WEDNESDAY 8/10/2022, 1:56 p.m.
(WFRV) The Wisconsin Department of Health Services has reported 1,584,203 total positive coronavirus test results in the state and 13,255 total COVID-19 deaths.
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The DHS announced an attempt to verify and ensure statistics are accurate, some numbers may be subject to change. The DHS is combing through current and past data to ensure accuracy.
Wisconsins hospitals are reporting, that the 7-day moving average of COVID-19 patients hospitalized was 534 patients. Of those,71 are in an ICU. ICU patients made up 13.5%of hospitalized COVID-19 patients.
The Wisconsin Department of Health Services reports that 10,040,933 vaccine doses and 2,613,637 booster doses have been administered in Wisconsin as of August 10.
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The Wisconsin Department of Health Services is using a new module to measure COVID-19 activity levels. They are now using the Center for Disease Control and Preventions (CDC) COVID-19 Community Levels. The map is measured by the impact of COVID-19 illness on health and health care systems in the communities.
The Center for Disease Control and Prevention (CDC) reports that 21 counties in Wisconsin are experiencing high COVID-19 community levels. Of those 21, three are in northeast Wisconsin: Brown, Door, and Marinette County.
36 counties in Wisconsin are experiencing medium COVID-19 community levels. Of those 30, thirteen are in northeast Wisconsin: Florence, Fond du Lac, Forest, Green Lake, Kewaunee, Langlade, Menominee, Oconto, Oneida, Sheboygan, Waupaca, Waushara, and Winnebago County.
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Every other county in Wisconsin is experiencing low COVID-19 community levels.
For more information on how the data is collected, visit theCDCs COVID-19 Community Levels data page.
Introduction
The coronavirus disease 2019 (COVID-19) pandemic is a global pandemic. As of December 23, 2021, the World Health Organization (WHO) data platform showed a total of 275,233,892 confirmed cases of COVID-19 and 5,364,996 deaths worldwide.1 The Delta variant and highly mutated Omicron variant have made the COVID-19 pandemic even worse.2,3 Because the population at large is generally susceptible to COVID-19, vaccination against COVID-19 is an effective means of preventing transmission.4 Patients with rheumatic disease are more likely to be infected with COVID-19 than the general population.5 Another study by Ungaro et al suggested that the systemic use of corticosteroids may add to the risk of severe COVID-19 for patients with autoimmune and chronic inflammatory diseases.6 A number of guidelines at home and abroad recommend that eligible patients with rheumatic disease receive the COVID-19 vaccine when their condition is stable.7,8 At present, however, the general population generally does not have strong vaccination intentions and hesitates to get vaccinated, which leads to delays in vaccination and prevention.911 In this study, we investigated the perceptions of COVID-19 infection in patients with rheumatic disease in our hospital through an online questionnaire on the Wenjuanxing platform (web link: www.wjx.cn), analyzed the factors influencing their willingness to receive a COVID-19 vaccine, and analyzed the characteristics of patients who had been vaccinated in an attempt to better counsel patients with rheumatic disease regarding vaccination.
Data from patients with rheumatic disease who presented to the Rheumatology and Immunology Department Outpatient Clinic at our hospital from July 320, 2021, were collected in the database. After cluster sampling by disease, these patients data were randomly sequenced using a random number table, and then patients were randomly selected. They completed the questionnaire under the instruction of a blinded medical worker. Four hundred sixty-three questionnaires were distributed, and 463 were effectively returned (recovery rate = 100%).
The inclusion criteria for patients with rheumatic immune disease were as follows: 1. Patients with rheumatoid arthritis who met the classification criteria for rheumatoid arthritis formulated by the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) in 2010; 2. Patients with systemic lupus erythematosus (SLE) who met the SLE classification criteria established by the EULAR/ACR in 2019; 3. Patients with Sjgrens syndrome who met the 2016 ACR/EULAR classification criteria for Sjgrens syndrome; 4. Patients with polymyositis/dermatomyositis who met the dermatomyositis diagnostic criteria developed by Bohan and Pete in 1975; 5. Patients with gout conforming to the gout classification criteria formulated by the ACR/EULAR in 2015; 6. Patients with osteoarthritis who met the diagnostic criteria for osteoarthritis revised by the ACR in 1995;
7. Patients with ankylosing spondylitis who met the classification criteria for axial spondylarthritis (SpA) recommended by the ASAS (International Spondylarthritis Expert Collaboration Group) in 2009; 8. Patients with psoriatic arthritis who met the 2006 CASPAR classification diagnostic criteria; 9. Patients who underwent enteroscopy and were diagnosed with inflammatory bowel disease-associated arthritis that is consistent with the diagnosis of ulcerative colitis and Crohns disease with peripheral arthritis and axial joint disease, in which the diagnosis could be made by excluding other joint diseases; 10. Patients with systemic sclerosis who met the 2013 ACR/EULAR classification criteria for systemic sclerosis;
11. Patients with Takayasu arteritis who met the 1990 ACR diagnostic criteria for Takayasu arteritis; 12. Patients with Antineutrophil cytoplasmic antibody-associated vasculitis who met the provisional classification criteria of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis included in the 2017 EULAR-ACR criteria; 13. Adult patients with Stills disease who met the 1992 Japanese Yamaguch criteria; 14. Patients with polymyalgia rheumatica who met the 2005 ACR/EULAR PMR classification criteria for polymyalgia rheumatica; 15. Patients with IgG4-related diseases who met the 2019 ACR/EULAR IgG4-related disease classification criteria; 16. Patients with mixed connective tissue disease who met the 1983 Kahn diagnostic criteria; 17. Patients with undifferentiated connective tissue disease with one or more typical symptoms or signs of rheumatism, one or more high-titer autoantibodies, and for whom the course of disease was > 2 years, excluding patients with any other connective tissue disease; and 18. Patients with antiphospholipid antibody syndrome who met the 2006 revised classification criteria for Sapporo antiphospholipid syndrome. Patients were evaluated for disease remission or acute exacerbation according to their symptoms, signs and auxiliary examinations according to the diseases evaluation criteria; for example, patients received a DAS28 score for rheumatoid arthritis (a DAS score <2.6 indicates remission), an SLE-DAI score for SLE (an SLEDAI score 4 indicates inactivity), and an ASDAS score for ankylosing spondylitis (an ASDAS score < 1.3 indicates inactivity). The exclusion criteria included patients aged <18 years old, patients who were illiterate, patients with a loss of comprehension and expression ability, and critically ill patients.
Each patient could only complete the questionnaire once. Verification of validity was established through a questionnaire setting the quality control conditions as follows: 1) Only when the response to Question 8 of the Questionnaire (Are you a patient with rheumatic immune disease? [single-choice question, if you choose yes, please continue to answer; if you choose no, the questionnaire is invalid]) was affirmative was the questionnaire considered valid; 2) A total answering time <10 s or > 2 min invalidated the questionnaire; and 3) Each question must be completed before the next question was presented. Incomplete answer sheets were not collected. The information of all questionnaires was checked by the Wenjuanxing online system and double-checked by the investigator. Forty-six (9.9%) invalid questionnaires were excluded; thus, 417 were valid.
The participants scanned the QR code of Wenjuanxing on WeChat and completed the self-designed online questionnaire titled A Survey on the Willingness of Patients with Rheumatic Disease to Receive a COVID-19 Vaccine. There were 25 questions in the questionnaire, covering the basic information of the respondents and assessing their rheumatic disease status, their perceptions of COVID-19 infection risk and its impact on rheumatic disease, their perception levels and willingness to receive a COVID-19 vaccine, and their COVID-19 vaccination status. The Cronbachs alpha coefficient of the questionnaire reliability test was 0.715, which was acceptable The KaiserMeyerOlkin (KMO) test of validity was 0.5, and the cumulative variance interpretation rate was 62.41%.
