We compare the neutralization of variants of concern, including B.1.617.2 (Delta) and B.1.1.529 (Omicron) in sera from individuals exposed to variant infection, vaccination, or both. We demonstrate that neutralizing antibody responses are strongest against variants sharing certain spike mutations with the immunizing exposure. We also observe that exposure to multiple spike variants increases the breadth of variant cross-neutralization.

The COVID-19 pandemic is caused by the betacoronavirus SARS-CoV-2. In November 2021, the Omicron variant was discovered and classified as a variant of concern (VOC). Omicron shows substantially more mutations in the spike protein than any previous variant, mostly in the receptor binding domain (RBD). We analyzed the binding of the Omicron RBD to the human ACE2 receptor and the ability of human sera from COVID-19 patients or vaccinees in comparison to Wuhan, Beta or Delta RBDs variants.

We illustrate more BTIs but reassuringly less severe Covid-19 with Omicron. Re-infections and Omicron-driven primary infections were likely driven by high population SARS-CoV-2 seroprevalence, waning vaccine effectiveness over time, increased Omicron infectivity, Omicron immune evasion or a combination of these and need further investigation. Follow-up of this cohort will continue and reports will be updated, as time and infections accrue.

In this cohort study of persons with COVID-19 in Qatar, infection with the SARS-CoV-2 Delta variant was associated with more severe disease than was infection with the Beta variant. Being unvaccinated was associated with greater odds of severe-critical disease.

After the initiation of an intensive BNT162b2 booster campaign with high vaccine uptake, we found a significant, rapid, and consistent reduction in the Covid-19 burden among persons in the same age group who were living in long-term care facilities. The reduction in the incidence of Covid-19 infection was delayed and of a lower magnitude among persons in the same age group in the general population during the booster period; among the younger age groups, no significant decreases were noted. Our results suggest the important real-life effects of the nationwide BNT162b2 vaccine booster program among residents in long-term care facilities.

We show that the Omicron RBD binds to human ACE2 with enhanced affinity, relative to the Wuhan-Hu-1 RBD, and binds to mouse ACE2. Marked reductions of plasma neutralizing activity were observed against Omicron compared to the ancestral pseudovirus for convalescent and vaccinated individuals, but this loss was less pronounced after a third vaccine dose. Furthermore, a fraction of broadly neutralizing sarbecovirus mAbs neutralized Omicron through recognition of antigenic sites outside the RBM, including sotrovimab2, S2X2593 and S2H974. The magnitude of Omicron-mediated immune evasion marks a major SARS-CoV-2 antigenic shift.

We used high-throughput yeast display screening1,2 to determine the RBD escaping mutation profiles for 247 human anti-RBD NAbs and showed that the NAbs could be unsupervised clustered into six epitope groups (A-F), which is highly concordant with knowledge-based structural classifications3-5. Strikingly, various single mutations of Omicron could impair NAbs of different epitope groups. Specifically, NAbs in Group A-D, whose epitope overlap with ACE2-binding motif, are largely escaped by K417N, G446S, E484A, and Q493R. Group E (S309 site)6 and F (CR3022 site)7 NAbs, which often exhibit broad sarbecovirus neutralizing activity, are less affected by Omicron, but still, a subset of NAbs are escaped by G339D, N440K, and S371L.

We investigated whether Omicron escapes antibody neutralization in South Africans vaccinated with Pfizer BNT162b2. We also investigated if Omicron requires the ACE2 receptor to infect cells. Neutralization of ancestral virus was much higher in infected and vaccinated versus vaccinated only participants but both groups showed a 22-fold escape from vaccine elicited neutralization by the Omicron variant. However, in the previously infected and vaccinated group, the level of residual neutralization of Omicron was similar to the level of neutralization of ancestral virus observed in the vaccination only group. Our data support the notion that, provided high neutralization capacity is elicited by vaccination/boosting approaches, reasonable effectiveness against Omicron may be maintained.

SARS-CoV-2 mRNA vaccines induce robust anti-spike (S) antibody and CD4+ T cell responses. It is not yet clear whether vaccine-induced follicular helper CD4+ T (TFH) cell responses contribute to this outstanding immunogenicity. Using fine needle aspiration of draining axillary lymph nodes from individuals who received the BNT162b2 mRNA vaccine, we evaluated the T cell receptor sequences and phenotype of lymph node TFH. Our results underscore the key role that robust TFH cell responses play in establishing long-term immunity by this efficacious human vaccine.

