Risk Of Severe COVID-19 Outcomes Research Articles

Immune Response after Anti-SARS-CoV-2 mRNA Vaccination in Relation to Cellular Immunity, Vitamin D and Comorbidities in Hemodialysis Patients

In the global threat of SARS-CoV-2, individuals undergoing maintenance dialysis represent a vulnerable population with an increased risk of severe COVID-19 outcomes. Therefore, immunization against SARS-CoV-2 is an essential component of healthcare strategy for these patients. Existing data indicate that they tend to exhibit a reduced immune response to vaccines compared to the general population. Our study aimed to assess both humoral and cellular immune responses following two doses of an anti-SARS-CoV-2 mRNA vaccine, an ability to maintain adequate antibody titers over time, and potential relations with vitamin D, comorbidities and other factors in hemodialysis patients based on a single center experience. A total of 41/45 patients (91.1%) responded to the second dose of the anti-SARS-CoV-2 mRNA vaccine. The titer of anti-SARS-CoV-2 IgG class antibodies and levels of T cells three to four weeks after vaccination were lower in dialysis patients than in healthy controls. Antibodies titer in dialysis patients had a positive correlation with B lymphocytes and was related to cardiovascular diseases. The level of CD4+ cells had a negative correlation with hemodialysis vintage, as did the vitamin D level with post-vaccination seroconversion and decline in anti-SARS-CoV-2 antibodies titer during six months after vaccination. Hemodialysis patients had decreased amounts of CD4+ and CD8+ cells and lower levels of anti-SARS-CoV-2 antibodies than healthy controls. Therefore, chronic hemodialysis could lead to diminished cellular immunity and humoral immune response to the anti-SARS-CoV-2 mRNA vaccination and reduced protection from COVID-19. Comorbidity in cardiovascular diseases was associated with a lower level of specific anti-SARS-CoV-2 antibody titer. Vitamin D may be important in maintaining stable levels of anti-SARS-CoV-2 antibodies, while the duration of dialysis treatment could be one of the factors decreasing anti-SARS-CoV-2 antibody titer and determining lower CD4+ cell counts.

Impact of prior antihypertensive treatment on COVID-19 outcomes, by active ingredient.

To assess the impact of prior chronic treatment with angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin-receptor blockers (ARBs), both as a group and by active ingredient, on severity (risk of hospitalization and mortality), progression of and susceptibility to COVID-19. We conducted a multiple population-based case-control study in Galicia (north-west Spain). The study data were sourced from medical, administrative and clinical databases. We assessed: (1) risk of hospitalization, by selecting all patients hospitalized due to COVID-19 with PCR + as cases, and a random sample of subjects without a PCR + as controls; (2) COVID-19 mortality risk; (3) risk of disease progression; and (4) susceptibility to SARS-CoV-2, considering all patients with PCR + as cases, and the same subjects used in the previous model as controls. Adjusted odds ratios (aORs) were calculated. ACEIs and ARBs were shown to decrease the risk of hospitalization (aOR = 0.78 [95%CI 0.69-0.89] and aOR = 0.80 [95%CI 0.72-0.90] respectively), risk of mortality (aOR = 0.71 [95%CI 0.52-0.98] and aOR = 0.69 [95%CI 0.52-0.91] respectively), and susceptibility to the virus (aOR = 0.88 [95%CI 0.82-0.94] and aOR = 0.92 [95%CI 0.86-0.97] respectively). By active ingredient: use of enalapril was associated with a significantly lower risk of hospitalization (aOR = 0.72 [95%CI 0.61-0.85]), mortality (aOR = 0.59 [95%CI 0.38-0.92]) and susceptibility to COVID-19 (aOR = 0.86 [95%CI 0.79-0.94]); and use of candesartan was associated with a decreased risk of hospitalization (aOR = 0.76 [95%CI 0.60-0.95]), mortality (aOR = 0.36 [95%CI 0.17-0.75]) and disease progression (aOR = 0.73 [95%CI 0.56-0.95]). This large-scale real-world data study suggest that enalapril and candesartan are associated with a considerable reduction in risk of severe COVID19 outcomes.

Attitudes Toward COVID-19 Vaccines Among Pregnant and Recently Pregnant Individuals

Pregnant people and infants are at high risk of severe COVID-19 outcomes. Understanding changes in attitudes toward COVID-19 vaccines among pregnant and recently pregnant people is important for public health messaging. To assess attitudinal trends regarding COVID-19 vaccines by (1) vaccination status and (2) race, ethnicity, and language among samples of pregnant and recently pregnant Vaccine Safety Datalink (VSD) members from 2021 to 2023. This cross-sectional surveye study included pregnant or recently pregnant members of the VSD, a collaboration of 13 health care systems and the US Centers for Disease Control and Prevention. Unvaccinated, non-Hispanic Black, and Spanish-speaking members were oversampled. Wave 1 took place from October 2021 to February 2022, and wave 2 took place from November 2022 to February 2023. Data were analyzed from May 2022 to September 2023. Self-reported or electronic health record (EHR)-derived race, ethnicity, and preferred language. Self-reported vaccination status and attitudes toward monovalent (wave 1) or bivalent Omicron booster (wave 2) COVID-19 vaccines. Sample- and response-weighted analyses assessed attitudes by vaccination status and 3 race, ethnicity, and language groupings of interest. There were 1227 respondents; all identified as female, the mean (SD) age was 31.7 (5.6) years, 356 (29.0%) identified as Black race, 555 (45.2%) identified as Hispanic ethnicity, and 445 (36.3%) preferred the Spanish language. Response rates were 43.5% for wave 1 (652 of 1500 individuals sampled) and 39.5% for wave 2 (575 of 1456 individuals sampled). Respondents were more likely than nonrespondents to be White, non-Hispanic, and vaccinated per EHR. Overall, 76.8% (95% CI, 71.5%-82.2%) reported 1 or more COVID-19 vaccinations; Spanish-speaking Hispanic respondents had the highest weighted proportion of respondents with 1 or more vaccination. Weighted estimates of somewhat or strongly agreeing that COVID-19 vaccines are safe decreased from wave 1 to 2 for respondents who reported 1 or more vaccinations (76% vs 50%; χ21 = 7.8; P < .001), non-Hispanic White respondents (72% vs 43%; χ21 = 5.4; P = .02), and Spanish-speaking Hispanic respondents (76% vs 53%; χ21 = 22.8; P = .002). Decreasing confidence in COVID-19 vaccine safety in a large, diverse pregnant and recently pregnant insured population is a public health concern.

