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As COVID-19 cases soared to new daily highs across the United States, November 2020 brought some exciting and promising vaccine efficacy results. Currently, the United States has four COVID-19 vaccines in phase 3 trials: the Moderna vaccine (mRNA-1273), the Oxford/AstraZeneca vaccine (AZD1222), Pfizer/BioNTech’s (BNT162), and the Johnson & Johnson vaccine (JNJ-78436735).
While Pfizer/ BioNTech and Moderna received fast-track designation by the Food and Drug Administration, AZD1222 and JNJ-78436735 trials were resumed after a temporary hold. Pfizer/BioNTech and Moderna have also submitted an emergency-use authorization application to the FDA after favorable results from a completed phase 3 clinical trial. The results so far seem promising, with Oxford/AstraZeneca’s combined analysis from different dosing regimens resulting in an average efficacy of 70%. Pfizer/ BioNTech and Moderna have each reported vaccines that are 90% and 95% effective respectively in trials.
However, even with a safe and effective vaccine, there must be an equal emphasis on a successful coronavirus vaccine program’s three pillars in the communities that are the hardest hit: participation in the vaccine trials by minority populations, equitable allocation and distribution of vaccine for minority populations, and immunization uptake by minority populations.
1. Participation in the vaccine trials by minority populations
With a great emphasis on the inclusion of diverse populations, the Moderna vaccine clinical trials gained participation by racial and ethnic minorities. As of Oct. 21, 2020, the Moderna vaccine trial participants were 10% African American, 20% Hispanic, 4% Asian, 63% White, and 3% other.1 Pharmaceutical giant Pfizer also had approximately 42% of overall – and 45% of U.S. – participants from diverse backgrounds. The proportional registration of racially and ethnically diverse participants in other vaccine trials is also anticipated to be challenging.
Though there has been an improvement in minority participation in COVID-19 vaccine trials, it is still below the ideal representation when compared with U.S. census data.2 Ideally, participants in a clinical trial should represent the U.S. population to get a full picture of a medical product’s risks and benefits. However, recruitment rates in clinical trials have remained low among minorities for various reasons. Historically, African Americans make up only 5% of participants in U.S. clinical trials, while they represent 13% of the country’s general population; likewise, Hispanics are also underrepresented.3
The legacy of distrust in the medical system is deep-rooted and is one of the most substantial barriers to clinical trial participation. A plethora of unethical trials and experiments on the African American population have left a lasting impact. The most infamous and widely known was the “Tuskegee Study,” conducted by the United States Public Health Service to “observe the natural history of untreated syphilis” in Black populations. In the study, performed without informed consent, Black men with latent or late syphilis received no treatment, even after penicillin was discovered as a safe and reliable cure for syphilis. This human experimentation lasted for 40 years, resulting in 128 male patients who died from syphilis or its complications, 40 of their spouses infected, and 19 of their children with acquired congenital syphilis.
In another case, the father of modern gynecology, J. Marion Sims, allegedly performed experimental surgeries on enslaved Black women without consent. For more than 4 decades, North Carolina’s statewide eugenics program forcibly sterilized almost 7,600 people, many of whom were Black. Another story of exploitation involves Henrietta Lacks, whose cancer cells are the source of the HeLa cell line, responsible for some of the most important medical advances of all time. Though her cells were commercialized and generated millions for medical researchers, neither Ms. Lacks nor her family knew the cell cultures existed until more than 20 years after her death from cervical cancer. Many years later, victims and families of the Tuskegee experiment, individuals sterilized by the Eugenics Board of North Carolina, and the family of Henrietta Lacks received compensation, and Sims’s statue was taken down in 2018. Not too long ago, many criticized the FDA’s “Exception from Informed Consent policy” for compromising patients’ exercise of autonomy, and concern for overrepresenting African Americans in the U.S. EFIC trials.
Racial disparities in medical treatment and unconscious biases among providers are among the reasons for mistrust and lack of trial participation by minority populations today. Francis Collins, director of the National Institutes of Health, said that recent social upheaval sparked by the death of George Floyd has likely added to feelings of mistrust between minority groups and government or pharmaceutical companies. “Yet we need their participation if this is going to have a meaningful outcome,” he said.