An outbreak of over one thousand COVID-19 cases in Provincetown, Massachusetts, in July 2021—the first large outbreak mostly in vaccinated individuals in the US—prompted a comprehensive public health response, motivating changes to national masking recommendations and raising questions about infection and transmission among vaccinated individuals. To address these questions, we combined genomic and epidemiological data from 467 individuals, including 40% of known outbreak-associated cases. The Delta variant accounted for 99% of outbreak-associated cases in this dataset; it was introduced from at least 40 sources, but 83% of cases derived from a single source, likely through transmission across multiple settings over a short time rather than a single event.

The unprecedented rise in SARS-CoV-2 infections is concurrent with rapid spread of the Omicron variant in England and globally. We analysed prevalence of SARS-CoV-2 and its dynamics in England from end of November to mid-December 2021 among almost 100,000 participants from the REACT-1 study. Prevalence was high during December 2021 with rapid growth nationally and in London, and of the proportion of infections due to Omicron. We observed a large fall in swab positivity among mostly vaccinated older children (12-17 years) compared with unvaccinated younger children (5-11 years), and in adults who received a third vs. two doses of vaccine.

Using circulating miRNA expression data as exposure, and severe COVID-19 cases as outcomes, we identified ten unique miRNAs that showed causality across three phenotype groups of COVID-19. Using expression data from an independent study, we validated and identified two high-confidence miRNAs, namely, hsa-miR-30a-3p and hsa-miR-139-5p, which have putative causal effects on developing cases of severe COVID-19. Using existing literature and publicly available databases, the potential causative roles of these miRNAs were investigated.

Is immune dysfunction associated with an increased risk for COVID-19 breakthrough infection after SARS-CoV-2 vaccination? In this cohort study of 664?722 patients who received at least 1 dose of a SARS-CoV-2 vaccine, those with immune dysfunction, such as HIV infection, rheumatoid arthritis, and solid organ transplant, had a higher rate for COVID-19 breakthrough infection and worse outcomes after full or partial vaccination, compared with persons without immune dysfunction.

We enrolled both previously vaccinated and unvaccinated individuals who were infected with SARS-CoV-2 in the Omicron infection wave in South Africa soon after symptom onset. We then measured their ability to neutralize both Omicron and Delta virus at enrollment versus a median of 14 days after enrollment. Neutralization of Omicron increased 14-fold over this time, showing a developing antibody response to the variant. Importantly, there was an enhancement of Delta virus neutralization, which increased 4.4-fold. The increase in Delta variant neutralization in individuals infected with Omicron may result in decreased ability of Delta to re-infect those individuals.

The RUO SARS-CoV-2 Variant Set 1 Test (RSCov2V1) RT-PCR for detection of spike gene N501Y, E484K and del69-70 was designed to differentiate Alpha from Beta and Gamma variants. While Delta lacks these three variants, Omicron has the N501Y and del69-70 mutation. We submitted 88 samples for RSCov2V1 identifying 9 samples with the N501Y and del69-70 mutations while all other samples (79) were negative for all three variants. 9/9 samples with the del69-70 and N501Y were identified by NGS to be Omicron while 47/47 other samples assessed by NGS were confirmed to be Delta family variants.

We developed an open-source stochastic SIR (Susceptible-Infectious-Removed) fast-model for simulating the transmission in the transition stage from the prevailing variant (most often Delta) to Omicron. The model is capable to predict trajectories of infection pressure and hospitalization needs, considering (a) uncertainties for the (Omicron) parametrization, (b) pre-existing vaccination and/or partial immunity status of the population, and demographic specific aspects regarding reference hospitalization needs, (c) effects of mitigating measures including social distancing and accelerated vaccination (booster) campaigns.

We found B.1.1.529 to be markedly resistant to neutralization by serum not only from convalescent patients, but also from individuals vaccinated with one of the four widely used COVID-19 vaccines. Even serum from persons vaccinated and boosted with mRNA-based vaccines exhibited substantially diminished neutralizing activity against B.1.1.529. By evaluating a panel of monoclonal antibodies to all known epitope clusters on the spike protein, we noted that the activity of 17 of the 19 antibodies tested were either abolished or impaired, including ones currently authorized or approved for use in patients

During the proxy omicron period, we found a vaccine effectiveness of 70% (95% confidence interval [CI], 62 to 76), a finding that was supported by the results of all sensitivity tests. This measure of vaccine effectiveness was significantly different from that during the comparator period, when the rate was 93% (95% CI, 90 to 94) against hospitalization for Covid-19.