Effectiveness of COVID-19 vaccines against severe outcomes in cancer patients: Real-world evidence from self-controlled risk interval and retrospective cohort studies

BackgroundThe effectiveness of COVID-19 vaccines is generally reduced in cancer patients compared to the general population. However, there are only a few studies that compare the relative risk of breakthrough infections and severe COVID-19 outcomes in fully vaccinated cancer patients versus their unvaccinated counterparts. MethodsTo assess the effectiveness of COVID-19 vaccines in cancer patients, we employed (1) a self-controlled risk interval (SCRI) design, and (2) a retrospective matched cohort design. A SCRI design was used to compare the risk of breakthrough infection in vaccinated cancer patients during the period immediately following vaccination (“control window”) and the period in which immunity is achieved (“exposure windows”). The retrospective matched cohort design was used to compare the risk of severe COVID-19 outcomes between vaccinated and unvaccinated cancer patients. For both studies, data were extracted from the Korea Disease Control and Prevention Agency-COVID-19-National Health Insurance Service cohort, including demographics, medical history, and vaccination records of all individuals confirmed with COVID-19. We used conditional Poisson regression to calculate the incidence rate ratio (IRR) for breakthrough infection and Cox regression to estimate the hazard ratio (HR) for severe outcomes. ResultsOf 14,448 cancer patients diagnosed with COVID-19 between October 2020 and December 2021, a total of 217 and 3996 cancer patients were included in the SCRI and cohort study respectively. While the risk of breakthrough infections, measured by the incidence rate in the control and exposure windows, did not show statistically significant difference in vaccinated cancer patients (IRR=0.88, 95% CI: 0.64–1.22), the risk of severe COVID-19 outcomes was significantly lower in vaccinated cancer patients compared to those unvaccinated (HR=0.27, 95% CI: 0.22–0.34). ConclusionCOVID-19 vaccines significantly reduce the risk of severe outcomes in cancer patients, though their efficacy against breakthrough infections is less evident.

Undervaccination and severe COVID-19 outcomes: meta-analysis of national cohort studies in England, Northern Ireland, Scotland, and Wales

Undervaccination (receiving fewer than the recommended number of SARS-CoV-2 vaccine doses) could be associated with increased risk of severe COVID-19 outcomes-ie, COVID-19 hospitalisation or death-compared with full vaccination (receiving the recommended number of SARS-CoV-2 vaccine doses). We sought to determine the factors associated with undervaccination, and to investigate the risk of severe COVID-19 outcomes in people who were undervaccinated in each UK nation and across the UK. We used anonymised, harmonised electronic health record data with whole population coverage to carry out cohort studies in England, Northern Ireland, Scotland, and Wales. Participants were required to be at least 5 years of age to be included in the cohorts. We estimated adjusted odds ratios for undervaccination as of June 1, 2022. We also estimated adjusted hazard ratios (aHRs) for severe COVID-19 outcomes during the period June 1 to Sept 30, 2022, with undervaccination as a time-dependent exposure. We combined results from nation-specific analyses in a UK-wide fixed-effect meta-analysis. We estimated the reduction in severe COVID-19 outcomes associated with a counterfactual scenario in which everyone in the UK was fully vaccinated on June 1, 2022. The numbers of people undervaccinated on June 1, 2022 were 26 985 570 (45·8%) of 58 967 360 in England, 938 420 (49·8%) of 1 885 670 in Northern Ireland, 1 709 786 (34·2%) of 4 992 498 in Scotland, and 773 850 (32·8%) of 2 358 740 in Wales. People who were younger, from more deprived backgrounds, of non-White ethnicity, or had a lower number of comorbidities were less likely to be fully vaccinated. There was a total of 40 393 severe COVID-19 outcomes in the cohorts, with 14 156 of these in undervaccinated participants. We estimated the reduction in severe COVID-19 outcomes in the UK over 4 months of follow-up associated with a counterfactual scenario in which everyone was fully vaccinated on June 1, 2022 as 210 (95% CI 94-326) in the 5-15 years age group, 1544 (1399-1689) in those aged 16-74 years, and 5426 (5340-5512) in those aged 75 years or older. aHRs for severe COVID-19 outcomes in the meta-analysis for the age group of 75 years or older were 2·70 (2·61-2·78) for one dose fewer than recommended, 3·13 (2·93-3·34) for two fewer, 3·61 (3·13-4·17) for three fewer, and 3·08 (2·89-3·29) for four fewer. Rates of undervaccination against COVID-19 ranged from 32·8% to 49·8% across the four UK nations in summer, 2022. Undervaccination was associated with an elevated risk of severe COVID-19 outcomes. UK Research and Innovation National Core Studies: Data and Connectivity.

