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Published on 04/22/2021

COVID-19 Genomics and Precision Public Health Weekly Update Content

Pathogen and Human Genomics Studies

  • SARS-CoV-2 within-host diversity and transmission.
    Lythgoe Katrina A et al. Science (New York, N.Y.) 2021 3
    The authors have undertaken in-depth sequencing of more than 1000 hospital patients' isolates to find out how the virus is mutating within individuals. Overall, there seem to be consistent and reproducible patterns of within-host virus diversity. The authors observed only one or two variants in most samples, but a few carried many variants.
  • Spike Antibody Levels of Nursing Home Residents With or Without Prior COVID-19 3 Weeks After a Single BNT162b2 Vaccine Dose
    H Blain et al, JAMA< April 15, 2021
    This preliminary study suggests that a single dose of BNT162b2 vaccine may be sufficient to obtain a high level of S-protein IgG antibody in nursing home residents previously diagnosed with COVID-19 based on RT-PCR results.
  • Viral sequencing reveals US healthcare personnel rarely become infected with SARS-CoV-2 through patient contact.
    Braun Katarina M et al. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2021 4
    We investigated SARS-CoV-2 infection clusters involving 95 HCP and 137 possible patient contact sequences. The majority of HCP infections could not be linked to a patient or co-worker (55/95; 57.9%) and were genetically similar to viruses circulating concurrently in the community. We found 10.5% of infections could be traced to a coworker (10/95). Strikingly, only 4.2% of HCP infections could be traced to a patient source (4/95).
  • Modeling vaccination rollouts, SARS-CoV-2 variants and the requirement for non-pharmaceutical interventions in Italy
    G Giordano et al, Nature Medicine, April 16, 2021
    Based on the Italian case study, we outline several scenarios: mass vaccination campaigns with different paces, different transmission rates due to new variants and different enforced countermeasures, including the alternation of opening and closure phases. Our results demonstrate that non-pharmaceutical interventions have a higher effect on the epidemic evolution than vaccination alone, advocating for the need to keep NPIs in place during the first phase of vaccination.
  • The impact of real-time whole genome sequencing in controlling healthcare-associated SARS-CoV-2 outbreaks
    H Billam et al, MEDRXIV, April 17, 2021
    Phylogenetic analysis from WGS and epidemiological data was used to identify an initial transmission that occurred in the admissions ward. It also showed high prevalence of asymptomatic staff infection with genetically identical viral sequences which may have contributed to the propagation of the outbreak. Actions were taken to help reduce the risk of nosocomial transmission by the introduction of rapid testing in the admissions ward and introduction of portable HEPA14 filters.
  • Germline variants in UNC13D and AP3B1 are enriched in COVID-19 patients experiencing severe cytokine storms
    H Luo et al, EJHG, April 19, 2021
    We conducted whole-exome sequencing in 233 hospitalized COVID-19 patients and identified four PID gene (UNC13D, AP3B1, RNF168, DHX58) variants were significantly enriched in COVID-19 patients experiencing severe cytokine storms. The total percentage of COVID-19 patients with variants in UNC13D or AP3B1, two typical HLH genes, was dramatically higher in high-level cytokine group than in low-level group (33.3 vs. 5.7%, P?<?0.001).
  • Saliva as a gold-standard sample for SARS-CoV-2 detection
    SH Tan, The Lancet Respiratory Medicine, April 19, 2021
    Saliva testing was successfully adopted for SARS-CoV-2 detection in numerous countries. In the US, saliva testing gained traction to facilitate the reopening of educational institutions, with its potential for pooling samples for processing, enabling sustainable testing program. As a preferable method for frequent, repeat testing, saliva could be particularly well suited for detecting SARS-CoV-2 during the prodromal phase,8 decreasing risk of further transmission.
  • Rapid vaccination and partial lockdown minimizes 4th waves from emerging highly contagious SARS-CoV-2 variants
    DB Reeves et al, Cell (Med), April 19, 2021
    It is often stated that vaccines do not save lives, vaccinations do. Our modeling reinforces this point. We project that despite considerable uncertainty about the timing and severity of variant waves in the United States, rapid vaccination must remain high to save the most lives and limit future time under partial lockdown.
  • Infection and transmission of SARS-CoV-2 in London care homes reporting no cases or outbreaks of COVID-19: Prospective observational cohort study, England 2020.
