Baseline Serology Research Articles

Seroprevalence of Trypanosoma cruzi among children from Veracruz, Mexico: Epidemiological baseline for a control model based on Chagas disease active transmission

Introduction. In 2021, the Secretaría de Salud de México and the Pan American Health Organization launched an initiative to interrupt intra-domiciliary vector transmission of Trypanosoma cruzi based on the prevalence of Chagas disease in children. The Mexican State of Veracruz was leading this initiative. Objective. To estimate the seroprevalence of T. cruzi infection among children under 15 years of age from rural areas of Veracruz, México. Materials and methods. We identified eight localities of high priority from the Municipality of Tempoal, Veracruz, for baseline serology. Blood samples were collected on filter paper from 817 individuals between June and August 2017, for screening with a third-generation enzyme immunoassay. Reactive cases were confirmed by indirect hemagglutination, enzyme-linked immunosorbent assay, and indirect immunofluorescence tests on peripheral blood serum samples. We calculated seroprevalence and 95% confidence intervals (CI). Results. We confirmed Chagas disease cases in children under 15 years of age with a seroprevalence of 1,9% (95 % CI = 1,12-3,16) in the localities of Citlaltepetl, Cornizuelo, Cruz de Palma and Rancho Nuevo. Conclusions. These results indicate recent transmission of T. cruzi in these communities and allow to establish an epidemiological baseline for the design and implementation of a model focused on geographical areas with active transmission to advance toward the elimination of intra-domiciliary vector transmission of this parasite in Mexico.

Unveiling Predictive Parameters for Rheumatoid Arthritis Development in Arthralgia Patients: Insights from a Prospective Longitudinal Study

Background: Early diagnosis of rheumatoid arthritis (RA) is crucial for timely intervention and improved outcomes. Although research on the preclinical phase of RA is a prominent topic, there remains an unmet need to effectively stratify patients at risk of developing RA based on basic clinical assessment and laboratory investigations. This prospective longitudinal study aimed to identify risk factors for RA development in individuals experiencing arthralgia. Method: Two hundred consecutive adults with arthralgia were enrolled from new referrals to our rheumatology clinic. Patients with synovitis or a known arthritis diagnosis were excluded. Follow-up assessments were conducted every 6 months, or sooner if symptoms worsened, for a maximum of 2 years. The study endpoint was the development of RA, according to the 2010 ACR/EULAR classification criteria. Baseline demographic characteristics, clinical parameters, serology, and acute phase reactant levels were compared between patients who developed RA and those who did not. In addition, the classification score based on the 2010 ACR/EULAR classification criteria was utilised as a composite weighted score summarising the clinical presentation in the cohort, although the patients were deemed not fulfilling the mandatory criteria of having synovitis at baseline. Results: By May 2024, 104 patients had been followed up for at least one year, with a median duration of 78 weeks (IQR: 58-97). The baseline symptom duration was 51 weeks (IQR: 29 – 97). Among these patients, 23 (22.1%) developed RA after a median follow-up duration of 41 weeks (IQR: 25 – 52). Patients who developed RA had a significantly higher proportion of joint symptoms <1 year, difficulty making a fist, positive rheumatoid factor (RF), anti-CCP antibodies, and elevated ESR and CRP levels at baseline. Multivariate logistic regression identified difficulty making a fist (OR: 4.87, 95% CI: 1.40 – 17.04, p = 0.013) and positive anti-CCP antibodies (OR: 13.04, 95% CI: 3.74 – 45.44, p < 0.001) as independent predictors for RA development. Meanwhile, patients who developed RA had significantly higher baseline scores extrapolating from the 2010 ACR/EULAR classification criteria compared to the non-RA group. Conclusion: Difficulty making a fist and positive anti-CCP antibodies are independent predictors of RA development. Additionally, patients who developed RA exhibited significantly higher baseline scores on the 2010 ACR/EULAR classification criteria. Early recognition of these variables and taking reference from the score of classification criteria may aid in RA risk stratification. Further research is needed to validate these findings and explore additional predictive markers.

Prospective Assessment of Humoral and Cellular Immune Responses to a Third COVID-19 mRNA Vaccine Dose Among Immunocompromised Individuals.

Improved coronavirus disease 2019 (COVID-19) prevention is needed for immunocompromised individuals. A prospective study was performed of health care workers (HCW) and immunocompromised participants with baseline serology following 2 mRNA vaccine doses and who were retested after dose 3 (D3); multivariable regression was used to identify predictors of serological responses. IFN-γ/TNF-α T-cell responses were assessed in a subset. In total, 536 participants were included: 492 immunocompromised (206 solid organ transplant [SOT], 128 autoimmune, 80 hematologic malignancy [HM], 48 solid tumor, 25 HIV), and 44 HCW. D3 significantly increased spike IgG levels among all, but SOT and HM participants had the lowest median antibody levels post-D3 (increase from 0.09 to 0.83 and 0.27 to 1.92, respectively), versus HCW and persons with HIV, autoimmune conditions, and solid tumors (increases from 4.44 to 19.79, 2.9 to 15.75, 3.82 to 16.32, and 4.1 to 25.54, respectively). Seropositivity post-D3 was lowest for SOT (49.0%) and HM (57.8%), versus others (>90%). Neutralization post-D3 was lowest among SOT and HM. Predictors of lower antibody levels included low baseline levels and shorter intervals between vaccines. T-cell responses against spike increased significantly among HCW and nonsignificantly among immunocompromised individuals. D3 significantly improves serological but not T-cell responses among immunocompromised individuals. SOT and HM patients have suboptimal responses to D3.