The survey data from the questionnaires were exported and analyzed using SPSS (version 22.0) statistical software. Univariate analysis was performed by a 2 test, and multivariate analysis was performed by logistic regression (=0.05, two-sided test). Analysis of variance (ANOVA) was used to analyze the impact of six variables, including the sex, age, marital status, educational level, place of residence, and occupation (medical or nonmedical) of the respondent, the respondents family members, relatives, and friends perceptions of COVID-19 infection risk, as well as the impact of the patients perception of COVID-19 infection on rheumatic disease. Twelve factors, including the sex, age, marital status, educational level, place of residence, and occupation (medical or nonmedical) of the respondent, the respondents family members, relatives and friends perceptions of COVID-19 infection risk, disease assessment, risk perception of COVID-19 infection, perception of the impact of COVID-19 infection on rheumatic disease, perception of the impact of COVID-19 vaccination on rheumatic disease, and vaccination with other vaccines in the last 5 years (other than the COVID-19 vaccine), were analyzed as independent variables and the willingness to receive COVID-19 vaccination was analyzed as a dependent variable in logistic linear regression analysis.
Since this was a survey study, the study was granted an exemption from the requirement of written informed consent by the institutional ethics committee of Heping Hospital Affiliated to Changzhi Medical College. Oral consent was obtained from the participants (or their parent/legal guardian/next of kin) for participation in the study. This study was conducted ethically in accordance with the World Medical Association Declaration of Helsinki and complied with the guidelines for human studies.
The demographic characteristics of the respondents are presented in Table 1. Among the participants, the majority were female (292 [70.02%]). The age distribution was as follows: 39 respondents were aged 1829 years (9.35%); 77 were aged 3039 years (18.47%); 123 were aged 4049 years (29.50%); 122 were aged 5059 years (29.26%); 39 were aged 6065 years (9.35%); and 17 were aged > 65 years (4.08%). Most of the respondents were married (376 [90.17%]). The respondents places of residence were as follows: 184 lived in cities (44.12%); 96 lived in counties (23.02%); 32 lived in towns (7.67%); 104 lived in villages (24.94%); and 1 had no permanent residence (0.24%). The occupations of the participants were as follows: 19 were medical workers (4.56%); and 398 were nonmedical workers (95.44%). The occupations of the respondents family members, relatives, and friends were as follows: 124 were medical workers (29.74%); and 293 were nonmedical workers (70.26%).
Table 1 Demographic Details of the Study Participants
Among the participants, 350 (83.93%) were in the remission stage of rheumatic disease, while 67 (16.07%) were in the active stage. Four hundred seventeen participants had 448 episodes of rheumatic disease. The composition of rheumatic disease among the participants was as follows (the respondents were permitted to choose more than one option): 171 had rheumatoid arthritis (38.17%); 74 had SLE (16.52%); 65 had ankylosing spondylitis (14.51%); 31 had gout (6.92%); 26 had Sjogrens syndrome (5.8%); 18 had osteoarthritis (4.02%); 14 had connective tissue disease (3. 13%); 7 had systemic sclerosis (1.56%); 5 had Takayasu arthritis (1.12%); 4 had polymyalgia rheumatica (0.90%); 3 had psoriatic arthritis (0.67%); 3 had ANCA-related vasculitis (0.67%); 3 had antiphospholipid antibody syndrome (0.67%); 2 had polymyositis (0.45%); 2 had dermatomyositis (0.45%); 2 had undifferentiated spondyloarthropathy, 2 (0.45%); 2 had adult-onset Stills disease (0.45%); and 16 had other rheumatic diseases (3.57%).
Among the participants, 127 (30.46%) believed they had no risk of COVID-19 infection, while 199 (47.72%) were uncertain about their risk. The results of ANOVA showed that the sexes had different risk perceptions of COVID-19 infection (p<0.05), while age, marital status, place of residence, respondent occupation (medical or nonmedical), and the occupations of the respondents family members, relatives, and friends had no statistical significance on the risk perception of COVID-19 infection (P > 0.05, Table 2). A chi-square test was performed regarding the risk perception of COVID-19 infection among the sexes: specifically, 36.80% of the men chose no risk at all compared to 27.74% of the women; 17.60% of the men chose basically no risk compared to 10.62% of the women; and 53.08% of the women chose unclear compared to 35.20% of the men (p<0.05; Table 3).
Table 2 Analysis of the Impact of Demographic Details on the Perception of COVID-19 Infection Risk
Table 3 Analysis of the Impact of Sex on the Perception of COVID-19 Infection Risk
Among the participants, 64 (15.35%) thought that even if they were infected with COVID-19, it would have no impact on their rheumatic disease, 30 (7.19%) thought it would have a negligible impact, 20 (4.8%) thought it would have a moderate impact, 29 (6.95%) thought it would have a considerable impact, 27 (6.47%) thought it would have an enormous impact, and 247 (59.23%) were not certain about the impact (Table 4). The results of ANOVA showed that the occupation (medical or nonmedical) of the respondents was significantly associated with the impact of COVID-19 infection on rheumatic disease (P <0.05); however, sex, age, marital status, place of residence, occupations of the respondents family members, relatives, and friends (medical or nonmedical), and the perception of the impact of COVID-19 infection on rheumatic disease were not statistically significant (P > 0.05). Chi-square test analysis showed that 31.58% and 26.32% of the participants who were medical workers chose no impact at all and unclear, respectively, compared to 14.57% and 60.89% of nonmedical workers, respectively (P <0.05; Table 5).
Table 4 ANOVA Between Demographic Details and the Perception of the Impact of COVID-19 Infection on Rheumatic Disease
Table 5 Chi-Square Analysis Between the Occupations (Medical versus Nonmedical) of the Participants and Their Perceptions of the Impact of COVID-19 Infection on Rheumatic Disease
Among the 417 collected questionnaires regarding COVID-19 vaccination willingness, 38 (9.11%) of the participants completely rejected vaccination, 5 (1.20%) were uncertain but inclined to reject vaccination, 7 (1.68%) were partially inclined to reject vaccination, and 52 (12.47%) wanted to postpone vaccination. In contrast, 21 (5.04%) of the participants partially intended to accept vaccination, 26 (6.24%) intended to accept vaccination but were also unsure, and 268 (64.27%) were willing to accept vaccination.
Logistic linear regression analysis showed that sex, the occupations of the respondents, their family members, relatives, and friends (medical or nonmedical), and the perception of the impact of COVID-19 infection on rheumatic disease had a statistically significant effect on the willingness to receive the COVID-19 vaccine (P <0.05; Table 6). ANOVA was performed regarding the degree of vaccination willingness and the four factors influencing vaccination willingness. Sex, occupation, the perception of the impact of COVID-19 infection on rheumatic disease, and vaccination willingness were analyzed by ANOVA (P <0.05) as follows: males (6.351.30) were more willing than females (5.552.12) to receive vaccination, nonmedical workers (5.841.89) were more willing than medical workers (4.632.65) to receive vaccination, and patients who thought COVID-19 infection had no impact on rheumatic disease (6.581.48) were more willing than those who were uncertain about vaccination (5.722.04) to receive vaccination; the OR values were negatively correlated (Table 7).
Table 6 Logistic Regression Analysis of Factors Influencing COVID-19 Vaccine Willingness
Table 7 ANOVA of the Degree of Willingness and Factors Influencing the Degree of Willingness to Be Vaccinated Against COVID-19
Among the 417 participants, 167 (44.60%) received the COVID-19 vaccine, and 231 (55.40%) did not. Of the 167 patients in the vaccinated group, 152 (91.02%) had no adverse reactions, while 15 (8.98%) had adverse reactions, including 3 with mild pain at the injection site, 3 with aggravated joint pain, 2 with mild dizziness, 2 with mild nausea, 2 with mild abdominal pain, 2 with mild rash, and 1 with a runny nose. Of the patients in the unvaccinated group, 245 options chose not to be vaccinated. The respondents were permitted to choose more than one option. Fourteen responses (5.71%) did not understand the vaccination process or found it to be too troublesome, 13 (5.31%) found it difficult to make an appointment due to the shortage of vaccines, 2 (0.82%) were not satisfied with the preventive effect of the vaccine, 44 (17.96%) were worried about the quality or side effects of the vaccine, 12 (4.90%) claimed their vaccinations had been scheduled but it was not time for the appointment, 117 (47.76%) thought they did not belong to the population that needed to be vaccinated, and 43 (17.55%) chose other reasons.