We compare the neutralization of variants of concern, including B.1.617.2 (Delta) and B.1.1.529 (Omicron) in sera from individuals exposed to variant infection, vaccination, or both. We demonstrate that neutralizing antibody responses are strongest against variants sharing certain spike mutations with the immunizing exposure. We also observe that exposure to multiple spike variants increases the breadth of variant cross-neutralization.

The COVID-19 pandemic is caused by the betacoronavirus SARS-CoV-2. In November 2021, the Omicron variant was discovered and classified as a variant of concern (VOC). Omicron shows substantially more mutations in the spike protein than any previous variant, mostly in the receptor binding domain (RBD). We analyzed the binding of the Omicron RBD to the human ACE2 receptor and the ability of human sera from COVID-19 patients or vaccinees in comparison to Wuhan, Beta or Delta RBDs variants.

We illustrate more BTIs but reassuringly less severe Covid-19 with Omicron. Re-infections and Omicron-driven primary infections were likely driven by high population SARS-CoV-2 seroprevalence, waning vaccine effectiveness over time, increased Omicron infectivity, Omicron immune evasion or a combination of these and need further investigation. Follow-up of this cohort will continue and reports will be updated, as time and infections accrue.

In this cohort study of persons with COVID-19 in Qatar, infection with the SARS-CoV-2 Delta variant was associated with more severe disease than was infection with the Beta variant. Being unvaccinated was associated with greater odds of severe-critical disease.

After the initiation of an intensive BNT162b2 booster campaign with high vaccine uptake, we found a significant, rapid, and consistent reduction in the Covid-19 burden among persons in the same age group who were living in long-term care facilities. The reduction in the incidence of Covid-19 infection was delayed and of a lower magnitude among persons in the same age group in the general population during the booster period; among the younger age groups, no significant decreases were noted. Our results suggest the important real-life effects of the nationwide BNT162b2 vaccine booster program among residents in long-term care facilities.

We show that the Omicron RBD binds to human ACE2 with enhanced affinity, relative to the Wuhan-Hu-1 RBD, and binds to mouse ACE2. Marked reductions of plasma neutralizing activity were observed against Omicron compared to the ancestral pseudovirus for convalescent and vaccinated individuals, but this loss was less pronounced after a third vaccine dose. Furthermore, a fraction of broadly neutralizing sarbecovirus mAbs neutralized Omicron through recognition of antigenic sites outside the RBM, including sotrovimab2, S2X2593 and S2H974. The magnitude of Omicron-mediated immune evasion marks a major SARS-CoV-2 antigenic shift.

We used high-throughput yeast display screening1,2 to determine the RBD escaping mutation profiles for 247 human anti-RBD NAbs and showed that the NAbs could be unsupervised clustered into six epitope groups (A-F), which is highly concordant with knowledge-based structural classifications3-5. Strikingly, various single mutations of Omicron could impair NAbs of different epitope groups. Specifically, NAbs in Group A-D, whose epitope overlap with ACE2-binding motif, are largely escaped by K417N, G446S, E484A, and Q493R. Group E (S309 site)6 and F (CR3022 site)7 NAbs, which often exhibit broad sarbecovirus neutralizing activity, are less affected by Omicron, but still, a subset of NAbs are escaped by G339D, N440K, and S371L.

We investigated whether Omicron escapes antibody neutralization in South Africans vaccinated with Pfizer BNT162b2. We also investigated if Omicron requires the ACE2 receptor to infect cells. Neutralization of ancestral virus was much higher in infected and vaccinated versus vaccinated only participants but both groups showed a 22-fold escape from vaccine elicited neutralization by the Omicron variant. However, in the previously infected and vaccinated group, the level of residual neutralization of Omicron was similar to the level of neutralization of ancestral virus observed in the vaccination only group. Our data support the notion that, provided high neutralization capacity is elicited by vaccination/boosting approaches, reasonable effectiveness against Omicron may be maintained.

SARS-CoV-2 mRNA vaccines induce robust anti-spike (S) antibody and CD4+ T cell responses. It is not yet clear whether vaccine-induced follicular helper CD4+ T (TFH) cell responses contribute to this outstanding immunogenicity. Using fine needle aspiration of draining axillary lymph nodes from individuals who received the BNT162b2 mRNA vaccine, we evaluated the T cell receptor sequences and phenotype of lymph node TFH. Our results underscore the key role that robust TFH cell responses play in establishing long-term immunity by this efficacious human vaccine.

