Covid-19 vaccine responses in individuals with type 1 diabetes are comparable to control subjects without diabetes

Aims/Hypothesis: Covid-19 has been associated with poorer outcomes in individuals with type 1 diabetes. Most existing data relate to hospitalised patients with few data available on seroprevalence and the effects of Covid-19 on people with diabetes in the general population. We examined antibody responses to SARS Cov-2 infection and vaccination in people with and without diabetes. Method(s): From June 2020, capillary blood samples collected remotely from 1828 individuals (type 1 diabetes n = 267) were analysed for SARS-CoV- 2 antibodies to RBD (infection pre-Jan 2021/vaccination post -Jan 21) and N (infection post Jan 21) antigens using low serum volume luciferase-based assays developed "in house". Questionnaire data recording experiences of Covid-19 and vaccinations dates were collected simultaneously with the samples. Median antibody levels were compared using Kruskal-Wallis tests. Result(s): There was evidence of SARS CoV-2 infection in 317/1828 (17%) of individuals screened with no evidence of more severe self-reported Covid-19 symptoms in those with diabetes (no participants were hospitalised) and almost a quarter of those with type 1 diabetes were asymptomatic. Although samples were collected at variable time points from vaccination, robust antibody responses to vaccination were observed (Pfizer, AstraZeneca, and Moderna) after the second vaccination with no differences in antibody levels between those with and without diabetes (p = 0.3). Conclusion(s): Hospitalised individuals with Covid-19 and type 1 diabetes were at greater risk of complications but this study shows that among the non-hospitalised population, clinical symptoms, antibody responses to infection, and vaccination in those with type 1 diabetes was similar to control subjects.

Comparison of HbA1c measurement in remotely prepared capillary versus standard venous blood samples

Background The COVID-19 pandemic has disrupted routine HbA1c testing. This has led to difficulties in monitoring glycaemic control and identifying people with suboptimal glycaemia. Delayed diagnosis of diabetes and suboptimal glycaemic control over extended periods can increase the risk of developing long-term complications of diabetes. The self-collection of capillary blood remotely (at home) for routine HbA1c testing can facilitate monitoring of glycaemic control whilst supporting virtual consultations. The aimof this study was to assess the clinical performance and user acceptance of capillary blood samples prepared remotely using the MiniCollect capillary blood collection device as an alternative to standard venous blood collection for HbA1c analysis. Methods Adult men and women with any type of diabetes were recruited. Following informed written consent, eligible participants provided a venous blood sample at their routine clinic appointment and subsequently prepared a capillary blood sample remotely. Participants also completed a bespoke usability questionnaire. Results Of 84 participants recruited, 62 capillary samples returned to the laboratory, with 41 having a paired venous sample for HbA1c analysis. HbA1c results using both collection methods demonstrated good agreement;Passing-Bablok Regression analysis, y=0 + 1x;R=0.986, Bland-Altman Difference Plot providing a mean difference of 0.3 mmol/mol. Conclusions Over half of participants found the MiniCollect device easy to use. The majority were in favour of the remote capillary blood collection service and would use it if routinely available. The remote self-collection of capillary blood for HbA1c is a convenient alternative for people with diabetes living and working in rural or urban settings ensuring optimal continuance of care.

Mechanisms of impaired gas exchange following hospitalisation for severe COVID-19

Introduction/Aim: Reduced carbon monoxide diffusing capacity (DL CO) is common after recovery from severe COVID-19 and cohort studies have found it to be more abnormal than either VC or TLC. There is no specific evidence that this relates to membrane disfunction or vascular injury. Concurrent measurement of nitric oxide diffusing capacity (DL NO) and DL CO can be used to partition gas diffusion into its two components - membrane conductance (D m CO) and capillary blood volume (V C). In this study, we sought to evaluate D m CO and V C in the early and later recovery periods after severe COVID-19. Method(s): Patients attended for post-COVID outpatient clinical review and complex lung function testing including DL NO /DL CO (Hyp'Air;Medisoft, Leeds). Further appointments and repeat testing occurred when indicated. Lung function comparisons were made using t-tests. Result(s): 46 (8 female) subjects (mean+/-SD age 58+/-13, BMI 34+/-8), who had severe COVID pneumonitis, WHO ordinal severity classification of 6+/-1 and prolonged (19+/-22 days) length of hospital stay, were assessed 51+/-29 days post discharge. Mean TLC [z-score -1.64+/-1.31] and D L CO [z-score -1.60+/-1.48] were both reduced. V C and D m CO were reduced to a similar extent (Z-score -1.36+/-1.19 and -1.14+/-1.06, p=0.4). 14 (1 female) patients returned for testing 70+/-35 days later. In this subgroup, D L CO improved but remained below LLN (Z-score -2.98+/-0.73 [Visit 1] Vs -2.17+/-0.69 [Visit 2], p=0.01). D m CO improved (Z-score -1.99+/-0.91 Vs -1.25+/-1.17, p=0.01) but V C was unchanged (Z-score -2.33+/-0.53 Vs -2.03+/-0.76, p=0.17). Conclusion(s): Gas exchange is persistently abnormal after severe COVID. Membrane conductance is abnormal in the earlier recovery phase but improves to a significant extent. In contrast, reduced capillary blood volume persists. Repeat testing at longer intervals after recovery from acute illness is still required but these data raise the possibility that persisting effects of acute vascular injury will contribute to physiological impairment long after severe COVID pneumonitis.

