SARS-CoV-2 has evolved variants with substitutions in the spike receptor-binding domain (RBD) that impact its affinity for ACE2 receptor and recognition by antibodies. These substitutions could also shape future evolution by modulating the effects of mutations at other sites-a phenomenon called epistasis. To investigate this possibility, we performed deep mutational scans to measure the effects on ACE2 binding of all single amino-acid mutations in the Wuhan-Hu-1, Alpha, Beta, Delta, and Eta variant RBDs. Some substitutions, most prominently N501Y, cause epistatic shifts in the effects of mutations at other sites. These epistatic shifts shape subsequent evolutionary change.

In this longitudinal cohort of participants, most of whom had symptomatic, nonsevere Covid-19 infection, the viral decay kinetics were similar with omicron infection and delta infection. Although vaccination has been shown to reduce the incidence of infection and the severity of disease, we did not find large differences in the median duration of viral shedding among participants who were unvaccinated, those who were vaccinated but not boosted, and those who were vaccinated and boosted.

Using data from the largest health care organization in Israel, we identified a cohort of children 5 to 11 years of age who were vaccinated on or after November 23, 2021, and matched them with unvaccinated controls to estimate the vaccine effectiveness of BNT162b2 among newly vaccinated children during the omicron wave. Our findings suggest that as omicron was becoming the dominant variant, two doses of the BNT162b2 messenger RNA vaccine provided moderate protection against documented SARS-CoV-2 infection and symptomatic Covid-19 in children 5 to 11 years of age.

Over the short term, heterologous boosting with the beta-adjuvanted MVB.1.351 vaccine resulted in a higher neutralizing-antibody response against the beta variant as well as against the original strain and the delta and omicron BA.1 variants than did the mRNA vaccine BNT162b2 or the MVD614 formulation. The use of new vaccines that contain beta spike protein may be an interesting strategy for broader protection against SARS-CoV-2 variants.

Based on viral microneutralization assays, we evaluated in 90 individuals the impact on antibody neutralization induction, against Omicron variant, by a booster dose of BNT162b2 mRNA vaccine after the CoronaVac primary vaccination scheme. Here we show that the percentage of seroconverted individuals 30 and 60 days after CoronaVac scheme was 16.6% and 10%, respectively. After booster dose administration, the seroconvertion rate increased to 76.6%. The neutralization mean titer against Omicron in the CoronaVac protocol decreased over time, but after the booster dose, the mean titer increased 43.1 times.

Peripheral blood samples were recruited from 43 confirmed MIS-C patients. 69 non-COVID-19 pediatric samples and 15 COVID-19 pediatric samples without MIS-C were used as controls. The cases in the two groups were mixed and divided into discovery (MIS-C = 29 and non-MIS-C = 56) and validation (MIS-C = 14 and non-MIS-C = 28) cohorts, and balanced for age, gender and ethnic background. We interrogated 850,000 CpG sites of the human genome for DNA methylation variants. The DNA methylation content of 33 CpG loci was linked with the presence of MIS-C. Of these sites, 18 (54.5%) were located in described genes. The top candidate gene was the immune T-cell mediator ZEB2; and others highly ranked candidates included the regulator of natural killer cell functional competence SH2D1B; VWA8, which contains a domain of the Von Willebrand factor A involved in the pediatric hemostasis disease; and human leukocyte antigen complex member HLA-DRB1; in addition to pro-inflammatory genes such as CUL2 and AIM2. The identified loci were used to construct a DNA methylation profile (EPIMISC) that was associated with MIS-C in both cohorts.

We included 9560 patients followed for a median of 61 (interquartile range = 34-88) days since COVID-19 diagnosis. The risk of severe COVID-19 increased with age and obesity, and was higher in men, current smokers, those living in socio-economically deprived areas, those with historic immunosuppressant use and individuals with morbidities and higher co-morbidity count. An optimized PRS, enriched for single-nucleotide polymorphisms in multiple immune-related pathways, including the 'oligoadenylate synthetase antiviral response' and 'interleukin-10 signalling' pathways, was associated with severe COVID-19 (adjusted odds ratio 1.32, 95% CI 1.11-1.58 for the highest compared with the lowest PRS quintile).

In this longitudinal observational study conducted among health care workers with SARS-CoV-2 infections not requiring hospitalization, 2 or 3 doses of vaccine, compared with no vaccination, were associated with lower long COVID prevalence. Study limitations include that symptoms and duration were self-reported, and causality cannot be inferred.