Effectiveness and safety of tetanus vaccine administration by intramuscular vs. subcutaneous route in anticoagulated patients: Randomized clinical trial in primary care.

Prospective, double-blind clinical trial comparing tetanus-diphtheria vaccine administration routes, intramuscular (IM) vs. subcutaneous (SC) injection, in patients with oral anticoagulants. ISRCTN69942081. Patients treated with oral anticoagulants, 15 health centers, Vigo (Spain). Sample size, 117 in each group. Safety analysis: systemic reactions and, at the vaccine administration site, erythematic, swelling, hematoma, granuloma, pain.Effectiveness analysis: differences in tetanus toxoid antibody titers.Independent variables: route, sex, age, baseline serology, number of doses administered. Following the CONSORT guidelines, we performed an intention-to-treat analysis. We conducted a descriptive study of the variables included in both groups (117 in each group) and a bivariate analysis. Fewer than 5% of missing values. Imputation in baseline and final serology with the median was performed. Lost values were assumed to be values missing at random. We conducted a descriptive study of the variables and compared routes. For safety, multivariate logistic regression was applied, with each safety criterion as outcome and the independent variables. Odds ratios (ORs) were calculated. For effectiveness, a generalized additive mixed model, with the difference between final and initial antibody titers as outcome. Due to the bimodal distribution of the outcome, the normal mixture fitting with gamlssMX was used. All statistical analyses were performed with the gamlss.mx and texreg packages of the R free software environment. A previously published protocol was used across the 6-year study period. The breakdown by sex and route showed: 102 women and 132 men; and 117 IM and 117 SC, with one dose administered in over 80% of participants. There were no differences between groups in any independent variable. The second and third doses administered were not analyzed, due to the low number of cases. In terms of safety, there were no severe general reactions. Locally, significant adjusted differences were observed: in pain, by sex (male, OR: 0.39) and route (SC, OR: 0.55); in erythema, by sex (male, OR: 0.34) and route (SC, OR: 5.21); and in swelling, by sex (male, OR: 0.37) and route (SC, OR: 2.75). In terms of effectiveness, the model selected was the one adjusted for baseline serology.

Efficacy of Preexposure Prophylaxis with Monoclonal-Antibody AZD7442 (tixagevimab-cilgavimab) Against Sars-Cov-2 Variants in Patients with CLL

Background: Patients with CLL are among the highest risk population of SARS-CoV-2 infection attributed to disease and therapy. Patients receiving treatment, particularly after recent anti-CD20 monoclonal antibodies therapy, have low seroconversion rates after mRNA COVID-19 vaccine. An emergent recommendation of preexposure prophylaxis with monoclonal-antibody combination AZD7442 in immunocompromised patients is based on a trial conducted before the emergence of the BA.1 (Omicron) and later variants and did not include patients with CLL. Methods: Patients with CLL tested for serologic response and neutralization effect of COVID-19 variants Wild Type (WT), Delta, Omicron (BA.1) BA.2, BA.4 and BA.5 , before and after a single dose of monoclonal-antibody combination AZD7442 (150 mg of tixagevimab and 150 mg of cilgavimab) administration. Results: Fifty patients (31 males/ 19 females) with CLL, median age 62 (range 38 to 81 years) were included in the study. Their baseline characteristics include CIRS score 6 (IQR, 4-8), IGHV unmutated 62% (15/24), Dohner scale (del13q 40%, Normal 16% del11q 9%, T12 18% , del17p/TP53mut 17%) and hypogammaglobulinemia 88% (42/48) with low IgG 65%, low IgA 54% and low IgM 79%. Thirty percent (15/50) were therapy naïve and 54% (27/50) received therapy with ongoing BTKi 30% (15/50) and ongoing BCL2i 20% (10/50), other therapies 4% (2). Fifty percent of patients (25/50) received monoclonal anti-CD20 antibodies (ab), of which 28% ≥12 month from AZD7442 and 22% <12 months from AZD7442. In this group, 3 patients received ongoing anti-CD20 ab. Four patients had previous COVID19 infection within 3 months from AZD7442. Baseline serology was tested 12 days (IQR, 4-22 days) before AZD7442 administration, and serologic response was tested 19 days (IQR,16-25 days) after AZD7442 administration. Anti-spike abs increased from 14 (IQR, 0.4-284) to 2308 (IQR, 1644-3219) BAU/ml. While only 56% (28/50) of patients had positive serology (>21.4 BAU/ml) before AZD7442, 98% (49/50) had positive serology after AZD7442. Viral neutralization of WT and Delta variants before and after AZD7442 increased 65 folds, and for BA.1 (Omicron), BA.2, BA.4 and BA.5 increased 3.4, 6.1, 2.5 and 9.5 folds respectively (figure 1). Over follow-up period of 3 months, 13 patients with CLL (26%) acquired COVID-19 infection, none of them required hospitalization and all recovered uneventfully. There was no significant statistical difference in neutralization ab levels between infected and uninfected patients for the prevalent variant at that time (BA.5). Time from previous mRNA vaccination and ongoing assessment of infected vs uninfected patients is being further evaluated. Conclusion: After receiving preexposure prophylaxis with AZD7442, patients with CLL have increased IgG antibodies titer to SARS-CoV-2 more than seventy folds higher. Neutralization effect to WT and Delta variants is much higher than Omicron, BA.2, BA.4 and BA.5 variants. The effectivity of a double dose of AZD7442 or more specific monoclonal antibodies to the prevalent variants need to be further evaluated. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The association between autoantibodies and risk for venous thromboembolic events among patients with rheumatoid arthritis.

