Prevalence and 24-month recovery of olfactory dysfunction in COVID-19 patients: A multicentre prospective study.

OBJECTIVE: To investigate the prevalence and recovery of olfactory dysfunction (OD) in COVID-19 patients 24 months after the infection. METHODS: From 22 March 2020 to 5 June 2022, 251 COVID-19 patients were followed in three European medical centres. Olfactory function was assessed with subjective patient-reported outcome questionnaires and odour identification tests at baseline, 6, 12, 18 and 24 months postinfection. The predictive values of epidemiological and clinical data were investigated with multivariate analysis. RESULTS: One hundred and seventy-one patients completed the evaluations. The odour identification test revealed that 123 patients (50.8%) had OD at baseline. The prevalence of persistent psychophysical abnormalities at 6, 12, 18 and 24 months post-COVID-19 was 24.2%, 17.9%, 5.8% and 2.9%, respectively (p = 0.001). Parosmia occurred in 40 patients (23.4%) and lasted 60 ± 119 days. At 2 years, 51 patients (29.8%) self reported that their olfaction was unnormalised. Older patients had better odour identification evaluations at baseline (p < 0.001) but those with OD reported lower odour identification test scores at the end of the follow-up. Parosmia occurred more frequently in young patients. The olfactory training was significantly associated with higher values of Sniffin' Sticks tests at 18 months postinfection (rs = 0.678; p < 0.001). CONCLUSION: Two years post-COVID-19, 29.8% of patients reported persistent OD, but only 2.9% had abnormal identification psychophysical evaluations.

Analysis and comparison of SARS-CoV-2 variant antibodies and neutralizing activity for 6 months after a booster mRNA vaccine in a healthcare worker population.

Introduction: In the context of recurrent surges of SARS-CoV-2 infections, a detailed characterization of antibody persistence over a 6-month period following vaccine booster dose is necessary to crafting effective public health policies on repeat vaccination. Methods: To characterize the SARS-CoV-2 antibody profile of a healthcare worker population over a 6-month period following mRNA vaccination and booster dose. 323 healthcare workers at an academic medical center in Orange County, California who had completed primary vaccination and booster dose against SARS-CoV-2 were recruited for the study. A total of 690 blood specimens over a 6-month period were collected via finger-stick blood and analyzed for the presence of antibodies against 9 SARS-CoV-2 antigens using a coronavirus antigen microarray. Results: The primary outcome of this study was the average SARS-CoV-2 antibody level as measured using a novel coronavirus antigen microarray. Additional outcomes measured include levels of antibodies specific to SARS-CoV-2 variants including Delta, Omicron BA.1, and BA.2. We also measured SARS-CoV-2 neutralization capacity for a subset of the population to confirm correlation with antibody levels. Although antibodies against SARS-CoV-2 wane throughout the 6-month period following a booster dose, antibody levels remain higher than pre-boost levels. However, a booster dose of vaccine based on the original Wuhan strain generates approximately 3-fold lower antibody reactivity against Omicron variants BA.1 and BA.2 as compared to the vaccine strain. Despite waning antibody levels, neutralization activity against the vaccine strain is maintained throughout the 6-month period. Discussion: In the context of recurrent surges of SARS-CoV-2 infections, our data indicate that breakthrough infections are likely driven by novel variants with different antibody specificity and not by time since last dose of vaccination, indicating that development of vaccinations specific to these novel variants is necessary to prevent future surges of SARS-CoV-2 infections.

SARS-CoV-2 IgG Spike antibody levels and avidity in natural infection or following vaccination with mRNA-1273 or BNT162b2 vaccines.

Certain aspects of the immunogenicity and effectiveness of the messenger ribonucleic acid (mRNA) vaccines (mRNA-1273 and BNT162b2) developed in response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic are still uncharacterized. Serum or plasma samples from healthy donor recipients of either vaccine (BNT162b2 n = 53, mRNA-1273 n = 49; age 23-67), and individuals naturally infected with SARS-CoV-2 (n = 106; age 18-82) were collected 0-2 months post-infection or 1- and 4 months after second dose of vaccination. Anti-Spike antibody levels and avidity were measured via an enzyme-linked immunosorbent assay (ELISA). Overall, vaccination induced higher circulating anti-Spike protein immunoglobulin G (IgG) antibody levels and avidity compared to infection at similar time intervals. Both vaccines produced similar anti-Spike IgG concentrations at 1 month, while mRNA-1273 demonstrated significantly higher circulating antibody concentrations after 4 months. mRNA-1273 induced significantly higher avidity at month 1 compared to BNT162b2 across all age groups. However, the 23-34 age group was the only group to maintain statistical significance by 4 months. Male BNT162b2 recipients were approaching statistically significant lower anti-Spike IgG avidity compared to females by month 4. These findings demonstrate enhanced anti-Spike IgG levels and avidity following vaccination compared to natural infection. In addition, the mRNA-1273 vaccine induced higher antibody levels by 4 months compared to BNT162b2.