Mechanisms of impaired gas exchange following hospitalisation for COVID-19

Introduction/Aim: Reduced carbon monoxide diffusing capacity (DL CO) is the most prevalent lung function abnormality post COVID-19 infection. Two studies suggested this relates to alveolar unit loss with preserved capillary blood volume. The measurement of nitric oxide diffusing capacity (D L NO) concurrently with D L CO allows for the quantitation of the membrane component of gas diffusion (D m CO) and capillary blood volume (V C). We sought to monitor D m CO and V C in the recovery period of patients hospitalised for severe COVID-19. Method(s): Patients attended outpatient clinical review and lung function testing including DL NO /DL CO (Hyp'Air;Medisoft, Leeds), with further appointment if indicated. Lung function comparisons were made using t-tests and clinical associations using Pearson correlation. Result(s): 46 (8 female) patients (mean+/-SD) (age 58+/-13, BMI 34+/-8), were assessed 51+/-29 days post discharge. WHO ordinal severity classification was 6+/-1, suggesting severe disease, with prolonged (19+/-22 days) length of admission. V C and D m CO were similarly reduced (Z-score -1.36+/-1.19 Vs -1.14+/-1.06, p = 0.4). V C was negatively correlated with length of stay (r=-0.42, p < 0.01). TLC (Z-score -1.64+/-1.31) and D L CO (-1.60+/-1.48) were significantly reduced and negatively correlated with length of stay (r>-0.41, p<=0.02). WHO severity negatively correlated with TLC only (r=-0.45, p < 0.01). Demographic and biochemical data did not correlate with lung function.14 (1 female) patients returned for repeat testing 70+/-35 days later. D m CO improved (Z-score -1.99+/-0.91 Vs -1.25+/-1.17, p = 0.01). V C was unchanged (Z-score -2.33+/-0.53 Vs -2.03+/-0.76, p = 0.17). D L CO improved but remained below LLN (Z-score -2.98+/-0.73 Vs -2.17+/-0.69, p = 0.01). Conclusion(s): Similar reductions in D m CO and V C following hospitalisation for COVID-19 were identified. In those who returned for repeat testing, D m CO values normalised, but V C did not improve. Abnormal lung function related to increasing severity and length of stay. These findings suggests vascular injury may play a more important role rather than alveolar unit loss as the primary contributor to gas exchange impairment following COVID-19.

Non-contrast cardiac magnetic resonance imaging after SARS-CoV2 infection or vaccination in asymptomatic adolescents: Insights from the EnIGMA study

Background: Myocarditis after SARS-CoV2 infection or vaccination is rare, but seems to be relatively more frequent in young population. Cardiac magnetic resonance (CMR) T2 weighted sequences have the potential to detect subclinical myocarditis. However, there is paucity of data on the potential myocardial involvement after SARS-CoV2 infection or vaccination in asymptomatic adolescents. Purpose(s): To evaluate the presence of subclinical myocardial damage in adolescents who were infected with SARS-CoV2 or vaccinated against SARS-CoV2 using non-contrast CMR imaging. Method(s): Asymptomatic adolescents enrolled in the Early ImaginG Markers of unhealthy lifestyles in Adolescents (EnIGMA) project were scanned using a 3-Tesla CMR scanner between March 2021 and October 2021. CMR scans included CINE imaging and myocardial T2-mapping sequences. SARS-CoV2 IgG antibody testing was performed in capillary blood samples, and date of confirmed SARS-CoV2 infection and/or vaccination if any was collected. Participants were assigned to three different groups according to SARS-CoV2 status: Group 1 (non-infected and nonvaccinated), Group 2 (infected and non-vaccinated), and Group 3 (vaccinated, independently of past infection status). CMR images were analyzed by experienced observers blinded to adolescent's SARS-CoV2 status. ANOVA and multiple regression analysis, together with correlation coefficients, were used to study between-group differences and associations among variables of interest. Result(s): A total of 115 adolescents with a mean age of 16.0 years (standard deviation (SD)=0.4), 54% girls, completed the CMR study and SARSCoV2 data successfully, and were assigned to Group 1 (n=72), Group 2 (n=22), and Group 3 (n=21). Left and right ventricular ejection fraction (LVEF/RVEF) did not significantly differ among groups: Mean LVEF was 62.8% (SD=4.1), 63.0% (SD=3.7) and 60.9% (SD=3.9) [p=0.12] and mean RVEF was 56.5% (SD=4.2), 56.5% (SD=5.5) and 54.5% (SD=5.1) [p=0.23] in Groups 1, 2 and 3, respectively. Similarly, there were no between-group significant differences in myocardial T2 relaxation values: Mean T2 values were 44.1 ms (SD=2.2), 44.1 ms (SD=1.8) and 44.4 ms (SD=1.9) in Groups 1, 2, and 3, respectively (p=0.63) (Figure 1). No differences were found either after adjusting for age and gender. Median time (interquartile range) from date of infection or vaccination to CMR acquisition was 133 (121) days and 28 (38) days in Group 2 and Group 3, respectively. No correlation between time from infection/vaccination to CMR acquisition and T2 values was detected (Figure 2). Conclusion(s): This observational study did not find evidence of subclinical myocardial involvement after SARS-CoV2 infection or vaccination in asymptomatic adolescents, as assessed with T2-mapping magnetic resonance imaging.