    Jeffery-Smith Anna et al. The Lancet regional health. Europe 2021 4 100038
    "We investigated the potential role of asymptomatic infection and silent transmission in London care homes that reported no cases of COVID-19 during the first wave of the pandemic.... We found high rates of asymptomatic infection and transmission even in care homes with no COVID-19 cases. The higher seropositivity rates compared to RT-PCR positivity highlights the true extent of the silent outbreak."
  • Single-cell multi-omics analysis of the immune response in COVID-19
    E Stephenson et al, Nature Medicine, April 20, 2021
    We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease.
  • Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant
    Y Deng et al, Cell, April 20, 2021
    We identified an emerging SARS-CoV-2 variant in 2,172 nasal/nasopharyngeal swab samples from 44 counties in California. The variant emerged in May 2020 and increased from 0% to >50% of sequenced cases from September 2020 to January 2021, showing 18.6-24% increased transmissibility relative to wild-type circulating strains. The variant carries 3 mutations in the spike protein, including an L452R substitution. We found 2-fold increased B.1.427/B.1.429 viral shedding in vivo.
  • COVID-19 Outbreak Associated with a SARS-CoV-2 R.1 Lineage Variant in a Skilled Nursing Facility After Vaccination Program — Kentucky, March 2021
    AM Cavanaugh et al, MMWR, April 21, 2021
    In a COVID-19 outbreak at a Kentucky skilled nursing facility involving a newly introduced variant to the region, unvaccinated residents and health care personnel (HCP) had 3.0 and 4.1 times the risk of infection as did vaccinated residents and HCP. Vaccine was 86.5% protective against symptomatic illness among residents and 87.1% protective among HCP.
  • Postvaccination SARS-CoV-2 Infections Among Skilled Nursing Facility Residents and Staff Members — Chicago, Illinois, December 2020–March 2021
    RA Teran et al, MMWR, April 21, 2021
    Twenty-two possible breakthrough SARS-CoV-2 infections occurred among fully vaccinated persons =14 days after their second dose of COVID-19 vaccine. Two thirds of persons were asymptomatic. A minority of persons with breakthrough infection experienced mild to moderate COVID-19–like symptoms; two COVID-19–related hospitalizations and one death occurred. No facility-associated secondary transmission was identified.
  • Vaccine Breakthrough Infections with SARS-CoV-2 Variants
    E Hacisuleyman et al, NEJM, April 21, 2021
    Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of clinical concern. In a cohort of 417 persons who had received the second dose of mRNA vaccine at least 2 weeks previously, we identified 2 women with vaccine breakthrough infection. Despite evidence of vaccine efficacy in both women, symptoms of coronavirus disease 2019 developed, and they tested positive for SARS-CoV-2 by polymerase-chain-reaction testing. Viral sequencing revealed variants of likely clinical importance, including E484K in 1 woman and three mutations (T95I, del142–144, and D614G) in both.

Non-Genomics Precision Health Studies

  • SARS-CoV-2 within-host diversity and transmission.
    Lythgoe Katrina A et al. Science (New York, N.Y.) 2021 3
    The authors have undertaken in-depth sequencing of more than 1000 hospital patients' isolates to find out how the virus is mutating within individuals. Overall, there seem to be consistent and reproducible patterns of within-host virus diversity. The authors observed only one or two variants in most samples, but a few carried many variants.
  • Spike Antibody Levels of Nursing Home Residents With or Without Prior COVID-19 3 Weeks After a Single BNT162b2 Vaccine Dose
    H Blain et al, JAMA< April 15, 2021
    This preliminary study suggests that a single dose of BNT162b2 vaccine may be sufficient to obtain a high level of S-protein IgG antibody in nursing home residents previously diagnosed with COVID-19 based on RT-PCR results.
  • Viral sequencing reveals US healthcare personnel rarely become infected with SARS-CoV-2 through patient contact.
    Braun Katarina M et al. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2021 4
    We investigated SARS-CoV-2 infection clusters involving 95 HCP and 137 possible patient contact sequences. The majority of HCP infections could not be linked to a patient or co-worker (55/95; 57.9%) and were genetically similar to viruses circulating concurrently in the community. We found 10.5% of infections could be traced to a coworker (10/95). Strikingly, only 4.2% of HCP infections could be traced to a patient source (4/95).