A serological survey of pathogens associated with the respiratory and digestive system in the Polish European bison (Bison bonasus) population in 2017-2022.

BACKGROUND: The European bison (Bison bonasus) is a near threatened species and requires health monitoring. The aim of the present study was to determine the prevalence of antibodies to pathogens known to cause respiratory and digestive illness in ruminants. RESULTS: In the studied 328 European bison, the highest seroprevalence was observed for Bovine herpesvirus-1 (BoHV-1) (50.27%), Bovine Coronavirus (BCoV) (26.36%), and Bluetongue Virus (BTV) (12.83%). For Mycoplasma bovis strains and Bovine Viral Diarrhea Virus (BVDV), positive results were rare. Interestingly, a higher prevalence of BTV antibodies was noted in the northeastern populations and older animals. CONCLUSIONS: Our findings indicate that the Polish European bison population appears to have considerable contact with BoHV-1; however, this does not appear to be of great significance, as clinical symptoms and post-mortem lesions are rarely noted in Polish European bison population. The high seroprevalence of BTV in the north-east of Poland is an ongoing trend, also noted in previous studies. It is possible that European bison may perpetuate the virus in this region. This is the first report of antibodies for BCoV in European bison.

Assessment of Anti-SARS-CoV-2 antibody levels among university students vaccinated with different COVID-19 primary and booster doses - fall 2021, Wisconsin.

BACKGROUND: University students commonly received COVID-19 vaccinations before returning to U.S. campuses in the Fall of 2021. Given likely immunologic variation among students based on differences in type of primary series and/or booster dose vaccine received, we conducted serologic investigations in September and December 2021 on a large university campus in Wisconsin to assess anti-SARS-CoV-2 antibody levels. METHODS: We collected blood samples, demographic information, and COVID-19 illness and vaccination history from a convenience sample of students. Sera were analyzed for both anti-spike (anti-S) and anti-nucleocapsid (anti-N) antibody levels using World Health Organization standardized binding antibody units per milliliter (BAU/mL). Levels were compared across categorical primary COVID-19 vaccine series received and binary COVID-19 mRNA booster status. The association between anti-S levels and time since most recent vaccination dose was estimated by mixed-effects linear regression. RESULTS: In total, 356 students participated, of whom 219 (61.5%) had received a primary vaccine series of Pfizer-BioNTech or Moderna mRNA vaccines and 85 (23.9%) had received vaccines from Sinovac or Sinopharm. Median anti-S levels were significantly higher for mRNA primary vaccine series recipients (2.90 and 2.86 log [BAU/mL], respectively), compared with those who received Sinopharm or Sinovac vaccines (1.63 and 1.95 log [BAU/mL], respectively). Sinopharm and Sinovac vaccine recipients were associated with a significantly faster anti-S decline over time, compared with mRNA vaccine recipients (P <.001). By December, 48/172 (27.9%) participants reported receiving an mRNA COVID-19 vaccine booster, which reduced the anti-S antibody discrepancies between primary series vaccine types. CONCLUSIONS: Our work supports the benefit of heterologous boosting against COVID-19. COVID-19 mRNA vaccine booster doses were associated with increases in anti-SARS-CoV-2 antibody levels; following an mRNA booster dose, students with both mRNA and non-mRNA primary series receipt were associated with comparable levels of anti-S IgG.

Evaluation of the Diagnostic Performance of Two Automated SARS-CoV-2 Neutralization Immunoassays following Two Doses of mRNA, Adenoviral Vector, and Inactivated Whole-Virus Vaccinations in COVID-19 Naïve Subjects.

BACKGROUND: Limited data are available on humoral responses determined by automated neutralization tests following the administration of the three different types of COVID-19 vaccinations. Thus, we here evaluated anti-SARS-CoV-2 neutralizing antibody titers via two different neutralization assays in comparison to total spike antibody levels. METHODS: Healthy participants (n = 150) were enrolled into three subgroups who were tested 41 (22-65) days after their second dose of mRNA (BNT162b2/mRNA-1273), adenoviral vector (ChAdOx1/Gam-COVID-Vac) and inactivated whole-virus (BBIBP-CorV) vaccines, with no history or serologic evidence of prior SARS-CoV-2 infection. Neutralizing antibody (N-Ab) titers were analyzed on a Snibe Maglumi® 800 instrument and a Medcaptain Immu F6® Analyzer in parallel to anti-SARS-CoV-2 S total antibody (S-Ab) levels (Roche Elecsys® e602). RESULTS: Subjects who were administered mRNA vaccines demonstrated significantly higher SARS-CoV-2 N-Ab and S-Ab levels compared to those who received adenoviral vector and inactivated whole-virus vaccinations (p < 0.0001). N-Ab titers determined by the two methods correlated with each other (r = 0.9608; p < 0.0001) and S-Ab levels (r = 0.9432 and r = 0.9324; p < 0.0001, respectively). Based on N-Ab values, a new optimal threshold of Roche S-Ab was calculated (166 BAU/mL) for discrimination of seropositivity showing an AUC value of 0.975 (p < 0.0001). Low post-vaccination N-Ab levels (median value of 0.25 µg/mL or 7.28 AU/mL) were measured in those participants (n = 8) who were infected by SARS-CoV-2 within 6 months after immunizations. CONCLUSION: Both SARS-CoV-2 N-Ab automated assays are effective to evaluate humoral responses after various COVID-19 vaccines.

