Published on 12/22/2022
COVID-19 Genomics and Precision Public Health Weekly Update Content
Pathogen and Human Genomics Studies
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Estimated BNT162b2 Vaccine Effectiveness Against Infection With Delta and Omicron Variants Among US Children 5 to 11 Years of Age.
Khan Farid L et al. JAMA network open 2022 12 (12) e2246915The VE of 2 doses of BNT162b2 against Delta was 85% (95% CI, 80%-89%; median follow-up, 1 month) compared with the Omicron period (20% [95% CI, 17%-23%]; median follow-up, 4 months). The adjusted VE of 2 doses against Omicron at less than 3 months was 39% (95% CI, 36%-42%), and at 3 months or more, it was -1% (95% CI, -6% to 3%). The study suggests that, among children aged 5 to 11 years, 2 doses of BNT162b2 provided modest short-term protection against Omicron infection that was higher for those with prior infection; however, VE waned after approximately 3 months in all children. -
BA.2 and BA.5 omicron differ immunologically from both BA.1 omicron and pre-omicron variants.
Rössler Annika et al. Nature communications 2022 12 (1) 7701Here, we characterized neutralization profiles against the BA.2 and BA.5 omicron sub-variants in plasma samples from individuals with different history of exposures to infection/vaccination and found that unvaccinated individuals after a single exposure to BA.2 had limited cross-neutralizing antibodies to pre-omicron variants and to BA.1. Consequently, our antigenic map including all Variants of Concern and BA.1, BA.2 and BA.5 omicron sub-variants, showed that all omicron sub-variants are distinct to pre-omicron variants, but that the three omicron variants are also antigenically distinct from each other. -
ACE2 polymorphisms impact COVID-19 severity in obese patients.
Jalaleddine Nour et al. Scientific reports 2022 12 (1) 21491A strong association between obesity and COVID-19 complications and a lack of prognostic factors that explain the unpredictable severity among these patients still exist despite the various vaccination programs. The expression of angiotensin converting enzyme 2 (ACE2), the main receptor for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is enhanced in obese individuals. The occurrence of frequent genetic single nucleotide polymorphisms (SNPs) in ACE2 is suggested to increase COVID-19 severity. -
Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19–Associated Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompetent Adults — VISION Network, Nine States, September–November 2022
MW Tenforde et al, CDC MMWR, December 16, 2022Bivalent mRNA COVID-19 booster doses containing an Omicron BA.4/BA.5 sublineage component were recommended on September 1, 2022. The effectiveness of these updated vaccines against COVID-19–associated medical encounters has not been established. Bivalent booster doses provided additional protection against COVID-19–associated emergency department/urgent care encounters and hospitalizations in persons who previously received 2, 3, or 4 monovalent vaccine doses. Because of waning of monovalent vaccine-conferred immunity, relative effectiveness of bivalent vaccines was higher with increased time since the previous monovalent dose. -
SARS-CoV-2 diagnostic testing rates determine the sensitivity of genomic surveillance programs.
Han Alvin X et al. medRxiv : the preprint server for health sciences 2022 12We simulated COVID-19 epidemics in a prototypical LMIC to investigate how testing rates, sampling strategies, and sequencing proportions jointly impact surveillance outcomes and showed that low testing rates and spatiotemporal biases delay time-to-detection of new variants by weeks-to-months and can lead to unreliable estimates of variant prevalence even when the proportion of samples sequenced is increased. -
Defining post-acute COVID-19 syndrome (PACS) by an epigenetic biosignature in peripheral blood mononuclear cells.
Nikesjö Frida et al. Clinical epigenetics 2022 12 (1) 172We compared DNAm patterns in patients with PACS with those in controls and in healthy COVID-19 convalescents and found a unique DNAm signature in PACS patients. This signature unravelled modified pathways that regulate angiotensin II and muscarinic receptor signalling and protein-protein interaction networks that have bearings on vesicle formation and mitochondrial function. -
Multi-omics identify falling LRRC15 as a COVID-19 severity marker and persistent pro-thrombotic signals in convalescence.