To assess the association between venous thromboembolic (VTE) events and autoantibodies, following patients from RA diagnosis, measuring occurrence, levels and collective load of different autoantibodies against post-translational protein modifications, in particular recognizing citrullination (e.g. citrullinated fibrinogen) and RF by isotype. A cohort of 2814 patients with newly diagnosed RA were followed for incident VTE through register linkages. Sera from RA diagnosis were centrally analysed for antibodies to second generation cyclic citrullinated peptides (anti-CCP2), 20 anti-citrullinated protein antibody (ACPA) fine-specificities, antibodies to additional protein modifications (carbamylation and acetylation) and RF by isotype. Association between baseline serology status and future VTE was analysed using Cox regression adjusted for age, sex and calendar period of RA diagnosis, overall and stratified by anti-CCP2 and RF positivity. During a median 16 years of follow-up, 213 first-ever VTE events were registered (5.0/1000 person-years). IgG anti-CCP2 (present in 65% of cohort) associated with VTE (hazard ratio [HR] = 1.33, 95% CI: 1.00, 1.78), in a dose-response manner. The risk of VTE increased with number of ACPA fine-specificities. IgM RF, but no other RF isotypes, associated with VTE (HR = 1.38, 95% CI: 1.04, 1.82). The associations were independent from smoking and HLA-DRB1 shared epitope alleles. None of the carbamylated or acetylated antibody reactivities associated with VTE. Anti-CCP2, load of ACPA fine-specificities and IgM RF at RA diagnosis are associated with an increased risk of future VTE in RA. Antibodies to citrullinated fibrinogen did not differ substantially from other ACPA fine-specificities. Autoreactivity to other post-translational modifications was not associated with VTE risk.

Serologic phenotypes distinguish systemic lupus erythematosus patients developing interstitial lung disease and/or myositis.

ObjectivesTo determine if serologic phenotypes could be identified in systemic lupus erythematosus patients developing interstitial lung disease (ILD) and/or myositis.MethodsAdult SLE patients (without myositis/ILD at baseline) had annual assessments and serum sampling between 2000 and 2017. New-onset ILD was identified using the SDI pulmonary fibrosis item. New-onset myositis was identified using the SLICC Damage Index muscle atrophy/weakness item, the SLEDAI-2K item for myositis, and annual creatinine kinase testing. Chart review confirmed ILD/myositis cases and randomly sampled SLE patients from baseline formed our sub-cohort (N = 72). Cases and sub-cohort were compared regarding myositis-related biomarkers at baseline and at a randomly selected follow-up between baseline and end of observation (date of ILD/myositis diagnosis or Dec. 31, 2017). Descriptive analyses and hazards ratios (HRs) were generated for ILD/myositis incidence, focusing on baseline serology and adjusting for sex, race/ethnicity, age at SLE diagnosis, and SLE duration.ResultsFourteen SLE patients developed ILD (N = 9), myositis (N = 3), and/or both (N = 2). Thirteen of those (92.9%) developing ILD/myositis had at least one biomarker at baseline, versus 47 (65.3%) SLE patients who never developed myositis/ILD. The most common biomarkers in myositis/ILD were KL-6, anti-Ro52, and anti-Ku. Baseline biomarkers tended to remain positive in follow-up. In multivariate Cox regressions, SLE patients had higher risk of developing myositis/ILD with elevated baseline KL-6 (adjusted hazard ratio 3.66; 95% confidence interval 1.01, 13.3). When updating biomarkers over time, we also saw correlations between anti-Smith and ILD/myositis.ConclusionsBaseline myositis-related biomarkers were highly associated with ILD/myositis incidence. This is the first identification of biomarker phenotypes with ILD/myositis risk in SLE.