We aimed to investigate whether SARS-CoV-2 variants were associated with the proportion of children with croup, as well as hospital and intensive care unit (ICU) admissions and racemic epinephrine (RE) treatment. The results of this cross-sectional study expand on recent single-center studies1,2 showing that hospitalizations for COVID-19–related croup increased after the onset of the Omicron variant.

Varying SARS-CoV-2 genomics capacity and capability levels have been established in public health laboratories across different Australian states and territories. Therefore, laboratories performing SARS-CoV-2 WGS for public health purposes are recommended to participate in an external proficiency testing program (PTP). This study describes the development of a SARS-CoV-2 WGS PTP. The PTP assessed the performance of laboratories while providing valuable insight into the current state of SARS-CoV-2 genomics in public health across Australia.

The total concentrations of N1 and N2 genes ranged from 714.85 to 7145.98 gc/L and 820.47 to 6219.05 gc/L, respectively, which were strongly correlated with the 7-day moving average of total daily COVID-19 cases in the associated areas, after 5 weeks of the viral measurement. The results indicate a potential 5-week lag time of wastewater surveillance preceding COVID-19 incidence for the Detroit metropolitan area. Four statistical models were established to analyze the relationship between SARS-CoV-2 concentrations in wastewater and COVID-19 incidence in the study areas.

We report findings from a systematic antigenic analysis of these surging Omicron subvariants. BA.2.12.1 is only modestly (1.8-fold) more resistant to sera from vaccinated and boosted individuals than BA.2. However, BA.4/5 is substantially (4.2-fold) more resistant and thus more likely to lead to vaccine breakthrough infections. Mutation at spike residue L452 found in both BA.2.12.1 and BA.4/5 facilitates escape from some antibodies directed to the so-called class 2 and 3 regions of the receptor-binding domain3. The F486V mutation found in BA.4/5 facilitates escape from certain class 1 and 2 antibodies but compromises the spike affinity for the viral receptor.

Molecular tests are highly reliable and sensitive but lack portability and are not simple to use; conversely, easy-to-use antigenic tests still lack high performance. BioScreen combines single-molecule sensitivity and outstanding reliability with ultraportability and simplicity of use. This digital platform is capable of artificial intelligence–based binary classification at the limit of identification of a single marker/virus in 0.1 ml. The diagnostic sensitivity, specificity, and accuracy reach 99.2% as validated through 240 assays, including a pilot clinical trial.

Using routine surveillance PCR tests as with S gene target failure as a proxy for Omicron detection, the authors found evidence that this emerging variant had almost entirely replaced the Delta variant in England within a month of its introduction. Omicron’s replacement of Delta was faster in individuals who had received vaccine boosters, suggesting that immune escape of the variant may have contributed to its success.

We found that neutralizing antibody titers increased with the increasing interval between the second and third doses, especially against the omicron subvariants. In vaccinees who had an interval of 4 to 6 months between the second and third doses, neutralizing antibody titers were higher by nearly a factor of 10 against the PT isolate and by a factor of approximately 30 against all omicron subvariants, as compared with vaccinees who had a 1-month interval between doses (P<0.001) (Table S3). Vaccinees in the prolonged-interval subgroup were 100% seropositive against all the omicron subvariants that were tested (Fig. S5).

SARS-CoV-2 has evolved variants with substitutions in the spike receptor-binding domain (RBD) that impact its affinity for ACE2 receptor and recognition by antibodies. These substitutions could also shape future evolution by modulating the effects of mutations at other sites-a phenomenon called epistasis. To investigate this possibility, we performed deep mutational scans to measure the effects on ACE2 binding of all single amino-acid mutations in the Wuhan-Hu-1, Alpha, Beta, Delta, and Eta variant RBDs. Some substitutions, most prominently N501Y, cause epistatic shifts in the effects of mutations at other sites. These epistatic shifts shape subsequent evolutionary change.

In this longitudinal cohort of participants, most of whom had symptomatic, nonsevere Covid-19 infection, the viral decay kinetics were similar with omicron infection and delta infection. Although vaccination has been shown to reduce the incidence of infection and the severity of disease, we did not find large differences in the median duration of viral shedding among participants who were unvaccinated, those who were vaccinated but not boosted, and those who were vaccinated and boosted.

Using data from the largest health care organization in Israel, we identified a cohort of children 5 to 11 years of age who were vaccinated on or after November 23, 2021, and matched them with unvaccinated controls to estimate the vaccine effectiveness of BNT162b2 among newly vaccinated children during the omicron wave. Our findings suggest that as omicron was becoming the dominant variant, two doses of the BNT162b2 messenger RNA vaccine provided moderate protection against documented SARS-CoV-2 infection and symptomatic Covid-19 in children 5 to 11 years of age.

