Severe COVID-19 Outcomes Research Articles

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.

Association between SARS-CoV-2 RNAemia, skewed T cell responses, inflammation, and severity in hospitalized COVID-19 people living with HIV

Severe COVID-19 outcomes have been reported in people living with HIV (PLWH), yet the underlying pathogenetic factors are largely unknown. We therefore aimed to assess SARS-CoV-2 RNAemia and plasma cytokines in PLWH hospitalized for COVID-19 pneumonia, exploring associations with magnitude and functionality of SARS-CoV-2-specific immune responses. Eighteen unvaccinated PLWH (16/18 on cART; median CD4 Tcell count 361.5/μL; HIV-RNA<50 cp/mL in 15/18) and 18 age/sex-matched people without HIV were consecutively recruited at a median time of 10days from symptoms onset. PLWH showed greater SARS-CoV-2 RNAemia, a distinct plasma cytokine profile, and worse respiratory function (lower PaO2/FiO2nadir), all correlating with skewed Tcell responses (higher perforin production by cytotoxic Tcells as well as fewer and less polyfunctional SARS-CoV-2-specific Tcells), despite preserved humoral immunity. In conclusion, these data suggest a link between HIV-related Tcell dysfunction and poor control over SARS-CoV-2 replication/dissemination that may in turn influence COVID-19 severity in PLWH.

The impact of multimorbidity on severe COVID-19 outcomes in community and congregate settings.

This study examined the impact of multimorbidity on severe COVID-19 outcomes in community and long-term care (LTC) settings, alone and in interaction with age and sex. We conducted a retrospective cohort study of all Ontarians who tested positive for COVID-19 between January-2020 and May-2021 with follow-up until June 2021. We used cox regression to evaluate the adjusted impact of multimorbidity, individual characteristics, and interactions on time to hospitalization and death (any cause). 24.5% of the cohort had 2 or more pre-existing conditions. Multimorbidity was associated with 28% to 170% shorter time to hospitalization and death, respectively. However, predictors of hospitalization and death differed for people living in community and LTC. In community, increasing multimorbidity and age predicted shortened time to hospitalization and death. In LTC, we found none of the predictors examined were associated with time to hospitalization, except for increasing age that predicted reduced time to death up to 40.6 times. Sex was a predictor across all settings and outcomes: among male the risk of hospitalization or death was higher shortly after infection (e.g. HR for males at 14days=30.3) while among female risk was higher for both outcome in the longer term (e.g. HR for males at 150days=0.16). Age and sex modified the impact of multimorbidity in the community. Community-focused public health measures should be targeted and consider sociodemographic and clinical characteristics such as multimorbidity. In LTC settings, further research is needed to identify factors that may contribute to improved outcomes.

Protection of the third-dose and fourth-dose mRNA vaccines against SARS-CoV-2 Omicron subvariant: a systematic review and meta-analysis

ObjectivesThe rapid spread of the SARS-CoV-2 Omicron variant has raised concerns regarding waning vaccine-induced immunity and durability. We evaluated protection of the third-dose and fourth-dose mRNA vaccines against SARS-CoV-2 Omicron...

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.

