Here, we determined the levels of antibodies, antigen-specific B cells, against a recombinant GFP-tagged SARS-CoV-2 spike (S) protein and total T and NK cell subsets in subjects up to 20 days after the injection of the BNT162b2 (Pfizer-BioNTech) vaccine using a combined approach of serological and flow cytometry analyses. In former COVID-19 patients and highly responsive individuals, a significant increase of antibody production was detected, simultaneous with an expansion of antigen-specific B cell response and the total number of NK-T cells. Additionally, through a genetic screening of a specific polymorphic region internal to the 3' regulatory region 1 (3'RR1) of human immunoglobulin constant-gene (IgH) locus, we identified different single-nucleotide polymorphic (SNP) variants associated with either highly or lowly responsive subjects.

Higher hospitalization risk was found for infections with Gamma (HR 3.23, 95% CI 2.19–4.76), Beta (HR 3.03, 95% CI 1.68–5.47), Delta (HR 2.35, 95% CI 1.7–3.22), and Alpha (HR 1.61, 95% CI 1.28–2.03) compared to infections with an ancestral lineage. Following VOC infection, unvaccinated patients show a similar higher hospitalization risk, while vaccinated patients show no significant difference in risk, both when compared to unvaccinated, ancestral lineage cases. Interpretation: Infection with a VOC results in a higher hospitalization risk, with an active vaccination attenuating that risk.

Vaccination reduces the risk of delta variant infection and accelerates viral clearance. Nonetheless, fully vaccinated individuals with breakthrough infections have peak viral load similar to unvaccinated cases and can efficiently transmit infection in household settings, including to fully vaccinated contacts. Host–virus interactions early in infection may shape the entire viral trajectory.

Imagine being born naturally resistant to SARS-CoV-2, and never having to worry about contracting COVID-19 or spreading the virus. If you have this superpower, researchers want to meet you, to enroll you in their study. An international team of scientists has launched a global hunt for people who are genetically resistant to infection with the pandemic virus. The team hopes that identifying the genes protecting these individuals could lead to the development of virus-blocking drugs that not only protect people from COVID-19, but also prevent them from passing on the infection.

Although there are reports of COVID-19 vaccine implementation in real-world populations, these come from high-income countries or from experience with messenger RNA technology vaccines. Data on outcomes of vaccine deployment in low- or middle-income countries are lacking.In this cohort study of 663?602 participants, the use of COVID-19 vaccines was associated with a significant reduction in all-cause death, COVID-related death, and documented infection with the use of 1 dose and even more with the use of 2 doses.

Using data from Clalit Health Services, which provides mandatory health-care coverage for over half of the Israeli population, individuals receiving a third vaccine dose between July 30, 2020, and Sept 23, 2021, were matched (1:1) to demographically and clinically similar controls who did not receive a third dose.Vaccine effectiveness evaluated at least 7 days after receipt of the third dose, compared with receiving only two doses at least 5 months ago, was estimated to be 93% (231 events for two doses vs 29 events for three doses; 95% CI 88–97) for admission to hospital, 92% (157 vs 17 events; 82–97) for severe disease, and 81% (44 vs seven events; 59–97) for COVID-19-related death.

We stood up an automated high-throughput clinical testing lab with the capacity to run 45,000 individual tests weekly by fall of 2020, with a purpose-built clinical testing laboratory, a multiplexed RT-PCR test, robotic instrumentation, and trained CLIA certified staff. There were challenges to overcome, including the supply chain issues for PPE testing materials, and equipment that were in high demand.

Are persons vaccinated after SARS-CoV-2 infection better protected against breakthrough infection than those vaccinated without prior infection? In this cohort study of 1 531 736 mRNA-vaccinated individuals in Qatar, prior SARS-CoV-2 infection was associated with a statistically significant reduced hazard of breakthrough infection among recipients of both the BNT162b2 (Pfizer-BioNTech) (adjusted hazard ratio, 0.62) and the mRNA-1273 (Moderna) vaccines (adjusted hazard ratio, 0.40).

Health care workers with prior SARS-CoV-2 infection followed by 2 doses of mRNA vaccine (3 independent exposures to spike antigen) developed higher spike antibody measurements than individuals with vaccination alone. Consistent with work comparing extended vaccine dosing intervals, the study showed that a longer interval between infection and first vaccine dose may enhance the antibody response.

