Published on 02/02/2023
COVID-19 Genomics and Precision Public Health Weekly Update Content
Pathogen and Human Genomics Studies
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Do bivalent boosters work against XBB.1.5? Vaccine questions, answered. New CDC data shows updated boosters are cutting risk of getting sick from covid-19 by about half
N Nerapil et al, Washington Post, January 25, 2023 -
Should COVID vaccines be yearly? Proposal divides US scientists
M Kozlov, Nature, January 27, 2023Scientists are split about a US Food and Drug Administration’s (FDA) proposal to update COVID-19 vaccines once a year, similar to the agency’s approach for annually updating influenza vaccines. At a meeting of the FDA’s vaccine advisory panel on 26 January, some researchers argued that the proposal to offer an updated vaccine every US autumn would help simplify the country’s complex COVID immunization schedule and might boost uptake as a result. But other scientists were less convinced about the timeline — or whether healthy adults should be urged to receive an annual COVID-19 jab at all. -
Risk Factors for Reinfection with SARS-CoV-2 Omicron Variant among Previously Infected Frontline Workers.
Katherine D Ellingson et al. Emerging infectious diseases 2023 1 (3)In a cohort of essential workers in the United States previously infected with SARS-CoV-2, risk factors for reinfection included being unvaccinated, infrequent mask use, time since first infection, and being non-Hispanic Black. Protecting workers from reinfection requires a multipronged approach including up-to-date vaccination, mask use as recommended, and reduction in underlying health disparities. -
Early risk-assessment of pathogen genomic variants emergence
Z Susswein et al, MEDRXIV, January 27, 2023Despite decades of use for influenza vaccine strain selection and PCR-based molecular diagnostics, data on pathogen variant prevalence and growth advantage has only risen to its current prominence during the SARS-CoV-2 pandemic. However, such data are still often sparse: novel variants are initially rare or a region has limited sequencing. To ensure real-time estimates of risk are available in these types of data-sparse conditions, we develop a hierarchical modeling approach that estimates variant fitness advantage and prevalence by pooling data across geographic regions. We apply this method to estimate SARS-CoV-2 variant dynamics at the country-level and assess its stability with retrospective validation. -
Identification of a molnupiravir-associated mutational signature in SARS-CoV-2 sequencing databases
T Sanderson et al, MEDRXIB, January 27, 2023 -
Omicron BA.1/BA.2 infections in triple-vaccinated individuals enhance a diverse repertoire of mucosal and blood immune responses
H Hornsby et al, MEDRXIV, January 29, 2023We characterized mucosal and blood immunity to both spike and non-spike antigens following BA.1/BA.2 infections in triple mRNA-vaccinated individuals, with and without a history of previous SARS-CoV-2 infection. We find that the majority of individuals increase BA.1/BA.2/BA.5-specific NAb following infection, but confirm that the magnitude of increase and post-omicron titres are indeed higher in those who were infection-naive. In contrast, significant increases in nasal antibody responses are seen regardless of prior infection history. -
High number of SARS-CoV-2 persistent infections uncovered through genetic analysis of samples from a large community-based surveillance study
M Ghafari et al, MEDRXIV, January 30, 2023We identified 381 infections lasting at least 30 days, of which 54 lasted at least 60 days. These persistently infected individuals had more than 50% higher odds of self-reporting Long Covid compared to the infected controls, and we estimate that 0.09-0.5% of SARS-CoV-2 infections can become persistent and last for at least 60 days. In nearly 70% of the persistent infections we identified, there were long periods during which there were no consensus changes in virus sequences, consistent with prolonged presence of non-replicating virus. -
Extensive SARS-CoV-2 testing reveals BA.1/BA.2 asymptomatic rates and underreporting in school children
MM Martignoni et al, MEDRXIV, January 30, 2023 -
Subtyping of major SARS-CoV-2 variants reveals different transmission dynamics based on 10 million genomes.
Hsin-Chou Yang et al. PNAS nexus 2023 1 (4) pgac181Here we developed systematic approaches based on sets of correlated single nucleotide variations (SNVs) for comprehensive subtyping and pattern recognition of transmission dynamics. The approach outperformed single-SNV and spike-centric scans. Moreover, the derived subtypes elucidate the relationship of signature SNVs and transmission dynamics. We found that different subtypes of the same variant, including Delta and Omicron exhibited distinct temporal trajectories. For example, some Delta and Omicron subtypes did not spread rapidly, while others did. -
Interleukin-1 receptor antagonist gene ( IL1RN ) variants modulate the cytokine release syndrome and mortality of SARS-CoV-2.