Covid-19 Induced Neonatal Immunity

December 2019 a few cases of severe pneumonia was detected in Wuhan, China The patients were exhibiting symptoms like fever, dry cough, sore throat, breathlessness, and fatigue. investigation employing next generation sequencing and phylogenetic analysis led to the identification of the causative agent of this respiratory disease, a novel coronavirus 2019 [1]. As more cases started to appear around the world, on February 11, 2020, the World Health Organization assigned a name, Corona Virus Disease 2019 or COVID-19, to the disease and declared it a pandemic on March 11, 2020. The virus was renamed from 2019-nCoV to SARS-CoV-2 by the International Committee on Taxonomy of Viruses on the basis of its genetic similarity to a previously known coronavirus, Severe Acute Respiratory Syndrome Coronavirus(SARS-CoV) [2].Coronavirus 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome SARS-CoV- 2, has resulted in more than six million deaths and has infected over 500 million people as of July 19, 2022 [3]. SARS-CoV-2 infected pregnant women are at increased risk of severe COVID- 19 than non-pregnant women and have a higher risk of adverse pregnancy outcomes like intrauterine/fetal distress and preterm birth.The most severe outcomes of COVID-19 have been documented in geriatric individuals and pregnant women with chronic diseases, including hypertension, diabetes, and cardiopulmonary problems [4]. Newborn protection from infection is primarily dependent on neonatal innate immune responses and maternally derived, transplacentally acquired antibodies. The extent to which maternal antibodies produced in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy cross the placenta is important for understanding potential neonatal protection from coronavirus disease 2019 (COVID- 19.We investigated humoral responses to SARS-CoV-2 inmaternalandcordbloodpairedsamples in the case of natural infection during late second and third trimesters of pregnancy recruited at TSMU Department of Obstetrics and Gynecology TSMU First University Clinic. Georgia, Tbilisi. Maternal nasopharyngeal swabs were collected for SARS-CoV-2 detection by rate-PCR for confirmation of viral infection at the admission to the hospital. We measured IgG to spike (S) receptor-binding domain and nucleocapsid (N) Sixty-eight pregnant women SARS-CoV-2 positive by rRT- PCR were included in our study. Serology samples of maternal and cord blood has been collected immediately after delivery. For study design we have determined inclusion and exclusion criteria’s. General medical data of patients included in the study have been collected from medical records and Informed written consent was obtained from all the patients involved in the study. SARS-CoV-2, IgG has been detected by ELISA method.infected mothers had increased levels of virus-specific antibodies maternal IgG levels showed positive correlations with their counterparts in cord blood. PCR positive mothers showed stronger effect when infection was closer to delivery.Our results show that SARS- CoV-2 infection during the second and third trimester of pregnancy induces antibody response at delivery and causes lower level of the SARS-CoV-2-specific IgG trans placental transfer, when the infection is closer to delivery.