Impact of SARS CoV2 infection on pulmonary gas exchange and exercise capacity in patients with mild to severe COVID-19

Since beginning of 2020, SARS-CoV2 pandemic has been prevailing in humans causing COVID-19. Airways are strongly impacted during virus mediated inflammation and damage. Exact pathomechanisms during COVID-19 are still under investigation. We now further characterized limitations in exercise capacity in outpatient patients after symptomatic infection with SARS-CoV2 using bicycle cardiopulmonary exercise testing (CPET). 45 patients (21female/24 male) underwent standard pulmonary function testing (PFT) including spirometry, bodyplethysmography, CO-diffusion-measurement (DLCO, DLCO/VA), capillary blood gas-analysis (BGA) and symptom limited CPET on a bicycle. Patients' disease history was evaluated in advance. Severity of the disease was quantified according to reported data. At rest, there were no statistically relevant abnormalities in spirometry, bodyplethysmography, CO-diffusion-measurement or blood gas-analysis, even in those patients less than 40 days post infection. We found significantly impaired alveolar-arterial oxygen gradients (A-aO2) and decreased peak V'O2 level post-COVID-19 patients up to up to 80days post infection. Reevaluating 10 patients 3 month later, a markedly increase in peak oxygen-uptake (V'O2) and a normalized A-aO2 at rest was noted. We conclude that COVID-19 resulted in decreased cardiopulmonary exercised capacity as demonstrated by CPET (significantly decreased peak V'O2). The underlying mechanism is limitation of oxygen-diffusion indicated by significantly elevated A-aO2 level in post-COVID-19 patients. Limitation was temporary and patients reached age-appropriate level 3 month later.

Acceptability and feasibility of selforganised blood sample collection for SARS-CoV-2 antibody screening in persons with a high risk for a severe COVID-19 disease progression

Background: The pandemic situation poses new challenges for research. Ethical issues might arise if especially vulnerable individuals expose themselves to a higher risk of infection for study purposes. Research question: How is the feasibility, quality and acceptance of self-organised blood sample collections to measure anti-SARS-CoV-2 Spike IgG antibodies in persons with a high risk for a severe COVID-19 disease progression? Methods: Persons with a high risk for a severe COVID-19 disease progression (immunocompromised, oncology or 80+ years) were recruited between January and September 2021 to send in blood samples (2.6 ml, 7.5 ml or 500 mul EDTA tubes) one month and six months after their second COVID- 19 vaccination. Participants were given the choice of drawing blood themselves (as capillary blood), with the research team, or in local practices or clinics. Participants were surveyed via a computer-assisted telephone interview in December 2021 and January 2022 about their choice of blood sampling methods, experiences, and influence of choice upon study participation. Result(s): Data from 366 participants was collected via telephone follow-up. First, blood samples were collected by the participants themselves (35.8%), local practices or clinics (32.0%) and the research team (22.7%). Second blood samples were mostly collected in local practices or clinics (43.7%) followed by participants themselves (32.5%) and the research team (14.3%). Only 3.3% of blood samples were not sent back or analysable. One-fourth (26%) of participants stated that they would not have participated in the study if it would have been required to travel to the university hospital to give their blood sample. Conclusion(s): Participants were able to self-organise blood collection, using several different blood sample methods. Nearly all blood samples were analyzable when self-collected and sent by post. One-fourth of the participants would not have participated in the study if required to give their blood samples at the study location.

Application of the New "Points in Range" Metrics in the Assessment of In-Hospital Glycemic Control.