MultiSero: An Open-Source Multiplex-ELISA Platform for Measuring Antibody Responses to Infection.

A multiplexed enzyme-linked immunosorbent assay (ELISA) that simultaneously measures antibody binding to multiple antigens can extend the impact of serosurveillance studies, particularly if the assay approaches the simplicity, robustness, and accuracy of a conventional single-antigen ELISA. Here, we report on the development of multiSero, an open-source multiplex ELISA platform for measuring antibody responses to viral infection. Our assay consists of three parts: (1) an ELISA against an array of proteins in a 96-well format; (2) automated imaging of each well of the ELISA array using an open-source plate reader; and (3) automated measurement of optical densities for each protein within the array using an open-source analysis pipeline. We validated the platform by comparing antibody binding to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antigens in 217 human sera samples, showing high sensitivity (0.978), specificity (0.977), positive predictive value (0.978), and negative predictive value (0.977) for classifying seropositivity, a high correlation of multiSero determined antibody titers with commercially available SARS-CoV-2 antibody tests, and antigen-specific changes in antibody titer dynamics upon vaccination. The open-source format and accessibility of our multiSero platform can contribute to the adoption of multiplexed ELISA arrays for serosurveillance studies, for SARS-CoV-2 and other pathogens of significance.

Seroprofiling of antibodies against endemic human coronaviruses and SARS-CoV-2 in an HIV cohort in Lesotho: correlates of antibody response and seropositivity.

BACKGROUND: Serological data on endemic human coronaviruses (HCoVs) and SARS-CoV-2 in southern Africa are scarce. Here, we report on i) endemic HCoV seasonality, ii) SARS-CoV-2 seroprevalence, and iii) predictive factors for SARS-CoV-2 seropositivity and strength of SARS-CoV-2 and HCoV serological response during a 17-month period at the start of the COVID-19 pandemic among adults living with HIV. METHODS: Plasma samples were collected from February 2020 to July 2021 within an outpatient HIV cohort in Lesotho. We used the ABCORA multiplex immunoassay to measure antibody responses to endemic HCoV (OC43, HKU1, NL63, and 229E) and SARS-CoV-2 antigens. RESULTS: Results of 3'173 samples from 1'403 adults were included. Serological responses against endemic HCoVs increased over time and peaked in winter/spring. SARS-CoV-2 seropositivity reached >35% among samples collected in early 2021 and was associated with female sex (p = 0.004), obesity (p < 0.001), working outside the home (p = 0.02), and recent tiredness (p = 0.005) or fever (p = 0.007). Positive correlations were observed between the strength of response to endemic HCoVs and to SARS-CoV-2, and between older age or obesity and the IgG response to SARS-CoV-2. CONCLUSIONS: These results add to our understanding of the impact of biological, clinical, and social/behavioural factors on serological responses to coronaviruses in southern Africa.

The association between the elevated serum levels of cardiac Trop I and mortality in patients with and without pre-existing CAD in COVID-19 patients: A retrospective observational study

