Protection against Omicron re-infection conferred by prior heterologous SARS-CoV-2 infection, with and without mRNA vaccination
Importance Omicron is phylogenetically- and antigenically-distinct from earlier SARS-CoV-2 variants and the original vaccine strain. Protection conferred by prior SARS-CoV-2 infection against Omicron re-infection, and the added value of vaccination, require quantification. Objective To estimate protection against Omicron re-infection and hospitalization conferred by prior heterologous SARS-CoV-2 (non-Omicron) infection and/or up to three doses of (ancestral, Wuhan-like) mRNA vaccine. Design Test-negative study between December 26 (epi-week 52), 2021 and March 12 (epi-week 10), 2022. Setting Population-based, province of Quebec, Canada Participants Community-dwelling ≥12-year-olds tested for SARS-CoV-2. Exposures Prior laboratory-confirmed infection with/without mRNA vaccination. Outcomes Laboratory-confirmed SARS-CoV-2 re-infection and hospitalization, presumed Omicron by genomic surveillance. The odds of prior non-Omicron infection with/without vaccination were compared among Omicron cases/hospitalizations versus test-negative controls (single randomly-selected per individual). Adjusted odds ratios controlled for age, sex, testing-indication and epi-week. Analyses were stratified by severity and time since last non-Omicron infection or vaccine dose. Results Without vaccination, prior non-Omicron infection reduced the Omicron re-infection risk by 44% (95%CI:38-48), decreasing from 66% (95%CI:57-73) at 3-5 months to 35% (95%CI:21-47) at 9-11 months post-infection and 2 doses of ancestral Wuhan-like vaccine may be of marginal incremental value to previously-infected individuals. ### Competing Interest Statement All authors have completed the ICMJE Form for Disclosure of Potential Conflicts of Interest. GDS received a grant from Pfizer unrelated to the current work. RG received honoraria as speaker at the RSV workshop financed by Abbvie. JF is chair of the provincial genomic surveillance committee of SARS-CoV-2. Others authors declare no conflict of interest. ### Funding Statement This work was supported by the Ministère de la santé et des services sociaux du Québec ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was conducted under the legal mandate of the National Director of Public Health of Quebec under the Public Health Act and was also approved by the Research Ethics Board of the Centre hospitalier universitaire de Québec-Université Laval. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors
Vaccination status of patients with persistent SARS-CoV-2 RNA in the gut mucosa:One dose: 21,9%Two doses: 40,6%Three doses: 6,2%Unvaccinated: 31,2% pic.twitter.com/oPD0naxhmw— Alexandre Freitas (@FreitasABR) May 2, 2022
Post-acute COVID-19 is characterized by gut viral antigen persistence in inflammatory bowel diseases
The coronavirus disease 2019 (COVID-19) pandemic affects populations, societies and lives for more than two years. Long-term sequelae of COVID-19, collectively termed the post-acute COVID-19 syndrome, are rapidly emerging across the globe. Here, we investigated whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen persistence underlies the post-acute COVID-19 syndrome.
Studie: Diese Blutgruppe bekommt seltener Covid-19, steckt aber häufiger an
Nürnberg - Dass die Blutgruppe des Patienten das Risiko für einen schweren Krankheitsverlauf nach einer Corona-Infektion beeinflussen kann, fanden Forscher bereits im Sommer 2020 heraus. Dass manche Blutgruppen das Risiko einer Ansteckung erhöhten, war ebenfalls bekannt. Welche Rolle das Schema von Blutspenden aber dabei spielt, legt nun eine französische Studie nahe.
Managing an evolving pandemic: Cryptic circulation of the Delta variant during the Omicron rise
SARS-CoV-2 continued circulation results in mutations and the emergence of various variants. Until now, whenever a new, dominant, variant appeared, it…
SARS-CoV-2 escape from a highly neutralizing COVID-19 convalescent plasma
To investigate the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the immune population, we coincupi bated the authentic virus with a highly neutralizing plasma from a COVID-19 convalescent patient. The plasma fully neutralized the virus for seven passages, but, after 45 d, the deletion of F140 in the spike N-terminal domain (NTD) N3 loop led to partial breakthrough. At day 73, an E484K substitution in the receptor-binding domain (RBD) occurred, followed, at day 80, by an insertion in the NTD N5 loop containing a new glycan sequon, which generated a variant completely resistant to plasma neutralization. Computational modeling predicts that the deletion and insertion in loops N3 and N5 prevent binding of neutralizing antibodies. The recent emergence in the United Kingdom, South Africa, Brazil, and Japan of natural variants with similar changes suggests that SARS-CoV-2 has the potential to escape an effective immune response and that vaccines and antibodies able to control emerging variants should be developed.