Over the short term, heterologous boosting with the beta-adjuvanted MVB.1.351 vaccine resulted in a higher neutralizing-antibody response against the beta variant as well as against the original strain and the delta and omicron BA.1 variants than did the mRNA vaccine BNT162b2 or the MVD614 formulation. The use of new vaccines that contain beta spike protein may be an interesting strategy for broader protection against SARS-CoV-2 variants.

Based on viral microneutralization assays, we evaluated in 90 individuals the impact on antibody neutralization induction, against Omicron variant, by a booster dose of BNT162b2 mRNA vaccine after the CoronaVac primary vaccination scheme. Here we show that the percentage of seroconverted individuals 30 and 60 days after CoronaVac scheme was 16.6% and 10%, respectively. After booster dose administration, the seroconvertion rate increased to 76.6%. The neutralization mean titer against Omicron in the CoronaVac protocol decreased over time, but after the booster dose, the mean titer increased 43.1 times.

Peripheral blood samples were recruited from 43 confirmed MIS-C patients. 69 non-COVID-19 pediatric samples and 15 COVID-19 pediatric samples without MIS-C were used as controls. The cases in the two groups were mixed and divided into discovery (MIS-C = 29 and non-MIS-C = 56) and validation (MIS-C = 14 and non-MIS-C = 28) cohorts, and balanced for age, gender and ethnic background. We interrogated 850,000 CpG sites of the human genome for DNA methylation variants. The DNA methylation content of 33 CpG loci was linked with the presence of MIS-C. Of these sites, 18 (54.5%) were located in described genes. The top candidate gene was the immune T-cell mediator ZEB2; and others highly ranked candidates included the regulator of natural killer cell functional competence SH2D1B; VWA8, which contains a domain of the Von Willebrand factor A involved in the pediatric hemostasis disease; and human leukocyte antigen complex member HLA-DRB1; in addition to pro-inflammatory genes such as CUL2 and AIM2. The identified loci were used to construct a DNA methylation profile (EPIMISC) that was associated with MIS-C in both cohorts.

We included 9560 patients followed for a median of 61 (interquartile range = 34-88) days since COVID-19 diagnosis. The risk of severe COVID-19 increased with age and obesity, and was higher in men, current smokers, those living in socio-economically deprived areas, those with historic immunosuppressant use and individuals with morbidities and higher co-morbidity count. An optimized PRS, enriched for single-nucleotide polymorphisms in multiple immune-related pathways, including the 'oligoadenylate synthetase antiviral response' and 'interleukin-10 signalling' pathways, was associated with severe COVID-19 (adjusted odds ratio 1.32, 95% CI 1.11-1.58 for the highest compared with the lowest PRS quintile).

In this longitudinal observational study conducted among health care workers with SARS-CoV-2 infections not requiring hospitalization, 2 or 3 doses of vaccine, compared with no vaccination, were associated with lower long COVID prevalence. Study limitations include that symptoms and duration were self-reported, and causality cannot be inferred.

We aimed to investigate whether SARS-CoV-2 variants were associated with the proportion of children with croup, as well as hospital and intensive care unit (ICU) admissions and racemic epinephrine (RE) treatment. The results of this cross-sectional study expand on recent single-center studies1,2 showing that hospitalizations for COVID-19–related croup increased after the onset of the Omicron variant.

Varying SARS-CoV-2 genomics capacity and capability levels have been established in public health laboratories across different Australian states and territories. Therefore, laboratories performing SARS-CoV-2 WGS for public health purposes are recommended to participate in an external proficiency testing program (PTP). This study describes the development of a SARS-CoV-2 WGS PTP. The PTP assessed the performance of laboratories while providing valuable insight into the current state of SARS-CoV-2 genomics in public health across Australia.

The total concentrations of N1 and N2 genes ranged from 714.85 to 7145.98 gc/L and 820.47 to 6219.05 gc/L, respectively, which were strongly correlated with the 7-day moving average of total daily COVID-19 cases in the associated areas, after 5 weeks of the viral measurement. The results indicate a potential 5-week lag time of wastewater surveillance preceding COVID-19 incidence for the Detroit metropolitan area. Four statistical models were established to analyze the relationship between SARS-CoV-2 concentrations in wastewater and COVID-19 incidence in the study areas.

We report findings from a systematic antigenic analysis of these surging Omicron subvariants. BA.2.12.1 is only modestly (1.8-fold) more resistant to sera from vaccinated and boosted individuals than BA.2. However, BA.4/5 is substantially (4.2-fold) more resistant and thus more likely to lead to vaccine breakthrough infections. Mutation at spike residue L452 found in both BA.2.12.1 and BA.4/5 facilitates escape from some antibodies directed to the so-called class 2 and 3 regions of the receptor-binding domain3. The F486V mutation found in BA.4/5 facilitates escape from certain class 1 and 2 antibodies but compromises the spike affinity for the viral receptor.