Although next-generation sequencing (NGS) has been adopted as the gold standard method for discriminating SARS-CoV-2 lineages, alternative methods may be required when processing samples with low viral loads or low RNA quality. An allele-specific probe polymerase chain reaction (ASP-PCR) targeting lineage-specific single nucleotide polymorphisms (SNPs) was developed and used to screen 1,082 samples from two clinical trials in the United Kingdom and Brazil.

Here, we develop SHINEv2, a Cas13-based nucleic acid diagnostic that combines quick and ambient temperature sample processing and lyophilized reagents to greatly simplify the test procedure and assay distribution. We benchmarked a SHINEv2 assay for SARS-CoV-2 detection against state-of-the-art antigen-capture tests using 96 patient samples, demonstrating 50-fold greater sensitivity and 100% specificity. We designed SHINEv2 assays for discriminating the Alpha, Beta, Gamma and Delta VOCs, which can be read out visually using lateral flow technology. We further demonstrate that our assays can be performed without any equipment in less than 90 minutes.

By analyzing viral loads of over 16,000 infections during the current, Delta-variant-dominated pandemic wave in Israel, we found that BTIs in recently fully vaccinated individuals have lower viral loads than infections in unvaccinated individuals. However, this effect starts to decline 2 months after vaccination and ultimately vanishes 6 months or longer after vaccination. Notably, we found that the effect of BNT162b2 on reducing BTI viral loads is restored after a booster dose. These results suggest that BNT162b2 might decrease the infectiousness of BTIs even with the Delta variant, and that, although this protective effect declines with time, it can be restored, at least temporarily, with a third, booster, vaccine dose.

With the global expansion of the highly transmissible SARS-CoV-2 Delta (B.1.617.2) variant, we conducted a matched test-negative case–control study to assess the real-world effectiveness of COVID-19 messenger RNA vaccines against infection with Delta in Qatar’s population. Our findings show robust effectiveness for both BNT162b2 and mRNA-1273 in preventing Delta hospitalization and death in Qatar’s population, despite lower effectiveness in preventing infection, particularly for the BNT162b2 vaccine.

Highlights: Identification of 23 genomic loci with suggestive associations for COVID-19 disease. Colocalized GWAS & eQTL signals associate with expression of 20 genes in 62 tissues. 45% of GWAS signals do not colocalize with eQTLs in blood or lung. Genetic fine mapping identifies putative causal variants at COVID-19 GWAS loci.

Overall, incidence rates of Covid-19 were lower among participants in the mRNA-1273p group (who had been vaccinated more recently) than among those in the mRNA-1273e group during July and August 2021, when the delta variant was dominant. The difference appears to have been driven by disease in younger participants, which indicates the presence of potential confounding behavioral factors in these participants that may have led to a higher exposure to the virus.

lAthough the beta variant (a variant of concern) was thought to be the most resistant variant to date,3,4 the mu variant was 2.0 as resistant to neutralization by convalescent serum and 1.5 times as resistant to neutralization by vaccine serum as the beta variant. Thus, the mu variant shows a pronounced resistance to antibodies elicited by natural SARS-CoV-2 infection and by the BNT162b2 mRNA vaccine.

Here, we determined the levels of antibodies, antigen-specific B cells, against a recombinant GFP-tagged SARS-CoV-2 spike (S) protein and total T and NK cell subsets in subjects up to 20 days after the injection of the BNT162b2 (Pfizer-BioNTech) vaccine using a combined approach of serological and flow cytometry analyses. In former COVID-19 patients and highly responsive individuals, a significant increase of antibody production was detected, simultaneous with an expansion of antigen-specific B cell response and the total number of NK-T cells. Additionally, through a genetic screening of a specific polymorphic region internal to the 3' regulatory region 1 (3'RR1) of human immunoglobulin constant-gene (IgH) locus, we identified different single-nucleotide polymorphic (SNP) variants associated with either highly or lowly responsive subjects.

Higher hospitalization risk was found for infections with Gamma (HR 3.23, 95% CI 2.19–4.76), Beta (HR 3.03, 95% CI 1.68–5.47), Delta (HR 2.35, 95% CI 1.7–3.22), and Alpha (HR 1.61, 95% CI 1.28–2.03) compared to infections with an ancestral lineage. Following VOC infection, unvaccinated patients show a similar higher hospitalization risk, while vaccinated patients show no significant difference in risk, both when compared to unvaccinated, ancestral lineage cases. Interpretation: Infection with a VOC results in a higher hospitalization risk, with an active vaccination attenuating that risk.