Mukundan Attur et al. medRxiv : the preprint server for health sciences 2023 1Mortality in the population was 15.3%, and was lower in women than men (13.1% vs.17.3%, p<0.0003). Carriers of the CTA-1/2 IL1RN haplotypes exhibited decreased inflammatory markers and increased plasma IL-1Ra relative to TTG carriers. Decreased mortality among CTA-1/2 carriers was observed in male patients between the ages of 55-74 [9.2% vs. 17.9%, p=0.001]. Evaluation of individual SNVs of the IL1RN gene (rs419598, rs315952, rs9005) indicated that carriers of the IL1RN rs419598 CC SNV exhibited lower inflammatory biomarker levels, and was associated with reduced mortality compared to the CT/TT genotype in men (OR 0.49 (0.23 - 1.00); 0.052). -
The impact of cross-reactive immunity on the emergence of SARS-CoV-2 variants.
Robin N Thompson et al. Frontiers in immunology 2023 1 1049458We find that, if cross-reactive immunity is complete (i.e. someone infected by the previously circulating virus is not susceptible to the novel variant), the novel variant must be more transmissible than the previous virus to invade the population. However, in a more realistic scenario in which cross-reactive immunity is partial, we show that it is possible for novel variants to invade, even if they are less transmissible than previously circulating viruses. -
Simultaneous Detection of Omicron and Other SARS-CoV-2 Variants by Multiplex PCR MassARRAY Technology.
Supaporn Wacharapluesadee et al. Research square 2023 1A nucleotide matrix-assisted laser-desorption-ionization time-of-flight mass spectrophotometry (MALDI-TOF MS)-based assay was developed (called point mutation array, PMA) to identify four major SARS-CoV-2 variants of concern (VOCs) including Alpha, Beta, Delta, and Omicron (namely PMA-ABDO) and differentiate Omicron subvariant (namely PMA-Omicron). PMA-ABDO and PMA-Omicron consist of 24 and 28 mutation sites of the spike gene. Both PMA panels specifically identified VOCs with as low as 10 viral copies/ µl. -
Multiomics single timepoint measurements to predict severe COVID-19.
Sina A Tegethoff et al. The Lancet. Digital health 2023 1 (2) e56 -
The effect of previous SARS-CoV-2 infection and COVID-19 vaccination on SARS-CoV-2 Omicron infection and relation with serological response – a prospective cohort study
B de Gier et al, MEDRXIV, January 31, 2023Our results showed that hybrid immunity is more protective against infection with SARS-CoV-2 Omicron than vaccine-induced immunity, up to at least 30 weeks after the last immunizing event. Among those with hybrid immunity, the sequence and number of immunizing events was not found to be of importance, and its protective effect was partly explained by circulating S-antibodies. -
The next generation of coronavirus vaccines: a graphical guide
E Callaway, Nature, February 1, 2023Vaccine developers around the world are working on dozens of ‘next-generation’ COVID-19 vaccines: not just updates of the first versions, but ones that use new technologies and platforms. These vaccines are a diverse group, but the overarching aim is to deliver long-lasting protection that is resilient to viral change. Some could protect against broader classes of coronavirus, including ones that have yet to emerge. Others might provide more potent immunity, might do so at lower doses, or might be better at preventing infection or transmission of the virus. -
Evaluation of a Commercially Available Rapid RT-PCR Assay's Detection of SARS-CoV-2 Novel Variants
L Back et al, MEDRXIV, February 1, 2023 -
Inequities in COVID-19 vaccine and booster coverage across Massachusetts ZIP codes after the emergence of Omicron: A population-based cross-sectional study.
Jacob Bor et al. PLoS medicine 2023 1 (1) e1004167We analyzed data on 418 ZIP codes. We observed wide geographic variation in primary series vaccination and booster rates, with marked inequities by ZIP code-level education, median household income, essential worker share, and racial/ethnic composition. In age-stratified analyses, primary series vaccine coverage was very high among the elderly. However, we found large inequities in vaccination rates among younger adults and children, and very large inequities in booster rates for all age groups.