While “Operation Warp Speed” is committed to developing and delivering a COVID-19 vaccine rapidly while adhering to safety and efficacy standards, the challenges to enrolling people from racial and ethnic minorities in trials have been a concern. The political partisanship and ever-shifting stances on widespread COVID-19 testing, use of facemasks, endorsement of unproven drugs for the disease, and accusations against the FDA for delaying human trials for the vaccine have contributed to the skepticism as well. Tremendous pressure for a rushed vaccine with unrealistic timelines, recent holds on AZD1222 and JNJ-78436735 as well as the AZD1222 dosage error during trials have also raised skepticism of the safety and efficacy of vaccine trials.
2. Equitable allocation and distribution of vaccine for minority populations
Enrollment in clinical trials is just a beginning; a more significant challenge would be the vaccine’s uptake when available to the general public. We still lack a consensus on whether it is lawful for race to be an explicit criterion for priority distribution of the COVID-19 vaccine. Recently the Centers for Disease Control and Prevention suggested that the vaccine amount allotted to jurisdictions might be based on critical populations recommended for vaccination by the Advisory Committee on Immunization Practices with input from the National Academies of Sciences, Engineering, and Medicine.
The NASEM framework lays out four-phased vaccine distribution approaches, emphasizing social equity by prioritizing vaccines for geographic areas identified through CDC’s social vulnerability index (SVI) or another more specific index. SVI has been a robust composite marker of minority status and language, household composition and transportation, and housing and disability, and predicted COVID-19 case counts in the United States in several studies. The National Academy of Medicine has also recommended racial minorities receive priority vaccination because they have been hard hit and are “worse off” socioeconomically.
3. Immunization uptake by minority populations
Though minority participation is crucial in developing the vaccine, more transparency, open discussions on ethical distribution, and awareness of side effects are required before vaccine approval or emergency-use authorization. Companies behind the four major COVID-19 vaccines in development have released their trials’ protocols, details on vaccine efficacy, and each product’s makeup to increase acceptance of the vaccine.
According to a recent Pew research study, about half of U.S. adults (51%) now say they would definitely or probably get a vaccine to prevent COVID-19 if it were available today. Nearly as many (49%) say they definitely or probably would not get vaccinated at this time. Intent to get a COVID-19 vaccine has fallen from 72% in May 2020, a 21–percentage point drop, and Black adults were much less likely to say they would get a vaccine than other Americans.3 This is concerning as previous studies have shown that race and ethnicity can influence immune responses to vaccination. There is evidence of racial and ethnic differences in immune response following rubella vaccination, Hib–tetanus toxoid conjugate vaccine, antibody responses to the influenza A virus components of IIV3 or 4, and immune responses after measles vaccination.4-9
On the other hand, significant differences in reporting rates of adverse events after human papillomavirus vaccinations were found in different race and ethnicity groups in the Vaccine Adverse Event Reporting System.10 Thus, there is ample evidence that race and ethnicity affect responsiveness to a vaccine. Inequity in participation in a clinical trial may lead to an ineffective or one with a suboptimal response or even an unsafe vaccine.
When we look at other immunization programs, according to various surveys in recent years, non-Hispanic Blacks have lower annual vaccination rates for flu, pneumonia, and human papillomavirus vaccinations nationally, compared with non-Hispanic White adults.11 It is a cause of concern as a proportion of the population must be vaccinated to reach “community immunity” or “herd immunity” from vaccination. Depending on varying biological, environmental, and sociobehavioral factors, the threshold for COVID-19 herd immunity may be between 55% and 82% of the population.12 Hence, neither a vaccine trial nor an immunization program can succeed without participation from all communities and age groups.
Role of hospitalists
Hospitalists, who give immunizations as part of the hospital inpatient quality reporting program, are uniquely placed in this pandemic. Working on the front lines, we may encounter questions, concerns, rejections, and discussions about the pros and cons of the COVID-19 vaccine from patients.
Investigators at Children’s National Hospital and George Washington University, both in Washington, recently recommended three steps physicians and others can take now to ensure more people get the COVID-19 vaccine when it is available. Engaging frontline health professionals was one of the suggested steps to encourage more people to get the vaccine.13 However, it is imperative to understand that vaccine hesitancy might be an issue for health care providers as well, if concerns for scientific standards and involvement of diverse populations are not addressed.