Vaccination reduces the risk of delta variant infection and accelerates viral clearance. Nonetheless, fully vaccinated individuals with breakthrough infections have peak viral load similar to unvaccinated cases and can efficiently transmit infection in household settings, including to fully vaccinated contacts. Host–virus interactions early in infection may shape the entire viral trajectory.

Imagine being born naturally resistant to SARS-CoV-2, and never having to worry about contracting COVID-19 or spreading the virus. If you have this superpower, researchers want to meet you, to enroll you in their study. An international team of scientists has launched a global hunt for people who are genetically resistant to infection with the pandemic virus. The team hopes that identifying the genes protecting these individuals could lead to the development of virus-blocking drugs that not only protect people from COVID-19, but also prevent them from passing on the infection.

Although there are reports of COVID-19 vaccine implementation in real-world populations, these come from high-income countries or from experience with messenger RNA technology vaccines. Data on outcomes of vaccine deployment in low- or middle-income countries are lacking.In this cohort study of 663?602 participants, the use of COVID-19 vaccines was associated with a significant reduction in all-cause death, COVID-related death, and documented infection with the use of 1 dose and even more with the use of 2 doses.

Using data from Clalit Health Services, which provides mandatory health-care coverage for over half of the Israeli population, individuals receiving a third vaccine dose between July 30, 2020, and Sept 23, 2021, were matched (1:1) to demographically and clinically similar controls who did not receive a third dose.Vaccine effectiveness evaluated at least 7 days after receipt of the third dose, compared with receiving only two doses at least 5 months ago, was estimated to be 93% (231 events for two doses vs 29 events for three doses; 95% CI 88–97) for admission to hospital, 92% (157 vs 17 events; 82–97) for severe disease, and 81% (44 vs seven events; 59–97) for COVID-19-related death.

We stood up an automated high-throughput clinical testing lab with the capacity to run 45,000 individual tests weekly by fall of 2020, with a purpose-built clinical testing laboratory, a multiplexed RT-PCR test, robotic instrumentation, and trained CLIA certified staff. There were challenges to overcome, including the supply chain issues for PPE testing materials, and equipment that were in high demand.

Are persons vaccinated after SARS-CoV-2 infection better protected against breakthrough infection than those vaccinated without prior infection? In this cohort study of 1 531 736 mRNA-vaccinated individuals in Qatar, prior SARS-CoV-2 infection was associated with a statistically significant reduced hazard of breakthrough infection among recipients of both the BNT162b2 (Pfizer-BioNTech) (adjusted hazard ratio, 0.62) and the mRNA-1273 (Moderna) vaccines (adjusted hazard ratio, 0.40).

Health care workers with prior SARS-CoV-2 infection followed by 2 doses of mRNA vaccine (3 independent exposures to spike antigen) developed higher spike antibody measurements than individuals with vaccination alone. Consistent with work comparing extended vaccine dosing intervals, the study showed that a longer interval between infection and first vaccine dose may enhance the antibody response.

Although next-generation sequencing (NGS) has been adopted as the gold standard method for discriminating SARS-CoV-2 lineages, alternative methods may be required when processing samples with low viral loads or low RNA quality. An allele-specific probe polymerase chain reaction (ASP-PCR) targeting lineage-specific single nucleotide polymorphisms (SNPs) was developed and used to screen 1,082 samples from two clinical trials in the United Kingdom and Brazil.

Here, we develop SHINEv2, a Cas13-based nucleic acid diagnostic that combines quick and ambient temperature sample processing and lyophilized reagents to greatly simplify the test procedure and assay distribution. We benchmarked a SHINEv2 assay for SARS-CoV-2 detection against state-of-the-art antigen-capture tests using 96 patient samples, demonstrating 50-fold greater sensitivity and 100% specificity. We designed SHINEv2 assays for discriminating the Alpha, Beta, Gamma and Delta VOCs, which can be read out visually using lateral flow technology. We further demonstrate that our assays can be performed without any equipment in less than 90 minutes.

By analyzing viral loads of over 16,000 infections during the current, Delta-variant-dominated pandemic wave in Israel, we found that BTIs in recently fully vaccinated individuals have lower viral loads than infections in unvaccinated individuals. However, this effect starts to decline 2 months after vaccination and ultimately vanishes 6 months or longer after vaccination. Notably, we found that the effect of BNT162b2 on reducing BTI viral loads is restored after a booster dose. These results suggest that BNT162b2 might decrease the infectiousness of BTIs even with the Delta variant, and that, although this protective effect declines with time, it can be restored, at least temporarily, with a third, booster, vaccine dose.