Clinical efficacy of different monoclonal antibody regimens among non-hospitalised patients with mild to moderate COVID-19 at high risk for disease progression: a prospective cohort study

This study aimed to compare the clinical progression of COVID-19 in high-risk outpatients treated with the monoclonal antibodies (mAb) bamlanivimab, bamlanivimab-etesevimab and casirivimab-imdevimab. This is an observational, multi-centre, prospective study conducted from 18 March to 15 July 2021 in eight Italian tertiary-care hospitals including mild-to-moderate COVID-19 outpatients receiving bamlanivimab (700 mg), bamlanivimab-etesevimab (700–1400 mg) or casirivimab-imdevimab (1200–1200 mg). All patients were at high risk of COVID-19 progression according to Italian Medicines Agency definitions. In a patient subgroup, SARS-CoV-2 variant and anti-SARS-CoV-2 serology were analysed at baseline. Factors associated with 28-day all-cause hospitalisation were identified using multivariable multilevel logistic regression (MMLR) and summarised with adjusted odds ratio (aOR) and 95% confidence interval (CI). A total of 635 outpatients received mAb: 161 (25.4%) bamlanivimab, 396 (62.4%) bamlanivimab-etesevimab and 78 (12.2%) casirivimab-imdevimab. Ninety-five (15%) patients received full or partial SARS-CoV-2 vaccination. The B.1.1.7 (Alpha) variant was detected in 99% of patients. Baseline serology showed no significant differences among the three mAb regimen groups. Twenty-eight-day all-cause hospitalisation was 11.3%, with a significantly higher proportion (p 0.001) in the bamlanivimab group (18.6%), compared to the bamlanivimab-etesevimab (10.1%) and casirivimab-imdevimab (2.6%) groups. On MMLR, aORs for 28-day all-cause hospitalisation were significantly lower in patients receiving bamlanivimab-etesevimab (aOR 0.51, 95% CI 0.30–0.88 p 0.015) and casirivimab-imdevimab (aOR 0.14, 95% CI 0.03–0.61, p 0.009) compared to those receiving bamlanivimab. No patients with a history of vaccination were hospitalised. The study suggests differences in clinical outcomes among the first available mAb regimens for treating high-risk COVID-19 outpatients. Randomised trials are needed to compare efficacy of mAb combination regimens in high-risk populations and according to circulating variants.

COVID-19 vaccine effectiveness among healthcare workers in Albania (COVE-AL): protocol for a prospective cohort study and cohort baseline data

IntroductionCritical questions remain about COVID-19 vaccine effectiveness (VE) in real-world settings, particularly in middle-income countries. We describe a study protocol to evaluate COVID-19 VE in preventing laboratory-confirmed SARS-CoV-2 infection in...

SARS-CoV-2 infections in households in a peri-urban community of Lima, Peru: A prospective cohort study.

BackgroundWe assessed the prevalence and incidence of SARS‐CoV‐2 infections in a prospective study of households in Lima, Peru.MethodsHouseholds with a child, a young adult 18–50 years, and an adult age >50 years in peri‐urban Lima were followed with twice‐a‐week household visits during a 2‐month period. Nasal swabs and saliva specimens were collected twice weekly, and nasopharyngeal swabs were collected weekly from each participant, regardless of symptoms. Laboratory‐confirmed SARS‐CoV‐2 infection was defined by two RT‐PCR tests from any of the collected specimens within a week. Blood samples collected at enrollment and end of follow‐up were tested with rapid serological tests. We calculated the prevalence and incidence of laboratory‐confirmed SARS‐CoV‐2 infections.ResultsWe enrolled 132 participants from 44 households: 44 children, 44 young adults, and 44 older adults. A total of 13 SARS‐CoV‐2 infections were detected in eight households, for an overall period prevalence of 9.85% (95% confidence interval [CI]: 5.35–16.25). Most (61.54%) infections were symptomatic. Eight of 11 (72.73%) SARS‐CoV‐2 detections corresponded to the Lambda variant. During 218.79 person‐months at risk of follow‐up, there were six new SARS‐CoV‐2 infections detected (2.74 per 100 person‐month, 95% CI: 1.25–6.04). At enrollment, 59 of 128 participants tested had positive SARS‐CoV‐2 IgG serology (46.09%, 95% CI: 37.25–55.12). Five of six new infections occurred among participants with negative baseline serology.ConclusionsWe demonstrated high incidence of SARS‐CoV‐2 infections in households, especially among subjects without evidence of prior infection, most of them not detected by the Ministry of Health system.

Hepatitis B Vaccination in Advanced Chronic Kidney Disease: A Quality Improvement Project at a Veteran Affairs Chronic Kidney Disease Clinic.