Non-Genomics Precision Health Studies
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Do bivalent boosters work against XBB.1.5? Vaccine questions, answered. New CDC data shows updated boosters are cutting risk of getting sick from covid-19 by about half
N Nerapil et al, Washington Post, January 25, 2023 -
Should COVID vaccines be yearly? Proposal divides US scientists
M Kozlov, Nature, January 27, 2023Scientists are split about a US Food and Drug Administration’s (FDA) proposal to update COVID-19 vaccines once a year, similar to the agency’s approach for annually updating influenza vaccines. At a meeting of the FDA’s vaccine advisory panel on 26 January, some researchers argued that the proposal to offer an updated vaccine every US autumn would help simplify the country’s complex COVID immunization schedule and might boost uptake as a result. But other scientists were less convinced about the timeline — or whether healthy adults should be urged to receive an annual COVID-19 jab at all. -
Risk Factors for Reinfection with SARS-CoV-2 Omicron Variant among Previously Infected Frontline Workers.
Katherine D Ellingson et al. Emerging infectious diseases 2023 1 (3)In a cohort of essential workers in the United States previously infected with SARS-CoV-2, risk factors for reinfection included being unvaccinated, infrequent mask use, time since first infection, and being non-Hispanic Black. Protecting workers from reinfection requires a multipronged approach including up-to-date vaccination, mask use as recommended, and reduction in underlying health disparities. -
Early risk-assessment of pathogen genomic variants emergence
Z Susswein et al, MEDRXIV, January 27, 2023Despite decades of use for influenza vaccine strain selection and PCR-based molecular diagnostics, data on pathogen variant prevalence and growth advantage has only risen to its current prominence during the SARS-CoV-2 pandemic. However, such data are still often sparse: novel variants are initially rare or a region has limited sequencing. To ensure real-time estimates of risk are available in these types of data-sparse conditions, we develop a hierarchical modeling approach that estimates variant fitness advantage and prevalence by pooling data across geographic regions. We apply this method to estimate SARS-CoV-2 variant dynamics at the country-level and assess its stability with retrospective validation. -
Identification of a molnupiravir-associated mutational signature in SARS-CoV-2 sequencing databases
T Sanderson et al, MEDRXIB, January 27, 2023 -
Omicron BA.1/BA.2 infections in triple-vaccinated individuals enhance a diverse repertoire of mucosal and blood immune responses
H Hornsby et al, MEDRXIV, January 29, 2023We characterized mucosal and blood immunity to both spike and non-spike antigens following BA.1/BA.2 infections in triple mRNA-vaccinated individuals, with and without a history of previous SARS-CoV-2 infection. We find that the majority of individuals increase BA.1/BA.2/BA.5-specific NAb following infection, but confirm that the magnitude of increase and post-omicron titres are indeed higher in those who were infection-naive. In contrast, significant increases in nasal antibody responses are seen regardless of prior infection history. -
High number of SARS-CoV-2 persistent infections uncovered through genetic analysis of samples from a large community-based surveillance study
M Ghafari et al, MEDRXIV, January 30, 2023We identified 381 infections lasting at least 30 days, of which 54 lasted at least 60 days. These persistently infected individuals had more than 50% higher odds of self-reporting Long Covid compared to the infected controls, and we estimate that 0.09-0.5% of SARS-CoV-2 infections can become persistent and last for at least 60 days. In nearly 70% of the persistent infections we identified, there were long periods during which there were no consensus changes in virus sequences, consistent with prolonged presence of non-replicating virus. -
Extensive SARS-CoV-2 testing reveals BA.1/BA.2 asymptomatic rates and underreporting in school children
MM Martignoni et al, MEDRXIV, January 30, 2023 -
Subtyping of major SARS-CoV-2 variants reveals different transmission dynamics based on 10 million genomes.
Hsin-Chou Yang et al. PNAS nexus 2023 1 (4) pgac181Here we developed systematic approaches based on sets of correlated single nucleotide variations (SNVs) for comprehensive subtyping and pattern recognition of transmission dynamics. The approach outperformed single-SNV and spike-centric scans. Moreover, the derived subtypes elucidate the relationship of signature SNVs and transmission dynamics. We found that different subtypes of the same variant, including Delta and Omicron exhibited distinct temporal trajectories. For example, some Delta and Omicron subtypes did not spread rapidly, while others did. -
Interleukin-1 receptor antagonist gene ( IL1RN ) variants modulate the cytokine release syndrome and mortality of SARS-CoV-2.