The results of this questionnaire survey showed that different sexes had different risk perceptions regarding COVID-19 infection. The proportion of men who thought there was no risk at all and that the risk was negligible was greater than that of women, while the proportion of women who chose unclear was greater than that of men, which indicated that men tend to underestimate the risk perception of COVID-19 infection, while women lack awareness of the risk of COVID-19 infection. There was a difference between medical workers and nonmedical workers in the perception of the impact of COVID-19 infection on rheumatic disease. The proportion of medical workers who thought there was no impact was 31.58%, which was greater than that of nonmedical workers (14.57%). The proportion of nonmedical workers who were unclear about the level of impact was 60.80%, which was greater than that of medical workers (26.32%). These results suggested that a large number of people are still unaware of or lack knowledge about the impact of COVID-19 infection on rheumatic disease, while a very high proportion of medical workers believe that there is no impact at all. A multicenter study showed that female sex, a fear of being infected, and the nursing profession are the main factors affecting vaccination for the population with mental health disturbances.12 Another study among adult participants found that males have a poor perception of the risk of COVID-19 and do not practice self-quarantining.13 Our results showed that sex and the medical profession have a significant impact on the perception of COVID-19 infection risk, which is consistent with published reports.1215
Among unvaccinated patients with rheumatic disease, 64.27% were completely willing to be vaccinated against COVID-19, while 26.62% were hesitant. The factors that influenced willingness to vaccinate included sex, occupation, and the perception of the impact of COVID-19 infection on rheumatic disease. The vaccination willingness of male patients was higher than that of female patients, and the vaccination willingness of nonmedical workers was higher than that of medical workers. The survey results by Yurttas et al compared the willingness to be vaccinated among the healthy population, patients with rheumatic diseases and medical workers and found that males and medical workers were more willing to be vaccinated.16 Therefore, clinically, male patients with rheumatic diseases are more likely to be persuaded to be vaccinated. The perception of the impact of COVID-19 infection on rheumatic disease was negatively correlated with vaccination willingness. The greater a patient thought of the impact of COVID-19 vaccines, the lower their vaccination willingness, which was consistent with the results of previous research.1720 High perceived susceptibility to COVID-19 also makes people more inclined to receive a COVID-19 vaccine.10 A survey in 2021 shows that only 54.9% of patients with rheumatic and musculoskeletal diseases were willing to receive the COVID-19 vaccine, although they perceived themselves to be at risk of being infected.21 Similar to the survey,21 64.27% of the patients with rheumatic disease in our study were willing to receive the vaccine, which indicates that their concept of vaccination should be improved.
In this survey, 167 patients (44.60%) with rheumatic disease received the COVID-19 vaccine. Looking at the management experience of other infectious diseases, herd immunity can help vaccination programs and protect unvaccinated, immunocompromised populations.22 A vaccination rate of 70%-80%, or more, will be effective in achieving herd immunity.22 A vaccination rate of 6072% is recommended for herd immunity, although a rate of 8490% is much better.23 The adverse reactions in the unvaccinated patients were mild pain at the injection site, dizziness, nausea, rash, a runny nose, and aggravated joint pain, which were general adverse reactions. As reported, pain, headache, and fatigue were the most frequent adverse reactions to COVID-19.24 Our results did not differ from the existing reports. The incidence of adverse reactions was 8.98%, which was higher than that in the COVID-19 vaccine surveillance report (11.86/100,000 doses) released by the China CDC on May 28, 2021.25 The relatively high rate of adverse reactions may be due to the relatively low immunity of patients with rheumatic disease. The reaction to the vaccine would be intensified, but because there were no serious adverse reactions, it can be concluded that the safety of the vaccine is relatively high. Among the unvaccinated participants, as many as 47.76% said that they did not receive the vaccine because they did not think they were among the population that needed to be vaccinated. This finding is closely related to a persons perception of COVID-19, as previously reported.1820
The global COVID-19 pandemic has not been controlled, and there have been many local outbreaks in China. Only when the vaccination rate reaches the level of herd immunity can the disease be controlled.23 Due to the characteristics of rheumatic disease, such as multisystem damage, repeated recurrence, long-term survival of patients with the disease, and massive application of immunosuppressive drugs, a number of vaccination guidelines and expert opinions have been published for this special population with rheumatic immune diseases at home and abroad.8,26 Patients with rheumatic disease are more susceptible to COVID-19 infection than the general population, have a high mortality rate and are very likely to have adverse reactions.8,26 The experts suggest that these patients should receive vaccines as early as possible, while adjusting their therapies against rheumatic disease;8,26 however, a patients low awareness of the risk of COVID-19 infection and vaccination and excessive anxiety about the disease have led to low vaccination willingness and a low vaccination rate.1720 Indeed, the publicity of professional medical knowledge should be enhanced. With the help of health care experts and social media, health communication campaigns should be improved and populations at risk should be targeted.27 We should provide verified communication from physicians offices to the public via multiple channels, such as the internet, newspapers, radio, television, popular medical science platforms, and health education programs, to eliminate hesitation for vaccination and comprehensively enhance confidence in vaccination.28 Under the requirement of herd immunity against COVID-19 infection, it is even more important to strengthen international cooperation, play a leading role in the government, and strengthen the quality control of COVID-19.29 According to our results and previous reports,1720,2329 we should improve the perception and education of patients with low immune capacity, thereby improving their vaccination willingness, achieving safe vaccination, accomplishing herd immunity as soon as possible, and avoiding the health hazards aggravated by COVID-19.
A limitation of this study was that this was a single-center small sample survey, so it is still necessary to expand the sample size to verify the results.
The sex of patients with rheumatoid diseases, whether they were medical workers or not, the level of knowledge about the risk of COVID-19 infection and the impact of vaccination on the disease were shown to be key factors influencing patients willingness to receive a COVID-19 vaccine. The vaccination rate of patients with rheumatic disease was correspondingly low, and the rate of adverse reactions was slightly higher than that in the general population.
The authors report no conflicts of interest in this work.
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6. Ungaro RC, Agrawal M, Park S, et al. Autoimmune and chronic inflammatory disease patients with COVID-19. ACR Open Rheumatol. 2021;3(2):111115. doi:10.1002/acr2.11221
7. Curtis JR, Johnson SR, Anthony DD, et al. American College of Rheumatology Guidance for COVID-19 vaccination in patients with rheumatic and Musculoskeletal diseases: version 3. Arthritis Rheumatol. 2021;73(10):e60e75. doi:10.1002/art.41928
8. Santosa A, Xu C, Arkachaisri T, et al. Recommendations for COVID-19 vaccination in people with rheumatic disease: developed by the Singapore Chapter of Rheumatologists. Int J Rheum Dis. 2021;24(6):746757. doi:10.1111/1756-185X.14107
9. Alley SJ, Stanton R, Browne M, et al. As the pandemic progresses, how does willingness to vaccinate against COVID-19 evolve? Int J Environ Res Public Health. 2021;18(2):797. doi:10.3390/ijerph18020797
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11. Yoda T, Katsuyama H. Willingness to receive COVID-19 vaccination in Japan. Vaccines. 2021;9(1):48. doi:10.3390/vaccines9010048
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13. Abir T, Kalimullah NA, Osuagwu UL, et al. Factors associated with the perception of risk and knowledge of contracting the SARS-Cov-2 among adults in Bangladesh: analysis of online surveys. Int J Environ Res Public Health. 2020;17(14):5252. doi:10.3390/ijerph17145252
14. Alsharawy A, Spoon R, Smith A, Ball S. Gender differences in fear and risk perception during the COVID-19 pandemic. Front Psychol. 2021;12:689467. doi:10.3389/fpsyg.2021.689467
15. Rana IA, Bhatti SS, Aslam AB, Jamshed A, Ahmad J, Shah AA. COVID-19 risk perception and coping mechanisms: does gender make a difference? Int J Disaster Risk Reduct. 2021;55:102096. doi:10.1016/j.ijdrr.2021.102096
16. Yurttas B, Poyraz BC, Sut N, et al. Willingness to get the COVID-19 vaccine among patients with rheumatic diseases, healthcare workers and general population in Turkey: a web-based survey. Rheumatol Int. 2021;41(6):11051114. doi:10.1007/s00296-021-04841-3
17. Nehal KR, Steendam LM, Campos Ponce M, van der Hoeven M, Smit GSA. Worldwide vaccination willingness for COVID-19: a systematic review and meta-analysis. Vaccines. 2021;9(10):1071. doi:10.3390/vaccines9101071
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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (lineage B.1.1.529) is currently the dominant circulating strain in most nations. Although millions of children have been affected by SARS-CoV-2 globally, accurate data on the pediatric burden of the coronavirus disease 2019 (COVID-19) is not available due to underreporting of cases and testing limitations.