Hepatitis B vaccination is recommended in all patients with end-stage kidney disease (ESKD). However, only 50–60% of these patients achieve protective antibody levels if immunized after starting dialysis. Strategies to overcome this low seroconversion rate include a 6-month vaccination schedule starting earlier [chronic kidney disease (CKD) stage 4 and 5] to ensure immunity when patients progress to ESKD. We conducted a quality improvement program to immunize pre-dialysis patients. Patients who were found to have a negative baseline serology with a negative hepatitis B surface antibody level (HBsAb) were offered vaccination on a 6-month schedule (0, 1 and 6 months) with one of two available vaccines within the VA system (Recombivax™ or Engerix™). HBsAb titers were checked 3–4 months later, and titers ≥ 12 mIU/mL were indicative of immunity at VA. Patients who did not seroconvert were offered a repeat schedule of three more doses. We screened 198 patients (187 males and 11 females) with CKD 4 and 5 [glomerular filtration rate (GFR) < 29 mL/min/1.73 m2]. The median age of this cohort was 72 years (range 38–92 years). During the study period of 5 years (2015–2020), 10 patients were excluded since their GFR had improved to more than 30 mL/min/1.73 m2, 24 others had baseline immunity and 2 refused vaccination. The hepatitis B vaccination series was not started on 106 patients. Of the remaining 56, 12 patients progressed to ESKD and started dialysis before completion of the vaccination schedule, 6 expired and 1 did not come to clinic in 2020 due to the pandemic. Of the 37 patients who completed the vaccination schedule, 16 achieved seroconversion with adequate HBsAb titers, 10 did not develop immunity despite a second hepatitis B vaccination series, while 11 did not get a second series. Given the low seroconversion rate, albeit in a small cohort, vaccination should be considered in patients with earlier stages of CKD. Other options include studies on FDA approved vaccines of shorter duration. We plan to increase awareness among nephrologists, patients and nursing staff about the importance of achieving immunity against hepatitis B.

Response to BNT162b2 Sars-Cov-2 Vaccine in Recipients of Allogeneic Hematopoietic Stem Cell Transplant

Recipients of allogeneic hematopoietic stem cell transplant (HSCT) have been excluded from clinical trials of SARS-CoV-2 messenger RNA (mRNA) vaccines; however, since these patients are at higher risk of severe complications following infection, they have been given high priority in vaccination campaigns worldwide. In this prospective observational study, we evaluated the immunogenicity of two BNT162b2 (Pfizer-BioNTech) vaccine doses in allogeneic HSCT recipients compared to healthy controls. IgG antibodies to the receptor-binding domain (RBD) of the S1 subunit of the spike protein of SARS-CoV-2 were analyzed by SARS-CoV-2 IgG II Quant (Abbott, Ireland). The cutoff value of the test used in this study is 7.1 BAU/mL (Binding Antibody Unit/mL) and the results greater than 7.1 indicate that seroconversion has occurred, as recommended by the manufacturer. Peripheral blood samples were collected for immunological analysis at three timepoints: pre-vaccine baseline (w0, before the first BNT162b2 dose), week 3 (w3, before the second vaccine dose) and week 5 (w5, 2 weeks following the second dose). Patients older than 18 years who received BNT162b2 vaccine following an HSCT at seven Italian centers were included in the study. Enrolled patients received two successive doses (at 3-week interval) at a median of 15 months (range 2-141) after HSCT. Twenty-nine age-matched health care workers who were vaccinated with BNT162b2 were recruited as the control group. Among the 34 patients evaluable for serological response, three patients were excluded from the analysis as the baseline serology demonstrated previous natural SARS-CoV-2 infection. On w3, after the first vaccine dose 7/31 (23%) patients developed anti-S IgG antibodies as compared to 28/29 (97%) controls (p<0.01). HSCT recipients showed lower antibody titers (median 1.8 BAU, range 0-481) as compared to healthy controls (median 118 BAU, range 6-1172, p<0.01). In univariate analysis, transplant-to-vaccination interval (>12 months, p<0.01), baseline CD4+ T cell count (>200/mm3, p=0.01), and CD4+CD45RA+ T naive cell count (>100/ mm3, p<0.01) were significantly associated with antibody response after the first vaccine dose. On w5, after the second vaccine dose, 24/31 (77%) of the patients showed antibody response, as compared to 99% of healthy controls (p<0.01); in fact, 71% of non-responders to the first dose developed IgG antibodies after vaccine boost (Figure 1). Median antibody titer after second dose was 350 BAU/ml (0-21.731). In univariate analysis, no significant association was found between patient characteristics and immunogenicity after vaccine boost. Adverse events were rare and modest. Nine percent of the patients reported mild local reactions after vaccine administration, including pain at the injection site and less commonly local erythema, local lymphadenopathy, or swelling; 35% of patients reported systemic adverse events, and all were mild. The most frequently reported systemic reactions included weakness (15%), headache (9%), and diarrhea (3%). In conclusion, in recipients of HSCT, a single dose of the BNT162b2 SARS-CoV-2 vaccine yielded poor efficacy, while immunogenicity increased significantly after vaccine boost at day 21 after the first dose. Patients who received vaccines beyond one year after transplant were more likely to mount anti-S IgG antibodies, which could be due to a broader immune reconstitution, as we observed an enhanced response to single BNT162b2 vaccine dose in patients with higher CD4+ T cell and particularly CD4+CD45RA+ naïve T cell counts. [Display omitted] DisclosuresKordasti: Alexion: Honoraria; Celgene: Research Funding; Beckman Coulter: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Pane: AbbVie; Amgen; Novartis: Other: Travel, accommodation, expenses; AbbVie; Amgen; Novartis, GSK, Incyte: Speakers Bureau; Novartis Pharma SAS;: Research Funding; AbbVie; Amgen; Novartis, GSK , Incyte: Consultancy.