Gisby Jack S et al. Nature communications 2022 12 (1) 7775Using plasma proteomics, and RNA-sequencing and flow cytometry of immune cells, we identify transcriptomic and proteomic signatures of COVID-19 severity, and find distinct temporal molecular profiles in patients with severe disease. Supervised learning reveals that the plasma proteome is a superior indicator of clinical severity than the PBMC transcriptome. We show that a decreasing trajectory of plasma LRRC15, a proposed co-receptor for SARS-CoV-2, is associated with a more severe clinical course. -
Estimating the transmission dynamics of Omicron in Beijing, November to December 2022
K Leung et al, MEDRXIV, December 16, 2022 -
Prognosis of Myocarditis Developing After mRNA COVID-19 Vaccination Compared With Viral Myocarditis.
Lai Francisco Tsz Tsun et al. Journal of the American College of Cardiology 2022 12 (24) 2255-2265A total of 866 patients were included for analysis. Over the follow-up period, 1 death (1.0%) of 104 patients with postvaccination myocarditis and 84 deaths (11.0%) of 762 patients with viral infection–related myocarditis were identified. This study found a significantly lower rate of mortality among individuals with myocarditis after mRNA vaccination compared with those with viral infection–related myocarditis. Prognosis of this iatrogenic condition may be less severe than naturally acquired viral infection–related myocarditis. -
Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19–Associated Hospitalization Among Immunocompetent Adults Aged =65 Years — IVY Network, 18 States, September 8–November 30, 2022
D Surie et al, MMWR, December 16, 2022Immunity from monovalent COVID-19 mRNA vaccination wanes over time. A bivalent COVID-19 mRNA booster dose is recommended for all eligible persons; however, little is known about its effectiveness against COVID-19 hospitalization. Among immunocompetent adults aged =65 years hospitalized in the multistate IVY Network, a bivalent booster dose provided 73% additional protection against COVID-19 hospitalization compared with past monovalent mRNA vaccination only. -
Effectiveness of fourth dose of COVID-19 vaccine against the Omicron variant compared with no vaccination.
Zeng Jessie et al. International journal of epidemiology 2022 12A fourth dose of the BNT162b2 vaccine appears to restore, if not boost even more (although uncertainty intervals overlap), the protection conferred by a third dose at an equivalent time post-vaccination. Our estimates are likely to be of interest to the public and policy makers weighing up the benefits and costs of a fourth dose in the context of waning immunity derived from triple vaccination who are asking the question: ‘Does a fourth dose return one to the same, or even higher, protection that one had shortly after a third dose? -
Evaluation of two different concentration methods for surveillance of human viruses in sewage and their effects on SARS-CoV-2 sequencing.
Girón-Guzmán Inés et al. The Science of the total environment 2022 12 160914 -
Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution
Y Cao et al, Nature, December 19, 2022To delineate the origin of the convergent evolution, we determined the escape mutation profiles and neutralization activity of monoclonal antibodies (mAbs) isolated from BA.2 and BA.5 breakthrough-infection convalescents 2,3. Due to humoral immune imprinting, BA.2 and especially BA.5 breakthrough infection reduced the diversity of the NAb binding sites and increased proportions of non-neutralizing antibody clones, which in turn focused humoral immune pressure and promoted convergent evolution in the RBD. These results suggest current herd immunity and BA.5 vaccine boosters may not efficiently prevent the infection of Omicron convergent variants. -
Digital PCR discriminates between SARS-CoV-2 Omicron variants and immune escape mutations
SC Holland et al, MEDRXIV, December 19, 2022We demonstrate their validity on 596 clinical saliva specimens that were sequence-verified using Illumina whole genome sequencing. Next, we developed dPCR assays for spike mutations R346T, K444T, N460K, F486V, and F486S mutations that are associated with host immune evasion and reduced therapeutic monoclonal antibody efficacy. We demonstrate that these assays can be run individually or multiplexed to detect the presence of up to 4 SNPs in a single assay. -
Infectious diseases genomic surveillance capacity in the Caribbean: A retrospective analysis of SARS-CoV-2
MA Ber Lucien et al, Lancet Regional Health, December 19, 2022As of August 6, 2022, the number of SARS-CoV-2 sequences from the Caribbean are underrepresented with only 40,190 (1.07%) of the over 3.76 million documented cases sequenced, which is further exacerbated by a disparity based not only on the country's income but also on its political status (sovereign country versus dependent or integrated) and accessibility to sequencing technologies. -
Inborn errors of OAS–RNase L in SARS-CoV-2–related multisystem inflammatory syndrome in children
D Lee et al, Science, December 20, 2022Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic dsRNA-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the ssRNA-degrading RNase L. Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNASEL deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or SARS-CoV-2 stimulation. -
The role of angiotensin I converting enzyme insertion/deletion polymorphism in the severity and outcomes of COVID-19 patients.