An outbreak of over one thousand COVID-19 cases in Provincetown, Massachusetts, in July 2021—the first large outbreak mostly in vaccinated individuals in the US—prompted a comprehensive public health response, motivating changes to national masking recommendations and raising questions about infection and transmission among vaccinated individuals. To address these questions, we combined genomic and epidemiological data from 467 individuals, including 40% of known outbreak-associated cases. The Delta variant accounted for 99% of outbreak-associated cases in this dataset; it was introduced from at least 40 sources, but 83% of cases derived from a single source, likely through transmission across multiple settings over a short time rather than a single event.

The unprecedented rise in SARS-CoV-2 infections is concurrent with rapid spread of the Omicron variant in England and globally. We analysed prevalence of SARS-CoV-2 and its dynamics in England from end of November to mid-December 2021 among almost 100,000 participants from the REACT-1 study. Prevalence was high during December 2021 with rapid growth nationally and in London, and of the proportion of infections due to Omicron. We observed a large fall in swab positivity among mostly vaccinated older children (12-17 years) compared with unvaccinated younger children (5-11 years), and in adults who received a third vs. two doses of vaccine.

Using circulating miRNA expression data as exposure, and severe COVID-19 cases as outcomes, we identified ten unique miRNAs that showed causality across three phenotype groups of COVID-19. Using expression data from an independent study, we validated and identified two high-confidence miRNAs, namely, hsa-miR-30a-3p and hsa-miR-139-5p, which have putative causal effects on developing cases of severe COVID-19. Using existing literature and publicly available databases, the potential causative roles of these miRNAs were investigated.

Is immune dysfunction associated with an increased risk for COVID-19 breakthrough infection after SARS-CoV-2 vaccination? In this cohort study of 664?722 patients who received at least 1 dose of a SARS-CoV-2 vaccine, those with immune dysfunction, such as HIV infection, rheumatoid arthritis, and solid organ transplant, had a higher rate for COVID-19 breakthrough infection and worse outcomes after full or partial vaccination, compared with persons without immune dysfunction.

We enrolled both previously vaccinated and unvaccinated individuals who were infected with SARS-CoV-2 in the Omicron infection wave in South Africa soon after symptom onset. We then measured their ability to neutralize both Omicron and Delta virus at enrollment versus a median of 14 days after enrollment. Neutralization of Omicron increased 14-fold over this time, showing a developing antibody response to the variant. Importantly, there was an enhancement of Delta virus neutralization, which increased 4.4-fold. The increase in Delta variant neutralization in individuals infected with Omicron may result in decreased ability of Delta to re-infect those individuals.

The RUO SARS-CoV-2 Variant Set 1 Test (RSCov2V1) RT-PCR for detection of spike gene N501Y, E484K and del69-70 was designed to differentiate Alpha from Beta and Gamma variants. While Delta lacks these three variants, Omicron has the N501Y and del69-70 mutation. We submitted 88 samples for RSCov2V1 identifying 9 samples with the N501Y and del69-70 mutations while all other samples (79) were negative for all three variants. 9/9 samples with the del69-70 and N501Y were identified by NGS to be Omicron while 47/47 other samples assessed by NGS were confirmed to be Delta family variants.

We developed an open-source stochastic SIR (Susceptible-Infectious-Removed) fast-model for simulating the transmission in the transition stage from the prevailing variant (most often Delta) to Omicron. The model is capable to predict trajectories of infection pressure and hospitalization needs, considering (a) uncertainties for the (Omicron) parametrization, (b) pre-existing vaccination and/or partial immunity status of the population, and demographic specific aspects regarding reference hospitalization needs, (c) effects of mitigating measures including social distancing and accelerated vaccination (booster) campaigns.

We found B.1.1.529 to be markedly resistant to neutralization by serum not only from convalescent patients, but also from individuals vaccinated with one of the four widely used COVID-19 vaccines. Even serum from persons vaccinated and boosted with mRNA-based vaccines exhibited substantially diminished neutralizing activity against B.1.1.529. By evaluating a panel of monoclonal antibodies to all known epitope clusters on the spike protein, we noted that the activity of 17 of the 19 antibodies tested were either abolished or impaired, including ones currently authorized or approved for use in patients

During the proxy omicron period, we found a vaccine effectiveness of 70% (95% confidence interval [CI], 62 to 76), a finding that was supported by the results of all sensitivity tests. This measure of vaccine effectiveness was significantly different from that during the comparator period, when the rate was 93% (95% CI, 90 to 94) against hospitalization for Covid-19.