Introduction Capillary blood glucose (CBG) monitoring remains the most used testing form in hospitals and allows for "points in range (PIR)" metric calculation. This study was conceived to evaluate the metabolic control in patients with diabetes mellitus (DM) at a hospital through PIR metrics. Methods This was an observational cross-sectional study conducted on October 9, 2020, that included non-critical adults admitted to Centro Hospitalar Universitário do Porto (except pregnant/postpartum women) with DM under CBG monitoring and a minimum of 24 hours of hospitalization. Glycemic control was evaluated by previous day CBG monitoring. Results The study sample consisted of 110 patients with DM (93.6% type 2) with a median number of CBG tests of 4.00 (1.00) and a median CBG of 166.20 (69.41) mg/dL, SD 41.93 ± 27.20 mg/dL, and variation coefficient of 22.56 ± 12.51%. Points below range were 0.5%, with 0% below 54 mg/dL. The points in ranges 70-140 mg/dL and 140-180 mg/dL were 32.8% and 22.0%, respectively, and the total number of patients with all points in range 70-180 mg/dL was 19 (17.3%), with only 3 (2.7%) having all points in range 140-180 mg/dL and 10 (9.1%) in range 70-140 mg/dL. Regarding points above range (PAR), 29.9% and 14.8% points were at levels 1 and 2 hyperglycemia, respectively, and 15 (13.6%) patients had all points above 180 mg/dL. Correlations were identified between PAR and the total number of CBG assessments (ρ = 0.689, p < 0.001). Conclusion We conclude that in-hospital glycemic control remains suboptimal: only few have adequate control according to the PIR metrics despite low glycemic variability. PIR metrics are a new, valuable, simple and valid way to take better advantage of CBG monitoring at no added cost.

Mechanisms of gas transfer impairment utilizing nitric oxide following severe COVID-19 pneumonitis.

Reduced carbon monoxide diffusing capacity (DLCO ) is common after recovery from severe COVID-19 pneumonitis. The extent to which this relates to alveolar membrane dysfunction as opposed to vascular injury is uncertain. Simultaneous measurement of nitric oxide diffusing capacity (DLNO ) and DLCO can partition gas diffusion into its two components: alveolar-capillary membrane conductance (DmCO ) and capillary blood volume (VC ). We sought to evaluate DmCO and VC in the early and later recovery periods after severe COVID-19. Patients attended for post-COVID-19 clinical review and lung function testing including DLNO /DLCO . Repeat testing occurred when indicated and comparisons made using t-tests. Forty-nine (eight female) subjects (mean ± SD age: 58 ± 13, BMI: 34 ± 8) who had severe COVID-19 pneumonitis, WHO severity classification of 6 ± 1, and prolonged (21 ± 22 days) hospital stay, were assessed 2 months (61 ± 35 days) post discharge. DLCO adj (z-score -1.70 ± 1.49, 25/49 < lower limit of normal [LLN]) and total lung capacity (z-score -1.71 ± 1.30) were both reduced. DmCO and VC and were reduced to a similar extent (z-score -1.19 ± 1.05 and -1.41 ± 1.20, p = 0.4). Seventeen (one female) patients returned for repeat testing 4 months (122 ± 61 days) post discharge. In this subgroup with more impaired lung function, DLCO adj improved but remained below LLN (z-score -3.15 ± 0.83 vs. -2.39 ± 0.86, p = 0.01), 5/17 improved to >LNN. DmCO improved (z-score -2.05 ± 0.89 vs. -1.41 ± 0.78, p = 0.01) but VC was unchanged (z-score -2.51 ± 0.55 vs. -2.29 ± 0.59, p = 0.16). Alveolar membrane conductance is abnormal in the earlier recovery phase following severe COVID-19 but significantly improves. In contrast, reduced VC persists. These data raise the possibility that persisting effects of acute vascular injury may contribute to gas diffusion impairment long after severe COVID-19 pneumonitis.

Concordance in COVID-19 serology, bone mineralization, and inflammatory analytes between venous and self-collected capillary blood samples exposed to various pre-analytical conditions.

BACKGROUND: The COVID-19 has led to a significant increase in demand for remote blood sampling in clinical trials. This study aims to ascertain the concordance between venous versus capillary samples, processed immediately or exposed to various pre-analytical conditions. METHODS: Participants (≥12 years old) provided a venous blood sample (processed immediately) and capillary samples allocated to one of the following conditions: processed immediately or exposed to 12-, 24-, or 36-h delays at room temperature or 36-h delays with a freeze-thaw cycle. The analytes of interest included SARS-CoV-2 IgG, 25-hydroxy vitamin D (25(OH)D), alkaline phosphate (ALP), calcium (Ca), phosphate (Ph), and c-reactive protein (CRP). Paired samples were considered interchangeable if they met three criteria: minimal within-subject mean difference, 95% of values within desirable total errors, and inter-class correlation (ICC) > 0.90. RESULTS: 90 participants (44.1% male) were enrolled. When comparing rapidly processed venous with capillary samples, 25(OH)D, ALP, and CRP met all three criteria; SARS-CoV-2 IgG met two criteria (mean difference and ICC); and Ca and Ph met one criterion (mean difference). When considering all three criteria, concentrations of 25(OH)D, CRP, and ALP remained unchanged after delays of up to 36 h; SARS-CoV-2 IgG met two criteria (mean difference and ICC); Ca and Ph met one criterion (mean difference). CONCLUSION: These findings suggest that remote blood collection devices can be used to measure anti-SARS-CoV-2 IgG, 25(OH)D, CRP, and ALP. Further analysis is required to evaluate the interchangeability between venous and capillary testing in Ca and Ph levels, which are more sensitive to pre-analytical conditions.