With the global expansion of the highly transmissible SARS-CoV-2 Delta (B.1.617.2) variant, we conducted a matched test-negative case–control study to assess the real-world effectiveness of COVID-19 messenger RNA vaccines against infection with Delta in Qatar’s population. Our findings show robust effectiveness for both BNT162b2 and mRNA-1273 in preventing Delta hospitalization and death in Qatar’s population, despite lower effectiveness in preventing infection, particularly for the BNT162b2 vaccine.

Highlights: Identification of 23 genomic loci with suggestive associations for COVID-19 disease. Colocalized GWAS & eQTL signals associate with expression of 20 genes in 62 tissues. 45% of GWAS signals do not colocalize with eQTLs in blood or lung. Genetic fine mapping identifies putative causal variants at COVID-19 GWAS loci.

Overall, incidence rates of Covid-19 were lower among participants in the mRNA-1273p group (who had been vaccinated more recently) than among those in the mRNA-1273e group during July and August 2021, when the delta variant was dominant. The difference appears to have been driven by disease in younger participants, which indicates the presence of potential confounding behavioral factors in these participants that may have led to a higher exposure to the virus.

lAthough the beta variant (a variant of concern) was thought to be the most resistant variant to date,3,4 the mu variant was 2.0 as resistant to neutralization by convalescent serum and 1.5 times as resistant to neutralization by vaccine serum as the beta variant. Thus, the mu variant shows a pronounced resistance to antibodies elicited by natural SARS-CoV-2 infection and by the BNT162b2 mRNA vaccine.

Here, we determined the levels of antibodies, antigen-specific B cells, against a recombinant GFP-tagged SARS-CoV-2 spike (S) protein and total T and NK cell subsets in subjects up to 20 days after the injection of the BNT162b2 (Pfizer-BioNTech) vaccine using a combined approach of serological and flow cytometry analyses. In former COVID-19 patients and highly responsive individuals, a significant increase of antibody production was detected, simultaneous with an expansion of antigen-specific B cell response and the total number of NK-T cells. Additionally, through a genetic screening of a specific polymorphic region internal to the 3' regulatory region 1 (3'RR1) of human immunoglobulin constant-gene (IgH) locus, we identified different single-nucleotide polymorphic (SNP) variants associated with either highly or lowly responsive subjects.

Higher hospitalization risk was found for infections with Gamma (HR 3.23, 95% CI 2.19–4.76), Beta (HR 3.03, 95% CI 1.68–5.47), Delta (HR 2.35, 95% CI 1.7–3.22), and Alpha (HR 1.61, 95% CI 1.28–2.03) compared to infections with an ancestral lineage. Following VOC infection, unvaccinated patients show a similar higher hospitalization risk, while vaccinated patients show no significant difference in risk, both when compared to unvaccinated, ancestral lineage cases. Interpretation: Infection with a VOC results in a higher hospitalization risk, with an active vaccination attenuating that risk.

Vaccination reduces the risk of delta variant infection and accelerates viral clearance. Nonetheless, fully vaccinated individuals with breakthrough infections have peak viral load similar to unvaccinated cases and can efficiently transmit infection in household settings, including to fully vaccinated contacts. Host–virus interactions early in infection may shape the entire viral trajectory.

Imagine being born naturally resistant to SARS-CoV-2, and never having to worry about contracting COVID-19 or spreading the virus. If you have this superpower, researchers want to meet you, to enroll you in their study. An international team of scientists has launched a global hunt for people who are genetically resistant to infection with the pandemic virus. The team hopes that identifying the genes protecting these individuals could lead to the development of virus-blocking drugs that not only protect people from COVID-19, but also prevent them from passing on the infection.

Although there are reports of COVID-19 vaccine implementation in real-world populations, these come from high-income countries or from experience with messenger RNA technology vaccines. Data on outcomes of vaccine deployment in low- or middle-income countries are lacking.In this cohort study of 663?602 participants, the use of COVID-19 vaccines was associated with a significant reduction in all-cause death, COVID-related death, and documented infection with the use of 1 dose and even more with the use of 2 doses.

Using data from Clalit Health Services, which provides mandatory health-care coverage for over half of the Israeli population, individuals receiving a third vaccine dose between July 30, 2020, and Sept 23, 2021, were matched (1:1) to demographically and clinically similar controls who did not receive a third dose.Vaccine effectiveness evaluated at least 7 days after receipt of the third dose, compared with receiving only two doses at least 5 months ago, was estimated to be 93% (231 events for two doses vs 29 events for three doses; 95% CI 88–97) for admission to hospital, 92% (157 vs 17 events; 82–97) for severe disease, and 81% (44 vs seven events; 59–97) for COVID-19-related death.