Rezaei Mitra et al. Frontiers in genetics 2022 12 1035796 -
Cross-Clade Memory Immunity in Adults Following SARS-CoV-1 Infection in 2003.
Ng Rita W Y et al. JAMA network open 2022 12 (12) e2247723Does SARS-CoV-1 infection confer long-lasting memory immunity against the closely related SARS-CoV-2? This cohort study of 12 participants with SARS-CoV-1 infection in 2003 showed robust antibody response at 7 days after receiving 1 dose of either inactivated or messenger RNA COVID-19 vaccine. After 2 doses, those with past SARS-CoV-1 infection developed significantly higher levels of neutralizing antibodies against wild-type SARS-CoV-2 and variants of concern compared with 40 sex- and age-matched SARS-CoV-1–naive controls. -
Evolution of long-term vaccine induced and hybrid immunity in healthcare workers after different COVID-19 vaccination regimens: a longitudinal observational cohort study
SC Moore et al, MEDRXIV, December 21, 2022 -
Neutralization against BA.2.75.2, BQ.1.1, and XBB from mRNA Bivalent Booster
ME Davis-Gardner et al, NEJM, December 21, 2022
Non-Genomics Precision Health Studies
-
Estimated BNT162b2 Vaccine Effectiveness Against Infection With Delta and Omicron Variants Among US Children 5 to 11 Years of Age.
Khan Farid L et al. JAMA network open 2022 12 (12) e2246915The VE of 2 doses of BNT162b2 against Delta was 85% (95% CI, 80%-89%; median follow-up, 1 month) compared with the Omicron period (20% [95% CI, 17%-23%]; median follow-up, 4 months). The adjusted VE of 2 doses against Omicron at less than 3 months was 39% (95% CI, 36%-42%), and at 3 months or more, it was -1% (95% CI, -6% to 3%). The study suggests that, among children aged 5 to 11 years, 2 doses of BNT162b2 provided modest short-term protection against Omicron infection that was higher for those with prior infection; however, VE waned after approximately 3 months in all children. -
BA.2 and BA.5 omicron differ immunologically from both BA.1 omicron and pre-omicron variants.
Rössler Annika et al. Nature communications 2022 12 (1) 7701Here, we characterized neutralization profiles against the BA.2 and BA.5 omicron sub-variants in plasma samples from individuals with different history of exposures to infection/vaccination and found that unvaccinated individuals after a single exposure to BA.2 had limited cross-neutralizing antibodies to pre-omicron variants and to BA.1. Consequently, our antigenic map including all Variants of Concern and BA.1, BA.2 and BA.5 omicron sub-variants, showed that all omicron sub-variants are distinct to pre-omicron variants, but that the three omicron variants are also antigenically distinct from each other. -
ACE2 polymorphisms impact COVID-19 severity in obese patients.
Jalaleddine Nour et al. Scientific reports 2022 12 (1) 21491A strong association between obesity and COVID-19 complications and a lack of prognostic factors that explain the unpredictable severity among these patients still exist despite the various vaccination programs. The expression of angiotensin converting enzyme 2 (ACE2), the main receptor for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is enhanced in obese individuals. The occurrence of frequent genetic single nucleotide polymorphisms (SNPs) in ACE2 is suggested to increase COVID-19 severity. -
Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19–Associated Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompetent Adults — VISION Network, Nine States, September–November 2022
MW Tenforde et al, CDC MMWR, December 16, 2022Bivalent mRNA COVID-19 booster doses containing an Omicron BA.4/BA.5 sublineage component were recommended on September 1, 2022. The effectiveness of these updated vaccines against COVID-19–associated medical encounters has not been established. Bivalent booster doses provided additional protection against COVID-19–associated emergency department/urgent care encounters and hospitalizations in persons who previously received 2, 3, or 4 monovalent vaccine doses. Because of waning of monovalent vaccine-conferred immunity, relative effectiveness of bivalent vaccines was higher with increased time since the previous monovalent dose. -
SARS-CoV-2 diagnostic testing rates determine the sensitivity of genomic surveillance programs.