Molecular tests are highly reliable and sensitive but lack portability and are not simple to use; conversely, easy-to-use antigenic tests still lack high performance. BioScreen combines single-molecule sensitivity and outstanding reliability with ultraportability and simplicity of use. This digital platform is capable of artificial intelligence–based binary classification at the limit of identification of a single marker/virus in 0.1 ml. The diagnostic sensitivity, specificity, and accuracy reach 99.2% as validated through 240 assays, including a pilot clinical trial.

Using routine surveillance PCR tests as with S gene target failure as a proxy for Omicron detection, the authors found evidence that this emerging variant had almost entirely replaced the Delta variant in England within a month of its introduction. Omicron’s replacement of Delta was faster in individuals who had received vaccine boosters, suggesting that immune escape of the variant may have contributed to its success.

We found that neutralizing antibody titers increased with the increasing interval between the second and third doses, especially against the omicron subvariants. In vaccinees who had an interval of 4 to 6 months between the second and third doses, neutralizing antibody titers were higher by nearly a factor of 10 against the PT isolate and by a factor of approximately 30 against all omicron subvariants, as compared with vaccinees who had a 1-month interval between doses (P<0.001) (Table S3). Vaccinees in the prolonged-interval subgroup were 100% seropositive against all the omicron subvariants that were tested (Fig. S5).

SARS-CoV-2 has evolved variants with substitutions in the spike receptor-binding domain (RBD) that impact its affinity for ACE2 receptor and recognition by antibodies. These substitutions could also shape future evolution by modulating the effects of mutations at other sites-a phenomenon called epistasis. To investigate this possibility, we performed deep mutational scans to measure the effects on ACE2 binding of all single amino-acid mutations in the Wuhan-Hu-1, Alpha, Beta, Delta, and Eta variant RBDs. Some substitutions, most prominently N501Y, cause epistatic shifts in the effects of mutations at other sites. These epistatic shifts shape subsequent evolutionary change.

In this longitudinal cohort of participants, most of whom had symptomatic, nonsevere Covid-19 infection, the viral decay kinetics were similar with omicron infection and delta infection. Although vaccination has been shown to reduce the incidence of infection and the severity of disease, we did not find large differences in the median duration of viral shedding among participants who were unvaccinated, those who were vaccinated but not boosted, and those who were vaccinated and boosted.

Using data from the largest health care organization in Israel, we identified a cohort of children 5 to 11 years of age who were vaccinated on or after November 23, 2021, and matched them with unvaccinated controls to estimate the vaccine effectiveness of BNT162b2 among newly vaccinated children during the omicron wave. Our findings suggest that as omicron was becoming the dominant variant, two doses of the BNT162b2 messenger RNA vaccine provided moderate protection against documented SARS-CoV-2 infection and symptomatic Covid-19 in children 5 to 11 years of age.

Over the short term, heterologous boosting with the beta-adjuvanted MVB.1.351 vaccine resulted in a higher neutralizing-antibody response against the beta variant as well as against the original strain and the delta and omicron BA.1 variants than did the mRNA vaccine BNT162b2 or the MVD614 formulation. The use of new vaccines that contain beta spike protein may be an interesting strategy for broader protection against SARS-CoV-2 variants.

Based on viral microneutralization assays, we evaluated in 90 individuals the impact on antibody neutralization induction, against Omicron variant, by a booster dose of BNT162b2 mRNA vaccine after the CoronaVac primary vaccination scheme. Here we show that the percentage of seroconverted individuals 30 and 60 days after CoronaVac scheme was 16.6% and 10%, respectively. After booster dose administration, the seroconvertion rate increased to 76.6%. The neutralization mean titer against Omicron in the CoronaVac protocol decreased over time, but after the booster dose, the mean titer increased 43.1 times.

Peripheral blood samples were recruited from 43 confirmed MIS-C patients. 69 non-COVID-19 pediatric samples and 15 COVID-19 pediatric samples without MIS-C were used as controls. The cases in the two groups were mixed and divided into discovery (MIS-C = 29 and non-MIS-C = 56) and validation (MIS-C = 14 and non-MIS-C = 28) cohorts, and balanced for age, gender and ethnic background. We interrogated 850,000 CpG sites of the human genome for DNA methylation variants. The DNA methylation content of 33 CpG loci was linked with the presence of MIS-C. Of these sites, 18 (54.5%) were located in described genes. The top candidate gene was the immune T-cell mediator ZEB2; and others highly ranked candidates included the regulator of natural killer cell functional competence SH2D1B; VWA8, which contains a domain of the Von Willebrand factor A involved in the pediatric hemostasis disease; and human leukocyte antigen complex member HLA-DRB1; in addition to pro-inflammatory genes such as CUL2 and AIM2. The identified loci were used to construct a DNA methylation profile (EPIMISC) that was associated with MIS-C in both cohorts.