Background: COVID-19 has appeared as a pandemic and public health issue at a universal level. First documented as a respiratory disease, COVID-19 has been found to interrelate with and disturb the cardiovascular system causing myocardial injury and also cardiac dysfunction. Initial documentation of cardiac pathology can play a substantial role in dropping the death rate. This study emphasizes on the relationship between the serum levels of cardiac Trop I and prognosis in patients with and without pre-existing CAD in COVID-19 patients. Aims and Objectives: The first objective was to explore the association among the serum levels of cardiac Trop I and bad prognosis in patients with antiquity of CAD and without CAD. The secondary objective was to explore and understand whether increased Trop I is an appreciated prognostic indicator for COVID-19 patient antagonistic prognosis. Material(s) and Method(s): This was conducted as a retrospective observational study in which a whole of 45 patients admitted in COVID Hospital of Malabar Medical College and Research Center category C were studied. The medical record of the patients whose COVID-19 confirmation done by combined conclusions of reverse transcription PCR, symptoms, and chest X-ray was studies by the team. Result(s): Mean age of the study participants was 59.3 +/- 13.7. Every study participants had elevated Trop I levels with a median Trop I in study subjects being 397.9. There was a statistically significant elevation in Trop I levels in patients with CAD linked with non-CAD patients with a median IQR of 641.6 and P = 0.003 and there was a significant increase in Trop I levels in patients who expired related to patients who got discharged with a median IQR of 587.3 and P = 0.003. Conclusion(s): From this study, we accomplish that rise in cardiac troponin-I level is connected with elevated mortality in patients with COVID-19. Hence, it can be used as significant biomarker of disease evolution, hospitalization, and worse prognosis in COVID-19 patients.Copyright © 2023, Mr Bhawani Singh. All rights reserved.

Findings from the ECHO Cohorts Regarding the Effects of the COVID-19 Pandemic

Background: Studies suggest perinatal infection with SARSCoV- 2 can induce adverse birth outcomes, but studies published to date have substantial limitations. Most have identified cases based upon their presentation for clinical care, and very few have examined pandemic-related stress which may also impact adverse birth outcomes. Objective(s): To evaluate the relationships between SARSCoV- 2 infection in pregnancy and pandemic-related stress with birth outcomes. Study Design: We conducted an observational study of 211 mother-newborn dyads in three urban cohorts participating in the Environmental Influences on Child Health Outcomes (ECHO) Program. Serology for SARS-CoV-2 was assessed in a convenience sample of prenatal maternal, cord serum or dried blood spots from births occurring between January 2020-September 2021. Specimens were assessed for IgG, IgM, and IgA antibodies to nucleocapsid, S1 spike, S2 spike, and receptor-binding domain. A Pandemic-related Traumatic Stress (PTS) scale was based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition Acute Stress Disorder criteria. Result(s): 36% were positive for at least one antibody type, chiefly IgG. Self-report of infection was not significantly correlated with combined serology. There were no differences in gestational age (GA), birth weight, preterm birth (PTB), or low birth weight (LBW) among seropositive mothers. However, IgM seropositive mothers had children with lower BW (434g, 95% CI: 116- 752), BW Z score-for-GA (0.73 SD, 95% CI 0.10-1.36) and were more likely to deliver preterm (OR 8.75, 95% CI 1.22-62.4). Associations with LBW sustained in sensitivity analyses limited to pre-vaccine samples, and PTS symptoms were not associated with birth outcomes. The addition of PTS did not substantially change associations with BW, although associations with PTB attenuated to near-significance. Conclusion(s): We identified decreased birth weight and increased prematurity in mothers IgM seropositive to SARS-CoV-2, independent of PTS. Though there are limits to interpretation, the data support efforts to prevent SARS-CoV-2 infections in pregnancy.

Serological Evidence and Self-Reported Outcomes in Patients with Adrenal Insufficiency During The First Waves of COVID-19 in the North- East Italy

Background: East during COVID-19 is a potentially serious and fatal new infection that first broke out in Italys North Eastduring Spring 2020. Among subjects considered more clinically vulnerable, patients with adrenal insufficiency (AI) have a known increased risk of infections, that could lead to poor prognosis and death due to adrenal crisis. Even the psychological and sociooccupational impact of COVID-19 could affect the health of AI patients, requiring a dynamic and continuous adaptation of the daily glucocorticoid (GC) therapy. Aim(s): To investigate if AI patients have a higher risk for COVID-19 infection than the general population, all residents in the red zone Veneto, in North-East Italy. Moreover, based on a purpose-built ADDI-COVID questionnaire, the study aimed to evaluate the subjective perception of an increased risk for COVID-19 infection and pandemic-related psycho-social impact, working life and self-adjustments of GC therapy. Method(s): Open-label, cross-sectional monocentric study on 84 (65 primary and 19 secondary) AI patients, all resident in Veneto, followed-up at the Endocrinology Unit, University-Hospital of Padua, for at least 3 years, in good and stable clinical conditions. At the end of the first COVID-19 wave (by August 2020), all patients underwent serological investigation of anti-SARS-CoV2 IgG and ADDI-COVID questionnaire. All AI patients enrolled were contacted during March-April 2021 to evaluate eventual COVID-19 infection occurrence after the second and third waves, completing a follow-up period of about 12 months. Result(s): All AI patients resulted negative to the serological test for anti-SARS-CoV2 IgG at the end of the first wave of COVID-19. After the second and third pandemic waves, COVID-19 infection occurred in 8 (10%) patients, and none needed intensive care or hospitalization. Half patients felt an increased risk of COVID-19 infection, significantly associated with an increased stress (p = 0,009) and the consequent increase of GC stress-dose (p = 0,002). Only one patient reported adrenal crisis stress correlated. The great majority of the 61 (73%) worker patients changed their working habits during the lockdown, which was inversely related with COVID-19-related stress (p = 0,0015). A significant association was found between workers and endocri- nologist contact (p= 0,046) since 18 among 20 AI patients who contacted the endocrinologist were workers. Discussion and Conclusion(s): Patients with AI residence in Veneto did not show a higher incidence of COVID19-infection compared with general population residents in Veneto after the first pandemic waves. However, the perception of increased COVID- 19 infection risk significantly impacted the psychological well-being, working habits and GC daily doses of AI patients. Especially during this pandemic period, therapeutic patient education was crucial to prevent and treat situations or conditions that could lead to an adrenal crisis. The endocrinologic consultation could help to strengthen the awareness of AI patients, especially if they were workers.