  • Modeling vaccination rollouts, SARS-CoV-2 variants and the requirement for non-pharmaceutical interventions in Italy
    G Giordano et al, Nature Medicine, April 16, 2021
    Based on the Italian case study, we outline several scenarios: mass vaccination campaigns with different paces, different transmission rates due to new variants and different enforced countermeasures, including the alternation of opening and closure phases. Our results demonstrate that non-pharmaceutical interventions have a higher effect on the epidemic evolution than vaccination alone, advocating for the need to keep NPIs in place during the first phase of vaccination.
  • The impact of real-time whole genome sequencing in controlling healthcare-associated SARS-CoV-2 outbreaks
    H Billam et al, MEDRXIV, April 17, 2021
    Phylogenetic analysis from WGS and epidemiological data was used to identify an initial transmission that occurred in the admissions ward. It also showed high prevalence of asymptomatic staff infection with genetically identical viral sequences which may have contributed to the propagation of the outbreak. Actions were taken to help reduce the risk of nosocomial transmission by the introduction of rapid testing in the admissions ward and introduction of portable HEPA14 filters.
  • Germline variants in UNC13D and AP3B1 are enriched in COVID-19 patients experiencing severe cytokine storms
    H Luo et al, EJHG, April 19, 2021
    We conducted whole-exome sequencing in 233 hospitalized COVID-19 patients and identified four PID gene (UNC13D, AP3B1, RNF168, DHX58) variants were significantly enriched in COVID-19 patients experiencing severe cytokine storms. The total percentage of COVID-19 patients with variants in UNC13D or AP3B1, two typical HLH genes, was dramatically higher in high-level cytokine group than in low-level group (33.3 vs. 5.7%, P?<?0.001).
  • Saliva as a gold-standard sample for SARS-CoV-2 detection
    SH Tan, The Lancet Respiratory Medicine, April 19, 2021
    Saliva testing was successfully adopted for SARS-CoV-2 detection in numerous countries. In the US, saliva testing gained traction to facilitate the reopening of educational institutions, with its potential for pooling samples for processing, enabling sustainable testing program. As a preferable method for frequent, repeat testing, saliva could be particularly well suited for detecting SARS-CoV-2 during the prodromal phase,8 decreasing risk of further transmission.
  • Rapid vaccination and partial lockdown minimizes 4th waves from emerging highly contagious SARS-CoV-2 variants
    DB Reeves et al, Cell (Med), April 19, 2021
    It is often stated that vaccines do not save lives, vaccinations do. Our modeling reinforces this point. We project that despite considerable uncertainty about the timing and severity of variant waves in the United States, rapid vaccination must remain high to save the most lives and limit future time under partial lockdown.
  • Infection and transmission of SARS-CoV-2 in London care homes reporting no cases or outbreaks of COVID-19: Prospective observational cohort study, England 2020.
    Jeffery-Smith Anna et al. The Lancet regional health. Europe 2021 4 100038
    "We investigated the potential role of asymptomatic infection and silent transmission in London care homes that reported no cases of COVID-19 during the first wave of the pandemic.... We found high rates of asymptomatic infection and transmission even in care homes with no COVID-19 cases. The higher seropositivity rates compared to RT-PCR positivity highlights the true extent of the silent outbreak."
  • Single-cell multi-omics analysis of the immune response in COVID-19
    E Stephenson et al, Nature Medicine, April 20, 2021
    We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease.
  • Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant
    Y Deng et al, Cell, April 20, 2021
    We identified an emerging SARS-CoV-2 variant in 2,172 nasal/nasopharyngeal swab samples from 44 counties in California. The variant emerged in May 2020 and increased from 0% to >50% of sequenced cases from September 2020 to January 2021, showing 18.6-24% increased transmissibility relative to wild-type circulating strains. The variant carries 3 mutations in the spike protein, including an L452R substitution. We found 2-fold increased B.1.427/B.1.429 viral shedding in vivo.
  • COVID-19 Outbreak Associated with a SARS-CoV-2 R.1 Lineage Variant in a Skilled Nursing Facility After Vaccination Program — Kentucky, March 2021
    AM Cavanaugh et al, MMWR, April 21, 2021
    In a COVID-19 outbreak at a Kentucky skilled nursing facility involving a newly introduced variant to the region, unvaccinated residents and health care personnel (HCP) had 3.0 and 4.1 times the risk of infection as did vaccinated residents and HCP. Vaccine was 86.5% protective against symptomatic illness among residents and 87.1% protective among HCP.