We compare the neutralization of variants of concern, including B.1.617.2 (Delta) and B.1.1.529 (Omicron) in sera from individuals exposed to variant infection, vaccination, or both. We demonstrate that neutralizing antibody responses are strongest against variants sharing certain spike mutations with the immunizing exposure. We also observe that exposure to multiple spike variants increases the breadth of variant cross-neutralization.

The COVID-19 pandemic is caused by the betacoronavirus SARS-CoV-2. In November 2021, the Omicron variant was discovered and classified as a variant of concern (VOC). Omicron shows substantially more mutations in the spike protein than any previous variant, mostly in the receptor binding domain (RBD). We analyzed the binding of the Omicron RBD to the human ACE2 receptor and the ability of human sera from COVID-19 patients or vaccinees in comparison to Wuhan, Beta or Delta RBDs variants.

We illustrate more BTIs but reassuringly less severe Covid-19 with Omicron. Re-infections and Omicron-driven primary infections were likely driven by high population SARS-CoV-2 seroprevalence, waning vaccine effectiveness over time, increased Omicron infectivity, Omicron immune evasion or a combination of these and need further investigation. Follow-up of this cohort will continue and reports will be updated, as time and infections accrue.

In this cohort study of persons with COVID-19 in Qatar, infection with the SARS-CoV-2 Delta variant was associated with more severe disease than was infection with the Beta variant. Being unvaccinated was associated with greater odds of severe-critical disease.

After the initiation of an intensive BNT162b2 booster campaign with high vaccine uptake, we found a significant, rapid, and consistent reduction in the Covid-19 burden among persons in the same age group who were living in long-term care facilities. The reduction in the incidence of Covid-19 infection was delayed and of a lower magnitude among persons in the same age group in the general population during the booster period; among the younger age groups, no significant decreases were noted. Our results suggest the important real-life effects of the nationwide BNT162b2 vaccine booster program among residents in long-term care facilities.

We show that the Omicron RBD binds to human ACE2 with enhanced affinity, relative to the Wuhan-Hu-1 RBD, and binds to mouse ACE2. Marked reductions of plasma neutralizing activity were observed against Omicron compared to the ancestral pseudovirus for convalescent and vaccinated individuals, but this loss was less pronounced after a third vaccine dose. Furthermore, a fraction of broadly neutralizing sarbecovirus mAbs neutralized Omicron through recognition of antigenic sites outside the RBM, including sotrovimab2, S2X2593 and S2H974. The magnitude of Omicron-mediated immune evasion marks a major SARS-CoV-2 antigenic shift.

We used high-throughput yeast display screening1,2 to determine the RBD escaping mutation profiles for 247 human anti-RBD NAbs and showed that the NAbs could be unsupervised clustered into six epitope groups (A-F), which is highly concordant with knowledge-based structural classifications3-5. Strikingly, various single mutations of Omicron could impair NAbs of different epitope groups. Specifically, NAbs in Group A-D, whose epitope overlap with ACE2-binding motif, are largely escaped by K417N, G446S, E484A, and Q493R. Group E (S309 site)6 and F (CR3022 site)7 NAbs, which often exhibit broad sarbecovirus neutralizing activity, are less affected by Omicron, but still, a subset of NAbs are escaped by G339D, N440K, and S371L.

We investigated whether Omicron escapes antibody neutralization in South Africans vaccinated with Pfizer BNT162b2. We also investigated if Omicron requires the ACE2 receptor to infect cells. Neutralization of ancestral virus was much higher in infected and vaccinated versus vaccinated only participants but both groups showed a 22-fold escape from vaccine elicited neutralization by the Omicron variant. However, in the previously infected and vaccinated group, the level of residual neutralization of Omicron was similar to the level of neutralization of ancestral virus observed in the vaccination only group. Our data support the notion that, provided high neutralization capacity is elicited by vaccination/boosting approaches, reasonable effectiveness against Omicron may be maintained.

SARS-CoV-2 mRNA vaccines induce robust anti-spike (S) antibody and CD4+ T cell responses. It is not yet clear whether vaccine-induced follicular helper CD4+ T (TFH) cell responses contribute to this outstanding immunogenicity. Using fine needle aspiration of draining axillary lymph nodes from individuals who received the BNT162b2 mRNA vaccine, we evaluated the T cell receptor sequences and phenotype of lymph node TFH. Our results underscore the key role that robust TFH cell responses play in establishing long-term immunity by this efficacious human vaccine.