Antibody levels of COVID-19 vaccine: A comparison between healthy subjects and psychiatric patients on antidepressants

This study compares the serological antibody level post-COVID-19 vaccine among healthy subjects and psychiatric patients on antidepressant therapy. It also examines the difference in antidepressants' side effects experienced by psychiatric patients following the completion of two vaccine doses. A comparative posttest quasi-experimental study was conducted among healthy subjects and psychiatric patients on antidepressant medication in a teaching hospital in Malaysia. Elecsys Anti-SARS-CoV-2 assay was used to detect the antibody titre between weeks 4 and 12 post vaccination. The antidepressant side-effect checklist (ASEC) was used to monitor the occurrence of antidepressant-related side effects pre-and post-vaccination. 24 psychiatric patients and 26 healthy subjects were included. There was no significant difference in the antibody level between the patients (median = 1509 u/ml) and the healthy subjects (median = 995 u/ml). There was no significant worsening in the antidepressant-related side effects. The antibody level post-COVID-19 vaccine did not differ significantly between patients on antidepressant therapy and healthy subjects. Additionally, there was no change in the antidepressant side effects experienced by the patients following the completion of the vaccine.Copyright © 2022, Research Trends (P) LTD.. All rights reserved.

Establishment of an infrastructure for rapid pandemic response at the Frederick National Laboratory

The sudden onset of the 2019 SARS-CoV-2 pandemic required agile development of standards and efficient validation of assays to assess prevalence of infection as well as immune responses to infection and vaccination. Leveraging their experience in HPV serology and standards, the Vaccine, Immunity and Cancer Directorate (VICD) at the Frederick National Laboratory for Cancer Research (FNCLR) pivoted to address this unmet need in SARS-Co-V2 serology clinical testing and research. This standardization effort required the collection and processing of large volumes of blood from SARS-Co-V2 infected and uninfected individuals into serum and peripheral blood mononuclear cells (PBMCs). Collaborations with specimen collection sites across the United States were established. Following qualification for anti-SARS-CoV-2 IgG and IgM levels in independent laboratories, VICD assembled reference evaluation panels, which were used to assist the FDA's performance evaluation of commercial assays submitted for EUA approval. To date, 185 different shipments of the standard or validation panel have been sent to both domestic and international labs. These materials are also available to the SARS-CoV-2 serology community for assay calibration and performance evaluation which greatly facilitates assay data harmonization. In addition, the NCI Serological Sciences Network (SeroNet) was born from this initiative and expertise, resulting in the establishment of Capacity Building Centers (CBCs) for sample collection from different healthy, cancer and immunocompromised cohorts at Mount Sinai, Arizona State University, the University of Minnesota, and Northwell Feinstein. The NCI and FNLCR simultaneously collaborated to develop a network of investigators focused on advancing research on the immune response to SARS-CoV-2 infection and vaccination among diverse and vulnerable populations, including cancer patients. Their research has resulted in over 326 peer-reviewed publications. The CBC's have enrolled patients in longitudinal studies, resulting in a centralized collection of annotated, well characterized serum, PBMCs and clinical data. Numerous cancer cohorts, but predominantly Multiple Myeloma, are included. Furthermore, technology development was supported at the CBC's. Based upon this success, the VICD in collaboration with NCI is pursuing an even more innovative effort in pandemic preparedness to establish a Center for Serology and Data Emergency Preparedness (CESDEP);a global network able to activate and pivot to address pandemic-level threats, while continuing to expand the development of immunological assays that can inform clinical decisions for cancer and other immunocompromised patients.