  • Postvaccination SARS-CoV-2 Infections Among Skilled Nursing Facility Residents and Staff Members — Chicago, Illinois, December 2020–March 2021
    RA Teran et al, MMWR, April 21, 2021
    Twenty-two possible breakthrough SARS-CoV-2 infections occurred among fully vaccinated persons =14 days after their second dose of COVID-19 vaccine. Two thirds of persons were asymptomatic. A minority of persons with breakthrough infection experienced mild to moderate COVID-19–like symptoms; two COVID-19–related hospitalizations and one death occurred. No facility-associated secondary transmission was identified.
  • Vaccine Breakthrough Infections with SARS-CoV-2 Variants
    E Hacisuleyman et al, NEJM, April 21, 2021
    Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of clinical concern. In a cohort of 417 persons who had received the second dose of mRNA vaccine at least 2 weeks previously, we identified 2 women with vaccine breakthrough infection. Despite evidence of vaccine efficacy in both women, symptoms of coronavirus disease 2019 developed, and they tested positive for SARS-CoV-2 by polymerase-chain-reaction testing. Viral sequencing revealed variants of likely clinical importance, including E484K in 1 woman and three mutations (T95I, del142–144, and D614G) in both.

News, Reviews and Commentaries

  • SARS-CoV-2 within-host diversity and transmission.
    Lythgoe Katrina A et al. Science (New York, N.Y.) 2021 3
    The authors have undertaken in-depth sequencing of more than 1000 hospital patients' isolates to find out how the virus is mutating within individuals. Overall, there seem to be consistent and reproducible patterns of within-host virus diversity. The authors observed only one or two variants in most samples, but a few carried many variants.
  • Spike Antibody Levels of Nursing Home Residents With or Without Prior COVID-19 3 Weeks After a Single BNT162b2 Vaccine Dose
    H Blain et al, JAMA< April 15, 2021
    This preliminary study suggests that a single dose of BNT162b2 vaccine may be sufficient to obtain a high level of S-protein IgG antibody in nursing home residents previously diagnosed with COVID-19 based on RT-PCR results.
  • Viral sequencing reveals US healthcare personnel rarely become infected with SARS-CoV-2 through patient contact.
    Braun Katarina M et al. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2021 4
    We investigated SARS-CoV-2 infection clusters involving 95 HCP and 137 possible patient contact sequences. The majority of HCP infections could not be linked to a patient or co-worker (55/95; 57.9%) and were genetically similar to viruses circulating concurrently in the community. We found 10.5% of infections could be traced to a coworker (10/95). Strikingly, only 4.2% of HCP infections could be traced to a patient source (4/95).
  • Modeling vaccination rollouts, SARS-CoV-2 variants and the requirement for non-pharmaceutical interventions in Italy
    G Giordano et al, Nature Medicine, April 16, 2021
    Based on the Italian case study, we outline several scenarios: mass vaccination campaigns with different paces, different transmission rates due to new variants and different enforced countermeasures, including the alternation of opening and closure phases. Our results demonstrate that non-pharmaceutical interventions have a higher effect on the epidemic evolution than vaccination alone, advocating for the need to keep NPIs in place during the first phase of vaccination.
  • The impact of real-time whole genome sequencing in controlling healthcare-associated SARS-CoV-2 outbreaks
    H Billam et al, MEDRXIV, April 17, 2021
    Phylogenetic analysis from WGS and epidemiological data was used to identify an initial transmission that occurred in the admissions ward. It also showed high prevalence of asymptomatic staff infection with genetically identical viral sequences which may have contributed to the propagation of the outbreak. Actions were taken to help reduce the risk of nosocomial transmission by the introduction of rapid testing in the admissions ward and introduction of portable HEPA14 filters.
  • Germline variants in UNC13D and AP3B1 are enriched in COVID-19 patients experiencing severe cytokine storms
    H Luo et al, EJHG, April 19, 2021
    We conducted whole-exome sequencing in 233 hospitalized COVID-19 patients and identified four PID gene (UNC13D, AP3B1, RNF168, DHX58) variants were significantly enriched in COVID-19 patients experiencing severe cytokine storms. The total percentage of COVID-19 patients with variants in UNC13D or AP3B1, two typical HLH genes, was dramatically higher in high-level cytokine group than in low-level group (33.3 vs. 5.7%, P?<?0.001).