Perimeter leakage of face masks and its effect on the mask's efficacy
Recent studies have shown that the effectiveness of the face masks depends not only on the mask material but also on their fit on faces. The mask porosity and fit dictate the amount of filtered flo...
Fertility related safety data was neither reported in the clinical trials nor evaluated in animal models prior to emergency use authorization (EUA) for two novel mRNA vaccines, BNT162b2 and mRNA-127.1,2 Despite excellent safety profiles for both vaccines, 44% of Americans are hesitant in receiving the vaccine. Although the specific reasons for COVID-19 vaccine hesitancy are unknown, concerns over fertility has previously decreased other vaccine uptake. As COVID-19 vaccination in the United States opens to children and adolescents, evaluating any potential impact of the vaccine on male reproduction is imperative for public reassurance. We hypothesized that since both vaccines only contain mRNA encoding the SARS-CoV-2 spike protein without biologic ability to replicate live virus, the vaccines would not decrease semen parameters.
Particle sizes of infectious aerosols: implications for infection control
The global pandemic of COVID-19 has been associated with infections and deaths among health-care workers. This Viewpoint of infectious aerosols is intended to inform appropriate infection control measures to protect health-care workers. Studies of cough ...
Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry
Antibody-dependent enhancement (ADE) of viral entry has been a major concern for epidemiology, vaccine development, and antibody-based drug therapy. However, the molecular mechanism behind ADE is still elusive. Coronavirus spike protein mediates viral ...
Two Different Antibody-Dependent Enhancement (ADE) Risks for SARS-CoV-2 Antibodies
COVID-19 (SARS-CoV-2) disease severity and stages varies from asymptomatic, mild flu-like symptoms, moderate, severe, critical, and chronic disease. COVID-19 disease progression include lymphopenia, elevated proinflammatory cytokines and chemokines, accumulation of macrophages and neutrophils in lungs, immune dysregulation, cytokine storms, acute respiratory distress syndrome (ARDS), etc. Development of vaccines to severe acute respiratory syndrome (SARS), Middle East Respiratory Syndrome coronavirus (MERS-CoV), and other coronavirus has been difficult to create due to vaccine induced enhanced disease responses in animal models. Multiple betacoronaviruses including SARS-CoV-2 and SARS-CoV-1 expand cellular tropism by infecting some phagocytic cells (immature macrophages and dendritic cells) via antibody bound Fc receptor uptake of virus. Antibody-dependent enhancement (ADE) may be involved in the clinical observation of increased severity of symptoms associated with early high levels of SARS-CoV-2 antibodies in patients. Infants with multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 may also have ADE caused by maternally acquired SARS-CoV-2 antibodies bound to mast cells. ADE risks associated with SARS-CoV-2 has implications for COVID-19 and MIS-C treatments, B-cell vaccines, SARS-CoV-2 antibody therapy, and convalescent plasma therapy for patients. SARS-CoV-2 antibodies bound to mast cells may be involved in MIS-C and multisystem inflammatory ...