Han Alvin X et al. medRxiv : the preprint server for health sciences 2022 12We simulated COVID-19 epidemics in a prototypical LMIC to investigate how testing rates, sampling strategies, and sequencing proportions jointly impact surveillance outcomes and showed that low testing rates and spatiotemporal biases delay time-to-detection of new variants by weeks-to-months and can lead to unreliable estimates of variant prevalence even when the proportion of samples sequenced is increased. -
Defining post-acute COVID-19 syndrome (PACS) by an epigenetic biosignature in peripheral blood mononuclear cells.
Nikesjö Frida et al. Clinical epigenetics 2022 12 (1) 172We compared DNAm patterns in patients with PACS with those in controls and in healthy COVID-19 convalescents and found a unique DNAm signature in PACS patients. This signature unravelled modified pathways that regulate angiotensin II and muscarinic receptor signalling and protein-protein interaction networks that have bearings on vesicle formation and mitochondrial function. -
Multi-omics identify falling LRRC15 as a COVID-19 severity marker and persistent pro-thrombotic signals in convalescence.
Gisby Jack S et al. Nature communications 2022 12 (1) 7775Using plasma proteomics, and RNA-sequencing and flow cytometry of immune cells, we identify transcriptomic and proteomic signatures of COVID-19 severity, and find distinct temporal molecular profiles in patients with severe disease. Supervised learning reveals that the plasma proteome is a superior indicator of clinical severity than the PBMC transcriptome. We show that a decreasing trajectory of plasma LRRC15, a proposed co-receptor for SARS-CoV-2, is associated with a more severe clinical course. -
Estimating the transmission dynamics of Omicron in Beijing, November to December 2022
K Leung et al, MEDRXIV, December 16, 2022 -
Prognosis of Myocarditis Developing After mRNA COVID-19 Vaccination Compared With Viral Myocarditis.
Lai Francisco Tsz Tsun et al. Journal of the American College of Cardiology 2022 12 (24) 2255-2265A total of 866 patients were included for analysis. Over the follow-up period, 1 death (1.0%) of 104 patients with postvaccination myocarditis and 84 deaths (11.0%) of 762 patients with viral infection–related myocarditis were identified. This study found a significantly lower rate of mortality among individuals with myocarditis after mRNA vaccination compared with those with viral infection–related myocarditis. Prognosis of this iatrogenic condition may be less severe than naturally acquired viral infection–related myocarditis. -
Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19–Associated Hospitalization Among Immunocompetent Adults Aged =65 Years — IVY Network, 18 States, September 8–November 30, 2022
D Surie et al, MMWR, December 16, 2022Immunity from monovalent COVID-19 mRNA vaccination wanes over time. A bivalent COVID-19 mRNA booster dose is recommended for all eligible persons; however, little is known about its effectiveness against COVID-19 hospitalization. Among immunocompetent adults aged =65 years hospitalized in the multistate IVY Network, a bivalent booster dose provided 73% additional protection against COVID-19 hospitalization compared with past monovalent mRNA vaccination only. -
Effectiveness of fourth dose of COVID-19 vaccine against the Omicron variant compared with no vaccination.
Zeng Jessie et al. International journal of epidemiology 2022 12A fourth dose of the BNT162b2 vaccine appears to restore, if not boost even more (although uncertainty intervals overlap), the protection conferred by a third dose at an equivalent time post-vaccination. Our estimates are likely to be of interest to the public and policy makers weighing up the benefits and costs of a fourth dose in the context of waning immunity derived from triple vaccination who are asking the question: ‘Does a fourth dose return one to the same, or even higher, protection that one had shortly after a third dose? -
Evaluation of two different concentration methods for surveillance of human viruses in sewage and their effects on SARS-CoV-2 sequencing.