Surveillance for SARS-CoV-2 in Norway Rats (Rattus norvegicus) from Southern Ontario

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from wildlife has raised concerns about spillover from humans to animals, the establishment of novel wildlife reservoirs, and the potential for future outbreaks caused by variants of wildlife origin. Norway rats (Rattus norvegicus) are abundant in urban areas and live in close proximity to humans, providing the opportunity for spillover of SARS-CoV-2. Evidence of SARS-CoV-2 infection and exposure has been reported in Norway rats. We investigated SARS-CoV-2 infection and exposure in Norway rats from Southern Ontario, Canada. From October 2019 to June 2021, 224 rats were submitted by collaborating pest control companies. The majority of samples were collected in Windsor (79.9%;n = 179), Hamilton (13.8%;n = 31), and the Greater Toronto Area (5.8%;n = 13). Overall, 50.0% (n = 112) were female and most rats were sexually mature (55.8%;n = 125). Notably, 202 samples were collected prior to the emergence of variants of concern (VOC) and 22 were collected while the Alpha variant (B.1.1.7) was the predominant circulating VOC in humans. Nasal turbinate (n = 164) and small intestinal (n = 213) tissue samples were analyzed for SARS-CoV-2 RNA by RT-PCR. Thoracic cavity fluid samples (n = 213) were tested for neutralizing antibodies using a surrogate virus neutralization test (sVNT) (GenScript cPass);confirmatory plaque reduction neutralization test (PRNT) was conducted on presumptive positive samples. We did not detect SARS-CoV-2 RNA in any samples tested. Two out of eleven samples positive on sVNT had neutralizing antibodies confirmed positive by PRNT (1 : 40 and 1 : 320 PRNT70);both were collected prior to the emergence of VOC. It is imperative that efforts to control and monitor SARS-CoV-2 include surveillance of rats and other relevant wildlife species as novel variants continue to emerge.

Trust in sources of information on COVID-19 at the beginning of the pandemic first wave and incident persistent symptoms: A prospective population-based cohort study

Background: Many patients affected by COVID-19 suffer from persistent symptoms after infection. Compared to biomedical mechanisms, psychosocial mechanisms have been less investigated. This study examined the association between trust in sources of information on COVID-19 and the burden of incident persistent symptoms. Method(s): A prospective study using data from the SAPRIS and SAPRIS-Serologie surveys nested in the French CONSTANCES cohort. Trust in medical doctors, government, scientists, journalists, and social media was measured between April 2020 and May 2020. The number of incident persistent symptoms lasting for at least two months was recorded. Psychological burden was measured with the somatic symptom disorder B criteria scale. Associations between trust in information sources and outcomes were examined with zero-inflated negative binomial regression and general linear models, adjusting for gender, age, education, income, self-rated health, SARS-CoV-2 serology tests, and self-reported COVID-19 Results: Among 20,985 participants, those with higher trust in government/journalists at baseline had fewer incident persistent symptoms at follow-up (estimate (SE): -0.21 (0.03), p < 0.001). Among 3372 participants (16.07%) who reported at least one symptom, those with higher trust in government/journalists and medical doctors/scientists had lower SSD-12 scores (-0.39 (0.17), p = 0.0219 and - 0.85 (0.24), p < 0.001, respectively), whereas higher trust in social media sources predicted higher SSD-12 scores in those with lower trust in government/journalists (0.90 (0.34), p = 0.008). These associations did not depend upon surrogate markers of past infection with SARS-CoV-2 Conclusion(s): Trust in information sources on COVID-19 should be tested as a target in the prevention of incident persistent symptoms.Copyright © 2023

PRE-EXPOSURE PROPHYLAXIS OF COVID-19 WITH TIXAGEVIMAB AND CILGAVIMAB IN RHEUMATOLOGIC PATIENTS TREATED WITH RITUXIMAB: DATA FROM A SINGLE-CENTRE COHORT