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

2364. Predictive Ability of mRNA COVID-19 Vaccines Against COVID-19 Disease Severity

Abstract Background Prior studies demonstrated the vaccine effectiveness and safety of mRNA COVID-19 vaccines, but additional data is needed regarding the effects of timing and number of doses on disease severity. This study determined predicted protection against severe COVID-19 by number of vaccine doses. Methods We enrolled adults hospitalized with acute respiratory infection (ARI) and/or related diagnoses at two Emory University hospitals from May 2021 – Aug 2022. This analysis included COVID-19 positive patients among unvaccinated and 2 or 3 doses of an mRNA vaccine. Vaccinations ≤ 14 days prior to admission were excluded. Medical and social histories were obtained from interviews, medical records, and the state vaccine registry. We used stepwise logistic regression to determine dose-specific odds ratios (OR) against severe outcomes (pneumonia (PNA), length of hospital stay (LOS) ≥ 4 days, ICU admission, mechanical ventilation, and death). Analysis was performed using SAS v9.4 software. Results Of the 1,677 total enrollments, 850 were positive for COVID-19. Another 168 were excluded due to lack of vaccine records or other vaccine dosages, 682 were eligible for analysis. Compared to those unvaccinated, vaccinated participants were older, male, and unemployed or on disability. Those with three doses obtained a higher education level than unvaccinated participants. Individuals with comorbidities – specifically blood disorders, chronic kidney disease, and immunocompromised – were more often vaccinated. When controlling for race, age, and employment, the odds of PNA (OR 0.5 (0.34, 0.74)) and ICU admission (0.61 (0.39, 0.97)) were less for those with two doses than those with none; whereas those with three mRNA doses had less odds of having PNA (OR 0.26 (0.15, 0.46) and LOS ≥ 4 days (OR 0.44 (0.25, 0.76)). Predicted protection against severe outcomes persisted 6 months from last dose for PNA, LOS ≥ 4 days, and ICU admission (Table 1).Table 1.Adjusted odds ratios of mRNA SARS-CoV-2 vaccination by dose number and time since administration against severe disease outcomes in those SARS-CoV-2 positive. OR adjusted for race, age and employment. Unable to calculate (UTC) due to having no patients with the outcome during specified vaccination timeframe and dose count. Conclusion Among COVID-19 positive adults hospitalized with ARIs, both two and three doses of a COVID-19 mRNA vaccine predicted protection against severe COVID-19 outcomes, with durability lasting more than 6 months. Future studies should explore the role of additional boosters and vaccine regimens in the prevention of severe COVID-19. Disclosures Laura A. Puzniak, PhD. MPH, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Robin Hubler, MS, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Srinivas Valluri, PhD, Pfizer Inc: Pfizer Employee and hold Pfizer stocks/options|Pfizer Inc: Ownership Interest|Pfizer Inc: Stocks/Bonds Timothy L. Wiemken, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Benjamin Lopman, PhD, Epidemiological Research and Methods, LLC: Advisor/Consultant|Hillevax, Inc: Advisor/Consultant Nadine Rouphael, MD, Icon, EMMES, Sanofi, Seqirus, Moderna: Advisor/Consultant Satoshi Kamidani, MD, CDC: Grant/Research Support|Emergent BioSolutions: Grant/Research Support|NIH: Grant/Research Support|Pfizer Inc: Grant/Research Support Evan J. Anderson, MD, GSK: Advisor/Consultant|GSK: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Kentucky Bioprocessing, Inc.: Safety Monitoring Board|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Moderna: Currently an employee|Moderna: Stocks/Bonds|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Grant/Research Support|Sanofi Pasteur: Safety Monitoring Board|WCG/ACI Clinical: Data Adjudication Board Christina A. Rostad, MD, BioFire Inc.: Grant/Research Support|GlaxoSmithKline Biologicals: Grant/Research Support|Janssen: Grant/Research Support|MedImmune LLC: Grant/Research Support|Meissa Vaccines, Inc.: RSV vaccine technology|Merck &amp; Co., Inc.: Grant/Research Support|Micron Technology, Inc.: Grant/Research Support|Moderna, Inc.: Grant/Research Support|Novavax: Grant/Research Support|PaxVax: Grant/Research Support|Pfizer, Inc.: Grant/Research Support|Regeneron: Grant/Research Support|Sanofi Pasteur: Grant/Research Support

2359. Relative effectiveness of mRNA-1273, BNT162b2, and Ad26.COV2.S vaccines in adults at higher risk for severe COVID-19 outcomes

Abstract Background Older age ( &amp;gt; 65 years) and underlying chronic medical conditions are risk factors associated with severe COVID-19 outcomes. In this study, we evaluated the relative vaccine effectiveness (rVE) of a primary series of mRNA-1273 (2 doses) versus BNT162b2 (2 doses) or Ad26.COV2.S (1 dose) and rVE of monovalent mRNA boosters - against medically attended (outpatient and hospitalizations cases), outpatient, and hospitalization cases due to COVID-19 in adults ≥ 18 years with at least one underlying medical condition and by age groups. Methods Data from a U.S. electronic health records system linked with medical claims data were used to evaluate rVE in patients with at least one underlying medical condition (such as immunosuppression, diabetes, chronic lung diseases, cardiovascular diseases, and renal diseases). Part 1 of the study evaluated the rVE of the primary series (February to October 2021), and Part 2 evaluated the rVE of a single monovalent mRNA booster dose (October 2021 to January 2022). Individuals were matched by sex, geographic region, age group, and race. Results In Part 1, mRNA-1273 prevented more medically-attended COVID-19 cases than BNT162b2 and Ad26.COV2.S, with rVEs of 24% (95% confidence interval [CI]: 22–25%) and 51% (49–52%), respectively. Similarly, mRNA-1273 also prevented more outpatient and hospitalized COVID-19 cases than the two comparator vaccines (Table 1). Findings were consistent across age groups. In Part 2, rVE of mRNA-1273 vs. BNT162b2 against medically-attended COVID-19 cases was 14% (95% CI: 9-19%). Importantly, following a booster dose, mRNA-1273 prevented more hospitalizations than BNT162b2 with an rVE of 22% (95% CI: 3–37%) in the overall study population and increased with age, with estimates of 32% (13–47%) and 46% (19–65%) in adults ≥ 50 years and ≥ 65 years, respectively. Conclusion In this study, a primary series of mRNA-1273 was more effective than BNT162b2 or Ad26.COV2.S in preventing medically-attended COVID-19 in individuals at higher risk for severe COVID-19 outcomes. Moreover, a booster dose of mRNA-1273 was more effective compared with BNT162b2, with additional significant benefits against COVID-19-related hospitalizations in older adults. Disclosures Van Hung Nguyen, MPH, Moderna, Inc.: Advisor/Consultant|VHN Consulting Inc.: Salary Catherine Boileau, PhD, Moderna, Inc.: Advisor/Consultant|VHN Consulting Inc.: Salary Alina Bogdanov, MA, Moderna, Inc.: Advisor/Consultant|Veradigm: Salary Ni Zeng, PhD, Moderna, Inc.: Advisor/Consultant|Veradigm: Salary Mac Bonafede, PhD, Moderna, Inc.: Advisor/Consultant|Veradigm: Salary Thierry Ducruet, MSc, Moderna, Inc.: Advisor/Consultant|VHN Consulting Inc.: Salary Andrew M. Rosen, PhD, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds David Martin, MD, MPH, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Daina Esposito, PhD, MPH, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Nicolas Van de Velde, PhD, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Hagit Kopel, PhD, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds James Mansi, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds

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

Impact of Risk Factors on COVID-19 Outcomes in Unvaccinated People With Rheumatic Diseases: A Comparative Analysis of Pandemic Epochs Using the COVID-19 Global Rheumatology Alliance Registry.

Approximately one third of individuals worldwide have not received a COVID-19 vaccine. Although studies have investigated risk factors linked to severe COVID-19 among unvaccinated people with rheumatic diseases (RDs), we know less about whether these factors changed as the pandemic progressed. We aimed to identify risk factors associated with severe COVID-19 in unvaccinated individuals in different pandemic epochs corresponding to major variants of concern. Patients with RDs and COVID-19 were entered into the COVID-19 Global Rheumatology Alliance Registry between March 2020 and June 2022. An ordinal logistic regression model (not hospitalized, hospitalized, and death) was used with date of COVID-19 diagnosis, age, sex, race and/or ethnicity, comorbidities, RD activity, medications, and the human development index (HDI) as covariates. The main analysis included all unvaccinated patients across COVID-19 pandemic epochs; subanalyses stratified patients according to RD types. Among 19,256 unvaccinated people with RDs and COVID-19, those who were older, male, had more comorbidities, used glucocorticoids, had higher disease activity, or lived in lower HDI regions had worse outcomes across epochs. For those with rheumatoid arthritis, sulfasalazine and B-cell-depleting therapy were associated with worse outcomes, and tumor necrosis factor inhibitors were associated with improved outcomes. In those with connective tissue disease or vasculitis, B-cell-depleting therapy was associated with worse outcomes. Risk factors for severe COVID-19 outcomes were similar throughout pandemic epochs in unvaccinated people with RDs. Ongoing efforts, including vaccination, are needed to reduce COVID-19 severity in this population, particularly in those with medical and social vulnerabilities identified in this study.

Association of Vaccination and Current Immunotherapy with COVID-19 Outcome in Patients with Follicular Lymphoma: A Retrospective Study