Girón-Guzmán Inés et al. The Science of the total environment 2022 12 160914 -
Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution
Y Cao et al, Nature, December 19, 2022To delineate the origin of the convergent evolution, we determined the escape mutation profiles and neutralization activity of monoclonal antibodies (mAbs) isolated from BA.2 and BA.5 breakthrough-infection convalescents 2,3. Due to humoral immune imprinting, BA.2 and especially BA.5 breakthrough infection reduced the diversity of the NAb binding sites and increased proportions of non-neutralizing antibody clones, which in turn focused humoral immune pressure and promoted convergent evolution in the RBD. These results suggest current herd immunity and BA.5 vaccine boosters may not efficiently prevent the infection of Omicron convergent variants. -
Digital PCR discriminates between SARS-CoV-2 Omicron variants and immune escape mutations
SC Holland et al, MEDRXIV, December 19, 2022We demonstrate their validity on 596 clinical saliva specimens that were sequence-verified using Illumina whole genome sequencing. Next, we developed dPCR assays for spike mutations R346T, K444T, N460K, F486V, and F486S mutations that are associated with host immune evasion and reduced therapeutic monoclonal antibody efficacy. We demonstrate that these assays can be run individually or multiplexed to detect the presence of up to 4 SNPs in a single assay. -
Infectious diseases genomic surveillance capacity in the Caribbean: A retrospective analysis of SARS-CoV-2
MA Ber Lucien et al, Lancet Regional Health, December 19, 2022As of August 6, 2022, the number of SARS-CoV-2 sequences from the Caribbean are underrepresented with only 40,190 (1.07%) of the over 3.76 million documented cases sequenced, which is further exacerbated by a disparity based not only on the country's income but also on its political status (sovereign country versus dependent or integrated) and accessibility to sequencing technologies. -
Inborn errors of OAS–RNase L in SARS-CoV-2–related multisystem inflammatory syndrome in children
D Lee et al, Science, December 20, 2022Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic dsRNA-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the ssRNA-degrading RNase L. Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNASEL deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or SARS-CoV-2 stimulation. -
The role of angiotensin I converting enzyme insertion/deletion polymorphism in the severity and outcomes of COVID-19 patients.
Rezaei Mitra et al. Frontiers in genetics 2022 12 1035796 -
Cross-Clade Memory Immunity in Adults Following SARS-CoV-1 Infection in 2003.
Ng Rita W Y et al. JAMA network open 2022 12 (12) e2247723Does SARS-CoV-1 infection confer long-lasting memory immunity against the closely related SARS-CoV-2? This cohort study of 12 participants with SARS-CoV-1 infection in 2003 showed robust antibody response at 7 days after receiving 1 dose of either inactivated or messenger RNA COVID-19 vaccine. After 2 doses, those with past SARS-CoV-1 infection developed significantly higher levels of neutralizing antibodies against wild-type SARS-CoV-2 and variants of concern compared with 40 sex- and age-matched SARS-CoV-1–naive controls. -
Evolution of long-term vaccine induced and hybrid immunity in healthcare workers after different COVID-19 vaccination regimens: a longitudinal observational cohort study
SC Moore et al, MEDRXIV, December 21, 2022 -
Neutralization against BA.2.75.2, BQ.1.1, and XBB from mRNA Bivalent Booster
ME Davis-Gardner et al, NEJM, December 21, 2022
News, Reviews and Commentaries
-
Estimated BNT162b2 Vaccine Effectiveness Against Infection With Delta and Omicron Variants Among US Children 5 to 11 Years of Age.
Khan Farid L et al. JAMA network open 2022 12 (12) e2246915The VE of 2 doses of BNT162b2 against Delta was 85% (95% CI, 80%-89%; median follow-up, 1 month) compared with the Omicron period (20% [95% CI, 17%-23%]; median follow-up, 4 months). The adjusted VE of 2 doses against Omicron at less than 3 months was 39% (95% CI, 36%-42%), and at 3 months or more, it was -1% (95% CI, -6% to 3%). The study suggests that, among children aged 5 to 11 years, 2 doses of BNT162b2 provided modest short-term protection against Omicron infection that was higher for those with prior infection; however, VE waned after approximately 3 months in all children. -
BA.2 and BA.5 omicron differ immunologically from both BA.1 omicron and pre-omicron variants.
Rössler Annika et al. Nature communications 2022 12 (1) 7701Here, we characterized neutralization profiles against the BA.2 and BA.5 omicron sub-variants in plasma samples from individuals with different history of exposures to infection/vaccination and found that unvaccinated individuals after a single exposure to BA.2 had limited cross-neutralizing antibodies to pre-omicron variants and to BA.1. Consequently, our antigenic map including all Variants of Concern and BA.1, BA.2 and BA.5 omicron sub-variants, showed that all omicron sub-variants are distinct to pre-omicron variants, but that the three omicron variants are also antigenically distinct from each other. -
ACE2 polymorphisms impact COVID-19 severity in obese patients.