COVID-19 Vaccination Imperatives in People on Maintenance Dialysis: An International Perspective.

COVID-19 Vaccination Imperatives in People on Maintenance Dialysis: An International Perspective.

COVID-19 prevention with subcutaneous administration of the monoclonal antibodies casirivimab and imdevimab: Subgroup analysis in participants with cardiovascular disease and diabetes

BackgroundIn a Phase 3 prevention trial, the monoclonal antibody combination casirivimab and imdevimab (REGEN-COVTM) administered subcutaneously (SC) prevented symptomatic SARS-CoV-2 infection in asymptomatic adults/adolescents living in the same household as a SARS-CoV-2-infected individual (index case). Individuals with cardiovascular disease (CVD) and/or diabetes are at increased risk of moderate/severe COVID-19. MethodsUninfected individuals ≥12 years, identified ≤96 hours of index case being diagnosed SARS-CoV-2 positive, were randomized 1:1 to REGEN-COV 1200mg SC or placebo. The primary endpoint was the proportion of participants who developed symptomatic infection (COVID-19) during the 28-day efficacy assessment period among those who were SARS-CoV-2 RT-qPCR negative and without evidence of immunity (seronegative) at baseline. A post-hoc analysis assessed efficacy in participants with CVD (including hypertension) and/or diabetes. Overall safety is reported. ResultsThe study included SARS-CoV-2 RT-qPCR negative participants at baseline (n=2067). There was an 81.4% relative risk reduction (RRR) of symptomatic infection with REGEN-COV in the overall seronegative population (n=1505; Figure 1; Table 1). In participants with CVD (n=332) or diabetes (n=103), the RRRs of developing symptomatic infection with REGEN-COV versus placebo were 54.9% and 69.0%, respectively. Similar results were observed when analyses were performed regardless of baseline serology status. Treatment-emergent adverse events occurring at ≥2% included COVID-19, asymptomatic COVID-19, headache, and injection-site reaction (Table 2). ConclusionsIn study participants with CVD and/or diabetes, who are known to be at increased risk of severe disease if infected, treatment with REGEN-COV SC reduced the risk of developing symptomatic SARS-CoV-2 infection, consistent with the overall study results..

Impact of baseline SARS-CoV-2 antibody status on syndromic surveillance and the risk of subsequent COVID-19\u2014a prospective multicenter cohort study

BackgroundIn a prospective healthcare worker (HCW) cohort, we assessed the risk of SARS-CoV-2 infection according to baseline serostatus.MethodsBaseline serologies were performed among HCW from 23 Swiss healthcare institutions between June and September 2020, before the second COVID-19 wave. Participants answered weekly electronic questionnaires covering information about nasopharyngeal swabs (PCR/rapid antigen tests) and symptoms compatible with coronavirus disease 2019 (COVID-19). Screening of symptomatic staff by nasopharyngeal swabs was routinely performed in participating facilities. We compared numbers of positive nasopharyngeal tests and occurrence of COVID-19 symptoms between HCW with and without anti-nucleocapsid antibodies.ResultsA total of 4812 HCW participated, wherein 144 (3%) were seropositive at baseline. We analyzed 107,807 questionnaires with a median follow-up of 7.9 months. Median number of answered questionnaires was similar (24 vs. 23 per person, P = 0.83) between those with and without positive baseline serology. Among 2712 HCW with ≥ 1 SARS-CoV-2 test during follow-up, 3/67 (4.5%) seropositive individuals reported a positive result (one of whom asymptomatic), compared to 547/2645 (20.7%) seronegative participants, 12 of whom asymptomatic (risk ratio [RR] 0.22; 95% confidence interval [CI] 0.07 to 0.66). Seropositive HCWs less frequently reported impaired olfaction/taste (6/144, 4.2% vs. 588/4674, 12.6%, RR 0.33, 95% CI 0.15–0.73), chills (19/144, 13.2% vs. 1040/4674, 22.3%, RR 0.59, 95% CI 0.39–0.90), and limb/muscle pain (28/144, 19.4% vs. 1335/4674, 28.6%, RR 0.68 95% CI 0.49–0.95). Impaired olfaction/taste and limb/muscle pain also discriminated best between positive and negative SARS-CoV-2 results.ConclusionsHaving SARS-CoV-2 anti-nucleocapsid antibodies provides almost 80% protection against SARS-CoV-2 re-infection for a period of at least 8 months.