Risk of severe COVID-19 outcomes after autumn 2022 COVID-19 booster vaccinations: a pooled analysis of national prospective cohort studies involving 7.4 million adults in England, Northern Ireland, Scotland and Wales

UK COVID-19 vaccination policy has evolved to offering COVID-19 booster doses to individuals at increased risk of severe Illness from COVID-19. Building on our analyses of vaccine effectiveness of first, second and initial booster doses, we aimed to identify individuals at increased risk of severe outcomes (i.e., COVID-19 related hospitalisation or death) post the autumn 2022 booster dose. We undertook a national population-based cohort analysis across all four UK nations through linked primary care, vaccination, hospitalisation and mortality data. We included individuals who received autumn 2022 booster doses of BNT162b2 (Comirnaty) or mRNA-1273 (Spikevax) during the period September 1, 2022 to December 31, 2022 to investigate the risk of severe COVID-19 outcomes. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) for the association between demographic and clinical factors and severe COVID-19 outcomes after the autumn booster dose. Analyses were adjusted for age, sex, body mass index (BMI), deprivation, urban/rural areas and comorbidities. Stratified analyses were conducted by vaccine type. We then conducted a fixed-effect meta-analysis to combine results across the four UK nations. Between September 1, 2022 and December 31, 2022, 7,451,890 individuals ≥18 years received an autumn booster dose. 3500 had severe COVID-19 outcomes (2.9 events per 1000 person-years). Being male (male vs female, aHR 1.41 (1.32-1.51)), older adults (≥80 years vs 18-49 years; 10.43 (8.06-13.50)), underweight (BMI <18.5 vs BMI 25.0-29.9; 2.94 (2.51-3.44)), those with comorbidities (≥5 comorbidities vs none; 9.45 (8.15-10.96)) had a higher risk of COVID-19 hospitalisation or death after the autumn booster dose. Those with a larger household size (≥11 people within household vs 2 people; 1.56 (1.23-1.98)) and from more deprived areas (most deprived vs least deprived quintile; 1.35 (1.21-1.51)) had modestly higher risks. We also observed at least a two-fold increase in risk for those with various chronic neurological conditions, including Down's syndrome, immunodeficiency, chronic kidney disease, cancer, chronic respiratory disease, or cardiovascular disease. Males, older individuals, underweight individuals, those with an increasing number of comorbidities, from a larger household or more deprived areas, and those with specific underlying health conditions remained at increased risk of COVID-19 hospitalisation and death after the autumn 2022 vaccine booster dose. There is now a need to focus on these risk groups for investigating immunogenicity and efficacy of further booster doses or therapeutics. National Core Studies-Immunity, UK Research and Innovation (Medical Research Council and Economic and Social Research Council), Health Data Research UK, the Scottish Government, and the University of Edinburgh.

Anti-Interleukin-1 Therapy Does Not Affect the Response to SARS-CoV-2 Vaccination and Infection in Patients with Systemic Autoinflammatory Diseases.

Patients with systemic autoinflammatory diseases (sAIDs) are a section of the population at high risk of severe COVID-19 outcomes, but evidence on the efficacy of SARS-CoV-2 vaccination in this group of patients is scarce. To investigate the efficacy of SARS-CoV-2 vaccination in patients with sAIDs receiving interleukin-1 (IL-1) inhibition is important. Vaccination and infection responses from 100 sAID patients and 100 healthy controls (HCs) were analyzed. In total, 98% of patients were treated with IL-1 inhibitors at the time of vaccination (n = 98). After the second SARS-CoV-2 vaccination, sAID patients showed similar anti-SARS-CoV-2 antibody responses (mean (standard deviation (SD)): 6.7 (2.7)) compared to HCs (5.7 (2.4)) as well as similar neutralizing antibodies (85.1 ± 22.9% vs. 82.5 ± 19.7%). Anti-SARS-CoV-2 antibody responses and neutralizing antibodies were similar in sAID patients after SARS-CoV-2 infection and double vaccination. Furthermore, while antibodies increased after the first and second vaccination in sAID patients, they did not further increase after the third and fourth vaccination. No difference was found in antibody responses between anakinra and anti-IL-1 antibody treatment and the additional use of colchicine or other drugs did not impair vaccination responses. Primary and booster SARS-CoV-2 vaccinations led to protective antibody responses in sAID patients, which were at the same level of vaccination responses in HCs and in sAID patients after SARS-CoV-2 infection. Immunomodulatory treatments used in sAID do not seem to affect antibody responses to the SARS-CoV-2 vaccine.