Evaluation of remote triazole capillary blood testing to facilitate remote therapeutic drug monitoring (TDM): A vali-dation study

Background: The advent of COVID-19 has meant that patients with chronic diseases needed to shield, however, investi-gations were needed to guide continual management of their disease. Remote monitoring options were evaluated to ensure the standard of care is not compromised. Purpose and Hypothesis: The aim was to validate remote (return-posted) capillary triazole blood testing and evaluate the potential role of remote TDM in chronic antifungal therapy. Material(s) and Method(s): A single-center prospective cross-sectional study of remote finger prick capillary blood testing compared with gold standard venesection was performed. Remote finger prick capillary blood testing was validated compared to local standard venesection using comparative statistical analysis Comparative statistical analysis: Paired t-test, correlation and Bland-Altman were used to determine if there was agreement or association between the sampling methods. Result(s): A total of 66 patients receiving triazole therapy were recruited and 57 pooled pairs of remote capillary and venous triazole concentrations and metabolites wereprospectively analyzed, with the rest of the blood samplesnot being analyzed due to insufficient sample, hemolysis, or undetectable triazole level of < 0.2 mg/l. There was a significant difference in the comparison of the two methods of sampling with paired t-test at P <.0001. Bland-Altman analysis yielded wide bias (-49.07%) and wide limits of agreement (-85.5% to -12.64%). On average capillary triazole, concentrations were 37% lower than venous concentrations (Fig. 1). There was however a very strong correlation between capillary and venous tests (Pearson's correlation coefficient r = 0.9219, P <.0001, Fig. 2). Conclusion(s): Remote capillary triazolesampling does not appear interchangeable with venoussampling, but being strongly correlated and on average 2/3rd of the venous value, could be a predictor of venous triazole level, or be useful for intra-patient longitudinal monitoring. When incorporated into an outpatient clinical pathway it can improve shared decision-making and patient experience.Further research is required to determine appropriate target reference ranges if the new lower capillary levels can be used routinely, especially in the climate of COVID-19 where social distancing measures limit patient access to hospitals and clinics for routine investigations.

Nebivolol: an effective option against long-lasting dyspnoea following COVID-19 pneumonia - a pivotal double-blind, cross-over controlled study.

Background: Pulmonary microvascular occlusions can aggravate SARS-CoV-2 pneumonia and result in a variable decrease in capillary blood volume (Vc). Dyspnoea may persist for several weeks after hospital discharge in many patients who have "radiologically recovered" from COVID-19 pneumonia. Dyspnoea is frequently "unexplained" in these cases because abnormalities in lung vasculature are understudied. Furthermore, even when they are identified, therapeutic options are still lacking in clinical practice, with nitric oxide (NO) supplementation being used only for severe respiratory failure in the hospital setting. Nebivolol is the only selective ß1 adrenoceptor antagonist capable of inducing nitric oxide-mediated vasodilation by stimulating endothelial NO synthase via ß3 agonism. The purpose of this study was to compare the effect of nebivolol versus placebo in patients who had low Vc and complained of dyspnoea for several weeks after COVID-19 pneumonia. Methods: Patients of both genders, aged ≥18 years, non-smokers, who had a CT scan that revealed no COVID-related parenchymal lesions but still complaining of dyspnoea 12-16 weeks after hospital discharge, were recruited. Spirometrical volumes, blood haemoglobin, SpO2, simultaneous diffusing capacity for carbon monoxide (CO) and NO (DLCO and DLNO, respectively), DLNO/DLCO ratio, Vc and exhaled NO (eNO) were measured together with their dyspnoea score (DS), heart frequency (HF), and blood arterial pressure (BAP). Data were collected before and one week after both placebo (P) and nebivolol (N) (2.5 mg od) double-blind cross-over administered at a two-week interval. Data were statistically compared, and p<0.05 assumed as statistically significant. Results: Eight patients (3 males) were investigated. In baseline, their mean DS was 2.5±0.6 SD, despite the normality of lung volumes. DLCO and DLNO mean values were lower than predicted, while mean DLNO/DLCO ratio was higher. Mean Vc proved substantially reduced. Placebo did not modify any variable (all p=ns) while N improved DLco and Vc significantly (+8.5%, p<0.04 and +17.7%, p<0.003, respectively). eNO also was significantly increased (+17.6%, p<0.002). Only N lowered the dyspnoea score (-76%, p<0.001). Systolic and diastolic BAP were slightly lowered (-7.5%, p<0.02 and -5.1%, p<0.04, respectively), together with HF (-16.8%, p<0.03). Conclusions: The simultaneous assessment of DLNO, DLCO, DLNO/DLCO ratio, and Vc confirmed that long-lasting dyspnoea is related to hidden abnormalities in the lung capillary vasculature. These abnormalities can persist even after the complete resolution of parenchymal lesions regardless of the normality of lung volumes. Nebivolol, but not placebo, improves DS and Vc significantly. The mechanism suggested is the NO-mediated vasodilation via the ß3 adrenoceptor stimulation of endothelial NO synthase. This hypothesis is supported by the substantial increase of eNO only assessed after nebivolol. As the nebivolol tolerability in these post-COVID normotensive patients was very good, the therapeutic use of nebivolol against residual and symptomatic signs of long-COVID can be suggested in out-patients.