Mukundan Attur et al. medRxiv : the preprint server for health sciences 2023 1Mortality in the population was 15.3%, and was lower in women than men (13.1% vs.17.3%, p<0.0003). Carriers of the CTA-1/2 IL1RN haplotypes exhibited decreased inflammatory markers and increased plasma IL-1Ra relative to TTG carriers. Decreased mortality among CTA-1/2 carriers was observed in male patients between the ages of 55-74 [9.2% vs. 17.9%, p=0.001]. Evaluation of individual SNVs of the IL1RN gene (rs419598, rs315952, rs9005) indicated that carriers of the IL1RN rs419598 CC SNV exhibited lower inflammatory biomarker levels, and was associated with reduced mortality compared to the CT/TT genotype in men (OR 0.49 (0.23 - 1.00); 0.052). -
The impact of cross-reactive immunity on the emergence of SARS-CoV-2 variants.
Robin N Thompson et al. Frontiers in immunology 2023 1 1049458We find that, if cross-reactive immunity is complete (i.e. someone infected by the previously circulating virus is not susceptible to the novel variant), the novel variant must be more transmissible than the previous virus to invade the population. However, in a more realistic scenario in which cross-reactive immunity is partial, we show that it is possible for novel variants to invade, even if they are less transmissible than previously circulating viruses. -
Simultaneous Detection of Omicron and Other SARS-CoV-2 Variants by Multiplex PCR MassARRAY Technology.
Supaporn Wacharapluesadee et al. Research square 2023 1A nucleotide matrix-assisted laser-desorption-ionization time-of-flight mass spectrophotometry (MALDI-TOF MS)-based assay was developed (called point mutation array, PMA) to identify four major SARS-CoV-2 variants of concern (VOCs) including Alpha, Beta, Delta, and Omicron (namely PMA-ABDO) and differentiate Omicron subvariant (namely PMA-Omicron). PMA-ABDO and PMA-Omicron consist of 24 and 28 mutation sites of the spike gene. Both PMA panels specifically identified VOCs with as low as 10 viral copies/ µl. -
Multiomics single timepoint measurements to predict severe COVID-19.
Sina A Tegethoff et al. The Lancet. Digital health 2023 1 (2) e56 -
The effect of previous SARS-CoV-2 infection and COVID-19 vaccination on SARS-CoV-2 Omicron infection and relation with serological response – a prospective cohort study
B de Gier et al, MEDRXIV, January 31, 2023Our results showed that hybrid immunity is more protective against infection with SARS-CoV-2 Omicron than vaccine-induced immunity, up to at least 30 weeks after the last immunizing event. Among those with hybrid immunity, the sequence and number of immunizing events was not found to be of importance, and its protective effect was partly explained by circulating S-antibodies. -
The next generation of coronavirus vaccines: a graphical guide
E Callaway, Nature, February 1, 2023Vaccine developers around the world are working on dozens of ‘next-generation’ COVID-19 vaccines: not just updates of the first versions, but ones that use new technologies and platforms. These vaccines are a diverse group, but the overarching aim is to deliver long-lasting protection that is resilient to viral change. Some could protect against broader classes of coronavirus, including ones that have yet to emerge. Others might provide more potent immunity, might do so at lower doses, or might be better at preventing infection or transmission of the virus. -
Evaluation of a Commercially Available Rapid RT-PCR Assay's Detection of SARS-CoV-2 Novel Variants
L Back et al, MEDRXIV, February 1, 2023 -
Inequities in COVID-19 vaccine and booster coverage across Massachusetts ZIP codes after the emergence of Omicron: A population-based cross-sectional study.
Jacob Bor et al. PLoS medicine 2023 1 (1) e1004167We analyzed data on 418 ZIP codes. We observed wide geographic variation in primary series vaccination and booster rates, with marked inequities by ZIP code-level education, median household income, essential worker share, and racial/ethnic composition. In age-stratified analyses, primary series vaccine coverage was very high among the elderly. However, we found large inequities in vaccination rates among younger adults and children, and very large inequities in booster rates for all age groups.