We are only starting to develop a safe and effective immunization program. We must bring more to unrepresented communities than just vaccine trials. Information, education, availability, and access to the vaccines will make for a successful COVID-19 immunization program.
Dr. Saigal is a hospitalist and clinical assistant professor of medicine in the division of hospital medicine at the Ohio State University Wexner Medical Center, Columbus.
References
1. Moderna. COVE study. 2020 Oct 21. https://www.modernatx.com/sites/default/files/content_documents/2020-COVE-Study-Enrollment-Completion-10.22.20.pdf
2. U.S. Census Bureau. Quick facts: Population estimates, July 1, 2019. https://www.census.gov/quickfacts/fact/table/US/PST045219
3. Pew Research Center. U.S. Public Now Divided Over Whether To Get COVID-19 Vaccine. 2020 Sep 17. https://www.pewresearch.org/science/2020/09/17/u-s-public-now-divided-over-whether-to-get-covid-19-vaccine/
4. Haralambieva IH et al. Associations between race sex and immune response variations to rubella vaccination in two independent cohorts. Vaccine. 2014;32:1946-53.
5. McQuillan GM et al. Seroprevalence of measles antibody in the U.S. population 1999-2004. J Infect Dis. 2007;196:1459–64. doi: 10.1086/522866.
6. Christy C et al. Effect of gender race and parental education on immunogenicity and reported reactogenicity of acellular and whole-cell pertussis vaccines. Pediatrics. 1995;96:584-7.
7. Poland GA et al. Measles antibody seroprevalence rates among immunized Inuit Innu and Caucasian subjects. Vaccine. 1999;17:1525-31.
8. Greenberg DP et al. Immunogenicity of Haemophilus influenzae type b tetanus toxoid conjugate vaccine in young infants. The Kaiser-UCLA Vaccine Study Group. J Infect Dis. 1994;170:76-81.
9. Kurupati R et al. Race-related differences in antibody responses to the inactivated influenza vaccine are linked to distinct prevaccination gene expression profiles in blood. Oncotarget. 2016;7(39):62898-911.
10. Huang J et al. Characterization of the differential adverse event rates by race/ethnicity groups for HPV vaccine by integrating data from different sources. Front Pharmacol. 2018;9:539.
11. https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=4&lvlid=22
12. Sanche S et al. High contagiousness and rapid spread of severe acute respiratory syndrome coronavirus 2. Emerg Infect Dis. 2020;26(7).
13. American Medical Association. How to ready patients now so they’ll get a COVID-19 vaccine later. 2020 May 27. https://www.ama-assn.org/delivering-care/public-health/how-ready-patients-now-so-they-ll-get-covid-19-vaccine-later
As COVID-19 cases soared to new daily highs across the United States, November 2020 brought some exciting and promising vaccine efficacy results. Currently, the United States has four COVID-19 vaccines in phase 3 trials: the Moderna vaccine (mRNA-1273), the Oxford/AstraZeneca vaccine (AZD1222), Pfizer/BioNTech’s (BNT162), and the Johnson & Johnson vaccine (JNJ-78436735).
While Pfizer/ BioNTech and Moderna received fast-track designation by the Food and Drug Administration, AZD1222 and JNJ-78436735 trials were resumed after a temporary hold. Pfizer/BioNTech and Moderna have also submitted an emergency-use authorization application to the FDA after favorable results from a completed phase 3 clinical trial. The results so far seem promising, with Oxford/AstraZeneca’s combined analysis from different dosing regimens resulting in an average efficacy of 70%. Pfizer/ BioNTech and Moderna have each reported vaccines that are 90% and 95% effective respectively in trials.
However, even with a safe and effective vaccine, there must be an equal emphasis on a successful coronavirus vaccine program’s three pillars in the communities that are the hardest hit: participation in the vaccine trials by minority populations, equitable allocation and distribution of vaccine for minority populations, and immunization uptake by minority populations.