Study:Anti-SARS-CoV-2 antibodies in breast milk during lactation after infection or vaccination: a cohort study. Image Credit: Rohappy / Shutterstock.com
Currently, COVID-19 messenger ribonucleic acid (mRNA) vaccines are the main protective measure for children against SARS-CoV-2 infection.
The United Nations International Childrens Emergency Fund (UNICEF) has reported over 12,300 deaths in children younger than 20 years of age due to COVID-19. More specifically, 42% of these deaths were reported in children between the ages of zero and nine years. Although short-term neonatal SARS-CoV-2 infection outcomes are rare, the long-term effects of COVID-19 on neurological and physical development remain unclear.
The vertical transfer of pathogen-specific immunoglobulin G (IgG) antibodies from the mother to fetus through the placenta has been reported. Aside from the passive immunity conferred to the infant from prior infection, recent studies have similarly demonstrated that the administration of COVID-19 mRNA vaccines during pregnancy reduces the risk of hospitalization among infants younger than six months who were born to these mothers.
Breast milk consists of several immunoprotective factors, including secretory immunoglobulin A (sIgA), as well as sIgG and sIgM, which confer protection to the infant against infections. However, this form of passive immunity is not as well understood as the transfer of antibodies to the infant through the placenta.
Natural infection with SARS-CoV-2, along with BNT162b2 mRNA vaccination, during pregnancy leads to the development of neutralizing SARS-CoV-2 antibodies that are capable of binding to different regions of the viral spike protein. These antibodies are also secreted in breast milk.
In a new Journal of Reproductive Immunology study, researchers assess the protection conferred by breast milk and serum in previously infected and/or vaccinated mothers against an early SARS-CoV-2 isolate (HH-1) and the Omicron variant for newborns for up to six months after delivery.
The current German study was conducted between February 2020 and December 2021, in which a total of 21 pregnant women were included. Sixteen of the study participants had previously tested positive for COVID-19 and recovered during pregnancy. Seven of the study participants had received at least one dose of the BNT162b2 mRNA vaccine.
Study participants who recovered from COVID-19 were referred to as the R group, while those who have recovered from COVID-19 and were vaccinated were referred to as RV group. Five pregnant women who had received two doses of the BNT162b2 vaccine and had not been infected with SARS-CoV-2 were referred to as V group .
Blood and breast milk samples were collected from the women during lactation for a maximum of six months post-delivery. The humoral response to natural infection and/or vaccination was evaluated by qualitative anti-SARS-CoV-2 IgA enzyme-linked immunosorbent assay (ELISA), quantitative anti-S1-RBD-SARS-CoV-2 assay, and anti- SARS-CoV-2 TrimericS IgG assay. Neutralization assays using Omicron and HH-1 isolates were also conducted.
The median age of all study participants was 36 years. A total of 16 study participants had previously been infected with SARS-CoV-2, two of whom had experienced severe COVID-19. Of those who had received one or two doses of the Pfizer-BioNTech BNT162b2 COVID-19 vaccine, no serious adverse effects were reported.
The median neutralizing antibody levels against the SARS-CoV-2 receptor binding domain (RBD) within the serum were 12,223 AU/ml, 1427 AU/ml, and 198 AU/ml for the RV, V, and R groups, respectively.
The levels of these antibodies within the breast milk were lower; however, a positive correlation was observed between serum and breast milk S1-RBD antibody levels. Similar patterns were observed for the anti-SARS-CoV-2 IgA levels within the serum and breast milk.
The anti-SARS-CoV-2 TrimericS IgG assay revealed median IgG levels of 6,860 BAU/ml, 704 BAU/ml, and 159 BAU/ml for the RV, V, and R groups, respectively. These same antibody levels within breast milk were below the detection level.
A single vaccine dose was found to increase SARS-CoV-2 specific antibody titers in breast milk. Additionally, breast milk samples with positive anti-RBD Ig neutralized both the HH-1 isolate and Omicronin vitro. However, lower antibody titers were observed against the SARS-CoV-2 Omicron variant.
The current study confirmed the presence of anti-SARS-CoV-2 antibodies in breast milk that were capable of neutralizing both an early pandemic SARS-CoV-2 isolate as well as the Omicron variant. Notably, mRNA vaccination improved maternal immune responses and provided passive protection in newborns.
Further studies are needed to determine the correlation that exists between maternal antibody levels and infant immune protection.
The sample size of the current study was small. Due to the limited number of remaining breast milk samples, neutralization assays could include only eight samples. A final limitation was that the six-month follow-up analysis was not available for all the participants.
Journal reference:
Even before the COVID-19 vaccine was authorized, there was a plan to discredit it.
Leaders in the anti-vaccination movement attended an online conference in October 2020 two months before the first shot was administered where one speaker presented on The 5 Reasons You Might Want to Avoid a COVID-19 Vaccine and another referred to the untested, unproven, very toxic vaccines.
But that was only the beginning. Misinformation seeped into every corner of social media, onto Facebook feeds and into Instagram images, pregnancy apps and Twitter posts. Pregnant people emerged as a target. A disinformation campaign preyed on their vulnerability, exploiting a deep psychological need to protect their unborn children at a moment when so much of the country was already gripped by fear.
Its just so powerful, said Imran Ahmed, the founder and chief executive officer of the U.S. nonprofit Center for Countering Digital Hate, which tracks online disinformation.
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A majority of the disinformation came from a group of highly organized, economically motivated actors, many of them selling supplements, books or even miracle cures, he said. They told people the vaccine may harm their unborn child or deprive them of the opportunity to become parents. Some even infiltrated online pregnancy groups and asked seemingly harmless questions, such as whether people had heard the vaccine could potentially lead to infertility.
The Center for Countering Digital Hate found that nearly 70% of anti-vaccination content could be traced to 12 people, whom they dubbed The Disinformation Dozen. They reached millions of people and tested their messaging online, Ahmed said, to see what was most effective what was most frequently shared or liked in real time.
The unregulated and unmoderated effects of social media where people are allowed to spread disinformation at scale without consequences meant that this took hold very fast, Ahmed said. Thats had a huge effect on women deciding not to take the vaccine.
Some people, such as Robert F. Kennedy Jr., seized on the initial dearth of research into vaccines in pregnant people. With no data showing COVID vaccines are safe for pregnant women, and despite reports of miscarriages among women who have received the experimental Pfizer and Moderna vaccines, Fauci and other health officials advise pregnant women to get the vaccine, Kennedy posted in February 2021 on Facebook. Kennedy did not respond to requests for comment.
Disinformation flourished, in part, because pregnant people were not included in the vaccines initial clinical trials. Excluding pregnant people also omitted them from the data on the vaccines safety, which created a vacuum where disinformation spread. Unsure about how getting the shots might affect their pregnancy and without clear guidance at the time from the Centers for Disease Control and Prevention pregnant people last year had some of the lowest vaccination rates among adults.
The decision to delay or avoid vaccination, often made out of an abundance of caution and love for the baby growing inside of them, had dire consequences: Unvaccinated women who contracted COVID-19 while pregnant were at a higher risk of stillbirths the death of a fetus at 20 weeks or more of pregnancy and several other complications, including maternal death.