News, Reviews and Commentaries
-
Do bivalent boosters work against XBB.1.5? Vaccine questions, answered. New CDC data shows updated boosters are cutting risk of getting sick from covid-19 by about half
N Nerapil et al, Washington Post, January 25, 2023 -
Should COVID vaccines be yearly? Proposal divides US scientists
M Kozlov, Nature, January 27, 2023Scientists are split about a US Food and Drug Administration’s (FDA) proposal to update COVID-19 vaccines once a year, similar to the agency’s approach for annually updating influenza vaccines. At a meeting of the FDA’s vaccine advisory panel on 26 January, some researchers argued that the proposal to offer an updated vaccine every US autumn would help simplify the country’s complex COVID immunization schedule and might boost uptake as a result. But other scientists were less convinced about the timeline — or whether healthy adults should be urged to receive an annual COVID-19 jab at all. -
Risk Factors for Reinfection with SARS-CoV-2 Omicron Variant among Previously Infected Frontline Workers.
Katherine D Ellingson et al. Emerging infectious diseases 2023 1 (3)In a cohort of essential workers in the United States previously infected with SARS-CoV-2, risk factors for reinfection included being unvaccinated, infrequent mask use, time since first infection, and being non-Hispanic Black. Protecting workers from reinfection requires a multipronged approach including up-to-date vaccination, mask use as recommended, and reduction in underlying health disparities. -
Early risk-assessment of pathogen genomic variants emergence
Z Susswein et al, MEDRXIV, January 27, 2023Despite decades of use for influenza vaccine strain selection and PCR-based molecular diagnostics, data on pathogen variant prevalence and growth advantage has only risen to its current prominence during the SARS-CoV-2 pandemic. However, such data are still often sparse: novel variants are initially rare or a region has limited sequencing. To ensure real-time estimates of risk are available in these types of data-sparse conditions, we develop a hierarchical modeling approach that estimates variant fitness advantage and prevalence by pooling data across geographic regions. We apply this method to estimate SARS-CoV-2 variant dynamics at the country-level and assess its stability with retrospective validation. -
Identification of a molnupiravir-associated mutational signature in SARS-CoV-2 sequencing databases
T Sanderson et al, MEDRXIB, January 27, 2023 -
Omicron BA.1/BA.2 infections in triple-vaccinated individuals enhance a diverse repertoire of mucosal and blood immune responses
H Hornsby et al, MEDRXIV, January 29, 2023We characterized mucosal and blood immunity to both spike and non-spike antigens following BA.1/BA.2 infections in triple mRNA-vaccinated individuals, with and without a history of previous SARS-CoV-2 infection. We find that the majority of individuals increase BA.1/BA.2/BA.5-specific NAb following infection, but confirm that the magnitude of increase and post-omicron titres are indeed higher in those who were infection-naive. In contrast, significant increases in nasal antibody responses are seen regardless of prior infection history. -
High number of SARS-CoV-2 persistent infections uncovered through genetic analysis of samples from a large community-based surveillance study
M Ghafari et al, MEDRXIV, January 30, 2023We identified 381 infections lasting at least 30 days, of which 54 lasted at least 60 days. These persistently infected individuals had more than 50% higher odds of self-reporting Long Covid compared to the infected controls, and we estimate that 0.09-0.5% of SARS-CoV-2 infections can become persistent and last for at least 60 days. In nearly 70% of the persistent infections we identified, there were long periods during which there were no consensus changes in virus sequences, consistent with prolonged presence of non-replicating virus. -
Extensive SARS-CoV-2 testing reveals BA.1/BA.2 asymptomatic rates and underreporting in school children
MM Martignoni et al, MEDRXIV, January 30, 2023 -
Subtyping of major SARS-CoV-2 variants reveals different transmission dynamics based on 10 million genomes.
Hsin-Chou Yang et al. PNAS nexus 2023 1 (4) pgac181Here we developed systematic approaches based on sets of correlated single nucleotide variations (SNVs) for comprehensive subtyping and pattern recognition of transmission dynamics. The approach outperformed single-SNV and spike-centric scans. Moreover, the derived subtypes elucidate the relationship of signature SNVs and transmission dynamics. We found that different subtypes of the same variant, including Delta and Omicron exhibited distinct temporal trajectories. For example, some Delta and Omicron subtypes did not spread rapidly, while others did. -
Interleukin-1 receptor antagonist gene ( IL1RN ) variants modulate the cytokine release syndrome and mortality of SARS-CoV-2.