1. Participation in the vaccine trials by minority populations
With a great emphasis on the inclusion of diverse populations, the Moderna vaccine clinical trials gained participation by racial and ethnic minorities. As of Oct. 21, 2020, the Moderna vaccine trial participants were 10% African American, 20% Hispanic, 4% Asian, 63% White, and 3% other.1 Pharmaceutical giant Pfizer also had approximately 42% of overall – and 45% of U.S. – participants from diverse backgrounds. The proportional registration of racially and ethnically diverse participants in other vaccine trials is also anticipated to be challenging.
Though there has been an improvement in minority participation in COVID-19 vaccine trials, it is still below the ideal representation when compared with U.S. census data.2 Ideally, participants in a clinical trial should represent the U.S. population to get a full picture of a medical product’s risks and benefits. However, recruitment rates in clinical trials have remained low among minorities for various reasons. Historically, African Americans make up only 5% of participants in U.S. clinical trials, while they represent 13% of the country’s general population; likewise, Hispanics are also underrepresented.3
The legacy of distrust in the medical system is deep-rooted and is one of the most substantial barriers to clinical trial participation. A plethora of unethical trials and experiments on the African American population have left a lasting impact. The most infamous and widely known was the “Tuskegee Study,” conducted by the United States Public Health Service to “observe the natural history of untreated syphilis” in Black populations. In the study, performed without informed consent, Black men with latent or late syphilis received no treatment, even after penicillin was discovered as a safe and reliable cure for syphilis. This human experimentation lasted for 40 years, resulting in 128 male patients who died from syphilis or its complications, 40 of their spouses infected, and 19 of their children with acquired congenital syphilis.
In another case, the father of modern gynecology, J. Marion Sims, allegedly performed experimental surgeries on enslaved Black women without consent. For more than 4 decades, North Carolina’s statewide eugenics program forcibly sterilized almost 7,600 people, many of whom were Black. Another story of exploitation involves Henrietta Lacks, whose cancer cells are the source of the HeLa cell line, responsible for some of the most important medical advances of all time. Though her cells were commercialized and generated millions for medical researchers, neither Ms. Lacks nor her family knew the cell cultures existed until more than 20 years after her death from cervical cancer. Many years later, victims and families of the Tuskegee experiment, individuals sterilized by the Eugenics Board of North Carolina, and the family of Henrietta Lacks received compensation, and Sims’s statue was taken down in 2018. Not too long ago, many criticized the FDA’s “Exception from Informed Consent policy” for compromising patients’ exercise of autonomy, and concern for overrepresenting African Americans in the U.S. EFIC trials.
Racial disparities in medical treatment and unconscious biases among providers are among the reasons for mistrust and lack of trial participation by minority populations today. Francis Collins, director of the National Institutes of Health, said that recent social upheaval sparked by the death of George Floyd has likely added to feelings of mistrust between minority groups and government or pharmaceutical companies. “Yet we need their participation if this is going to have a meaningful outcome,” he said.
While “Operation Warp Speed” is committed to developing and delivering a COVID-19 vaccine rapidly while adhering to safety and efficacy standards, the challenges to enrolling people from racial and ethnic minorities in trials have been a concern. The political partisanship and ever-shifting stances on widespread COVID-19 testing, use of facemasks, endorsement of unproven drugs for the disease, and accusations against the FDA for delaying human trials for the vaccine have contributed to the skepticism as well. Tremendous pressure for a rushed vaccine with unrealistic timelines, recent holds on AZD1222 and JNJ-78436735 as well as the AZD1222 dosage error during trials have also raised skepticism of the safety and efficacy of vaccine trials.
2. Equitable allocation and distribution of vaccine for minority populations
Enrollment in clinical trials is just a beginning; a more significant challenge would be the vaccine’s uptake when available to the general public. We still lack a consensus on whether it is lawful for race to be an explicit criterion for priority distribution of the COVID-19 vaccine. Recently the Centers for Disease Control and Prevention suggested that the vaccine amount allotted to jurisdictions might be based on critical populations recommended for vaccination by the Advisory Committee on Immunization Practices with input from the National Academies of Sciences, Engineering, and Medicine.