Jalaleddine Nour et al. Scientific reports 2022 12 (1) 21491A strong association between obesity and COVID-19 complications and a lack of prognostic factors that explain the unpredictable severity among these patients still exist despite the various vaccination programs. The expression of angiotensin converting enzyme 2 (ACE2), the main receptor for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is enhanced in obese individuals. The occurrence of frequent genetic single nucleotide polymorphisms (SNPs) in ACE2 is suggested to increase COVID-19 severity. -
Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19–Associated Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompetent Adults — VISION Network, Nine States, September–November 2022
MW Tenforde et al, CDC MMWR, December 16, 2022Bivalent mRNA COVID-19 booster doses containing an Omicron BA.4/BA.5 sublineage component were recommended on September 1, 2022. The effectiveness of these updated vaccines against COVID-19–associated medical encounters has not been established. Bivalent booster doses provided additional protection against COVID-19–associated emergency department/urgent care encounters and hospitalizations in persons who previously received 2, 3, or 4 monovalent vaccine doses. Because of waning of monovalent vaccine-conferred immunity, relative effectiveness of bivalent vaccines was higher with increased time since the previous monovalent dose. -
SARS-CoV-2 diagnostic testing rates determine the sensitivity of genomic surveillance programs.
Han Alvin X et al. medRxiv : the preprint server for health sciences 2022 12We simulated COVID-19 epidemics in a prototypical LMIC to investigate how testing rates, sampling strategies, and sequencing proportions jointly impact surveillance outcomes and showed that low testing rates and spatiotemporal biases delay time-to-detection of new variants by weeks-to-months and can lead to unreliable estimates of variant prevalence even when the proportion of samples sequenced is increased. -
Defining post-acute COVID-19 syndrome (PACS) by an epigenetic biosignature in peripheral blood mononuclear cells.
Nikesjö Frida et al. Clinical epigenetics 2022 12 (1) 172We compared DNAm patterns in patients with PACS with those in controls and in healthy COVID-19 convalescents and found a unique DNAm signature in PACS patients. This signature unravelled modified pathways that regulate angiotensin II and muscarinic receptor signalling and protein-protein interaction networks that have bearings on vesicle formation and mitochondrial function. -
Multi-omics identify falling LRRC15 as a COVID-19 severity marker and persistent pro-thrombotic signals in convalescence.
Gisby Jack S et al. Nature communications 2022 12 (1) 7775Using plasma proteomics, and RNA-sequencing and flow cytometry of immune cells, we identify transcriptomic and proteomic signatures of COVID-19 severity, and find distinct temporal molecular profiles in patients with severe disease. Supervised learning reveals that the plasma proteome is a superior indicator of clinical severity than the PBMC transcriptome. We show that a decreasing trajectory of plasma LRRC15, a proposed co-receptor for SARS-CoV-2, is associated with a more severe clinical course. -
Estimating the transmission dynamics of Omicron in Beijing, November to December 2022
K Leung et al, MEDRXIV, December 16, 2022 -
Prognosis of Myocarditis Developing After mRNA COVID-19 Vaccination Compared With Viral Myocarditis.
Lai Francisco Tsz Tsun et al. Journal of the American College of Cardiology 2022 12 (24) 2255-2265A total of 866 patients were included for analysis. Over the follow-up period, 1 death (1.0%) of 104 patients with postvaccination myocarditis and 84 deaths (11.0%) of 762 patients with viral infection–related myocarditis were identified. This study found a significantly lower rate of mortality among individuals with myocarditis after mRNA vaccination compared with those with viral infection–related myocarditis. Prognosis of this iatrogenic condition may be less severe than naturally acquired viral infection–related myocarditis. -
Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19–Associated Hospitalization Among Immunocompetent Adults Aged =65 Years — IVY Network, 18 States, September 8–November 30, 2022
D Surie et al, MMWR, December 16, 2022Immunity from monovalent COVID-19 mRNA vaccination wanes over time. A bivalent COVID-19 mRNA booster dose is recommended for all eligible persons; however, little is known about its effectiveness against COVID-19 hospitalization. Among immunocompetent adults aged =65 years hospitalized in the multistate IVY Network, a bivalent booster dose provided 73% additional protection against COVID-19 hospitalization compared with past monovalent mRNA vaccination only. -
Effectiveness of fourth dose of COVID-19 vaccine against the Omicron variant compared with no vaccination.