Hepatic involvement in COVID-19 is typically characterized as mild hepatitis with preserved synthetic function in children. Severe hepatitis is a rare complication of COVID-19 infection that has not been extensively described in the pediatric population. We report a case series of 4 previously healt …
Evolution of nasal and olfactory infection characteristics of SARS-CoV-2 variants | bioRxiv
SARS-CoV-2 infection of the upper airway and the subsequent immune response are early, critical factors in COVID-19 pathogenesis. By studying infection of human biopsies in vitro and in a hamster model in vivo, we demonstrated a transition in tropism from olfactory to respiratory epithelium as the virus evolved. Analyzing each variants revealed that SARS-CoV-2 WA1 or Delta infects a proportion of olfactory neurons in addition to the primary target sustentacular cells. The Delta variant possesses broader cellular invasion capacity into the submucosa, while Omicron displays longer retention in the sinonasal epithelium. The olfactory neuronal infection by WA1 and the subsequent olfactory bulb transport via axon is more pronounced in younger hosts. In addition, the observed viral clearance delay and phagocytic dysfunction in aged olfactory mucosa is accompanied by a decline of phagocytosis related genes. Furthermore, robust basal stem cell activation contributes to neuroepithelial regeneration and restores ACE2 expression post-infection. Together, our study characterized the nasal tropism of SARS-CoV-2 strains, immune clearance, and regeneration post infection. The shifting characteristics of viral infection at the airway portal provides insight into the variability of COVID-19 clinical features and may suggest differing strategies for early local intervention.
SARS-CoV-2-specific T-cell epitope repertoire in convalescent and mRNA-vaccinated individuals
Nature Microbiology - A comparison of the repertoire of SARS-CoV-2-specific epitopes targeted by T cells induced by vaccination or natural infection reveals that T cells predominantly target...
Lab interests
Pathogen evolution and long-term persistence including that of SARS-CoV-2
Effects of HIV co-infection on SARS-CoV-2 and other pathogens
Escape of SARS-CoV-2 variants from the antibody neutralization immune response elicited by vaccines and other variants
North Carolina health officials watch for unusual hepatitis cases in children
North Carolina health officials are on the lookout for unusual hepatitis cases in children after two children in the state had severe liver inflammation with no known cause. The World Health Organization this month reported a global outbreak of hepatitis affecting at least 169 children ages 1 month to 16 years old.
SARS-associated viral hepatitis caused by a novel coronavirus: report of three cases - PubMed
Liver impairment is commonly reported in up to 60% of patients who suffer from severe acute respiratory syndrome (SARS). Here we report the clinical course and liver pathology in three SARS patients with liver impairment. Three patients who fulfilled the World Health Organization case definition of …
COVID-19 mortality preventable by vaccines - Peterson-KFF Health System Tracker
In this analysis, we estimate the number of adult deaths that could have been prevented by timely vaccination. We find that approximately 234,000 deaths since June 2021 could have been prevented with primary series vaccination. These vaccine-preventable deaths represent 60% of all adult COVID-19 deaths since June 2021, and a quarter (24%) of the nearly 1 million COVID-19 deaths since the pandemic began.
Ich möchte nochmal darauf hinweisen, dass es keinerlei Hinweise auf einen Zusammenhang zwischen CoViD und Leberproblemen gibt! https://t.co/sGvW9IKrbwhttps://t.co/tDuwmUsR9jhttps://t.co/vVpl9UXXsWhttps://t.co/FSeGf2l8mehttps://t.co/t2YhwzLDkchttps://t.co/xy9vYN1KKL— Philipp S. Holstein (@PSHolstein) April 21, 2022
COVID-19 Associated Hepatitis in Children (CAH-C) during the second wave of SARS-CoV-2 infections in Central India: Is it a complication or transient phenomenon
Objectives While pediatric population has largely remained free of severe COVID-19, in some cases SARS-CoV-2 infection has been associated with complications like Multiple Inflammatory Syndrome in children (MIS-C). We mention another unique presentation subsequent to asymptomatic infection of SARS-CoV-2, a transient form of hepatitis designated as COVID-19 Associated Hepatitis in Children (CAH-C). The clinical presentations, temporal association and viral parameters of the cases of CAH-C contrasting to MIS-C hepatitis are presented here. Design As a retrospective and follow-up observational study we reviewed all pediatric patients presenting to our hospital with acute hepatitis. Increased number of such cases of hepatitis during the second wave of SARS CoV-2 infections, where children or adolescents developing sudden onset acute hepatitis with temporal relation to SARS-CoV-2 