We stood up an automated high-throughput clinical testing lab with the capacity to run 45,000 individual tests weekly by fall of 2020, with a purpose-built clinical testing laboratory, a multiplexed RT-PCR test, robotic instrumentation, and trained CLIA certified staff. There were challenges to overcome, including the supply chain issues for PPE testing materials, and equipment that were in high demand.

Are persons vaccinated after SARS-CoV-2 infection better protected against breakthrough infection than those vaccinated without prior infection? In this cohort study of 1 531 736 mRNA-vaccinated individuals in Qatar, prior SARS-CoV-2 infection was associated with a statistically significant reduced hazard of breakthrough infection among recipients of both the BNT162b2 (Pfizer-BioNTech) (adjusted hazard ratio, 0.62) and the mRNA-1273 (Moderna) vaccines (adjusted hazard ratio, 0.40).

Health care workers with prior SARS-CoV-2 infection followed by 2 doses of mRNA vaccine (3 independent exposures to spike antigen) developed higher spike antibody measurements than individuals with vaccination alone. Consistent with work comparing extended vaccine dosing intervals, the study showed that a longer interval between infection and first vaccine dose may enhance the antibody response.

Although next-generation sequencing (NGS) has been adopted as the gold standard method for discriminating SARS-CoV-2 lineages, alternative methods may be required when processing samples with low viral loads or low RNA quality. An allele-specific probe polymerase chain reaction (ASP-PCR) targeting lineage-specific single nucleotide polymorphisms (SNPs) was developed and used to screen 1,082 samples from two clinical trials in the United Kingdom and Brazil.

Here, we develop SHINEv2, a Cas13-based nucleic acid diagnostic that combines quick and ambient temperature sample processing and lyophilized reagents to greatly simplify the test procedure and assay distribution. We benchmarked a SHINEv2 assay for SARS-CoV-2 detection against state-of-the-art antigen-capture tests using 96 patient samples, demonstrating 50-fold greater sensitivity and 100% specificity. We designed SHINEv2 assays for discriminating the Alpha, Beta, Gamma and Delta VOCs, which can be read out visually using lateral flow technology. We further demonstrate that our assays can be performed without any equipment in less than 90 minutes.

By analyzing viral loads of over 16,000 infections during the current, Delta-variant-dominated pandemic wave in Israel, we found that BTIs in recently fully vaccinated individuals have lower viral loads than infections in unvaccinated individuals. However, this effect starts to decline 2 months after vaccination and ultimately vanishes 6 months or longer after vaccination. Notably, we found that the effect of BNT162b2 on reducing BTI viral loads is restored after a booster dose. These results suggest that BNT162b2 might decrease the infectiousness of BTIs even with the Delta variant, and that, although this protective effect declines with time, it can be restored, at least temporarily, with a third, booster, vaccine dose.

With the global expansion of the highly transmissible SARS-CoV-2 Delta (B.1.617.2) variant, we conducted a matched test-negative case–control study to assess the real-world effectiveness of COVID-19 messenger RNA vaccines against infection with Delta in Qatar’s population. Our findings show robust effectiveness for both BNT162b2 and mRNA-1273 in preventing Delta hospitalization and death in Qatar’s population, despite lower effectiveness in preventing infection, particularly for the BNT162b2 vaccine.

Highlights: Identification of 23 genomic loci with suggestive associations for COVID-19 disease. Colocalized GWAS & eQTL signals associate with expression of 20 genes in 62 tissues. 45% of GWAS signals do not colocalize with eQTLs in blood or lung. Genetic fine mapping identifies putative causal variants at COVID-19 GWAS loci.

Overall, incidence rates of Covid-19 were lower among participants in the mRNA-1273p group (who had been vaccinated more recently) than among those in the mRNA-1273e group during July and August 2021, when the delta variant was dominant. The difference appears to have been driven by disease in younger participants, which indicates the presence of potential confounding behavioral factors in these participants that may have led to a higher exposure to the virus.

lAthough the beta variant (a variant of concern) was thought to be the most resistant variant to date,3,4 the mu variant was 2.0 as resistant to neutralization by convalescent serum and 1.5 times as resistant to neutralization by vaccine serum as the beta variant. Thus, the mu variant shows a pronounced resistance to antibodies elicited by natural SARS-CoV-2 infection and by the BNT162b2 mRNA vaccine.