Zeng Jessie et al. International journal of epidemiology 2022 12A fourth dose of the BNT162b2 vaccine appears to restore, if not boost even more (although uncertainty intervals overlap), the protection conferred by a third dose at an equivalent time post-vaccination. Our estimates are likely to be of interest to the public and policy makers weighing up the benefits and costs of a fourth dose in the context of waning immunity derived from triple vaccination who are asking the question: ‘Does a fourth dose return one to the same, or even higher, protection that one had shortly after a third dose? -
Evaluation of two different concentration methods for surveillance of human viruses in sewage and their effects on SARS-CoV-2 sequencing.
Girón-Guzmán Inés et al. The Science of the total environment 2022 12 160914 -
Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution
Y Cao et al, Nature, December 19, 2022To delineate the origin of the convergent evolution, we determined the escape mutation profiles and neutralization activity of monoclonal antibodies (mAbs) isolated from BA.2 and BA.5 breakthrough-infection convalescents 2,3. Due to humoral immune imprinting, BA.2 and especially BA.5 breakthrough infection reduced the diversity of the NAb binding sites and increased proportions of non-neutralizing antibody clones, which in turn focused humoral immune pressure and promoted convergent evolution in the RBD. These results suggest current herd immunity and BA.5 vaccine boosters may not efficiently prevent the infection of Omicron convergent variants. -
Digital PCR discriminates between SARS-CoV-2 Omicron variants and immune escape mutations
SC Holland et al, MEDRXIV, December 19, 2022We demonstrate their validity on 596 clinical saliva specimens that were sequence-verified using Illumina whole genome sequencing. Next, we developed dPCR assays for spike mutations R346T, K444T, N460K, F486V, and F486S mutations that are associated with host immune evasion and reduced therapeutic monoclonal antibody efficacy. We demonstrate that these assays can be run individually or multiplexed to detect the presence of up to 4 SNPs in a single assay. -
Infectious diseases genomic surveillance capacity in the Caribbean: A retrospective analysis of SARS-CoV-2
MA Ber Lucien et al, Lancet Regional Health, December 19, 2022As of August 6, 2022, the number of SARS-CoV-2 sequences from the Caribbean are underrepresented with only 40,190 (1.07%) of the over 3.76 million documented cases sequenced, which is further exacerbated by a disparity based not only on the country's income but also on its political status (sovereign country versus dependent or integrated) and accessibility to sequencing technologies. -
Inborn errors of OAS–RNase L in SARS-CoV-2–related multisystem inflammatory syndrome in children
D Lee et al, Science, December 20, 2022Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic dsRNA-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the ssRNA-degrading RNase L. Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNASEL deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or SARS-CoV-2 stimulation. -
The role of angiotensin I converting enzyme insertion/deletion polymorphism in the severity and outcomes of COVID-19 patients.
Rezaei Mitra et al. Frontiers in genetics 2022 12 1035796 -
Cross-Clade Memory Immunity in Adults Following SARS-CoV-1 Infection in 2003.
Ng Rita W Y et al. JAMA network open 2022 12 (12) e2247723Does SARS-CoV-1 infection confer long-lasting memory immunity against the closely related SARS-CoV-2? This cohort study of 12 participants with SARS-CoV-1 infection in 2003 showed robust antibody response at 7 days after receiving 1 dose of either inactivated or messenger RNA COVID-19 vaccine. After 2 doses, those with past SARS-CoV-1 infection developed significantly higher levels of neutralizing antibodies against wild-type SARS-CoV-2 and variants of concern compared with 40 sex- and age-matched SARS-CoV-1–naive controls. -
Evolution of long-term vaccine induced and hybrid immunity in healthcare workers after different COVID-19 vaccination regimens: a longitudinal observational cohort study
SC Moore et al, MEDRXIV, December 21, 2022 -
Neutralization against BA.2.75.2, BQ.1.1, and XBB from mRNA Bivalent Booster
ME Davis-Gardner et al, NEJM, December 21, 2022
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- Page last updated:Apr 25, 2024
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