Sample average treatment effect on the treated (SATT) analysis using counterfactual explanation identifies BMT and SARS-CoV-2 vaccination as protective risk factors associated with COVID-19 severity and survival in patients with multiple myeloma

Patients with multiple myeloma (MM), an age-dependent neoplasm of antibody-producing plasma cells, have compromised immune systems and might be at increased risk for severe COVID-19 outcomes. This study characterizes risk factors associated with clinical indicators of COVID-19 severity and all-cause mortality in myeloma patients utilizing NCATS’ National COVID Cohort Collaborative (N3C) database. The N3C consortium is a large, centralized data resource representing the largest multi-center cohort of COVID-19 cases and controls nationwide (>16 million total patients, and >6 million confirmed COVID-19+ cases to date). Our cohort included myeloma patients (both inpatients and outpatients) within the N3C consortium who have been diagnosed with COVID-19 based on positive PCR or antigen tests or ICD-10-CM diagnosis code. The outcomes of interest include all-cause mortality (including discharge to hospice) during the index encounter and clinical indicators of severity (i.e., hospitalization/emergency department/ED visit, use of mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)). Finally, causal inference analysis was performed using the Coarsened Exact Matching (CEM) and Propensity Score Matching (PSM) methods. As of 05/16/2022, the N3C consortium included 1,061,748 cancer patients, out of which 26,064 were MM patients (8,588 were COVID-19 positive). The mean age at COVID-19 diagnosis was 65.89 years, 46.8% were females, and 20.2% were of black race. 4.47% of patients died within 30 days of COVID-19 hospitalization. Overall, the survival probability was 90.7% across the course of the study. Multivariate logistic regression analysis showed histories of pulmonary and renal disease, dexamethasone, proteasome inhibitor/PI, immunomodulatory/IMiD therapies, and severe Charlson Comorbidity Index/CCI were significantly associated with higher risks of severe COVID-19 outcomes. Protective associations were observed with blood-or-marrow transplant/BMT and COVID-19 vaccination. Further, multivariate Cox proportional hazard analysis showed that high and moderate CCI levels, International Staging System (ISS) moderate or severe stage, and PI therapy were associated with worse survival, while BMT and COVID-19 vaccination were associated with lower risk of death. Finally, matched sample average treatment effect on the treated (SATT) confirmed the causal effect of BMT and vaccination status as top protective factors associated with COVID-19 risk among US patients suffering from multiple myeloma. To the best of our knowledge, this is the largest nationwide study on myeloma patients with COVID-19.

Impact of COVID-19 on immunocompromised populations during the Omicron era: insights from the observational population-based INFORM study.

Immunocompromised individuals are not optimally protected by COVID-19 vaccines and potentially require additional preventive interventions to mitigate the risk of severe COVID-19. We aimed to characterise and describe the risk of severe COVID-19 across immunocompromised groups as the pandemic began to transition to an endemic phase. COVID-19-related hospitalisations, intensive care unit (ICU) admissions, and deaths (01/01/2022-31/12/2022) were compared among different groups of immunocompromised individuals vs the general population, using a retrospective cohort design and electronic health data from a random 25% sample of the English population aged ≥12 years (Registration number: ISRCTN53375662). Overall, immunocompromised individuals accounted for 3.9% of the study population, but 22% (4585/20,910) of COVID-19 hospitalisations, 28% (125/440) of COVID-19 ICU admissions, and 24% (1145/4810) of COVID-19 deaths in 2022. Restricting to those vaccinated with ≥3 doses of COVID-19 vaccine (∼84% of immunocompromised and 51% of the general population), all immunocompromised groups remained at increased risk of severe COVID-19 outcomes, with adjusted incidence rate ratios (aIRR) for hospitalisation ranging from 1.3 to 13.1. At highest risk for COVID-19 hospitalisation were individuals with: solid organ transplant (aIRR 13.1, 95% confidence interval [95% CI] 11.2-15.3), moderate to severe primary immunodeficiency (aIRR 9.7, 95% CI 6.3-14.9), stem cell transplant (aIRR 11.0, 95% CI 6.8-17.6), and recent treatment for haematological malignancy (aIRR 10.6, 95% CI 9.5-11.9). Results were similar for COVID-19 ICU admissions and deaths. Immunocompromised individuals continue to be impacted disproportionately by COVID-19 and have an urgent need for additional preventive measures beyond current vaccination programmes. These data can help determine the immunocompromised groups for which targeted prevention strategies may have the highest impact. This study was funded by AstraZeneca UK.

Joint exposure to urban-rural status and medically underserved area residence and risk of severe COVID-19 outcomes in 2020.

The purpose of this study is to estimate the risk of severe COVID-19 among individuals residing in rural, medically underserved counties compared to those living in other counties. Individual-level COVID-19 hospitalization and death data and demographic variables were downloaded from the Centers for Disease Control and Prevention. The 2013 National Center for Health Statistics Urban-Rural Classification Scheme was used to classify urban and rural counties. Health Resources and Services Administration's medically underserved area (MUA) designation was used to identify underserved counties. County-level data were drawn from the 2015-2019 American Community Survey 5-year estimates. Analytic samples included data from Minnesota and Montana in 2020. Urban-rural/MUA joint exposure categories were created: rural/MUA, rural/non-MUA, urban/MUA, urban/non-MUA. Hierarchical logistic regression models estimated associations (odds ratios and 95% confidence intervals (CI)) between rurality, MUA status, joint urban-rural/MUA status, and severe COVID-19, overall and stratified by age and state. Models were adjusted for individual- and county-level demographics. The odds of severe outcomes among those living in rural counties were 13% lower (95%CI: 0.83-0.91) than those in urban counties. The odds of severe outcomes among those living in MUA counties were 24% higher (95%CI: 1.18-1.30) than those in non-MUA counties. For joint exposure analyses, the odds of severe outcomes were highest among those living in urban/MUA counties compared to those in rural/non-MUA counties (adjusted odds ratio: 1.36, 95%CI: 1.27-1.44). In 2020, the risk of severe COVID-19 was more pronounced in urban counties and underserved areas. Results highlight the need for locality-based public health recommendations that account for rural and underserved areas and may inform future pandemic preparedness by identifying counties most in need of resources and education at various stages of the pandemic.