Although initial clinical trials did not include pregnant people, the Food and Drug Administration ensured that vaccines met a host of regulatory safety standards before authorizing them. Citing numerous studies that have since come out showing the vaccine is safe, the CDC now strongly recommends that people who are pregnant, breastfeeding or planning to become pregnant get vaccinated. The major obstetric organizations, including The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine, also urge pregnant people to get vaccinated.
But two and a half years into the pandemic, misinformation is proving resilient.
A May 2022 Kaiser Family Foundation poll found more than 70% of pregnant people or those planning to become pregnant believed or were unsure whether to believe at least one of the following popular examples of misinformation about the COVID-19 vaccine: that pregnant people should not get vaccinated; that its unsafe to get vaccinated while breastfeeding; or that the vaccine has been shown to cause infertility. None of which are true.
Dr. Laura Morris, a University of Missouri, Columbia family physician who delivers babies, has heard all those falsehoods and more from her patients. She has long relied on science to help encourage them to make well-informed decisions.
But when officials rolled out the vaccine, she found herself without her most powerful tool, data. The disinformation didnt have to completely convince people that the vaccine was dangerous; creating doubt often was sufficient.
That level of uncertainty is enough to knock them off the path to accepting vaccination, Morris said. Instead of seeing vaccines as something that will make them healthier and improve their pregnancy outcomes, they havent received the right information to make them feel confident that this is actually healthy.
Before COVID-19, Morris typically saw one stillbirth every couple of years. Since the pandemic started, she said she has been seeing them more often. All followed a COVID-19 diagnosis in an unvaccinated patient just weeks before they were due. Not only did Morris have to deliver the painful news that their baby had died, she also told them that the outcome might have been different had they been vaccinated. Some, she said, felt betrayed at having believed the lies surrounding the vaccine.
You have to have that conversation very carefully, Morris said, because this is a time where the people are feeling awful and grieving and theres a lot of guilt associated with these situations thats not deserved.
In December 2021, the Federation of State Medical Boards found a proliferation of misinformation about COVID-19 among health care workers. Two-thirds of state medical boards reported an increase in complaints about misinformation, but fewer than 1 in 4 of them reported disciplining the doctors or other health care workers.
Dr. Sherri Tenpenny, an osteopath, was the speaker at the October 2020 conference who called the COVID-19 vaccine toxic. She later testified at an Ohio state House Health Committee hearing on the Enact Vaccine Choice and Anti-Discrimination Act. She falsely claimed that the vaccine could magnetize people. They can put a key on their forehead, it sticks, she said. They can put spoons and forks all over them, and they could stick. She also questioned the connection between the vaccine and 5G towers.
Despite her statements, the State Medical Board of Ohio has not taken any disciplinary action against her. Her medical license remains active. Tenpenny did not respond to requests for comment.
Its difficult to know exactly how many doctors were disciplined, a term that can mean anything from sending them letters of guidance to revoking their license. State medical boards in some cases refused to disclose even the number of complaints received.
Some records were made public if formal disciplinary action was taken, as in the case of Dr. Mark Brody. The Rhode Island physician sent a letter to his patients that the state medical board determined contained several falsehoods, including claims that there exists the possibility of sterilizing all females in the population who receive the vaccination. The Rhode Island Board of Medical Licensure and Discipline reprimanded him for the letter, then suspended his medical license after other professional conduct issues were uncovered. He surrendered his license in December.
Brody said in an interview that he stands by the letter. He said the word misinformation has been politicized and used to discredit statements with which people disagree.
This term doesnt really apply to science, he said, because science is an ever-evolving field where todays misinformation is tomorrows information.
The Washington Medical Commission has received more than 50 complaints about COVID-19 misinformation since the start of the pandemic, a spokesperson there said. California does not track misinformation complaints specifically, but a Medical Board of California spokesperson said that, in that same time period, the group received more than 1,300 COVID-19-related complaints. They included everything from fraudulent promotion of unproven medications to the spreading of misinformation.
We were certainly surprised that more than half of boards said they had seen an increase in complaints about false or misleading information, said Joe Knickrehm, vice president of communications for the Federation of State Medical Boards, which in April adopted a policy stating that false information is harmful and dangerous to patients, and to the public trust in the medical profession.
Other groups, including The American College of Obstetricians and Gynecologists, warned doctors about spreading misinformation. In October, the organization asked its members to sign a letter endorsing the COVID-19 vaccine, writing that the spread of misinformation and mistrust in doctors and science is contributing to staggeringly low vaccination rates among pregnant people. But the letter was never published. We didnt achieve the numbers we had hoped, a spokesperson for the organization said, and did not want to release it if it was not going to be compelling to patients.
The fact that some medical professionals have been spreading disinformation or failing to engage with their patients about the vaccine is profoundly disappointing, said Dr. Rachel Villanueva, a clinical assistant professor of obstetrics and gynecology at New York Universitys Grossman School of Medicine and president of the National Medical Association, which represents Black doctors.
Research has shown that hearing directly from a health care provider can increase the likelihood that patients get vaccinated. And doctors, Villanueva said, have a responsibility to tell their patients the benefits of getting vaccinated and the risks of choosing not to. She has explained to her patients that although the vaccine development program was named Operation Warp Speed, for example, manufacturers followed proper safety protocols.
Before COVID, there already existed a baseline distrust of the health care system, especially for women of color, feeling marginalized and feeling dismissed in the health care system, she said. I think that just compounded the already lack of confidence that existed in the system.
Study population
The study was conducted among 331 healthy individuals mainly including health care personnel at Saarland University Medical Center, who either received homologous regimens with ChAdOx (n=62), BNT (n=43), or mRNA-1273 (n=59), or heterologous vaccinations with ChAdOx-priming followed by a boost with either the BNT (n=66) or the mRNA-1273 vaccine (n=101) (Fig.1 and Table1). Despite no known history of SARS-CoV-2 infection, one female was positive for nucleocapsid-specific IgG, and was excluded from further analysis. Due to convenience sampling based on current recommendations, the mean time between the two vaccinations was shorter for the homologous mRNA regimens (5.70.7 weeks) as compared to the vector-based regimens (11.90.9 weeks). In addition, the group showed some differences in age and gender (Table1). Blood sampling was carried out at a median of 14 (IQR 2) days after the second vaccination. In differential blood counts, leukocyte and granulocyte numbers differed between the groups with the highest numbers found after homologous mRNA-1273 vaccination. The numbers of monocytes, lymphocytes, and lymphocyte subpopulations such as B cells, CD4, and CD8 T cells did not differ. Among B cells, plasmablast numbers, which were identified as CD38 positive cells among IgD-CD27+ CD19-positive switched-memory B cells were also highest in individuals after homologous mRNA-1273 vaccination (Table1).
Schematic representation of the five vaccine regimens (three homologous: ChAdOx/ChAdOx n=62, BNT/BNT n=43, mRNA-1273/mRNA-1273 n=59; two heterologous: ChAdOx/BNT n=66, ChAdOx/mRNA-1273 n=101). Shown are the time frames between the first (prime) and the second (boost) vaccination, and between the boost vaccination and the day of blood analysis. #One individual of the mRNA-1273/mRNA-1273 group was excluded from further analysis due to detectable IgG towards the SARS-CoV-2 nucleocapsid.
Spike-specific IgG was detectable in all individuals, but their levels were significantly higher in individuals boosted with mRNA vaccines as compared to individuals after homologous ChAdOx vaccination (Fig.2a, p<0.0001). When comparing heterologous regimens, boosting with mRNA-1273 led to numerically higher IgG levels (6043 (IQR 4396) BAU/ml) than boosting with BNT (4275 (IQR 4080) BAU/ml). Likewise, among homologous regimens, IgG levels were higher after mRNA-1273 vaccination (5529 (IQR 5755) BAU/ml) than in BNT vaccinated individuals (3438 (IQR 3287) BAU/ml), although the differences did not reach statistical significance. As with IgG levels, neutralizing inhibitory capacity of spike-specific antibodies determined using a surrogate assay was high and reached a maximum of 100% in the majority of mRNA-boosted individuals, which contrasted with significantly lower neutralizing activity after homologous ChAdOx vaccination (median 77.8% (IQR 33.5%), p<0.0001, Fig.2a).
