19, including hospitalization, long COVID, multisystem inflammatory syndrome in children and death.

On Ellies first birthday, we celebrated her doljabi, a Korean tradition that determines ones destiny. As we watched her choose from a myriad of items before her, I secretly hoped shed choose the yarn that signifies long life. Of course, we knew wed be happy no matter what she chose, especially knowing she is better protected in her early years. We have so much to celebrate.

If you or other members of your family are not yet vaccinated against COVID-19, now is a good time to consider the tools available, including the recently authorized Novavax vaccine a new option for adults that uses a protein-based technology.

Whether to have your children vaccinated against COVID-19 is an important decision for every parent and caregiver to make. As a parent, I urge you to discuss any questions you have with your childs health care provider. If youre ready to take the step toward full-family protection against COVID-19, call your provider or community health clinic to get your child vaccinated. Or go to myturn.ca.gov or call 833-422-4255 to find a vaccination site near you.

Sonya Logman Harris is the senior adviser to Californias Vaccinate ALL 58 campaign and oversees the COVID-19 Vaccine Task Forces statewide outreach and education efforts. She previously served as chief of staff for the 2020 census in California.

Dr. Fauci: Youll get into trouble if youre not up to date on COVID vaccines and boosters here are 3 stocks that could get a shot in the arm

With summer travel season under full swing, the COVID-19 pandemic may seem like a thing of the past.

But if you dont stay up to date on your vaccines and boosters, the consequences could be dire, according to President Bidens chief medical advisor Dr. Anthony Fauci.

If they dont get vaccinated or they dont get boosted, theyre going to get into trouble, Dr. Fauci told KNX News 97.1 a Los Angeles radio station earlier this week.

He points out that the vaccine and booster rates in America are quite discouraging.

According to the Kaiser Family Foundation, 228 million Americans (or 70% of the U.S. population) were not up to date with COVID-19 vaccines as of July 20, 2022. Staying up to date on vaccines means having received the primary series and at least one booster dose.

Its hard to say whether Dr. Faucis warning will lead to more Americans getting COVID-19 vaccines and booster shots. But it does give investors a reason to check in on companies making those vaccines.

Right now, the most dominant strain of COVID in the U.S. is Omicrons BA.5 subvariant. And Moderna could help the country fight it.

Earlier this week, the companys CEO Stphane Bancel told Yahoo Finance that they are working really hard to get a variant-specific booster ready this fall.

We are already making the BA.4/5 vaccine as we speak, he says. We'll give more data as we get closer to it, but we know how important it is. And know every day matters.

In Q2, Moderna generated $4.7 billion of total revenue, up from $4.4 billion earned a year ago. Management attributed the top line increase to higher product sales of the companys COVID-19 vaccine.

Story continues

But Moderna shares are not immune to the market sell-off this year. They have fallen about 20% in 2022.

Piper Sandler analyst Edward Tenthoff has an overweight rating on Moderna and a price target of $214 roughly 14% above where the stock sits today.

BioNTech is another big name in the COVID vaccine business.

According to Statista, more than 355,396,322 doses of Pfizer-BioNTech COVID-19 vaccine have been administered in the U.S. as of July 20 more than vaccines made by any other manufacturer.

On June 25, Pfizer and BioNTech announced that their Omicron-adapted vaccine candidates showed high immune response against Omicron.

Theres also hope for tackling new subvariants.

Preliminary laboratory studies demonstrate both Omicron-adapted candidates neutralize Omicron BA.4 and BA.5 though to a lesser extent than they do for BA.1, the companies said as they continue to collect additional study data on Omicron BA.4/BA.5.

BioNTech will be reporting Q2 earnings on Monday Aug. 8 before the bell.

Previously, management said that they expect BioNTech COVID-19 vaccine revenue to come in between 13 billion and 17 billion for full-year 2022.

Last month, SVB Securities analyst Daina Graybosch upgraded BioNTech from market perform to outperform. Her price target of $233 on the shares implies a potential upside of 28%.

When it comes COVID vaccine stocks, Novavax is a new name worth considering.

Last month, the U.S. Food and Drug Administration granted emergency use authorization to Novavax COVID-19 vaccine Adjuvanted (NVX-CoV2373). In the critical Phase 3 clinical trial, the two-dose vaccine was 90.4% effective in preventing mild, moderate, or severe COVID-19.

This authorization reflects the strength of our COVID-19 vaccine's efficacy and safety data, and it underscores the critical need to offer another vaccine option for the U.S. population while the pandemic continues, said Novavaxs president and chief executive officer Stanley C. Erck in a press release.

Novavax shares, however, have been pummeled its down a staggering 57% year to date.

B. Riley Securities analyst Mayank Mamtani sees a rebound on the horizon. He has a Buy rating on Novavax and a price target of $171.

Considering that Novavax currently trades at around $60 per share, Mamtanis price target implies a potential upside of 185%.

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This article provides information only and should not be construed as advice. It is provided without warranty of any kind.