A Highly Sensitive Immunoassay for Determination of Immune Response to SARS-CoV-2 in Capillary Blood Samples.

Throughout the pandemic, serological assays have been revealed as crucial for detecting previous exposures to the virus and determining the timing of antibody maintenance after vaccination or natural infection. This study aimed to develop an optimized enzyme-linked immunosorbent assay (ELISA)-based serology, which could be used in case of reagent shortages, such as that occurred in the beginning of this health emergency. As a result, we present a high-sensitive immunoassay for the determination of IgG levels in venous serum samples, using 2 µg/mL antigen (receptor-binding domain of the spike protein S1) for coating the plate and utilizing human samples at a dilution 1:1000. This method showed non-inferiority features versus a commercial kit, is less expensive, and has a higher spectrophotometric range that allows for a better quantification of the antibody titers. The optical density values before and after heating venous serum samples at 56 °C during 30 min was quite similar, showing that heat inactivation can be used to reduce the biohazardous risks while handling samples. Furthermore, we show that finger-stick capillary blood samples can also serve as a suitable source for IgG detection, bypassing the need for serum isolation and being suitable for point-of-care application (Pearson's coefficient correlation with capillary serum was 0.95, being statistically significant).

Self-collection of capillary blood and saliva to determine COVID-19 vaccine immunogenicity in patients with immune-mediated inflammatory diseases and health professionals.

Introduction: Being able to independently determine vaccine induced antibody responses by minimal-invasive methods is of great interest to enable a flexible and effective vaccination strategy. This study aimed to evaluate (1) the accuracy, feasibility, usability and acceptability of capillary blood and saliva self-sampling to determine SARS-CoV-2 antibody responses in patients with immune-mediated inflammatory diseases (IMIDs) and health professionals (HP). Methods: IMID patients and HP having received two doses of SARS-CoV-2 vaccines, self-collected capillary blood (Tasso+) and saliva samples. Capillary samples were considered interchangeable with venous blood if three criteria were met: Spearman's correlation coefficient (r) > 0.8, non-significant Wilcoxon signed-rank test (i.e., p > 0.05), and a small bias or 95% of tests within 10% difference through Bland-Altman. Participants completed a survey to investigate self-sampling usability (system usability scale; SUS) and acceptability (net promoter score; NPS). Study personnel monitored correct self-sampling completion and recorded protocol deviations. Results: 60 participants (30 IMID patients and 30 HP) were analyzed. We observed interchangeability for capillary samples with an accuracy of 98.3/100% for Anti-SARS-CoV-2 IgG/IgA antibodies, respectively. Fifty-eight capillary blood samples and all 60 saliva samples were successfully collected within the first attempt. Usability of both self-sampling procedures was rated as excellent, with significantly higher saliva ratings (p < 0.001). Capillary self-sampling was perceived as significantly (p < 0.001) less painful compared to traditional venous blood collection. Participants reported a NPS for capillary and saliva self-sampling of +68% and +63%, respectively. The majority of both groups (73%) preferred capillary self-sampling over professional venous blood collection. Conclusion: Our results indicate that capillary self-sampling is accurate, feasible and preferred over conventional venous blood collection. Implementation could enable easy access, flexible vaccination monitoring, potentially leading to a better protection of vulnerable patient groups. Self-collection of saliva is feasible and safe however more work is needed to determine its application in clinical practice.

Increased humoral immune response after vaccination with mRNA-1273 vs BNT162b2 in patients with inflammatory rheumatic diseases

Patients with inflammatory rheumatic diseases (IRD) have an increased risk for a worse COVID-19 outcome, and impaired immune responses following mRNA COVID-19 vaccines have been observed. In this prospective observational study, we compared the anti-S1 response following vaccination with BNT162b2 and mRNA- 1273 in a large cohort of IRD patients and assessed the effect of different immunomodulatory treatments. Patients from SCQM, the Swiss IRD cohort, who assented to an mRNA COVID-19 vaccine were recruited into the study between 3/2021-9/2021. Participants answered the study questionnaire via the mySCQM patient app and provided self-collected capillary blood samples at baseline, 4, 12, and 24 weeks post second vaccine dose. Samples were tested for IgG antibodies against the S1 domain of the SARS-CoV-2 spike protein using the EUROIMMUN ELISA. We examined differences in antibody titres depending on the vaccine and treatment received, while adjusting for age and history of SARSCoV- 2 infection, by applying mixed effects continuous outcome logistic regression models at each timepoint. Eligible samples were obtained from 564 IRD patients (mean age 53 y (s.d. 12 y), 66% female) with 36% RA, 37%, axSpA, 21% PsA, and 6% UA (undifferentiated arthritis), on no medication (no DMARD & no steroids 15%), csDMARD (9%), TNFi (48%), IL-6/17/23i (14%), JAKi (6%), rituximab (4%), abatacept (3%), and PDE4i (1%) in mono/combination therapy at baseline. 10% of patients had a past SARS-CoV-2 infection, 54% received BNT162b2, 46% mRNA-1273. Independently of the disease, treatment, and history of SARS-CoV- 2 infection, the odds of having higher anti-S1 titres at 4, 12, and 24 weeks post second vaccine dose were, respectively, 3.3, 3.9, and 3.8 times higher with mRNA-1273 compared to BNT162b2 for the average-aged patient of this population (p <0.0001). Moreover, with every year of age, the odds of higher anti-S1 levels increased by 3% to 5% following mRNA-1273 vs BNT162b2 vaccination (p <0.05), indicating an additional benefit for elderly IRD patients. Among monotherapies, rituximab, abatacept, JAKi, and TNFi had the highest odds of reduced anti-S1 responses compared to no medication. Patients on specific combination therapies showed significantly reduced antibody responses compared to respective monotherapies. Our results suggest that in IRD patients, vaccination with mRNA- 1273 vs BNT162b2 results in higher anti-S1 antibody titres, and has an additional benefit in elderly patients.