Introduction Immunotherapy (IO) based on anti-CD20 monoclonal antibodies significantly improves the prognosis of patients with follicular lymphoma (FL) in terms of disease progression, progression-free survival (PFS) and serious adverse events. Vaccination is protective in the general population, however, FL patients infected with COVID-19 have exacerbated damage to their immune system, and the effects of IO and vaccination on COVID-19 outcomes remain unknown. The aim of this study was to estimate the association between IO therapy based on anti-CD20 monoclonal antibody and COVID-19 severity by analyzing population-based data of FL patients. And to determine the true utility of vaccination in this immunocompromised population. Patients and methods We retrospectively assessed the clinical characteristics and follow-up data of patients with newly diagnosed FL from December 1, 2012 to April 1, 2023 at Shandong Provincial Hospital. Patients were divided into 2 groups: those who received IO, defined as anti-CD20 immunotherapy, within 12 months prior to COVID-19 diagnosis (IO group); those who received non-IO antitumor regimens with no systemic therapy (non-IO group), defined as cytotoxic chemotherapy, targeted therapies, endocrine therapies or those who did not receive any systemic therapy. Inclusion of data on anti-CD20 immunotherapy drugs Rituximab and Obinutuzumab applied in our center, stage of treatment, etc. COVID-19 outcomes were graded primarily on the basis of hospitalization, oxygenation, and need for mechanical ventilation, and patients' overall survival (OS) as well as PFS were studied. Multivariate logistic regression analyses were performed to assess associations between variables and COVID-19 outcomes, and unadjusted odds ratios (OR) and 95% confidence intervals (95%CI) were reported. Results Out of 160 patients included in the study ,77 (48.0%) were female, the median age was 53 (28-85 years) years, and the median follow-up was 54 (12-168 months) months. 131 (81.9%) patients had Ann Arbor stage III-IV on initial admission at our center, and 84 (52.5%) patients received the COVID-19 vaccine. Regarding COVID-19 infection, 137 (85.6%) were positive for COVID-19. 60 patients (37.5%) received IO, whereas 100 patients (62.5%) did not. Significant differences (P &amp;lt; 0.05) were found between the IO and non-IO groups in terms of COVID-19 outcome, time between COVID-19 diagnosis and FL diagnosis, and time to conversion after COVID-19 positivity (Figure 1A). There were also significant differences between the two groups in survival time and recurrent lung infection after COVID-19 cure (Figure 1B). No significant effect of vaccination on outcome of COVID-19 was found regardless of IO treatment. In the IO group, 42 (70.0%) patients received Rituximab and 18 (30%) patients received Obinutuzumab. No significant differences in COVID-19 infection rate, COVID-19 clinical outcome, time to COVID-19 conversion, and survival time were found between the two drugs. Of the patients who received IO therapy, 19 (31.7%) were in the induction phase and 41 (68.3%) were in the maintenance phase. Patients receiving maintenance therapy had a greater likelihood of longer survival（P&amp;lt;0.0001）and less severe COVID-19 outcomes（P=0.003）. Of the 60 patients treated with IO, 36 (60.0%) had an unchanged chemotherapy course and 24 (40.0%) had a delayed or interrupted chemotherapy course. No significant associations were found between IO therapeutic agents, vaccinations, or other variables with chemotherapy progression. Conclusions Among FL patients included in the analysis, IO was associated with worse COVID-19 outcomes, but no significant correlation was found between vaccination and COVID-19 infection rates and severity at this time. These findings provide insights into the immunocompromised population of FL-combined COVID-19 patients that can be used in the clinical setting to estimate COVID-19 outcomes based on factors such as chemotherapy stage and vaccination.

Dimensions of equality in uptake of COVID-19 vaccination in Wales, UK: A multivariable linked data population analysis