The NASEM framework lays out four-phased vaccine distribution approaches, emphasizing social equity by prioritizing vaccines for geographic areas identified through CDC’s social vulnerability index (SVI) or another more specific index. SVI has been a robust composite marker of minority status and language, household composition and transportation, and housing and disability, and predicted COVID-19 case counts in the United States in several studies. The National Academy of Medicine has also recommended racial minorities receive priority vaccination because they have been hard hit and are “worse off” socioeconomically.
3. Immunization uptake by minority populations
Though minority participation is crucial in developing the vaccine, more transparency, open discussions on ethical distribution, and awareness of side effects are required before vaccine approval or emergency-use authorization. Companies behind the four major COVID-19 vaccines in development have released their trials’ protocols, details on vaccine efficacy, and each product’s makeup to increase acceptance of the vaccine.
According to a recent Pew research study, about half of U.S. adults (51%) now say they would definitely or probably get a vaccine to prevent COVID-19 if it were available today. Nearly as many (49%) say they definitely or probably would not get vaccinated at this time. Intent to get a COVID-19 vaccine has fallen from 72% in May 2020, a 21–percentage point drop, and Black adults were much less likely to say they would get a vaccine than other Americans.3 This is concerning as previous studies have shown that race and ethnicity can influence immune responses to vaccination. There is evidence of racial and ethnic differences in immune response following rubella vaccination, Hib–tetanus toxoid conjugate vaccine, antibody responses to the influenza A virus components of IIV3 or 4, and immune responses after measles vaccination.4-9
On the other hand, significant differences in reporting rates of adverse events after human papillomavirus vaccinations were found in different race and ethnicity groups in the Vaccine Adverse Event Reporting System.10 Thus, there is ample evidence that race and ethnicity affect responsiveness to a vaccine. Inequity in participation in a clinical trial may lead to an ineffective or one with a suboptimal response or even an unsafe vaccine.
When we look at other immunization programs, according to various surveys in recent years, non-Hispanic Blacks have lower annual vaccination rates for flu, pneumonia, and human papillomavirus vaccinations nationally, compared with non-Hispanic White adults.11 It is a cause of concern as a proportion of the population must be vaccinated to reach “community immunity” or “herd immunity” from vaccination. Depending on varying biological, environmental, and sociobehavioral factors, the threshold for COVID-19 herd immunity may be between 55% and 82% of the population.12 Hence, neither a vaccine trial nor an immunization program can succeed without participation from all communities and age groups.
Role of hospitalists
Hospitalists, who give immunizations as part of the hospital inpatient quality reporting program, are uniquely placed in this pandemic. Working on the front lines, we may encounter questions, concerns, rejections, and discussions about the pros and cons of the COVID-19 vaccine from patients.
Investigators at Children’s National Hospital and George Washington University, both in Washington, recently recommended three steps physicians and others can take now to ensure more people get the COVID-19 vaccine when it is available. Engaging frontline health professionals was one of the suggested steps to encourage more people to get the vaccine.13 However, it is imperative to understand that vaccine hesitancy might be an issue for health care providers as well, if concerns for scientific standards and involvement of diverse populations are not addressed.
We are only starting to develop a safe and effective immunization program. We must bring more to unrepresented communities than just vaccine trials. Information, education, availability, and access to the vaccines will make for a successful COVID-19 immunization program.
Dr. Saigal is a hospitalist and clinical assistant professor of medicine in the division of hospital medicine at the Ohio State University Wexner Medical Center, Columbus.
References
1. Moderna. COVE study. 2020 Oct 21. https://www.modernatx.com/sites/default/files/content_documents/2020-COVE-Study-Enrollment-Completion-10.22.20.pdf
2. U.S. Census Bureau. Quick facts: Population estimates, July 1, 2019. https://www.census.gov/quickfacts/fact/table/US/PST045219
3. Pew Research Center. U.S. Public Now Divided Over Whether To Get COVID-19 Vaccine. 2020 Sep 17. https://www.pewresearch.org/science/2020/09/17/u-s-public-now-divided-over-whether-to-get-covid-19-vaccine/
4. Haralambieva IH et al. Associations between race sex and immune response variations to rubella vaccination in two independent cohorts. Vaccine. 2014;32:1946-53.
5. McQuillan GM et al. Seroprevalence of measles antibody in the U.S. population 1999-2004. J Infect Dis. 2007;196:1459–64. doi: 10.1086/522866.