TYPE of MRNA COVID-19 VACCINE and TREATMENT INFLUENCE ANTIBODY KINETICS in PATIENTS with INFLAMMATORY RHEUMATIC DISEASES

Background: Patients on immunomodulatory treatments mount an attenuated immune response following mRNA COVID-19 vaccination, yet longterm studies of vaccine-induced anti-SARS-CoV-2 antibody (Ab) kinetics are missing. Objectives: In this prospective observational study, we mapped the humoral antibody response to mRNA COVID-19 vaccines up to 24 weeks post full vaccination in patients with infammatory rheumatic diseases (IRDs). We aimed to assess differences due to treatment, age, past SARS-CoV-2 infection, and vaccine (BNT162b2 vs. mRNA-1273). Methods: Adult patients from the SCQM cohort who assented to an mRNA COVID-19 vaccine were recruited between 3/21-9/21. Participants answered questionnaires via an app and received kits for the self-collection of capillary blood samples at baseline, 4, 12, and 24 weeks post full vaccination. Samples were tested for IgG Ab against the S1 domain of the SARS-CoV-2 spike protein (anti-S1-IgG) using the EUROIMMUN ELISA. To examine differences in Ab titres arising from the defned parameters, while accounting for inter-assay variability, mixed effects continuous outcome logistic regression models were applied at each timepoint. Results: Samples were obtained from 570 patients: 67% female, mean age 53 y (SD 12 y) with 37% RA, 36% axSpA, 21% PsA, and 6% UA (undifferentiated arthritis), on no medication (no DMARDs & no glucocorticoids;15%), csD-MARDs (10%), TNFi (48%), IL-1/6/17/23i (14%), JAKi (6%), rituximab (RTX;4%), or abatacept (ABA;2%) in mono/combination therapy at the frst vaccination. 10% of patients had a past SARS-CoV-2 infection, 54% received BNT162b2, 46% mRNA-1273. For any Ab threshold, the odds of having a higher Ab titre at 4, 12, and 24 weeks post full vaccination were 3.3-4 times higher with mRNA-1273 compared to BNT162b2 (Table 1, Figure 1). TNFi, JAKi, RTX, and ABA as monotherapy resulted in signifcantly lower Ab levels compared to no medication at almost all timepoints. In combination therapy, TNFi, IL-1/6/17/23i, RTX, and csDMARDs led to consistently lower Ab titres at all timepoints compared to respective monotherapy. Conclusion: Compared to no medication, some immunomodulatory therapies resulted in markedly lower Ab levels at all timepoints. In IRD patients, a past SARS-CoV-2 infection resulted in strikingly increased immunogenicity, as did mRNA-1273 compared to BNT162b2.

SARS-CoV-2 antibody prevalence in Sierra Leone, March 2021: a cross-sectional, nationally representative, age-stratified serosurvey

Introduction/ Background: As of March 2021, the Africa CDC had reported 4,159,055 cases of COVID-19 and 111,357 deaths among the 55 African Union Member States;however, no country has published a nationally representative serosurvey. Such data are vital for understanding the pandemic's progression on the continent, evaluating containment measures, and policy planning. Methods: We conducted a cross-sectional, nationally representative, age-stratified serosurvey in Sierra Leone in March 2021 by randomly selecting 120 Enumeration Areas throughout the country and 10 randomly selected households in each of these. One to two persons per selected household were interviewed to collect information on sociodemographics, symptoms suggestive of COVID-19, exposure history to laboratory-confirmed COVID-19 cases, and history of COVID-19 illness. Capillary blood was collected by fingerstick, and blood samples were tested using the Hangzhou Biotest Biotech RightSign COVID-19 IgG/IgM Rapid Test Cassette. Total seroprevalence was estimated after applying sampling weights. Results: The overall weighted seroprevalence was 2.6% (95% CI 1.9-3.4). This was 43 times higher than the reported number of cases. Rural seropositivity was 1.8% (95% CI 1.0-2.5), and urban seropositivity was 4.2% (95% CI 2.6-5.7). Stratifying by age group and weighting, 1.7% (95% CI 0.2-3.2) of participants age 5-9 tested positive for anti-SARS-CoV-2 antibodies, as did 2.6% (95% CI 0.8- 4.2) of those 10-19, 1.2% (95% 0.2-2.3) of those 20-39, 4.4% (95% CI 2.4-6.4) of those 40-59, and 3.6% (95% CI 1.6-5.6) of those 60 and above. There was a significant difference in seropositivity between rural/urban populations (Rao-Scott Chi-square p=0.002). Impact: This has ramifications for the country's third wave, where the average number of daily reported cases was 87 by the end of the Jone 2021-this could potentially be on the order of 3,700 actual infections, calling for stronger containment measures in a country with only 0.2% of people fully vaccinated. Conclusion: Overall seroprevalence was low compared to countries in Europe and the Americas (suggesting relatively successful containment in Sierra Leone). The results may reflect significant underreporting of incidence and mortality across the continent.