Vaccination has proven to be effective at preventing severe outcomes of COVID-19 infection, and uptake in the population has been high in Wales. However, there is a risk that high-level vaccination coverage statistics may mask hidden inequalities in under-served populations, many of whom may be at increased risk of severe outcomes of COVID-19 infection.The study population included 1,436,229 individuals aged 18 years and over, alive and residence in Wales as at 31st July 2022, and excluded immunosuppressed or care home residents. We compared people who had received one or more vaccinations to those with no vaccination using linked data from nine datasets within the Secure Anonymised Information Linkage (SAIL) databank. Multivariable analysis was undertaken to determine the impact of a range of sociodemographic characteristics on vaccination uptake, including ethnicity, country of birth, severe mental illness, homelessness and substance use.We found that overall uptake of first dose of COVID-19 vaccination was high in Wales (92.1 %), with the highest among those aged 80 years and over and females. Those aged under 40 years, household composition (aOR 0.38 95 %CI 0.35–0.41 for 10+ size household compared to two adult household) and being born outside the UK (aOR 0.44 95 %CI 0.43–0.46) had the strongest negative associations with vaccination uptake. This was followed by a history of substance misuse (aOR 0.45 95 %CI 0.44–0.46).Despite high-level population coverage in Wales, significant inequalities remain across several underserved groups. Factors associated with vaccination uptake should not be considered in isolation, to avoid drawing incorrect conclusions. Ensuring equitable access to vaccination is essential to protecting under-served groups from COVID-19 and further work needs to be done to address these gaps in coverage, with focus on tailored vaccination pathways and advocacy, using trusted partners and communities.

ԿՈՎԻԴ-19 ԱՍՈՑԱՑՎԱԾ ԿՈԳՆԻՏԻՎ ԽԱՆԳԱՐՈՒՄՆԵՐԻ ԳՐԱԿԱՆ ԱԿՆԱՐԿ

From 2019 to 2023, the global population experienced a period characterized by the outbreak of the coronavirus pandemic, which was attributed to the SARS-CoV-2 virus. Cognitive impairment, particularly memory loss, is frequently reported by individuals who have recovered from Covid-19, alongside other neurological symptoms. This phenomenon not only carries implications for individual health, but also extends to social and economic domains. This phenomenon garners the interest of scholars. Numerous empirical investigations have established a correlation between the COVID-19 pandemic and mental health disorders. The infection caused by SARS-CoV-2 has been associated with the manifestation of psychiatric symptoms. Additionally, individuals with pre-existing mental illness are more susceptible to experiencing more severe outcomes of COVID-19, increased mortality rates, and enduring residual symptoms over an extended period of time. Dementia itself encompasses a multitude of risk factors, including but not limited to advanced age, vascular and metabolic disorders, obesity, hypodynamic lifestyle, various infections, depression, smoking and social isolation. These factors should be considered collectively when evaluating cognitive impairment following COVID-19 infection. Nevertheless, it is obvious that COVID-19 survivors frequently experience health concerns related to memory, attention, perception, and other cognitive domains, necessitating thorough assessment and, in certain cases, intervention. Given the frequency of “memory decline” in the post-Covid period, especially in young and middle age, it is evident that cognitive dysfunction caused by COVID-19 impairment can have detrimental effects on both quality of life and the ability to perform daily tasks efficiently. In summary, the existing literature review indicates a lack of comprehensive understanding regarding the impact of COVID-19 on cognitive impairment. Consequently, there is a pressing need for further research endeavors that are more focused and specific in nature.

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.

Clinical and echocardiographic findings in patients with COVID-19 across different severity levels.

Cardiovascular pathology can complicate the course of COVID-19. The study aimed to identify echocardiographic abnormalities and key prognostic factors influencing severe and fatal COVID-19 outcomes. This retrospective cohort study included clinical and echocardiogram data from 194 medical records of hospitalized patients with COVID-19: 100 moderate cases, 34 severe cases with favorable outcomes, and 60 severe cases with fatal outcomes. Severe patients with favorable outcomes had greater reductions in left ventricular systolic fraction of left ventricle compared to moderate cases (23.5% vs. 7.0%, respectively, p=0.008) and ejection fraction of left ventricle (14.7% vs. 3.0%, respectively, p=0.013), grade I diastolic dysfunction of the left ventricle (20.6% vs. 8.0%, respectively, p=0.044), and pulmonary hypertension (29.41% vs. 10.0%, respectively, p=0.006). Patients with fatal outcomes had a mean age of 67.1±1.51 years, chronic heart failure functional class II (58.3%), hypertension (50.0%), type 2 diabetes (43.3%), and obesity (33.3%). Compared to severe cases but with favorable outcomes, fatal cases had a greater decrease in left ventricular ejection fraction (36.7% vs. 14.7%, respectively, p=0.024), various types of myocardial dysfunction (51.7% vs. 29.4%, respectively, p=0.037) and a trend towards increased pulmonary hypertension (48.3% vs. 29.4%, respectively, p=0.074). Consequently, chronic heart failure class II, reduced left ventricular ejection fraction, various myocardial dysfunctions, and pulmonary hypertension emerged as key cardiac risk factors for severe disease progression and mortality in patients with COVID-19.