6. Christy C et al. Effect of gender race and parental education on immunogenicity and reported reactogenicity of acellular and whole-cell pertussis vaccines. Pediatrics. 1995;96:584-7.
7. Poland GA et al. Measles antibody seroprevalence rates among immunized Inuit Innu and Caucasian subjects. Vaccine. 1999;17:1525-31.
8. Greenberg DP et al. Immunogenicity of Haemophilus influenzae type b tetanus toxoid conjugate vaccine in young infants. The Kaiser-UCLA Vaccine Study Group. J Infect Dis. 1994;170:76-81.
9. Kurupati R et al. Race-related differences in antibody responses to the inactivated influenza vaccine are linked to distinct prevaccination gene expression profiles in blood. Oncotarget. 2016;7(39):62898-911.
10. Huang J et al. Characterization of the differential adverse event rates by race/ethnicity groups for HPV vaccine by integrating data from different sources. Front Pharmacol. 2018;9:539.
11. https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=4&lvlid=22
12. Sanche S et al. High contagiousness and rapid spread of severe acute respiratory syndrome coronavirus 2. Emerg Infect Dis. 2020;26(7).
13. American Medical Association. How to ready patients now so they’ll get a COVID-19 vaccine later. 2020 May 27. https://www.ama-assn.org/delivering-care/public-health/how-ready-patients-now-so-they-ll-get-covid-19-vaccine-later
As COVID-19 cases soared to new daily highs across the United States, November 2020 brought some exciting and promising vaccine efficacy results. Currently, the United States has four COVID-19 vaccines in phase 3 trials: the Moderna vaccine (mRNA-1273), the Oxford/AstraZeneca vaccine (AZD1222), Pfizer/BioNTech’s (BNT162), and the Johnson & Johnson vaccine (JNJ-78436735).
While Pfizer/ BioNTech and Moderna received fast-track designation by the Food and Drug Administration, AZD1222 and JNJ-78436735 trials were resumed after a temporary hold. Pfizer/BioNTech and Moderna have also submitted an emergency-use authorization application to the FDA after favorable results from a completed phase 3 clinical trial. The results so far seem promising, with Oxford/AstraZeneca’s combined analysis from different dosing regimens resulting in an average efficacy of 70%. Pfizer/ BioNTech and Moderna have each reported vaccines that are 90% and 95% effective respectively in trials.
However, even with a safe and effective vaccine, there must be an equal emphasis on a successful coronavirus vaccine program’s three pillars in the communities that are the hardest hit: participation in the vaccine trials by minority populations, equitable allocation and distribution of vaccine for minority populations, and immunization uptake by minority populations.
1. Participation in the vaccine trials by minority populations
With a great emphasis on the inclusion of diverse populations, the Moderna vaccine clinical trials gained participation by racial and ethnic minorities. As of Oct. 21, 2020, the Moderna vaccine trial participants were 10% African American, 20% Hispanic, 4% Asian, 63% White, and 3% other.1 Pharmaceutical giant Pfizer also had approximately 42% of overall – and 45% of U.S. – participants from diverse backgrounds. The proportional registration of racially and ethnically diverse participants in other vaccine trials is also anticipated to be challenging.
Though there has been an improvement in minority participation in COVID-19 vaccine trials, it is still below the ideal representation when compared with U.S. census data.2 Ideally, participants in a clinical trial should represent the U.S. population to get a full picture of a medical product’s risks and benefits. However, recruitment rates in clinical trials have remained low among minorities for various reasons. Historically, African Americans make up only 5% of participants in U.S. clinical trials, while they represent 13% of the country’s general population; likewise, Hispanics are also underrepresented.3
The legacy of distrust in the medical system is deep-rooted and is one of the most substantial barriers to clinical trial participation. A plethora of unethical trials and experiments on the African American population have left a lasting impact. The most infamous and widely known was the “Tuskegee Study,” conducted by the United States Public Health Service to “observe the natural history of untreated syphilis” in Black populations. In the study, performed without informed consent, Black men with latent or late syphilis received no treatment, even after penicillin was discovered as a safe and reliable cure for syphilis. This human experimentation lasted for 40 years, resulting in 128 male patients who died from syphilis or its complications, 40 of their spouses infected, and 19 of their children with acquired congenital syphilis.