398. Increased Risk of Severe COVID-19 Outcomes Across all Groups of Individuals with Hematological Malignancies, Solid Tumors, and Solid Organ Transplants Compared with the General Population: Initial Results from INFORM, a Retrospective Health Database Observational Study in England

Abstract Background Despite COVID-19 vaccination, individuals who are immunocompromised due to underlying conditions, such as cancer and organ transplant, are at a greater risk of severe COVID-19 outcomes compared with the general population that is vaccinated. However, there are limited data quantifying this risk during the omicron-predominant period, particularly for important sub-groups that may have variable risk for severe COVID-19 outcomes. We report initial findings from the INFORM study describing the clinical burden and severe COVID-19 outcomes in patients with immunocompromised conditions (IC) in England, UK in 2022. Methods This retrospective cohort study utilized National Health Service database in England. The study period was from Jan 1–Dec 31, 2022 and the baseline period for assessment of patient characteristics, including IC, was from Jan 1, 2017–Dec 31, 2021. Definitions of IC sub-groups are provided in Table 1. Severe COVID-19 outcomes were defined as COVID-19–related hospitalization, COVID-19–related intensive care unit (ICU) admission, and/or COVID-related death. Results Of the 11,990,730 individuals in the general population sample aged ≥ 12 years, 468,745 (3.9%) were immunocompromised and accounted for approximately one-quarter of severe COVID-19–related outcomes (22% of hospitalizations, 28% of ICU admissions, and 23% of deaths; Table 2). The risk of severe COVID-19 outcomes was higher in well-recognized IC conditions (eg, solid organ transplants, hematological malignancies, and solid tumors) across all the sub-groups compared with the overall population (Table 2). Conclusion There is an increased burden in the prevalence of severe COVID-19 outcomes among all individuals with IC, highlighting the need for additional protection to target this population. Disclosures Richard McNulty, MD, AstraZeneca: Employee Sabada Dube, PhD, AstraZeneca: Employee Yi Lu, PhD, Evidera: Employee Sophie Graham, MSc, Evidera: Employee Sofie Arnetorp, MS, AstraZeneca: Employee Nahila Justo, PhD, MBA, Evidera: Employee|Karolinska Institute: Employee Renata Yokota, PhD, AstraZeneca: Employee Kathryn Evans, MPH, Evidera: Employee Sudhir Venkatesan, MPH, PhD, AstraZeneca: Employee Mark Yates, PhD, Evidera: Employee Sylvia Taylor, PhD, MPH, MBA, AstraZeneca: Stocks/Bonds Jennifer Quint, PhD, AstraZeneca: Grant/Research Support|Evidera: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Insmed: Grant/Research Support Rachael A. Evans, PhD FRCP, AstraZeneca: Advisor/Consultant|Boehringer: Advisor/Consultant|Evidera: Advisor/Consultant

1096. Fully Vaccinated Individuals with Immunocompromised Conditions (IC) are Still at Increased Risk of Severe COVID-19 Outcomes From the Omicron Variant: Initial Results From INFORM, a Retrospective Health Database Observational Study in England

Abstract Background UK vaccination programs have reduced COVID-19–related hospitalizations and deaths in the overall population, yet vaccinated individuals with immunocompromised conditions (IC) are still at high risk of severe COVID-19 outcomes. Contemporary evidence on severe outcomes in vaccinated individuals with IC is needed, particularly in the post-pandemic omicron period. Initial results from INFORM, an observational retrospective cohort study describing COVID-19 health burden in individuals with and without IC vaccinated with ≥ 3 doses of a COVID-19 vaccine in England, are presented. Methods Data from primary and secondary care linked to COVID-19 surveillance, vaccination records, primary care dispensations, and mortality, were accessed via National Health Service (NHS) database (Figure 1). The study period was Jan 1, 2022–Dec 31, 2022. Baseline characteristics were identified during the period Jan 1, 2017–Dec 31, 2021. Incidence rates (IR) are presented per 100 person-years (PY).Figure 1.Study design: observational retrospective database study Results Almost 90% of individuals with IC received ≥ 3 vaccine doses compared with 60% in the overall population aged ≥ 12 years (Table 1). Among individuals receiving ≥ 3 vaccine doses, COVID-19 hospitalization IRs were 0.92 (95% confidence interval [CI]: 0.89–0.95) in individuals with IC, compared with 0.22 (95% CI: 0.21–0.23) per 100 PY in the overall population. When analyzed by IC type, IRs were higher than the total vaccinated population across all IC subgroups (RR = 2.5–21) (Table 2). COVID-19 hospitalization IRs in patients with hematological malignancies currently under treatment were 4.65 (95% CI: 4.42–4.88) and those with organ transplants were 2.95 per 100 PY (95% CI: 2.7–3.2) (Table 2). Mortality IRs per 100 PY were also consistently higher across all IC groups. Conclusion Within a population vaccinated with ≥ 3 doses, individuals with IC had a higher risk of COVID-19 hospitalization and COVID-19 death compared with the overall population. This risk of severe COVID-19 outcomes was elevated across all IC groups, regardless of past or current treatment or procedure despite being vaccinated. Disclosures Sabada Dube, PhD, AstraZeneca: Employee Yi Lu, PhD, Evidera: Employee Richard McNulty, MD, AstraZeneca: Employee Sophie Graham, MSc, Evidera: Employee Sofie Arnetorp, MS, AstraZeneca: Employee Nahila Justo, PhD, MBA, Evidera: Employee|Karolinska Institute: Employee Renata Yokota, PhD, AstraZeneca: Employee Kathryn Evans, MPH, Evidera: Employee Sudhir Venkatesan, MPH, PhD, AstraZeneca: Employee Mark Yates, PhD, Evidera: Employee Sylvia Taylor, PhD, MPH, MBA, AstraZeneca: Stocks/Bonds Jennifer Quint, PhD, AstraZeneca: Grant/Research Support|Evidera: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Insmed: Grant/Research Support Rachael A. Evans, PhD FRCP, AstraZeneca: Advisor/Consultant|Boehringer: Advisor/Consultant|Evidera: Advisor/Consultant