infection and without prior liver disease or familiar etiology of acute hepatitis are described. Results Among 47 pediatric patients presented with hepatitis, 37 patients had features of CAH-C, they had symptoms of hepatitis only, with majority having unelevated inflammatory markers and uneventful recovery following supportive treatment. Whereas remaining 10 MIS-C hepatitis had protracted illness, multiple system involvement, required admission to critical care, and had mortality of 30% (3/10). Conclusion With the emergence of newer variants of concern (VOC) including the Delta variant which has now spread to more than 60 countries and was responsible for the massive wave of COVID-19 across India, with changing presentations, CAH-C might be one of them. Such new entities need to be identified and differentiated from other emerging syndromes in children for a timely and appropriate intervention. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement No external grant has been used for the study. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the IRB and the institutional human ethics committee, Bundelkhand Medical College, Sagar registration number ECR/1252/Inst/MP/2019. The follow-up and analysis work was performed after the ethical approval was granted by the institutional human ethics committee of our institute. Wide reference letter IEC/BMC/80/21. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data related to the manuscript is available with the author. [https://main.icmr.nic.in/sites/default/files/press\_realease\_files/ICMR\_PR\_IgG\_Elisa\_30052020.pdf][1] [1]: https://main.icmr.nic.in/sites/default/files/press_realease_files/ICMR_PR_IgG_Elisa_30052020.pdf
Post-COVID‑19-Arthritis. Manifestation unter dem klinischen Bild einer reaktiven Arthritis
Es werden 13 Fallberichte einer reaktiven Arthritis im Zusammenhang mit einer Coronavirus-Krankheit-2019 (COVID‑19) referiert. Männer sind häufiger betroffen als Frauen. Die Arthritis manifestiert sich 4 bis 44 Tage ...
Cycle threshold values in symptomatic Covid-19 cases in England
Since the start of the pandemic SARS-CoV-2 infection has most commonly been confirmed using reverse transcriptase polymerase chain reaction (RT-PCR), with results translated into a binary positive/negative outcomes. Previous studies have found that there is additional useful information in the level of the Cycle threshold (Ct value) of positive cases. Here we characterise variation in Ct values as a proxy for viral loads in more than 3 million test-positive COVID-19 cases in England with the aim of better quantifying the utility of such data.
Methods
We used individual N gene Ct values from symptomatic PCR positive (with Ct value less than 30) Pillar 2 cases in England who self-reported the date of symptom onset, and for whome age, reinfection status, variant status, and the number of vaccines recieved was available. Those with a positive test result more than 6 days after their reported symptom onset were excluded to mitigate the potential impact of recall bias. We used a generalised additive model, to estimate Ct values empirical mean Ct values for each strata of interest independently as well as to predict Ct values using a model that adjusted for a range of demographic and epidemiological covariates jointly. We present empirical Ct values and compare them to predicted mean Ct values.
Results
We found that mean Ct values varied by vaccine status, and reinfection status with the number of vaccine doses having little apparent effect. Modelling Ct values as a smooth function of time since onset and other variables struggled to reproduce the individual variation in the data but did match the population-level variation over time relatively well with this being apparently dominated by large differences between variants. Other variation over time was also captured to some degree though their remained several periods where the model could not capture the empirical means with a potential explanation being epidemic phase bias.
Conclusions
Analysising a large dataset of routine Ct values from symptomatic COVID-19 cases in England we found variation based on time since symptom onset, vaccine status, age, and variant. Ct values were highest 1-3 days after symptom onset and differed most due to variant status. We found no clear correlation between previously estimated differences in intrinsic transmissibility and Ct values indicating that this is potentially mediated at least partly by factors other than viral load as estimated using Ct values. We found evidence that a model adjusting for a range of covariates could explain some of the population-level variation over time but systematically underestimated Ct values when incidence was increasing, and overestimated them when incidence was decreasing. This indicates the utility of Ct values from this data source as a tool for surveillance, potentially avoiding some of the biases of aggregated positive counts.