Covid-19 vaccination coverage by birth country and underlying risk for severe Covid-19 disease

Abstract Backround It is unknown whether differences in age and health profiles contribute to explain the observed variation in Covid-19 vaccination coverage between birth countries. If the unvaccinated are mostly young and healthy, the consequences for severe illness and healthcare capacity will be less than if the unvaccinated have underlying risk for severe Covid-19 disease. This study aims to investigate whether differences in Covid-19 vaccination coverage by birth country in Norway are equally prominent among individuals with underlying risk for a severe Covid-19 disease course. Methods With register data from the Norwegian Emergency Preparedness Register, we linked vaccination coverage to demographic and socioeconomic variables for all Norwegian residents. Using Poisson regression, we examined if demonstrated differences in vaccination coverage between countries of birth were as prominent among individuals with underlying risk factors for severe Covid-19 disease, controlled for gender, age, education level, household income, and county. Results The demonstrated variation in Covid-19 vaccination coverage between Norwegian-born and foreign-born is lower when we limit the study population to those with underlying risk factors. Among people without underlying risk, the incidence rate ratio for being vaccinated was lowest for people born in Poland (IRR = 0.55; 95% CI 0.55 to 0.56) and Lithuania (IRR = 0.61; 95% CI 0.6 to 0.62), but the greatest increase in IRR was found for people with underlying risk factors born in these countries. Conclusions The study illuminates two facets of the difference in vaccination coverage between Norwegian-born and foreign-born individuals. First, the difference in vaccination coverage was smaller within groups with underlying risk for severe Covid-19 outcomes than for groups without. Second, the differences in vaccination coverage by birth country remains, even constrained on individuals with underlying risk. Key messages • The observed differences in Covid-19 vaccination coverage by birth country are smaller within groups with underlying risk factors. • Foreign-born individuals are a heterogenous group, crucial in considering all health policy formulations.

Features of the course of COVID-19 in pregnant women

Aim. To study the features of the course of COVID-19 in pregnant women, the outcomes of a new coronavirus infection and pregnancy, the effect of concomitant pathology on the severity of the course and the frequency of complications of COVID-19.Materials and methods. In the course of the work, a retrospective analysis of 109 medical histories of pregnant women who were treated in the infectious diseases department in 2021 with a diagnosis of COVID-19 was carried out. Anamnesis, concomitant pathology, results of objective examination, laboratory and instrumental methods of research, therapy, complications, outcomes of COVID-19 and pregnancy were evaluated.Results. The majority of pregnant women had moderate – 55 % and severe – 24 % COVID-19, 7 % – extremely severe and only 14 % – mild. A third of pregnant women had concomitant pathology, arterial hypertension was the most common; 80 % of pregnant women had complications of COVID-19: cytokine storm – in 50 % of patients, acute respiratory distress syndrome – in 17 %, of which 5 % required artificial lung ventilation. The mortality rate was 4.6 %. The structure of pregnancy complications was dominated by gestational hypertension, gestational diabetes, premature placental abruption, preeclampsia. Complications of childbirth – premature birth and premature discharge of amniotic fluid. However, in most cases, pregnancy (75 %) and childbirth (71 %) proceeded without complications. Women in 95 % of cases were discharged from the hospital with recovery or significant clinical improvement.Conclusion. Despite the prevalence of moderate and severe forms of COVID-19 in pregnant women, a high percentage of concomitant pathology and complications, in most cases favorable outcomes of both COVID-19 and pregnancy were noted. The presence of hypertension syndrome should probably be considered as a prognostically unfavorable marker of severe course and adverse outcomes of COVID-19 in pregnant women.