  • Saliva as a gold-standard sample for SARS-CoV-2 detection
    SH Tan, The Lancet Respiratory Medicine, April 19, 2021
    Saliva testing was successfully adopted for SARS-CoV-2 detection in numerous countries. In the US, saliva testing gained traction to facilitate the reopening of educational institutions, with its potential for pooling samples for processing, enabling sustainable testing program. As a preferable method for frequent, repeat testing, saliva could be particularly well suited for detecting SARS-CoV-2 during the prodromal phase,8 decreasing risk of further transmission.
  • Rapid vaccination and partial lockdown minimizes 4th waves from emerging highly contagious SARS-CoV-2 variants
    DB Reeves et al, Cell (Med), April 19, 2021
    It is often stated that vaccines do not save lives, vaccinations do. Our modeling reinforces this point. We project that despite considerable uncertainty about the timing and severity of variant waves in the United States, rapid vaccination must remain high to save the most lives and limit future time under partial lockdown.
  • Infection and transmission of SARS-CoV-2 in London care homes reporting no cases or outbreaks of COVID-19: Prospective observational cohort study, England 2020.
    Jeffery-Smith Anna et al. The Lancet regional health. Europe 2021 4 100038
    "We investigated the potential role of asymptomatic infection and silent transmission in London care homes that reported no cases of COVID-19 during the first wave of the pandemic.... We found high rates of asymptomatic infection and transmission even in care homes with no COVID-19 cases. The higher seropositivity rates compared to RT-PCR positivity highlights the true extent of the silent outbreak."
  • Single-cell multi-omics analysis of the immune response in COVID-19
    E Stephenson et al, Nature Medicine, April 20, 2021
    We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease.
  • Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant
    Y Deng et al, Cell, April 20, 2021
    We identified an emerging SARS-CoV-2 variant in 2,172 nasal/nasopharyngeal swab samples from 44 counties in California. The variant emerged in May 2020 and increased from 0% to >50% of sequenced cases from September 2020 to January 2021, showing 18.6-24% increased transmissibility relative to wild-type circulating strains. The variant carries 3 mutations in the spike protein, including an L452R substitution. We found 2-fold increased B.1.427/B.1.429 viral shedding in vivo.
  • COVID-19 Outbreak Associated with a SARS-CoV-2 R.1 Lineage Variant in a Skilled Nursing Facility After Vaccination Program — Kentucky, March 2021
    AM Cavanaugh et al, MMWR, April 21, 2021
    In a COVID-19 outbreak at a Kentucky skilled nursing facility involving a newly introduced variant to the region, unvaccinated residents and health care personnel (HCP) had 3.0 and 4.1 times the risk of infection as did vaccinated residents and HCP. Vaccine was 86.5% protective against symptomatic illness among residents and 87.1% protective among HCP.
  • Postvaccination SARS-CoV-2 Infections Among Skilled Nursing Facility Residents and Staff Members — Chicago, Illinois, December 2020–March 2021
    RA Teran et al, MMWR, April 21, 2021
    Twenty-two possible breakthrough SARS-CoV-2 infections occurred among fully vaccinated persons =14 days after their second dose of COVID-19 vaccine. Two thirds of persons were asymptomatic. A minority of persons with breakthrough infection experienced mild to moderate COVID-19–like symptoms; two COVID-19–related hospitalizations and one death occurred. No facility-associated secondary transmission was identified.
  • Vaccine Breakthrough Infections with SARS-CoV-2 Variants
    E Hacisuleyman et al, NEJM, April 21, 2021
    Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of clinical concern. In a cohort of 417 persons who had received the second dose of mRNA vaccine at least 2 weeks previously, we identified 2 women with vaccine breakthrough infection. Despite evidence of vaccine efficacy in both women, symptoms of coronavirus disease 2019 developed, and they tested positive for SARS-CoV-2 by polymerase-chain-reaction testing. Viral sequencing revealed variants of likely clinical importance, including E484K in 1 woman and three mutations (T95I, del142–144, and D614G) in both.
Disclaimer: Articles listed in COVID-19 Genomics and Precision Public Health Weekly Update are selected by Public Health Genomics Branch to provide current awareness of the scientific literature and news. Inclusion in the update does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.
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