Cellular and humoral immune parameters were analyzed 1318 days post vaccination and compared between individuals with different homologous or heterologous COVID-19 vaccine regimens: homologous ChAdOx vaccination (n=62), heterologous ChAdOx/BNT vaccination (n=66), heterologous ChAdOx/mRNA-1273-vaccination (n=101), homologous BNT vaccination (n=43) or homologous mRNA-1273-vaccination (n=58). a ELISA and surrogate neutralization assays were performed to quantify levels of spike-specific IgG and neutralizing antibodies. Intracellular cytokine staining after antigen-specific stimulation of whole blood samples allowed for flow-cytometrical determination of SARS-CoV-2 spike-specific (b) and SEB-reactive (c) CD4 and CD8 T-cell levels. Reactive cells were identified by co-expression of CD69 and IFN among CD4 or CD8 T cells and subtraction of reactivity of respective negative control stimulations. CTLA-4 expression was determined on d spike-specific and e SEB-reactive CD4 and CD8 T cells in all samples with at least 20 cytokine-positive CD4 and CD8 T cells. f Correlation matrix of spike-specific T-cell and antibody responses among each group. Bars in ae represent medians with interquartile ranges. Differences between the groups were calculated using two-sided KruskalWallis test with Dunns multiple comparisons post-test. Correlations in f were analyzed according to two-tailed Spearman (see also Supplementary Table1). Dotted lines indicate detection limits for antibodies in a, indicating negative, intermediate, and positive levels or levels of inhibition, respectively as per manufacturers instructions, and detection limits for SARS-CoV-2-specific CD4 T cells in b and c. Source data are provided as a Source Data file. IFN Interferon, MFI median fluorescence intensitiy, SEB Staphylococcus aureus enterotoxin B.
Vaccine-induced CD4 and CD8 T cells were quantified after stimulation with overlapping peptides encompassing the spike protein. Activation-induced T cells were identified based on CD69 and IFN, TNF, and IL-2. A representative example of CD69-positive spike-specific CD4 and CD8 T cells producing IFN from a 49-year-old female after the second homologous mRNA-1273 vaccination is shown in Supplementary Fig.1, and data from all individuals analyzed after the second vaccination are summarized in Fig.2b. Spike-specific CD4 T-cell levels in the homologous ChAdOx vaccine group were significantly lower than in all other groups. Among mRNA-boosted regimens, median levels of spike-specific CD4 T cells were highest after heterologous ChAdOx1/mRNA-1273 vaccination (0.29% (IQR 0.23%)). Not only did a boost with mRNA-1273 outperform heterologous boosting with BNT after ChAdOx-priming (0.18% (IQR 0.17%), p<0.01), but CD4 T-cell levels were also higher after homologous vaccination with mRNA-1273 (0.24% (IQR 0.27%) than with BNT (0.10% (IQR 0.08%), p<0.0001). Interestingly, the two heterologous regimens also led to a strong induction of spike-specific CD8 T cells (0.29% (IQR 0.57%) for BNT and 0.40% (IQR 0.60%) for mRNA-1273), with significantly higher levels than all three homologous regimens (Fig.2b, p<0.0001). All vaccine-induced effects on CD4 and CD8 T cells were specific, as no differences in Staphylococcus aureus Enterotoxin B (SEB)-reactive CD4 and CD8 T cells were observed between the five groups (Fig.2c). Finally, in line with a pronounced induction of vaccine-induced T cells, CTLA-4 expression was strongly induced on spike-specific CD4 and CD8 T cells of all individuals after heterologous vaccination and in both homologous mRNA regimens, whereas CTLA-4 expression on specific T cells after homologous ChAdOx vaccination was significantly lower (Fig.2d). These differences in CTLA-4 expression were also spike-specific, as CTLA-4 expression on SEB-reactive CD4 and CD8 T cells were similarly low in all five groups (Fig.2e).
When analyzing correlations between spike-specific IgG levels, neutralizing activity, and spike-specific CD4 and CD8 T cells (Fig.2f and Supplementary Table1), neutralizing activity showed a strong correlation with IgG levels in each vaccine subgroup. Likewise, spike-specific CD4 and CD8 T cells showed a significant correlation. In line with the previous findings3, CD4 T cells correlated with IgG in ChAdOx/ChAdOx and ChAdOx/BNT vaccinated individuals only. In addition, it is interesting to note that IgG levels correlated with CD8 T-cell levels in the three homologous vaccine groups only, whereas no such correlation was found for the two heterologous vaccine groups, which may be a result of the exceptionally high CD8 T-cell response in these two groups (see Fig.2b).
As the five groups differed in age and gender due to convenience sampling and recruitment according to national recommendations (Table1), a subgroup analysis was performed among 40 individuals per vaccination regimen which were matched for age and gender (Supplementary Table2). As shown in Supplementary Fig.2, between-group differences in IgG levels, neutralizing activity and spike-specific T cells largely remain the same. In the whole cohort, adjusting for age and gender as confounders in a non-parametric regression analysis showed that both confounders did not have any significant effect on immunological parameters (Supplementary Table3). When testing for interactions of age within each vaccine group with the homologous ChAdOx group as a reference, age had no effect on T-cell levels and neutralizing antibody activity; the only effect of age was found for IgG levels within each of the two homologous regimens (p=0.003 for BNT/BNT and p=0.015 for mRNA-1273/mRNA-1273, Supplementary Table3).
Based on national recommendations, the interval between the first and the second dose was longer for ChAdOx-primed groups than for individuals on homologous mRNA regimens (see Table1). If within-group comparisons were restricted to regimens with the same interval, differences between the respective groups remain the same as those indicated in Fig.2.
Apart from IFN, we also analyzed spike-specific induction of the cytokines TNF and IL-2. As with IFN, differences between the groups were similar for CD4 T cells producing TNF or IL-2 (Fig.3a, b), or for cells producing any of the three cytokines alone or in combination (Fig.3c). This also held true for spike-specific CD8 T cells, except for IL-2 producing CD8 T cells, where levels were generally lower and only showed subtle differences between the groups (Fig.3b). To assess functionality on a single cell level, cytokine profiles of spike-specific CD4 and CD8 T cells were characterized after Boolean gating (Supplementary Fig.3). This allowed distinction of seven subpopulations including polyfunctional cells simultaneously expressing all three cytokines, two cytokines or one cytokine only (Fig.4). The cytokine-expression profiles showed significant differences between the vaccine regimens, and the highest percentage of polyfunctional CD4 T cells was observed for the three vector-primed regimens. These three regimens also showed the highest percentage of CD8 T cells expressing IFN and TNF, which was the dominant fraction among spike-specific CD8 T cells (Fig.4a). The differences in cytokine-expression profiles were spike-specific, as SEB-reactive cytokine expression did not differ among the groups (Fig.4b).
Levels of TNF and IL-2-expressing T cells and combined expression of either of the cytokine IFN, TNF and/or IL-2 were compared between individuals who either received homologous ChAdOx vaccination (n=62), heterologous ChAdOx/BNT vaccination (n=66), heterologous ChAdOx/mRNA-1273-vaccination (n=101), homologous BNT vaccination (n=43) or homologous mRNA-1273 vaccination (n=58). Percentages of CD69+ TNF+ (a), CD69+ IL-2+ b or CD69-positive cells co-expressing at least one of the cytokines TNF, IL-2, or IFN (c) among total CD4 (upper panel) or CD8 T cells (lower panel) were determined after stimulation of whole blood samples with overlapping peptides of SARS-CoV-2 spike protein and subtraction of background reactivity from negative control stimulations. Bars represent medians with interquartile ranges and two-sided KruskalWallis test with Dunns multiple comparisons post-test was used to calculate differences between the groups. Source data are provided as a Source Data file. IFN interferon, IL interleukin, SEB Staphylococcus aureus enterotoxin B, TNF tumor necrosis factor.