We included 9560 patients followed for a median of 61 (interquartile range = 34-88) days since COVID-19 diagnosis. The risk of severe COVID-19 increased with age and obesity, and was higher in men, current smokers, those living in socio-economically deprived areas, those with historic immunosuppressant use and individuals with morbidities and higher co-morbidity count. An optimized PRS, enriched for single-nucleotide polymorphisms in multiple immune-related pathways, including the 'oligoadenylate synthetase antiviral response' and 'interleukin-10 signalling' pathways, was associated with severe COVID-19 (adjusted odds ratio 1.32, 95% CI 1.11-1.58 for the highest compared with the lowest PRS quintile).

In this longitudinal observational study conducted among health care workers with SARS-CoV-2 infections not requiring hospitalization, 2 or 3 doses of vaccine, compared with no vaccination, were associated with lower long COVID prevalence. Study limitations include that symptoms and duration were self-reported, and causality cannot be inferred.

We aimed to investigate whether SARS-CoV-2 variants were associated with the proportion of children with croup, as well as hospital and intensive care unit (ICU) admissions and racemic epinephrine (RE) treatment. The results of this cross-sectional study expand on recent single-center studies1,2 showing that hospitalizations for COVID-19–related croup increased after the onset of the Omicron variant.

Varying SARS-CoV-2 genomics capacity and capability levels have been established in public health laboratories across different Australian states and territories. Therefore, laboratories performing SARS-CoV-2 WGS for public health purposes are recommended to participate in an external proficiency testing program (PTP). This study describes the development of a SARS-CoV-2 WGS PTP. The PTP assessed the performance of laboratories while providing valuable insight into the current state of SARS-CoV-2 genomics in public health across Australia.

The total concentrations of N1 and N2 genes ranged from 714.85 to 7145.98 gc/L and 820.47 to 6219.05 gc/L, respectively, which were strongly correlated with the 7-day moving average of total daily COVID-19 cases in the associated areas, after 5 weeks of the viral measurement. The results indicate a potential 5-week lag time of wastewater surveillance preceding COVID-19 incidence for the Detroit metropolitan area. Four statistical models were established to analyze the relationship between SARS-CoV-2 concentrations in wastewater and COVID-19 incidence in the study areas.

We report findings from a systematic antigenic analysis of these surging Omicron subvariants. BA.2.12.1 is only modestly (1.8-fold) more resistant to sera from vaccinated and boosted individuals than BA.2. However, BA.4/5 is substantially (4.2-fold) more resistant and thus more likely to lead to vaccine breakthrough infections. Mutation at spike residue L452 found in both BA.2.12.1 and BA.4/5 facilitates escape from some antibodies directed to the so-called class 2 and 3 regions of the receptor-binding domain3. The F486V mutation found in BA.4/5 facilitates escape from certain class 1 and 2 antibodies but compromises the spike affinity for the viral receptor.

Molecular tests are highly reliable and sensitive but lack portability and are not simple to use; conversely, easy-to-use antigenic tests still lack high performance. BioScreen combines single-molecule sensitivity and outstanding reliability with ultraportability and simplicity of use. This digital platform is capable of artificial intelligence–based binary classification at the limit of identification of a single marker/virus in 0.1 ml. The diagnostic sensitivity, specificity, and accuracy reach 99.2% as validated through 240 assays, including a pilot clinical trial.

Using routine surveillance PCR tests as with S gene target failure as a proxy for Omicron detection, the authors found evidence that this emerging variant had almost entirely replaced the Delta variant in England within a month of its introduction. Omicron’s replacement of Delta was faster in individuals who had received vaccine boosters, suggesting that immune escape of the variant may have contributed to its success.

We found that neutralizing antibody titers increased with the increasing interval between the second and third doses, especially against the omicron subvariants. In vaccinees who had an interval of 4 to 6 months between the second and third doses, neutralizing antibody titers were higher by nearly a factor of 10 against the PT isolate and by a factor of approximately 30 against all omicron subvariants, as compared with vaccinees who had a 1-month interval between doses (P<0.001) (Table S3). Vaccinees in the prolonged-interval subgroup were 100% seropositive against all the omicron subvariants that were tested (Fig. S5).