BackgroundRheumatologic patients treated with Rituximab (RTX) are at higher risk of severe COVID-19 and death. The B-cell depletive treatment significantly affects B cell functions involved in anti-SARS-CoV-2 response, leading to relevant impacts on the clinical and serological course of infection, long-term immunity, and vaccine responses. In light of these observations, pre-exposure prophylaxis (PrEP) of COVID-19 with Tixagevimab and Cilgavimab (TGM/CGM) was recently approved in Italy for all patients treated with RTX in the previous year, independently of their serological status against SARS-CoV-2.ObjectivesWe aimed to evaluate the efficacy and safety of TGM/CGM in a single-centre cohort of rheumatologic patients treated with RTX.MethodsFrom October 2022, all patients who had been treated with RTX in the previous 12 months and who underwent clinical assessment at our rheumatologic tertiary centre were screened for eligibility to PrEP of COVID-19 with TGM/CGM. According to the indications of the Italian Medicines Agency (AIFA), we excluded subjects with major cardiovascular risk factors and/or coagulation abnormalities;those who reported a previous allergic reaction to any anti-COVID19 vaccine were referred to an allergologist for an evaluation before TGM/CGM administration. Patients who agreed to be treated with TGM/CGM signed an informed consent. Clinical and demographic features were collected at baseline, and follow-up phone assessment was performed the day after and 1 month after TGM/CGM administration, to assess treatment tolerability and new COVID-19- related events. A descriptive analysis was performed.ResultsFrom 1 October 2022 to 31 December 2022, 90 subjects were screened for eligibility to TGM/CGM. Among them, 11 were excluded for contraindications due to comorbidities and 55 refused TGM/CGM administration. Among patients who agreed to receive PrEP of COVID-19, 21 received TGM/CGM before 31 December 2022 and 3 were scheduled for January2023. Patients treated with TGM/CGM had a mean age of 54 years (standard deviation: 17) and 19 (90.5%) were female;9 were affected by rheumatoid arthritis and 12 by other rheumatologic diseases (3 systemic lupus erythematosus, 2 systemic sclerosis, 1 Sjögren syndrome, 1 juvenile idiopathic arthritis, 3 anti-synthetase syndrome, 2 vasculitides). Most of them had completed the vaccination schedule against COVID-19 (19, 90.5%) and 9 (42.8%) reported an infectious event by SARS-CoV-2 in the previous year. One month after TGM/CGM administration, no patient reported adverse events related to TGM/CGM nor COVID-19 related symptoms.ConclusionPrEP of COVID-19 with TGM/CGM was well tolerated in our population of rheumatologic patients treated with RTX in the previous year and no COVID-19 related symptoms were observed in the month of follow-up after TGM/CGM administration. Future observations may provide further data on long-term efficacy of TGM/CGM in preventing COVID-19.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsMaria Manara Speakers bureau: Novartis, Angelini, Consultant of: Lilly, MSD, Manuel Sette: None declared, Laura Giudice: None declared, Martina Biggioggero: None declared, Nicoletta Del Papa Speakers bureau: Janssen, Boehringer-Ingelheim, Actelion, Ennio Giulio Favalli Speakers bureau: AbbVie, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Consultant of: AbbVie, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Maria Gerosa: None declared, Francesca Ingegnoli: None declared, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Fresenius, Galapagos, Janssen, Lilly, Novartis, Pfizer, UCB, Consultant of: AbbVie, Fresenius, Galapagos, Lilly, Novartis, Pfizer, UCB.

Disseminated Mucormycosis in a patient on long term immunosuppression: Severe fungal infections as multi-system disorders

Introduction: Mucormycosis is a rare, severe fungal infection with an incidence of 0.005 to 0.17 per million.1 but incidence has risen recently, particularly in the Asian subcontinent, due to use of immunosuppression for Covid19.2 Presentations can vary and are classified into: rhino-orbito-cerebral, pulmonary, cutaneous, disseminated, renal and gastrointestinal. Risk factors include diabetes, immunosuppression, iron overload, malnutrition, and prematurity.1,3 Although mucormycosis has an extremely high mortality rate and disseminated infection is usually fatal, treatment options exist if diagnosed early and surgical debridement may be curative. Objective(s): We present a case of mucormycois in a female patient in her 40s who was immunosuppressed with methotrexate for rheumatoid disease. This case is discussed to increase awareness of critical illness caused by opportunistic invasive fungal infections in immunosuppressed patients and promote timely identification and management. Method(s): We detail the clinical context and management of a patient with mucormycosis and discuss relevant literature. Result(s): A female patient in her 40s who had been experiencing upper respiratory tract symptoms for several weeks, including cough and brown sputum, was admitted with a presumptive diagnosis of methotrexate toxicity after a full blood count performed by the general practitioner demonstrated pancytopenia. Initially, National Early Warning System 2 score (NEWS2) was 2 but became intensely hypertensive during blood transfusion and then profoundly shocked with an escalating NEWS2. Broad-spectrum antibiotics and fluconazole were commenced for neutropenic sepsis and the patient was referred to critical care in multiple organ failure. Computerised tomography (CT) scan of the chest, abdomen and pelvis showed "left upper lobe consolidation, which with neutropenia might represent an angioinvasive aspergillosis". She had multiple areas of skin discolouration and desquamation. Haematology and Infectious Diseases opinions were sought, and a bone marrow biopsy was performed which showed severe toxic effects consistent with sepsis/life threatening infection. Progressive proptosis was noted, and CT scan of her head was requested. Sadly, she was never stable enough for CT transfer. Beta D Glucan and aspergillus antigen serology was negative. Broncho-alveolar lavage demonstrated Candida albicans and then, later, Rhizopus arrhizus was isolated and anti-fungal treatment changed to voriconazole and then amphotericin B. Upon reviewing the notes in light of the positive culture for Rhizopus, the patient had likely been exhibiting symptomatic Mucormycosis sinus infection for some time prior to this admission with disseminated infection. The patient's condition continued to deteriorate and she sadly died. Conclusion(s): * The Early Warning Score significantly underestimated how unwell the patient was upon arrival in ED, a systems-based assessment would have demonstrated that the patient had multiple system dysfunction and significant potential to deteriorate suddenly despite having stable observations * The methotrexate level has no clinical value in diagnosing or refuting a diagnosis of methotrexate toxicity * A full examination of the immunosuppressed patient including ENT is a necessity when searching for a source of infection * Invasive fungal infections can cause multi-system symptoms and atypical presentations * As a greater proportion of patients have received systemic immunosuppression for Covid-19, vigilance for more unusual pathogens, including Mucormycosis by clinicians is advised.