In another case, the father of modern gynecology, J. Marion Sims, allegedly performed experimental surgeries on enslaved Black women without consent. For more than 4 decades, North Carolina’s statewide eugenics program forcibly sterilized almost 7,600 people, many of whom were Black. Another story of exploitation involves Henrietta Lacks, whose cancer cells are the source of the HeLa cell line, responsible for some of the most important medical advances of all time. Though her cells were commercialized and generated millions for medical researchers, neither Ms. Lacks nor her family knew the cell cultures existed until more than 20 years after her death from cervical cancer. Many years later, victims and families of the Tuskegee experiment, individuals sterilized by the Eugenics Board of North Carolina, and the family of Henrietta Lacks received compensation, and Sims’s statue was taken down in 2018. Not too long ago, many criticized the FDA’s “Exception from Informed Consent policy” for compromising patients’ exercise of autonomy, and concern for overrepresenting African Americans in the U.S. EFIC trials.
Racial disparities in medical treatment and unconscious biases among providers are among the reasons for mistrust and lack of trial participation by minority populations today. Francis Collins, director of the National Institutes of Health, said that recent social upheaval sparked by the death of George Floyd has likely added to feelings of mistrust between minority groups and government or pharmaceutical companies. “Yet we need their participation if this is going to have a meaningful outcome,” he said.
While “Operation Warp Speed” is committed to developing and delivering a COVID-19 vaccine rapidly while adhering to safety and efficacy standards, the challenges to enrolling people from racial and ethnic minorities in trials have been a concern. The political partisanship and ever-shifting stances on widespread COVID-19 testing, use of facemasks, endorsement of unproven drugs for the disease, and accusations against the FDA for delaying human trials for the vaccine have contributed to the skepticism as well. Tremendous pressure for a rushed vaccine with unrealistic timelines, recent holds on AZD1222 and JNJ-78436735 as well as the AZD1222 dosage error during trials have also raised skepticism of the safety and efficacy of vaccine trials.
2. Equitable allocation and distribution of vaccine for minority populations
Enrollment in clinical trials is just a beginning; a more significant challenge would be the vaccine’s uptake when available to the general public. We still lack a consensus on whether it is lawful for race to be an explicit criterion for priority distribution of the COVID-19 vaccine. Recently the Centers for Disease Control and Prevention suggested that the vaccine amount allotted to jurisdictions might be based on critical populations recommended for vaccination by the Advisory Committee on Immunization Practices with input from the National Academies of Sciences, Engineering, and Medicine.
The NASEM framework lays out four-phased vaccine distribution approaches, emphasizing social equity by prioritizing vaccines for geographic areas identified through CDC’s social vulnerability index (SVI) or another more specific index. SVI has been a robust composite marker of minority status and language, household composition and transportation, and housing and disability, and predicted COVID-19 case counts in the United States in several studies. The National Academy of Medicine has also recommended racial minorities receive priority vaccination because they have been hard hit and are “worse off” socioeconomically.
3. Immunization uptake by minority populations
Though minority participation is crucial in developing the vaccine, more transparency, open discussions on ethical distribution, and awareness of side effects are required before vaccine approval or emergency-use authorization. Companies behind the four major COVID-19 vaccines in development have released their trials’ protocols, details on vaccine efficacy, and each product’s makeup to increase acceptance of the vaccine.
According to a recent Pew research study, about half of U.S. adults (51%) now say they would definitely or probably get a vaccine to prevent COVID-19 if it were available today. Nearly as many (49%) say they definitely or probably would not get vaccinated at this time. Intent to get a COVID-19 vaccine has fallen from 72% in May 2020, a 21–percentage point drop, and Black adults were much less likely to say they would get a vaccine than other Americans.3 This is concerning as previous studies have shown that race and ethnicity can influence immune responses to vaccination. There is evidence of racial and ethnic differences in immune response following rubella vaccination, Hib–tetanus toxoid conjugate vaccine, antibody responses to the influenza A virus components of IIV3 or 4, and immune responses after measles vaccination.4-9
On the other hand, significant differences in reporting rates of adverse events after human papillomavirus vaccinations were found in different race and ethnicity groups in the Vaccine Adverse Event Reporting System.10 Thus, there is ample evidence that race and ethnicity affect responsiveness to a vaccine. Inequity in participation in a clinical trial may lead to an ineffective or one with a suboptimal response or even an unsafe vaccine.