Comparative effectiveness of nirmatrelvir/ritonavir versus sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised high-risk patients during Omicron waves: observational cohort study using the OpenSAFELY platform.

Timely evidence of the comparative effectiveness between COVID-19 therapies in real-world settings is needed to inform clinical care. This study aimed to compare the effectiveness of nirmatrelvir/ritonavir versus sotrovimab and molnupiravir in preventing severe COVID-19 outcomes in non-hospitalised high-risk COVID-19 adult patients during Omicron waves. With the approval of NHS England, we conducted a real-world cohort study using the OpenSAFELY-TPP platform. Patient-level primary care data were obtained from 24 million people in England and were securely linked with data on COVID-19 infection and therapeutics, hospital admission, and death, covering a period where both nirmatrelvir/ritonavir and sotrovimab were first-line treatment options in community settings (February 10, 2022-November 27, 2022). Molnupiravir (third-line option) was used as an exploratory comparator to nirmatrelvir/ritonavir, both of which were antivirals. Cox proportional hazards model stratified by area was used to compare the risk of 28-day COVID-19 related hospitalisation/death across treatment groups. A total of 9026 eligible patients treated with nirmatrelvir/ritonavir (n=5704) and sotrovimab (n=3322) were included in the main analysis. The mean age was 52.7 (SD=14.9) years and 93% (8436/9026) had three or more COVID-19 vaccinations. Within 28 days after treatment initiation, 55/9026 (0.61%) COVID-19 related hospitalisations/deaths were observed (34/5704 [0.60%] treated with nirmatrelvir/ritonavir and 21/3322 [0.63%] with sotrovimab). After adjusting for demographics, high-risk cohort categories, vaccination status, calendar time, body mass index and other comorbidities, we observed no significant difference in outcome risk between nirmatrelvir/ritonavir and sotrovimab users (HR=0.89, 95% CI: 0.48-1.63; P=0.698). Results from propensity score weighted model also showed non-significant difference between treatment groups (HR=0.82, 95% CI: 0.45-1.52; P=0.535). The exploratory analysis comparing nirmatrelvir/ritonavir users with 1041 molnupiravir users (13/1041 [1.25%] COVID-19 related hospitalisations/deaths) showed an association in favour of nirmatrelvir/ritonavir (HR=0.45, 95% CI: 0.22-0.94; P=0.033). In routine care of non-hospitalised high-risk adult patients with COVID-19 in England, no substantial difference in the risk of severe COVID-19 outcomes was observed between those who received nirmatrelvir/ritonavir and sotrovimab between February and November 2022, when Omicron subvariants BA.2, BA.5, or BQ.1 were dominant. UK Research and Innovation, Wellcome Trust, UK Medical Research Council, National Institute for Health and Care Research, and Health Data Research UK.

Age, successive waves, immunization, and mortality in elderly COVID-19 hematological patients: EPICOVIDEHA findings

ObjectivesElderly patients with hematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection's impact on different age groups remains unstudied in detail. MethodsWe analyzed elderly patients (age groups: 65-70, 71-75, 76-80, and >80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with hematological malignancy. ResultsThe study included data from 3,603 elderly patients (aged 65 or older) with hematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves. The 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. Factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. ConclusionThese data underscore the heterogeneity of elderly hematological patients, highlight the different impacts of COVID-19 waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts.

Effect of Immunosuppressive or Immunomodulatory Agents on Severe COVID-19 Outcomes: A Population-Based Cohort Study.

We estimated the association between immunosuppressive and immunomodulatory agent (IIA) exposure and severe COVID-19 outcomes in a population-based cohort study. Participants were 18 years or older, tested positive for SARS-CoV-2 between February 6, 2020, and August 15, 2021, and were from administrative health data for the entire province of British Columbia, Canada. IIA use within 3 months prior to positive SARS-CoV-2 test included conventional disease-modifying antirheumatic drugs (antimalarials, methotrexate, leflunomide, sulfasalazine, individually), immunosuppressants (azathioprine, mycophenolate mofetil/mycophenolate sodium [MMF], cyclophosphamide, cyclosporine, individually and collectively), tumor necrosis factor inhibitor (TNFi) biologics (adalimumab, certolizumab, etanercept, golimumab, infliximab, collectively), non-TNFi biologics or targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) (rituximab separately from abatacept, anakinra, secukinumab, tocilizumab, tofacitinib and ustekinumab collectively), and glucocorticoids. Severe COVID-19 outcomes were hospitalizations for COVID-19, ICU admissions, and deaths within 60 days of a positive test. Exposure score-overlap weighting was used to balance baseline characteristics of participants with IIA use compared with nonuse of that IIA. Logistic regression measured the association between IIA use and severe COVID-19 outcomes. From 147,301 participants, we identified 515 antimalarial, 573 methotrexate, 72 leflunomide, 180 sulfasalazine, 468 immunosuppressant, 378 TNFi biologic, 49 rituximab, 144 other non-TNFi biologic or tsDMARD, and 1348 glucocorticoid prescriptions. Risk of hospitalizations for COVID-19 was significantly greater for MMF (odds ratio [95% CI]): 2.82 [1.81-4.40], all immunosuppressants: 2.08 [1.51-2.87], and glucocorticoids: 1.63 [1.36-1.96], relative to nonuse. Similar outcomes were seen for ICU admission and MMF: 2.52 [1.34-4.74], immunosuppressants: 2.88 [1.73-4.78], and glucocorticoids: 1.86 [1.37-2.54]. Only glucocorticoids use was associated with a significant increase in 60-day mortality: 1.58 [1.21-2.06]. No other IIAs displayed statistically significant associations with severe COVID-19 outcomes. Current use of MMF and glucocorticoids were associated with an increased risk of severe COVID-19 outcomes compared with nonuse. These results emphasize the variety of circumstances of patients taking IIAs.