Effects of COVID-19 in Care Homes - A Mixed Methods Review
The report provides an up-to-date review of the global effects of the COVID-19 pandemic in care homes. We used a mixed methods approach to assess care home mortality by country, how the deaths compared with previous periods, and how excess deaths may be explained. We retrieved national datasets for 25 countries on mortality, 17 cohort studies assessing deaths compared to a previous period, and 16 cohort studies reporting interventions or factors associated with excess mortality. The COVID-19 pandemic disproportionately impacted those living in care homes at the highest risk for severe outcomes. However, the pandemic only highlighted and exacerbated a long-running problem: underfunding, poor structural layout, undertraining, under-skilling, under-equipping, and finally, lack of humanity in dealing with the most vulnerable members of society. The 17 cohort studies point to excess mortality worsening during the pandemic. Despite involving vast numbers of care homes around the globe, the quality of the evidence is not good. For example, the majority of the studies infer the cause of extra deaths from the observation window (mainly the spring of 2020) rather than through detailed investigations. This is why we do not draw any clear conclusions about the specific causes of death, apart from noting their significantly high numbers. In addition, we did not review all policy actions since 2020 but note there has been a scarcity of studies since then - an indicator that interest in this problem has waned and likely not been addressed. Analysis of national datasets for 25 countries shows that care home deaths were, on average, 30% of the total COVID-19 deaths (range: 9-64%). The quality of the current evidence base is limited, short term, and lacks standardised methods to prevent robust countrywide comparisons. Residual excess deaths were also observed, with excess mortality being reported for both COVID-19 positive and negative patients. Several reported interventions or factors suggest the potential to mitigate the risk in care homes substantially. Interventions that could reduce mortality include improving the care home quality, increasing staffing levels, reducing the number of beds in the facility, employing staff confinement strategies with residents, and improving clinical care such as implementing daily examinations. Some care home solutions like US ‘Green House’ homes, which usually have fewer than 12 beds, may provide crucial insights into the care home problem compared with larger homes. Furthermore, care home residents faced barriers accessing emergency treatments during the pandemic waves. Finally, interventions targeting care homes should be subject to smaller trials given large effect sizes in some studies. Approximately one per cent of the global population resides in care homes, while care home residents account for nearly one-third of deaths attributed to COVID-19 in the 25 countries studied. Reducing this ratio requires analysing current care home infrastructures, funding models, and incentives for providing high-quality care. The scale of the problem in care homes requires robust evaluation and coordinated strategies to improve outcomes for those most vulnerable to COVID-19. Failure to address these systemic problems could mean global care home populations will be similarly affected by future crises and pandemics. ### Competing Interest Statement TJ's disclosure is available here: . CH holds grant funding from the NIHR, the NIHR School of Primary Care Research, the NIHR BRC Oxford and the World Health Organization for a series of Living rapid reviews on the modes of transmission of SARS-CoV-2 reference WHO registration No2020/1077093. He has received financial remuneration from an asbestos case and legal advice on mesh and hormone pregnancy tests cases. He has received expenses and fees for his media work, including periodic payments from the BBC, The Spectator, and other media outlets. He receives expenses for teaching EBM and is also paid for his G.P. work in NHS out of hours and regularly goes into care homes. He has also received income from publishing a series of toolkit books and appraising treatment recommendations in non-NHS settings. He is the Director of CEBM and is an NIHR Senior Investigator. He is co-director of the Global Centre for Healthcare and Urbanization based at Kellogg College at Oxford. He is a scientific advisor to Collateral Global that funds this review. JB is a significant shareholder in the Trip Database search engine ([www.tripdatabase.com][1]) and an employee. He has previously received funding from institutions such as WHO, NIHR. Collateral Global funds MD. ### Funding Statement This review received funding from Collateral Global. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data included in the review is linked to Figshare, an open access repository. See . [1]: http://www.tripdatabase.com
Safety and immunogenicity of the Pfizer/BioNTech SARS-CoV-2 mRNA third booster vaccine dose against the SARS-CoV-2 BA.1 and BA.2 Omicron variants
The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in Japan in November 2021. This variant contains up to 36 mutations in the spike protein, the target of neutralizing antibodies, and can escape vaccine-induced immunity. A booster vaccination campaign began with healthcare workers and high-risk groups. Safety and immunogenicity of the three-dose vaccination against Omicron remain unknown.
Methods
A total of 272 healthcare workers were initially evaluated for long-term vaccine safety and immunogenicity. We further established a vaccinee panel to evaluate the safety and immunogenicity against variants of concern (VOCs), including the Omicron variants, using a live virus microneutralization assay.