Inflammatory Biomarkers and Intracranial Hemorrhage after Endovascular Thrombectomy

Intracranial hemorrhage after endovascular thrombectomy is associated with poorer prognosis compared with those who do not develop the complication. Our study aims to determine predictors of post-EVT hemorrhage - more specifically, inflammatory biomarkers present in baseline serology. We performed a retrospective review of consecutive patients treated with EVT for acute large vessel ischemic stroke. The primary outcome of the study is the presence of ICH on the post-EVT scan. We used four definitions: the SITS-MOST criteria, the NINDS criteria, asymptomatic hemorrhage, and overall hemorrhage. We identified nonredundant predictors of outcome using backward elimination based on Akaike Information Criteria. We then assessed prediction accuracy using area under the receiver operating curve. Then we implemented variable importance ranking from logistic regression models using the drop in Naegelkerke R2 with the exclusion of each predictor. Our study demonstrates a 6.3% SITS (16/252) and 10.0% NINDS (25/252) sICH rate, as well as a 19.4% asymptomatic (49/252) and 29.4% (74/252) overall hemorrhage rate. Serologic markers that demonstrated association with post-EVT hemorrhage were: low lymphocyte count (SITS), high neutrophil count (NINDS, overall hemorrhage), low platelet to lymphocyte ratio (NINDS), and low total WBC (NINDS, asymptomatic hemorrhage). Higher neutrophil counts, low WBC counts, low lymphocyte counts, and low platelet to lymphoycyte ratio were baseline serology biomarkers that were associated with post-EVT hemorrhage. Our findings, particularly the association of diabetes mellitus and high neutrophil, support experimental data on the role of thromboinflammation in hemorrhagic transformation of large vessel occlusions.

Serologic Status and SARS-CoV-2 Infection over 6 Months of Follow Up in Healthcare Workers in Chicago: A Cohort Study.

To determine the changes in severe acute respiratory coronavirus virus 2 (SARS-CoV-2) serologic status and SARS-CoV-2 infection rates in healthcare workers (HCWs) over 6-months of follow-up. Prospective cohort study. HCWs in the Chicago area. Cohort participants were recruited in May and June 2020 for baseline serology testing (Abbott anti-nucleocapsid IgG) and were then invited for follow-up serology testing 6 months later. Participants completed monthly online surveys that assessed demographics, medical history, coronavirus disease 2019 (COVID-19), and exposures to SARS-CoV-2. The electronic medical record was used to identify SARS-CoV-2 polymerase chain reaction (PCR) positivity during follow-up. Serologic conversion and SARS-CoV-2 infection or possible reinfection rates (cases per 10,000 person days) by antibody status at baseline and follow-up were assessed. In total, 6,510 HCWs were followed for a total of 1,285,395 person days (median follow-up, 216 days). For participants who had baseline and follow-up serology checked, 285 (6.1%) of the 4,681 seronegative participants at baseline seroconverted to positive at follow-up; 138 (48%) of the 263 who were seropositive at baseline were seronegative at follow-up. When analyzed by baseline serostatus alone, 519 (8.4%) of 6,194 baseline seronegative participants had a positive PCR after baseline serology testing (4.25 per 10,000 person days). Of 316 participants who were seropositive at baseline, 8 (2.5%) met criteria for possible SARS-CoV-2 reinfection (ie, PCR positive >90 days after baseline serology) during follow-up, a rate of 1.27 per 10,000 days at risk. The adjusted rate ratio for possible reinfection in baseline seropositive compared to infection in baseline seronegative participants was 0.26 (95% confidence interval, 0.13-0.53). Seropositivity in HCWs is associated with moderate protection from future SARS-CoV-2 infection.

MRI-detected synovitis of the small joints predicts rheumatoid arthritis development in large joint undifferentiated inflammatory arthritis.

ObjectivesNew onset undifferentiated large joint inflammatory arthritis can be diagnostically challenging. It is unknown how often these patients progress to RA, and how they can be identified at first presentation. We assessed clinical and serological features associated with RA development in patients with an undifferentiated mono- or oligo-articular large joint arthritis, and with keen interest in whether an MRI of the small joints of the hand and foot would aid diagnosis.MethodsLeiden Early Arthritis Clinic includes 4018 patients; this prospective study follows 221 consecutively included patients with new onset undifferentiated large joint arthritis. Baseline clinical data and serology were obtained. Forty-five patients had MRIs (hand and foot). MRIs were scored according to the OMERACT RAMRIS. Univariable and multivariable logistic regression were assessed. Test characteristics, predictive values and net reclassification index (NRI) for RA were determined.ResultsPatients mostly presented with knee or ankle mono-arthritis. During the 12 months’ follow-up 17% developed RA. Autoantibody positivity (ACPA and/or RF) and MRI-detected synovitis in hands and feet were independently associated with RA development in multivariable analyses [odds ratio 10.29 (P = 0.014) and 7.88 (P = 0.017), respectively]. Positive predictive value of autoantibodies, MRI-detected synovitis and combination of both features was 63%, 55% and 100%, respectively. The addition of MRI-detected synovitis to autoantibody status improved diagnostic accuracy (NRI 18.1%).ConclusionIn patients presenting with undifferentiated large joint arthritis, 17% will develop RA. Autoantibody positivity and subclinical synovitis are independent predictors. The data suggest MRI of small joints is beneficial for early identification of RA in large joint arthritis.