Association of weight changes with SARS-CoV-2 infection and severe COVID-19 outcomes: A nationwide retrospective cohort study

BackgroundObesity is a risk factor for COVID-19. However, it is unknown whether weight changes can alter this risk. We investigated the association of weight changes with SARS-CoV-2 infection and acute severe COVID-19 outcomes occurring within two months of the infection. MethodsWe used 6.3 million nationwide cohort. The body weight was classified as follows: (1) underweight, body mass index (BMI) < 18.5 kg/m2; (2) normal, BMI 18.5–22.9 kg/m2; (3) overweight, BMI 23–24.9 kg/m2; (4) obese, BMI≥ 25 kg/m2. Weight changes were defined by comparing the classification of body weight during the health screening period I and II. The outcomes were SARS-CoV-2 infection and severe COVID-19 outcomes within two months after the infection. The association was evaluated using multivariable-adjusted logistic regression. The following covariates were adjusted: age, sex, household income, cigarette smoking, alcohol consumption, physical activity, hypertension, diabetes mellitus, dyslipidemia, Charlson comorbidity index score, and dose of all COVID-19 vaccinations prior to SARS-CoV-2 infection. ResultsOf the 2119,460 study participants, 184,204 were infected with SARS-CoV-2. Weight gain showed a higher risk of SARS-CoV-2 infection in underweight to normal and normal to overweight groups. Conversely, weight loss showed a lower risk of SARS-CoV-2 infection in normal to underweight, overweight to underweight, overweight to normal, obese to normal, and obese to overweight groups. In addition, weight gain revealed a higher risk of severe COVID-19 outcomes, whereas weight loss showed a lower risk of severe COVID-19 outcomes. ConclusionThis study found that weight loss and gain are associated with a lower and higher risk of both SARS-CoV-2 infection and severe COVID-19 outcomes, respectively. Healthy weight management may be beneficial against the risk of COVID-19.

The impact of periodontal disease on the clinical outcomes of COVID-19: A systematic review and meta-analysis

BackgroundA possible relationship between periodontitis (PD) and COVID-19 and its adverse outcomes has been suggested. Hence, the present systematic review and meta-analysis aimed to investigate the available evidence regarding the potential association between periodontitis (PD) and COVID-19 and its adverse outcomes.Materials and methodsPubMed, Scopus, Web of Science, and Google Scholar were searched for relevant studies published up to April 15th, 2023. Studies that evaluated the association between PD and COVID-19 were included. Risk of bias was evaluated by two reviewers, and meta-analyses were performed using RevMan 5.3 software.ResultsA total of 22 studies involving 92,535 patients from USA, Europe, Asia, the Middle East and South America were included; of these, 12 were pooled into the meta-analysis. Most of the studies (19 studies) reported a significant association between PD and COVID-19. The pooled data found a significant association between PD and COVID-19 outcomes: more severe symptoms (OR = 6.95, P = 0.0008), ICU admissions (OR = 3.15, P = 0.0001), and mortality (OR = 1.92, P = 0.21). Additionally, compared to mild PD, severe PD was significantly associated with higher risks of severe COVID-19 outcomes: severe symptoms (P = 0.02); ICU admission (P = 0.0001); and higher mortality rates (P = 0.0001). The results also revealed 58% higher risk for COVID-19 infection in patients with PD (P = 0.00001).ConclusionsThe present findings suggest a possible association between poor periodontal health and the risk of poor COVID-19 outcomes. However, owing to the observed methodological heterogeneity across the included studies, further prospective cohort studies with standardized methodologies are warranted to further unravel the potential association between periodontal disease and COVID-19 and its adverse outcomes.