When we look at other immunization programs, according to various surveys in recent years, non-Hispanic Blacks have lower annual vaccination rates for flu, pneumonia, and human papillomavirus vaccinations nationally, compared with non-Hispanic White adults.11 It is a cause of concern as a proportion of the population must be vaccinated to reach “community immunity” or “herd immunity” from vaccination. Depending on varying biological, environmental, and sociobehavioral factors, the threshold for COVID-19 herd immunity may be between 55% and 82% of the population.12 Hence, neither a vaccine trial nor an immunization program can succeed without participation from all communities and age groups.
Role of hospitalists
Hospitalists, who give immunizations as part of the hospital inpatient quality reporting program, are uniquely placed in this pandemic. Working on the front lines, we may encounter questions, concerns, rejections, and discussions about the pros and cons of the COVID-19 vaccine from patients.
Investigators at Children’s National Hospital and George Washington University, both in Washington, recently recommended three steps physicians and others can take now to ensure more people get the COVID-19 vaccine when it is available. Engaging frontline health professionals was one of the suggested steps to encourage more people to get the vaccine.13 However, it is imperative to understand that vaccine hesitancy might be an issue for health care providers as well, if concerns for scientific standards and involvement of diverse populations are not addressed.
We are only starting to develop a safe and effective immunization program. We must bring more to unrepresented communities than just vaccine trials. Information, education, availability, and access to the vaccines will make for a successful COVID-19 immunization program.
Dr. Saigal is a hospitalist and clinical assistant professor of medicine in the division of hospital medicine at the Ohio State University Wexner Medical Center, Columbus.
References
1. Moderna. COVE study. 2020 Oct 21. https://www.modernatx.com/sites/default/files/content_documents/2020-COVE-Study-Enrollment-Completion-10.22.20.pdf
2. U.S. Census Bureau. Quick facts: Population estimates, July 1, 2019. https://www.census.gov/quickfacts/fact/table/US/PST045219
3. Pew Research Center. U.S. Public Now Divided Over Whether To Get COVID-19 Vaccine. 2020 Sep 17. https://www.pewresearch.org/science/2020/09/17/u-s-public-now-divided-over-whether-to-get-covid-19-vaccine/
4. Haralambieva IH et al. Associations between race sex and immune response variations to rubella vaccination in two independent cohorts. Vaccine. 2014;32:1946-53.
5. McQuillan GM et al. Seroprevalence of measles antibody in the U.S. population 1999-2004. J Infect Dis. 2007;196:1459–64. doi: 10.1086/522866.
6. Christy C et al. Effect of gender race and parental education on immunogenicity and reported reactogenicity of acellular and whole-cell pertussis vaccines. Pediatrics. 1995;96:584-7.
7. Poland GA et al. Measles antibody seroprevalence rates among immunized Inuit Innu and Caucasian subjects. Vaccine. 1999;17:1525-31.
8. Greenberg DP et al. Immunogenicity of Haemophilus influenzae type b tetanus toxoid conjugate vaccine in young infants. The Kaiser-UCLA Vaccine Study Group. J Infect Dis. 1994;170:76-81.
9. Kurupati R et al. Race-related differences in antibody responses to the inactivated influenza vaccine are linked to distinct prevaccination gene expression profiles in blood. Oncotarget. 2016;7(39):62898-911.
10. Huang J et al. Characterization of the differential adverse event rates by race/ethnicity groups for HPV vaccine by integrating data from different sources. Front Pharmacol. 2018;9:539.
11. https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=4&lvlid=22
12. Sanche S et al. High contagiousness and rapid spread of severe acute respiratory syndrome coronavirus 2. Emerg Infect Dis. 2020;26(7).
13. American Medical Association. How to ready patients now so they’ll get a COVID-19 vaccine later. 2020 May 27. https://www.ama-assn.org/delivering-care/public-health/how-ready-patients-now-so-they-ll-get-covid-19-vaccine-later