Findings
Two-dose vaccination induced robust anti-spike antibodies and neutralization titers (NTs) against the ancestral strain WK-521, whereas NTs against VOCs were significantly lower. Within 93–247 days of the second vaccine dose, NTs against Omicron were completely abolished in up to 80% of individuals in the vaccinee panel. Booster dose induced a robust increase in anti-spike antibodies and NTs against the WK-521, Delta, and Omicron variants. There were no significant differences in the neutralization ability of sera from boosted individuals among the Omicron subvariants BA.1, BA.1.1, and BA.2. Boosting increased the breadth of humoral immunity and cross-reactivity with Omicron without changes in cytokine signatures and adverse event rate.
Conclusions
The third vaccination dose is safe and increases neutralization against Omicron variants.
Das Mittel von Johnson und Johnson galt bislang als der am wenigsten wirksame Impfstoff gegen das Coronavirus. Neue Daten aus den USA zeichnen jetzt ein anderes Bild – Fachleute sind verblüfft.
Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study
The omicron variant (B.1.1.529) of SARS-CoV-2 has demonstrated partial vaccine escape and high transmissibility, with early studies indicating lower severity of infection than that of the delta variant (B.1.617.2). We aimed to better characterise omicron severity relative to delta by assessing the relative risk of hospital attendance, hospital admission, or death in a large national cohort.
Methods
Individual-level data on laboratory-confirmed COVID-19 cases resident in England between Nov 29, 2021, and Jan 9, 2022, were linked to routine datasets on vaccination status, hospital attendance and admission, and mortality. The relative risk of hospital attendance or admission within 14 days, or death within 28 days after confirmed infection, was estimated using proportional hazards regression. Analyses were stratified by test date, 10-year age band, ethnicity, residential region, and vaccination status, and were further adjusted for sex, index of multiple deprivation decile, evidence of a previous infection, and year of age within each age band. A secondary analysis estimated variant-specific and vaccine-specific vaccine effectiveness and the intrinsic relative severity of omicron infection compared with delta (ie, the relative risk in unvaccinated cases).
Findings
The adjusted hazard ratio (HR) of hospital attendance (not necessarily resulting in admission) with omicron compared with delta was 0·56 (95% CI 0·54–0·58); for hospital admission and death, HR estimates were 0·41 (0·39–0·43) and 0·31 (0·26–0·37), respectively. Omicron versus delta HR estimates varied with age for all endpoints examined. The adjusted HR for hospital admission was 1·10 (0·85–1·42) in those younger than 10 years, decreasing to 0·25 (0·21–0·30) in 60–69-year-olds, and then increasing to 0·47 (0·40–0·56) in those aged at least 80 years. For both variants, past infection gave some protection against death both in vaccinated (HR 0·47 [0·32–0·68]) and unvaccinated (0·18 [0·06–0·57]) cases. In vaccinated cases, past infection offered no additional protection against hospital admission beyond that provided by vaccination (HR 0·96 [0·88–1·04]); however, for unvaccinated cases, past infection gave moderate protection (HR 0·55 [0·48–0·63]). Omicron versus delta HR estimates were lower for hospital admission (0·30 [0·28–0·32]) in unvaccinated cases than the corresponding HR estimated for all cases in the primary analysis. Booster vaccination with an mRNA vaccine was highly protective against hospitalisation and death in omicron cases (HR for hospital admission 8–11 weeks post-booster vs unvaccinated: 0·22 [0·20–0·24]), with the protection afforded after a booster not being affected by the vaccine used for doses 1 and 2. Interpretation
The risk of severe outcomes following SARS-CoV-2 infection is substantially lower for omicron than for delta, with higher reductions for more severe endpoints and significant variation with age. Underlying the observed risks is a larger reduction in intrinsic severity (in unvaccinated individuals) counterbalanced by a reduction in vaccine effectiveness. Documented previous SARS-CoV-2 infection offered some protection against hospitalisation and high protection against death in unvaccinated individuals, but only offered additional protection in vaccinated individuals for the death endpoint. Booster vaccination with mRNA vaccines maintains over 70% protection against hospitalisation and death in breakthrough confirmed omicron infections.
Antigenic evolution will lead to new SARS-CoV-2 variants with unpredictable severity
Nature Reviews Microbiology - The comparatively milder infections with the Omicron variant and higher levels of population immunity have raised hopes for a weakening of the pandemic. We argue that...