An outbreak of over one thousand COVID-19 cases in Provincetown, Massachusetts, in July 2021—the first large outbreak mostly in vaccinated individuals in the US—prompted a comprehensive public health response, motivating changes to national masking recommendations and raising questions about infection and transmission among vaccinated individuals. To address these questions, we combined genomic and epidemiological data from 467 individuals, including 40% of known outbreak-associated cases. The Delta variant accounted for 99% of outbreak-associated cases in this dataset; it was introduced from at least 40 sources, but 83% of cases derived from a single source, likely through transmission across multiple settings over a short time rather than a single event.

The unprecedented rise in SARS-CoV-2 infections is concurrent with rapid spread of the Omicron variant in England and globally. We analysed prevalence of SARS-CoV-2 and its dynamics in England from end of November to mid-December 2021 among almost 100,000 participants from the REACT-1 study. Prevalence was high during December 2021 with rapid growth nationally and in London, and of the proportion of infections due to Omicron. We observed a large fall in swab positivity among mostly vaccinated older children (12-17 years) compared with unvaccinated younger children (5-11 years), and in adults who received a third vs. two doses of vaccine.

Using circulating miRNA expression data as exposure, and severe COVID-19 cases as outcomes, we identified ten unique miRNAs that showed causality across three phenotype groups of COVID-19. Using expression data from an independent study, we validated and identified two high-confidence miRNAs, namely, hsa-miR-30a-3p and hsa-miR-139-5p, which have putative causal effects on developing cases of severe COVID-19. Using existing literature and publicly available databases, the potential causative roles of these miRNAs were investigated.

Is immune dysfunction associated with an increased risk for COVID-19 breakthrough infection after SARS-CoV-2 vaccination? In this cohort study of 664?722 patients who received at least 1 dose of a SARS-CoV-2 vaccine, those with immune dysfunction, such as HIV infection, rheumatoid arthritis, and solid organ transplant, had a higher rate for COVID-19 breakthrough infection and worse outcomes after full or partial vaccination, compared with persons without immune dysfunction.

We enrolled both previously vaccinated and unvaccinated individuals who were infected with SARS-CoV-2 in the Omicron infection wave in South Africa soon after symptom onset. We then measured their ability to neutralize both Omicron and Delta virus at enrollment versus a median of 14 days after enrollment. Neutralization of Omicron increased 14-fold over this time, showing a developing antibody response to the variant. Importantly, there was an enhancement of Delta virus neutralization, which increased 4.4-fold. The increase in Delta variant neutralization in individuals infected with Omicron may result in decreased ability of Delta to re-infect those individuals.

The RUO SARS-CoV-2 Variant Set 1 Test (RSCov2V1) RT-PCR for detection of spike gene N501Y, E484K and del69-70 was designed to differentiate Alpha from Beta and Gamma variants. While Delta lacks these three variants, Omicron has the N501Y and del69-70 mutation. We submitted 88 samples for RSCov2V1 identifying 9 samples with the N501Y and del69-70 mutations while all other samples (79) were negative for all three variants. 9/9 samples with the del69-70 and N501Y were identified by NGS to be Omicron while 47/47 other samples assessed by NGS were confirmed to be Delta family variants.

We developed an open-source stochastic SIR (Susceptible-Infectious-Removed) fast-model for simulating the transmission in the transition stage from the prevailing variant (most often Delta) to Omicron. The model is capable to predict trajectories of infection pressure and hospitalization needs, considering (a) uncertainties for the (Omicron) parametrization, (b) pre-existing vaccination and/or partial immunity status of the population, and demographic specific aspects regarding reference hospitalization needs, (c) effects of mitigating measures including social distancing and accelerated vaccination (booster) campaigns.

We found B.1.1.529 to be markedly resistant to neutralization by serum not only from convalescent patients, but also from individuals vaccinated with one of the four widely used COVID-19 vaccines. Even serum from persons vaccinated and boosted with mRNA-based vaccines exhibited substantially diminished neutralizing activity against B.1.1.529. By evaluating a panel of monoclonal antibodies to all known epitope clusters on the spike protein, we noted that the activity of 17 of the 19 antibodies tested were either abolished or impaired, including ones currently authorized or approved for use in patients

During the proxy omicron period, we found a vaccine effectiveness of 70% (95% confidence interval [CI], 62 to 76), a finding that was supported by the results of all sensitivity tests. This measure of vaccine effectiveness was significantly different from that during the comparator period, when the rate was 93% (95% CI, 90 to 94) against hospitalization for Covid-19.