After antigen-specific stimulation (a) or polyclonal stimulation with Staphylococcus aureus enterotoxin B (SEB, b) of whole blood samples from individuals with different homologous or heterologous vaccination regimens, cytokine-expressing CD4 and CD8 T cells were subclassified into seven subpopulations according to single or combined expression of IFN, IL-2, and TNF. Blood samples from all individuals were analyzed. To ensure robust statistics, only samples with at least 30 cytokine-expressing CD4 or CD8 T cells after normalization to the negative control stimulation were considered (with the number of samples in each vaccine group indicated in the figures). Bars in a and b represent means and standard deviations, and ordinary one-way ANOVA tests were performed. Source data are provided as a Source Data file. IFN interferon, IL interleukin, TNF tumor necrosis factor.
Local and systemic adverse events within the first week after the first and the second vaccination were self-recorded using a questionnaire (Fig.5 and Supplementary Tables4 and 5). Irrespective of the vaccine type, local adverse events such as pain at the injection site were reported with similar frequency in individuals after the first vaccination. Swelling at the injection site was overall less frequently observed with the lowest percentage among BNT-primed individuals (Fig.5b). Systemic adverse events including fever, headache, fatigue, chills, gastrointestinal manifestations, myalgia, and arthralgia after priming were most frequent in individuals after ChAdOx vaccination, which also was associated with more frequent use of antipyretic medication (Fig.5c and Supplementary Table4). After the second vaccination, local adverse events were least frequent after homologous ChAdOx vaccination, and most frequent in both heterologous and in the homologous mRNA-1273 regimens. The occurrence of systemic adverse events clearly dominated in individuals after heterologous boosting with mRNA-1273, followed by homologous mRNA-1273 vaccination and heterologous BNT-boosting (Fig.5a, c, Supplementary Table5). Individual perception of severity was scored higher after secondary vaccination in both homologous mRNA regimens (Fig.5d). In contrast, more than 75% of subjects after both the homologous ChAdOx and heterologous BNT vaccination were more affected by the primary vaccination with the vector. Despite the strong reactogenicity after vector-priming, it was interesting to note that a sizable fraction of subjects after heterologous boosting with mRNA-1273 was more severely affected by the secondary vaccination, which contrasts with observations in the heterologous BNT vaccine group. Likewise, among individuals after homologous vaccination, the second vaccination with mRNA-1273 was more frequently perceived as more severe, although this vaccine was already strongly reactogenic after the primary vaccination. Overall, it therefore appeared that both the homologous and the heterologous regimens that included BNT were better tolerated than the respective mRNA-1273 regimens.
According to their COVID-19 vaccine regimens, individuals were classified into three groups after dose 1 (ChAdOx vector (n=229), BNT (n=43) or mRNA-1273 vaccine (n=58)) and five groups after dose 2 (homologous: ChAdOx/ChAdOx, n=62; BNT/BNT, n=43; mRNA-1273/mRNA-1273, n=58; heterologous: ChAdOx/BNT, n=66; ChAdOx/mRNA-1273, n=101). Self-reported reactogenicity within the first week after each vaccine dose was assessed using a standardized questionnaire. The presence of local or systemic adverse events in general (a), substantial local (b) or systemic adverse events (c), and individual perception of which of the two vaccinations affected more (d) are shown. Statistical analyses of differences between the groups after the first and the second vaccination are shown in Supplementary Tables2 and 3. Source data are provided as a Source Data file.
However, officials are unsure how long that strategy will work, particularly if cases increase sharply in the weeks ahead and whether the virus spreads outside the community of men who have sex with men.
Nearly 9,500 monkeypox infections have been reported, according to the CDC, up about 50 percent in the last week. Nearly all cases have been reported in men and CDC Director Rochelle Walensky has urged men who have sex with men, including those who are vaccinated, to avoid skin-to-skin contact with infected people.
The administration is trying to shore up more vaccines by striking deals with companies including Grand River Aseptic Manufacturing in Michigan to bottle doses, a process known as fill and finish. The vaccine that needs to be bottled is currently stored by Bavarian Nordic in Denmark, the officials said. There are as many as 12 million doses available in that stockpile, the two people with knowledge of the matter said.
Once the deals are finalized and the vaccines bottled, American regulators will likely have to inspect the doses before they are distributed. Depending on what agreements the Biden administration strikes, the process could stretch into 2023, one of the senior administration officials said.
That timeline is also dependent on how many doses the U.S. pulls from the stockpile in Denmark for fill and finish.
An HHS official said the administration is exploring multiple avenues to accelerate production and distribution of the vaccine. Despite comments made by health officials during Tuesdays briefing, the HHS official said the administration made a decision on the dose-sparing independently of [its]efforts ... to procure and produce additional vaccine.
The CDC is collecting case information from states, but the agency is still working to set up a system to track the transmission of the virus and to model how it could change over the course of the next several months, one of the people with knowledge of the matter said. The CDC did not respond to questions about its monkeypox modeling.
So far, the administration has secured just over 1 million doses from Bavarian Nordic, a Danish vaccine company. The U.S. needs about 3.2 million doses in total to fully inoculate the more than 1.6 million at-risk Americans. More than 600,000 doses have made it out to the public with thousands more rolling out in the coming weeks.
While the dose-sparing strategy announced Tuesday received broad support from top health officials, the data on this approach is limited to one 2015 study first reported by POLITICO. There is no clinical trial or real-world efficacy information available that backs up the administrations recommendation. The NIH is developing a study. The CDC is also working to gather efficacy data from states.
The administration could revert back to recommending providers administer the full dose of the vaccine normally via a subcutaneous administration under the fatty tissue of the skin, one of the senior officials said.
Patricia Neves (left) and Ana Paula Ano Bom helped launch a global project to revolutionize access to mRNA technology. Ian Cheibub for NPR hide caption
Patricia Neves (left) and Ana Paula Ano Bom helped launch a global project to revolutionize access to mRNA technology.
When Moderna and Pfizer first came out with their mRNA vaccines for COVID-19, supply was limited to rich countries and they did not share the details of how to create it. That left middle income countries like Brazil in the lurch. But for Brazilian scientists Patricia Neves and Ana Paula Ano Bom, that wasn't the end. They decided to invent their own mRNA vaccine.
Their story, today: Aaron talks to global health correspondent Nurith Aizenman about the effort and how it has helped launch a wider global project to revolutionize access to mRNA vaccine technology.
Further reading:
This episode was produced for Short Wave by Margaret Cirino and edited by Rebecca Ramirez. It was edited for broadcast by Vikki Valentine. Fact-checking by Rachel Carlson and audio engineering by Brian Jarboe.
More than 2,000 appointments are available this weekend to receive the JYNNEOS monkeypox vaccine in Chicago, the city's department of public health announced Wednesday.
The following locations will offer the vaccine by appointment:
9 a.m.-4 p.m. Aug. 13 at CDPH MPV Vaccination Clinics at City College locations:
Aug. 14 at the MPV Vaccination Clinic hosted by RUSH and UIC at the College of Nursing
In addition, MPV vaccine appointments are now available up to six days per week at three CDPH STI Clinics around the city by visiting getvaxchi.chicago.gov.
To access remaining available appointments this week at CDPH STI Clinics, use the following codes:
"Our MPV vaccine supply continues to increase, and we are pleased to be opening up larger clinics to serve even more Chicagoans, while still working to vaccinate those at highest risk to help stop the spread, said CDPH Commissioner Dr. Allison Arwady in a statement. "CDPH has been working closely with healthcare providers, clinics, and community-based organizations who work with individuals disconnected from medical services to schedule vaccination appointments."
Close contacts, including household members with close physical contact or intimate partners, of someone diagnosed with MPV are prioritized for vaccination regardless of sex, gender or sexual orientation, Arwady said. In addition, the vaccine is available to gay or bisexual men and transgender persons 18 years of age and older who:
For more information about monkeypox, head here Chicago.gov/MPV.
Federal authorities are permitting health providers to administer much smaller doses of monkeypox vaccine to stretch the limited supply of the shots, but the Philadelphia Public Health Department is holding off on committing to the new approach, saying it wants more information.