SeroNet Pooling Project of immunocompromised populations

Introduction: COVID-19 vaccination substantially reduces morbidity and mortality associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe illness. However, despite effective COVID-19 vaccines many questions remain about the efficacy of vaccines and the durability and robustness of immune responses, especially in immunocompromised persons. The NCI-funded Serological Sciences Network (SeroNet) is a coordinated effort including 11 sites to advance research on the immune response to SARS-CoV-2 infection and COVID-19 vaccination among diverse and vulnerable populations. The goals of the Pooling Project are: (1) to conduct real-world data (RWD) analyses using electronic medical records (EMR) data from four health care systems (Kaiser Permanente Northern California, Northwell Health, Veterans Affairs-Case Western, and Cedars-Sinai) to determine vaccine effectiveness in (a) cancer patients;(b) autoimmune diseases and (c) solid organ transplant recipients (SOTR);(2) to conduct meta-analyses of prospective cohort studies from eight SeroNet institutions (Cedars-Sinai, Johns Hopkins, Northwell Health, Emory University, University of Minnesota, Mount Sinai, Yale University) to determine post-vaccine immune responses in (a) lung cancer patients;(b) hematologic cancers/hematopoietic stem cell transplant (HSCT) recipients;(c) SOTR;(d) lupus. Method(s): For our RWD analyses, data is extracted from EMR using standardized algorithms using ICD-10 codes to identify immunocompromised persons (hematologic and solid organ malignancy;SOTR;autoimmune disease, including inflammatory bowel disease, rheumatoid arthritis, and SLE). We use common case definitions to extract data on demographic, laboratory values, clinical co morbidity, COVID-19 vaccination, SARS-CoV-2 infection and severe COVID-19, and diseasespecific variables. In addition, we pool individual-level data from prospective cohorts enrolling patients with cancer and other immunosuppressed conditions from across network. Surveys and biospecimens from serology and immune profiling are collected at pre-specified timepoints across longitudinal cohorts. Result(s): Currently, we have EMR data extracted from 4 health systems including >715,000 cancer patients, >9,500 SOTR and >180,000 with autoimmune conditions. Prospective cohorts across the network have longitudinal data on >450 patients with lung cancer, >1,200 patients with hematologic malignancies, >400 SOTR and >400 patients with lupus. We will report results examining vaccine effectiveness for prevention of SARS-CoV-2 infection, severe COVID-19 and post-acute sequelae of COVID-19 (PAS-C or long COVID) in cancer patients compared to other immunocompromised conditions. Conclusion(s): Our goal is to inform public health guidelines on COVID-19 vaccine and boosters to reduce SARS-CoV-2 infection and severe illness in immunocompromised populations.

Infectious mononucleosis combined with SARS-CoV-2 infection.

A clinical analysis of COVID-19 cases combined with acute respiratory diseases is presented. The aim of the study was to analyze clinical and laboratory data of patients with combined COVID-19 infection. In patient A. infected with SARS-CoV-2 without X-ray confirmation of lung damage, acute tonsillitis, polyadenopathy, hepatosplenomegaly, moderate leukocytosis, lymphomonocytosis and the presence of reactive lymphocytes were detected. Serological and molecular biological studies were carried out for the purpose of differential diagnosis. A positive test result for IgM antibodies to EBV was obtained. The method of polymerase chain reaction (PCR) revealed EBV DNA in blood plasma. The result of the determination of heterogeneous IgG antibodies to the EBV caspid antigen is negative. Clinical symptoms of the patient with coronavirus infection COVID-19, confirmed by radiological and serological screening, included: fever, sore throat, hyperemia and hypertrophy of the palatine tonsils, hepatomegaly, changes of the cellular composition of the blood. At the same time, the lymph nodes in the neck, chest and abdominal cavity were not enlarged;the presence of reactive lymphocytes and plasma cells was not detected. Serological markers of EBV were also not detected. A PCR test for Epstein-Barr virus DNA was negative.Copyright © 2022 Infectious Diseases: News, Opinions, Training.