Mukundan Attur et al. medRxiv : the preprint server for health sciences 2023 1Mortality in the population was 15.3%, and was lower in women than men (13.1% vs.17.3%, p<0.0003). Carriers of the CTA-1/2 IL1RN haplotypes exhibited decreased inflammatory markers and increased plasma IL-1Ra relative to TTG carriers. Decreased mortality among CTA-1/2 carriers was observed in male patients between the ages of 55-74 [9.2% vs. 17.9%, p=0.001]. Evaluation of individual SNVs of the IL1RN gene (rs419598, rs315952, rs9005) indicated that carriers of the IL1RN rs419598 CC SNV exhibited lower inflammatory biomarker levels, and was associated with reduced mortality compared to the CT/TT genotype in men (OR 0.49 (0.23 - 1.00); 0.052). -
The impact of cross-reactive immunity on the emergence of SARS-CoV-2 variants.
Robin N Thompson et al. Frontiers in immunology 2023 1 1049458We find that, if cross-reactive immunity is complete (i.e. someone infected by the previously circulating virus is not susceptible to the novel variant), the novel variant must be more transmissible than the previous virus to invade the population. However, in a more realistic scenario in which cross-reactive immunity is partial, we show that it is possible for novel variants to invade, even if they are less transmissible than previously circulating viruses. -
Simultaneous Detection of Omicron and Other SARS-CoV-2 Variants by Multiplex PCR MassARRAY Technology.
Supaporn Wacharapluesadee et al. Research square 2023 1A nucleotide matrix-assisted laser-desorption-ionization time-of-flight mass spectrophotometry (MALDI-TOF MS)-based assay was developed (called point mutation array, PMA) to identify four major SARS-CoV-2 variants of concern (VOCs) including Alpha, Beta, Delta, and Omicron (namely PMA-ABDO) and differentiate Omicron subvariant (namely PMA-Omicron). PMA-ABDO and PMA-Omicron consist of 24 and 28 mutation sites of the spike gene. Both PMA panels specifically identified VOCs with as low as 10 viral copies/ µl. -
Multiomics single timepoint measurements to predict severe COVID-19.
Sina A Tegethoff et al. The Lancet. Digital health 2023 1 (2) e56 -
The effect of previous SARS-CoV-2 infection and COVID-19 vaccination on SARS-CoV-2 Omicron infection and relation with serological response – a prospective cohort study
B de Gier et al, MEDRXIV, January 31, 2023Our results showed that hybrid immunity is more protective against infection with SARS-CoV-2 Omicron than vaccine-induced immunity, up to at least 30 weeks after the last immunizing event. Among those with hybrid immunity, the sequence and number of immunizing events was not found to be of importance, and its protective effect was partly explained by circulating S-antibodies. -
The next generation of coronavirus vaccines: a graphical guide
E Callaway, Nature, February 1, 2023Vaccine developers around the world are working on dozens of ‘next-generation’ COVID-19 vaccines: not just updates of the first versions, but ones that use new technologies and platforms. These vaccines are a diverse group, but the overarching aim is to deliver long-lasting protection that is resilient to viral change. Some could protect against broader classes of coronavirus, including ones that have yet to emerge. Others might provide more potent immunity, might do so at lower doses, or might be better at preventing infection or transmission of the virus. -
Evaluation of a Commercially Available Rapid RT-PCR Assay's Detection of SARS-CoV-2 Novel Variants
L Back et al, MEDRXIV, February 1, 2023 -
Inequities in COVID-19 vaccine and booster coverage across Massachusetts ZIP codes after the emergence of Omicron: A population-based cross-sectional study.
Jacob Bor et al. PLoS medicine 2023 1 (1) e1004167We analyzed data on 418 ZIP codes. We observed wide geographic variation in primary series vaccination and booster rates, with marked inequities by ZIP code-level education, median household income, essential worker share, and racial/ethnic composition. In age-stratified analyses, primary series vaccine coverage was very high among the elderly. However, we found large inequities in vaccination rates among younger adults and children, and very large inequities in booster rates for all age groups.
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- Page last updated:May 02, 2024
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