The Food and Drug Administration on Wednesday issued an emergency use authorization that increases the availability of vaccine fivefold by shrinking the amount administered with each dose. The new rules are in response to an increase in new cases that outpaces vaccine supply. Monkeypox cases in the United States topped 9,000 this week, up from 40 two months ago. In Philadelphia, providers are keeping waiting lists of people seeking doses, and a health department hotline to direct people to vaccines has been swamped with calls.
READ MORE: U.S. will stretch monkeypox vaccine supply with smaller doses
The city health department, though, wants more information before committing to the smaller doses. Philadelphia health officials said the FDA update leaves unanswered questions about the safety and efficacy of the smaller doses, and doesnt specify whether patients can choose between the original vaccine amount or smaller doses.
While we continue to work to ensure that as many at risk Philadelphians are protected as possible while we wait for those answers, the Health Department is beginning to plan for implementation of this new vaccine strategy, if its required, the department said in its statement.
In an interview last week, Philadelphia Health Commissioner Cheryl Bettigole estimated the city could use at least double the approximately 5,000 doses it has been shipped so far to cover people at high risk from the virus.
The Pennsylvania Department of Health said in a statement Wednesday that access to intradermal injections may depend on the provider.
While there are providers prepared to begin administering intradermal injections right away, other providers will need additional supplies, training or technical assistance, a department spokesperson said.
The New Jersey Department of Health credited the FDAs decision Tuesday with expanding vaccine access.
The state health department is working with vaccine providers to be able to implement the new recommendations as soon as they are able, a statement from the department said.
READ MORE: Monkeypox vaccine limits cause frustration and fear in Philly
The FDA announcement changes not just dose amounts but how theyre injected. Monkeypox shots have been administered subcutaneously, into the fatty tissue beneath the skin. The smaller doses approved by the FDA would be given intradermally, directly into the patients skin. The same dose amount that has been administered to one person can now be expanded to five while providing for each a similar immune response, the FDA reported in a statement Tuesday, citing a 2015 study that evaluated both kinds of injections.
Switching to smaller doses isnt something that can be done immediately, though, because the approach requires more precision, said Jay Kostman, a doctor at Philadelphia FIGHT, a city health center focused on LGBTQ patients.
I think its going to require training for the people who administer the vaccine because people arent used to doing intradermal vaccines, he said. If you dont do it right and you do it with a smaller dose, youre less likely to get the immune benefit.
READ MORE: Exposed to monkeypox? Heres how to get a vaccination appointment in Philly.
Philadelphia FIGHT has been going through doses quickly, Kostman said. The health center went through its initial shipment of 100 doses, he said, with people left on the waiting list. Those people are getting vaccinated now with another shipment received this week.
The decision to allow smaller doses was prompted by case counts that continue to outstrip the availability of vaccine doses.
In recent weeks the monkeypox virus has continued to spread at a rate that has made it clear our current vaccine supply will not meet the current demand, said FDA Commissioner Robert M. Califf in a statement Tuesday. By increasing the number of available doses, more individuals who want to be vaccinated against monkeypox will now have the opportunity to do so.
So far, the federal Department of Health and Human Services has shipped almost 618,000 doses of vaccine, with 11,329 going to New Jersey, 10,311 to Pennsylvania, and 4,790 to Philadelphia, with a small number of additional doses coming to the city through the state Health Department. Pennsylvania reported 251 cases as of Tuesday, according to the Centers for Disease Control and Prevention, and New Jersey reported 251.
READ MORE: Many people dont know basic facts about monkeypox, making them susceptible to public health messaging but also to conspiracy theories
Monkeypox is typically not fatal but causes painful rashes and lesions that can last up to a month. Extended physical contact with those blemishes, which at some stages of the virus are barely noticeable, is the most common mode of transmission, and sex has proven to be particularly effective at spreading it, though the virus does not require sexual contact to infect a person.
The virus is overwhelmingly infecting men who have sex with men, and health officials have said men who have recently had multiple sex partners or anonymous sex are at the highest risk of infection. There hasnt been enough vaccine to reach that entire population, though. Other groups, including health-care workers who treat people with monkeypox and sex workers, are not yet eligible for doses.
Even among those who are eligible, many cant get the shot. Health officials have had to prioritize vaccinating people who have already been exposed to the virus. If the shot is given quickly after exposure, the vaccine does a good job of preventing the person from getting sick, but focusing only on those who have already been exposed isnt a strategy that will contain the virus, health experts have said.
COVID-19 vaccines are now approved for children aged from six months up to five years of age, and are already being rolled out to about 70,000 at-risk youngsters.
But what about babies even younger than that? Will there be a vaccine for them? And what role does the vaccination of pregnant people play in the process?
Let's take a closer look at the issues.
Children of all ages can get COVID-19 and experience its complications.
However,asnoted by an infectious diseases physician at Monash and Melbourne universities,Michelle Giles, young infants aren't at risk of the severe disease that has been seen with older Australians.
Research published this week in the Medical Journal of Australia lookedat children under 16 years of age with COVID-19 between June 1 and October 31, 2021, and found most infections in children were either asymptomatic or associated with mild disease.
The paper foundthe likelihood of admission to hospital with the Delta variant for medical reasons declined for younger children.
However, that doesn't mean that babies are completely immune from infection.
A study published in July in the New England Journal of Medicine and funded by the US Centers for Disease Control and Prevention looked at 537 cases among babies under six months who had been admitted to hospital with COVID-19, and found more than 20 per cent had been placed in intensive care, with 12 per cent needing mechanical ventilation.
Professor Giles notes thatstudy was done in the US, across the Delta and Omicron waves, and looked at children who were already in hospital as opposed to ones who may have caught COVID-19 and not needed serious medical intervention.
"Some young infants can get very sick from COVID but that is much more the exception," Professor Giles said.
"By far and away, the majority of infants do not get severe disease from COVID."
The benefits of maternal vaccination to the infant they are carrying have been known for a long time.
As far back as the 1870s, babies born to mothers who had received the smallpox vaccination were found unlikely to have smallpox early in life.
"When we give a vaccine to the mother, her immune system responds to that vaccine by making antibodies," Professor Giles explained.
"And these antibodies are able to cross the placenta so that the baby has them in its system when its born, so it can be protected straightaway if it gets exposed to that virus."
It's typically a two-for-one deal, with vaccines benefiting both the pregnant person and their unborn baby.
Take the flu vaccine for example.It stops pregnant women from getting severe illness that might require admission to hospital, while offering babies protection.
It's a new and evolving area, but some research has suggested that giving vaccines to pregnant people can reduce the risk of hospital admissions and severe illness from COVID-19 for infants under six months.
Remember that study in the New England Journal of Medicine we spoke about earlier?
It found maternal vaccination with two doses of an mRNA vaccine was associated with reduced risk of hospitalisation including critical illness among infants younger than six months of age.
That researchalso found effectiveness was higher when the vaccination occurred after 20 weeks of pregnancy.
"It is promising that it might afford some protection to young infants that can't yet be vaccinated," Professor Giles said.
"And it wouldn't be surprising if this was the casebecause, as mentioned, we know that this happens with other vaccines that we give pregnant women where they protect the child in the first six months of life."
The simple answer is no, they shouldn't.
Professor Giles says it isimportant women don't delay vaccination, because they themselves need to be protected.
"The risk with delaying vaccination is that whilethey remain unvaccinated, they're at a higher risk of severe disease, and that is not good for their pregnancy or for their baby," she said.
Not in the foreseeable future, if ever.
There aren't any clinical trials running yet for babies under six months of age.
Australia is one of the first countries to roll out the vaccine for children aged six months to five years and, even then, the vaccines are not yet being given to all children, with the vaccine advisory body ATAGI noting there was a low likelihood of severe illness from COVID-19.
So, for the time being, there is one main way to protect babies, according to Professor Giles.
"If we want to give any protection to infants under six months of age from COVID-19, at this stage, there are no vaccines available. So the only way of protecting them is through maternal antibodies," she said.