Calcitonin Gene–Related Peptide Monoclonal Antibodies and Risk of SARS-CoV-2 Infection and Severe COVID-19 Outcomes Among Veterans With Migraine Disorder

Calcitonin gene-related peptide (CGRP), a neuropeptide involved in migraine pathophysiology, is also a key neuroimmune modulator. CGRP antagonists may help mitigate the hyperinflammatory response observed in patients with COVID-19; however, findings from the literature are contradictory, and to date, no study has investigated the safety and effectiveness of CGRP antagonists against COVID-19. To evaluate the association between CGRP monoclonal antibody (mAb) treatment and risk of SARS-CoV-2 infection and sequela hospitalization, requiring supplemental oxygen, use of mechanical ventilation, or death. This retrospective cohort study analyzed the electronic health records of US veterans aged 18 to 65 years who were diagnosed with migraine disorder and were at risk of COVID-19 between January 20, 2020, and May 19, 2022. Initiation of CGRP mAbs. The main outcome was cumulative incidence of SARS-CoV-2 infection. Odds of 30-day hospitalization, requiring supplemental oxygen, use of mechanical ventilation, or death were secondary outcomes. Among 8 178 652 eligible person-trials (354 294 veterans), 9992 (mean [SD] age, 46.0 [9.5] years; 53.9% male) initiated CGRP mAbs and 8 168 660 (mean [SD] age, 46.6 [10.2] years; 65.7% male) did not initiate CGRP mAbs. Over a 28-month follow-up period, 1247 initiators (12.5%) and 780 575 noninitiators (9.6%) tested positive for SARS-CoV-2. After censoring persons who deviated from treatment, the incidence was 7.4 cases per 1000 person-months among initiators and 6.9 per 1000 person-months among noninitiators. The inverse probability-weighted observational analogs of intention-to-treat and per-protocol hazard ratios were 0.95 (95% CI, 0.89-1.01) and 0.93 (95% CI, 0.86-1.02), respectively. No significant differences in the likelihood of hospitalization (odds ratio [OR], 0.93; 95% CI, 0.62-1.41), requiring supplemental oxygen (OR, 0.77; 95% CI, 0.45-1.30), use of mechanical ventilation (OR, 0.85; 95% CI, 0.26-2.84), or death (OR, 0.67; 95% CI, 0.09-5.23) were observed between CGRP mAb initiators and noninitiators who tested positive for SARS-CoV-2. In this cohort study, CGRP mAb treatment was not associated with positive SARS-CoV-2 test results or risk of severe COVID-19 outcomes, suggesting that CGRP mAbs may be used for migraine prevention during the COVID-19 pandemic. Given the few events of requiring supplemental oxygen, use of mechanical ventilation, and death, replication analysis in a larger sample of patients later in the course of disease is warranted.

Efficacy and safety of tixagevimab-cilgavimab (Evusheld®) in people with Multiple Sclerosis on Ocrelizumab: preliminary evidence.

Evusheld (EVS) was authorized by FDA and EMA as pre-exposure prophylaxis (PrEP) in people at high risk of severe Covid-19 outcomes, including people with Multiple Sclerosis (pwMS) on B-cell depleting (BCD) therapies-such as Ocrelizumab (OCR). In this population, no data on possible adverse drug reactions (ADRs) to EVS, B-lymphocytes (CD20 +) counts pre- and post-EVS injection, and comparison of percentage increase of IgGantibodies directed against SARS-CoV-2trimericspikeprotein (anti-TSP IgG) post-EVS and Covid-19 vaccine was available. The aim of this study was to better characterize the efficacy and safety profile of EVS in pwMS on BCD agents. 17 pwMS on OCR agreed to receive EVS as PrEP for Covid-19. Sera samples were collected before the first dose of Covid-19 vaccine (T0), 4weeks after the second dose (T1), 4weeks after third dose (T2), immediately before (T3) and 4weeks after (T4) EVS. Covid-19 vaccine ADRs were mild-to-moderate, whereas no ADRs were reported after EVS injection.A significant increase of anti-TSP IgG was found only at T0-T1 (Z = -3.059, p = .002) and T3-T4 (Z = -3.621, p < .001) time-points. The median percentage increase between T3-T4 was significantly higher with respect to the T0-T1(Z = -3.296, p = .001) and T1-T2 (Z = -3.059, p = .002) time-points. These results further support EVS safety and efficacy in boosting anti-TSP IgG titers in pwMS on OCR, with a statistically greater increase than that observed after completion of a full Covid-19 vaccine cycle, plus a booster dose.

Assessing the risk and costs of COVID-19 in immunocompromised populations in a large United States commercial insurance health plan: the EPOCH-US Study

Objective To estimate the prevalence of patients with an immunocompromising condition at risk for COVID-19, estimate COVID-19 prevalence rate (PR) and incidence rate (IR) by immunocompromising condition, and describe COVID-19-related healthcare resource utilization (HCRU) and costs. Methods Using the Healthcare Integrated Research Database (HIRD)®, patients with ≥1 claim for an immunocompromising condition of interest or ≥2 claims for an immunosuppressive (IS) treatment and COVID-19 diagnosis during the infection period (April 1, 2020–March 31, 2022) and had ≥12 months baseline data were included. Cohorts (other than the composite cohort) were not mutually exclusive and were defined by each immunocompromising condition. Analyses were descriptive in nature. Results Of the 16,873,161 patients in the source population, 2.7% (n = 458,049) were immunocompromised (IC). The COVID-19 IR for the composite IC cohort during the study period was 101.3 per 1,000 person-years and the PR was 13.5%. The highest IR (195.0 per 1,000 person-years) and PR (20.1%) was seen in the end-stage renal disease (ESRD) cohort; the lowest IR (68.3 per 1,000 person-years) and PR (9.4%) was seen in the hematologic or solid tumor malignancy cohort. Mean costs for hospitalizations associated with first COVID-19 diagnosis were estimated at nearly $1 billion (2021 United States dollars [USD]) for 14,516 IC patients, with a mean cost of $64,029 per patient. Conclusions Immunocompromised populations appear to be at substantial risk of severe COVID-19 outcomes, leading to increased costs and HCRU. Effective prophylactic options are still needed for these high-risk populations as the COVID-19 landscape evolves.