Reactive synovitis of the knee joint after COVID19 vaccination: The first ultrastructural analysis of synovial fluid  Wiley

President Joe Biden was officially cleared to emerge from isolation Sunday after a second negative COVID-19 test, his physician announced."This morning, the president's SARS-CoV-2 antigen testing was negative for a second consecutive day," presidential physician Kevin O'Connor wrote in a letter Sunday. "He will safely return to public engagement and presidential travel."Biden tested negative on an antigen test Saturday as well, but remained in isolation until Sunday morning before departing for Rehoboth Beach, Delaware.Departing the White House for Rehoboth Beach, the president told reporters he was "feeling good," saying, "After 18 days, I'm clear!"Biden had not left the White House since initially testing positive for COVID-19 on July 21. After taking a five-day course of Pfizer's antiviral drug, Paxlovid, he tested positive for a rebound case of COVID-19 last Saturday and resumed isolation. There are currently no events on his public schedule for the weekend.During isolation, the president has participated virtually in public events from the White House residence. On two occasions, he delivered socially distanced remarks to a restricted pool from the Blue Room balcony, announcing a successful strike that killed al Qaeda leader Ayman al-Zawahiri Monday and signing two bills cracking down on COVID-19 relief fraud Friday.The president and first lady Jill Biden are scheduled to travel on Monday to visit Kentucky after deadly floods in the eastern part of the state killed dozens of people and devastated the area.According to the U.S. Centers for Disease Control and Prevention, "People with recurrence of COVID-19 symptoms or a new positive viral test after having tested negative should restart isolation and isolate again for at least 5 days."During Biden's first bout with the disease, he experienced mild symptoms, including runny nose, fatigue, high temperature and a cough, according to his doctor. The five-day course of Paxlovid the president completed requires a doctor's prescription and is available via emergency use authorization from the U.S. Food and Drug Administration for treatment of mild-to-moderate COVID-19 in people 12 and older who are at high risk of severe illness.The CDC issued a health alert to doctors on May 24 advising that COVID-19 symptoms sometimes come back, and that may just be how the infection plays out in some people, regardless of whether they're vaccinated or treated with medications such as Paxlovid. The CDC said that most rebound cases involve mild disease and that there have been no reports of serious illness.Biden is fully vaccinated and received two booster shots. He received his first two doses of the Pfizer/BioNTech COVID-19 vaccine ahead of his inauguration in January 2021, his first booster shot in September and his second booster vaccination in March.

President Joe Biden was officially cleared to emerge from isolation Sunday after a second negative COVID-19 test, his physician announced.

"This morning, the president's SARS-CoV-2 antigen testing was negative for a second consecutive day," presidential physician Kevin O'Connor wrote in a letter Sunday. "He will safely return to public engagement and presidential travel."

Biden tested negative on an antigen test Saturday as well, but remained in isolation until Sunday morning before departing for Rehoboth Beach, Delaware.

Departing the White House for Rehoboth Beach, the president told reporters he was "feeling good," saying, "After 18 days, I'm clear!"

Biden had not left the White House since initially testing positive for COVID-19 on July 21. After taking a five-day course of Pfizer's antiviral drug, Paxlovid, he tested positive for a rebound case of COVID-19 last Saturday and resumed isolation. There are currently no events on his public schedule for the weekend.

During isolation, the president has participated virtually in public events from the White House residence. On two occasions, he delivered socially distanced remarks to a restricted pool from the Blue Room balcony, announcing a successful strike that killed al Qaeda leader Ayman al-Zawahiri Monday and signing two bills cracking down on COVID-19 relief fraud Friday.

The president and first lady Jill Biden are scheduled to travel on Monday to visit Kentucky after deadly floods in the eastern part of the state killed dozens of people and devastated the area.

According to the U.S. Centers for Disease Control and Prevention, "People with recurrence of COVID-19 symptoms or a new positive viral test after having tested negative should restart isolation and isolate again for at least 5 days."

During Biden's first bout with the disease, he experienced mild symptoms, including runny nose, fatigue, high temperature and a cough, according to his doctor. The five-day course of Paxlovid the president completed requires a doctor's prescription and is available via emergency use authorization from the U.S. Food and Drug Administration for treatment of mild-to-moderate COVID-19 in people 12 and older who are at high risk of severe illness.

The CDC issued a health alert to doctors on May 24 advising that COVID-19 symptoms sometimes come back, and that may just be how the infection plays out in some people, regardless of whether they're vaccinated or treated with medications such as Paxlovid. The CDC said that most rebound cases involve mild disease and that there have been no reports of serious illness.

Biden is fully vaccinated and received two booster shots. He received his first two doses of the Pfizer/BioNTech COVID-19 vaccine ahead of his inauguration in January 2021, his first booster shot in September and his second booster vaccination in March.

The vaccine deployment in December 2020 signaled a turning point in the COVID-19 pandemic. By the end of May 2021, 40% of the U.S. population was fully vaccinated. But as vaccination rates lagged over the summer, new surges of COVID-19 came, including Delta in the summer of 2021, and now the Omicron variant, which comprises the majority of cases in the U.S.

The United States as of Aug. 5 reached over 1 million COVID-19-related deaths and 91.9 million COVID-19 cases, according to Johns Hopkins University. Currently, 67.2% of the population is fully vaccinated, and 48.2% of vaccinated people have received booster doses.

Stacker compiled a list of the counties with highest COVID-19 vaccination rates in Michigan using data from the U.S. Department of Health & Human Services and Covid Act Now. Counties are ranked by the highest vaccination rate as of Aug. 4, 2022. Due to inconsistencies in reporting, some counties do not have vaccination data available. Keep reading to see whether your county ranks among the highest COVID-19 vaccination rates in your state.