Lack of correlation of Brucella antibody titers with clinical outcomes and culture positivity of brucellosis

BackgroundBrucellosis is a zoonotic disease caused by Brucella spp., namely B. melitensis and B. abortus in humans. Culturing is the gold standard method for diagnosis; however, because Brucella is a slow-growing bacterium, which may delay diagnosis, other faster methods, such as serology, are used. Studies on the correlation between Brucella antibody titers and clinical outcomes are limited. Therefore, this study assessed such correlation and evaluated the correlation between baseline serological results with culture positivity and clinical picture.MethodsPatients tested positive for Brucella antibodies at baseline and diagnosed with brucellosis between January 2008 and December 2018 were included. Collected data included clinical outcomes, baseline culture positivity (growth in culture), arthralgia, baseline and end of therapy (EOT) temperature, white blood cell count, C-reactive protein level, and erythrocyte sedimentation rate.ResultsOf 695 patients tested for Brucella antibodies, only 94 had positive baseline serology and diagnosed with acute brucellosis, among whom 63 had EOT serology. No significant correlations were found between EOT antibody titers of both Brucella spp. and clinical cure, mortality, length of stay, and duration of therapy. Additionally, no correlations were found between baseline serology and culture positivity, arthralgia, temperature, and other lab values.ConclusionBrucella serology does not correlate with clinical outcomes at EOT nor with culture positivity at baseline. Therefore, healthcare providers are advised to consider the whole clinical picture of a brucellosis patient without relying solely on serological results during follow up and not replace culturing with serology testing alone at the time of diagnosis.

SARS-CoV-2 Infections in Households in a Peri-Urban Community of Lima, Peru: A Prospective Cohort Study

Background: Few studies have prospectively evaluated SARS-CoV-2 infections in households. We assessed the prevalence and incidence of SARS-CoV-2 infections in a prospective study of households in Lima, Peru.Methods: We conducted a prospective cohort study in a peri-urban district of Lima, Peru. Households with at least a child, a young adult (age 18 to 50 years) and an older adult age >50 years, were followed with twice-a-week household visits during a two-month period for health surveillance. Nasal swabs and saliva specimens were collected twice weekly, and nasopharyngeal swabs were collected weekly from each participant, regardless of symptoms. Laboratory-confirmed SARS-CoV-2 infection was defined by two RT-PCR tests from any of the collected specimens within a week. Blood samples collected at enrolment and end of follow­-up were tested with rapid serological tests. We calculated the prevalence and incidence of laboratory-confirmed SARS-CoV-2 infections during the study period.Findings: We enrolled 132 participants from 44 households, including 44 children, 44 young adults and 44 older adults. A total of 13 SARS-CoV-2 infections were detected in 9 households, for an overall period prevalence of 9·85% (95% confidence interval [CI]:5·35-16·25). Most (66·67%) infections were symptomatic. Eight of 11 (72·73%) SARS-CoV-2 detections corresponded to the Lambda variant. During 218·79 person-months at risk of follow-up there were six new SARS-CoV-2 infections detected (2·74 per 100 person-month, 95% CI: 1·25– 6·04). At enrollment, 59 of 128 participants tested had positive SARS-CoV-2 IgG serology (46·09%, 95% CI: 37·25-55·12). Five of six new infections occurred among participants with negative baseline serology.Interpretation: We demonstrated high incidence of SARS-CoV-2 infections in households during periods of active circulation of the Lambda variant, especially among subjects without evidence of prior infection, most of them not detected by the Ministry of Health system.Funding Information: Consejo Nacional de Ciencia y Tecnología – CONCYTEC-PROCIENCIA, Lima, Peru (contract No. 082-2020); Vanderbilt University Medical Center, Nashville TN, USA; and Instituto de Investigación Nutricional, Lima, Peru. Declaration of Interests: None to declare. Ethics Approval Statement: The study was approved by the ethics review boards (ERBs) of the Instituto de Investigacion Nutricional and Vanderbilt University. All adults signed their own ERB approved written informed consent form (ICF). For individuals under 18 years of age, either the mother or the father signed an ICF. Additionally, children 8 years and older signed a written informed assent form.