Correlation between Oxygen Saturation of patient and Severity Index of Covid 19 Pneumonia on CT

Aim: To investigate the correlation between capillary blood oxygen saturation and Computerized tomography (CT) severity index in patients with Covid-19 pneumonia. Study design: A cross sectional study design Setting & duration: Ibne-sina hospital Multan Medical & Dental College Multan, from 1stJune 2020 to 1stJune 2021 Methods: A cross-sectional analytical study was conducted at the COVID-19 ward of Ibne-sina hospital Multan Medical & Dental College Multan for 1 year. At the time of admission, all capillary oxygen saturation of all the included patients was measured. Pulmonary CT scans were then performed on these patients and CT severity index was calculated. SPSS was used for data analysis. Results: A total of 170 Covid-19 infected patients were included in the study. At the time of admission, the mean oxygen saturation was found to be 88.9%±6.53%. Whereas, the mean severity index was 15.01±7.79. 22 patients had hypoxia when presented in hospital and a significantly high iCT severity index was found in these patients (p=0.001). Chronic obstructive pulmonary disease (COPD), hypertension, and diabetes were significantly related to reduced blood oxygen saturation (p<0.05). A significant inverse correlation was found between capillary oxygen saturation and CT severity index (r= -0.41, p< 0.01). Conclusions: The study revealed a significant inverse correlation between capillary oxygen saturation and CT severity index. Moreover, it was found that underlying commodities (i.e., past medical history) can also affect the CT severity index.

Comparison of a Blood Self-Collection System with Routine Phlebotomy for SARS-CoV-2 Antibody Testing.

The Coronavirus Disease 2019 (COVID-19) pandemic forced researchers to reconsider in-person assessments due to transmission risk. We conducted a pilot study to evaluate the feasibility of using the Tasso-SST (Tasso, Inc, Seattle, Washington) device for blood self-collection for use in SARS-CoV-2 antibody testing in an ongoing COVID-19 prevalence and immunity research study. 100 participants were recruited between January and March 2021 from a previously identified sub-cohort of the Cabarrus County COVID-19 Prevalence and Immunity (C3PI) Study who were under-going bimonthly COVID-19 antibody testing. Participants were given a Tasso-SST kit and asked to self-collect blood during a scheduled visit where trained laboratory personnel performed routine phlebotomy. All participants completed an after-visit survey about their experience. Overall, 70.0% of participants were able to collect an adequate sample for testing using the device. Among those with an adequate sample, there was a high concordance in results between the Tasso-SST and phlebotomy blood collection methods (Cohen's kappa coefficient = 0.88, Interclass correlation coefficient 0.98 [0.97, 0.99], p < 0.0001). The device received a high-level (90.0%) of acceptance among all participants. Overall, the Tasso-SST could prove to be a valuable tool for seroprevalence testing. However, future studies in larger, diverse populations over longer periods may provide a better understanding of device usability and acceptance among older participants and those with comorbidities in various use scenarios.

Evaluation of independent self-collected blood specimens for COVID-19 antibody detection among the US veteran population.

Feasibility of home blood sample collection methods for the presence of SARS-CoV-2 antibodies from VA Million Veteran Program (MVP) participants was tested to determine COVID-19 infection or vaccination status. Participants (n = 312) were randomly assigned to self-collect blood specimens using the Neoteryx Mitra Clamshell (n = 136) or Tasso-SST (n = 176) and asked to rate their experience. Mitra tip blood was eluted and Tasso tubes were centrifuged. All samples were stored at -80 °C until tested with InBios SCoV-2 Detect™ IgG ELISA, BioRad Platelia SARS-CoV-2 Total Ab Assay, Abbott SARS-CoV-2 IgG and AdviseDx SARS-CoV-2 IgG II assays. Participants rated both devices equally. The Abbott assay had the highest sensitivity (87% Mitra, 98% Tasso-SST) for detecting known COVID infection and/or vaccination. The InBios assay with Tasso-SST had the best sensitivity (97%) and specificity (80%) for detecting known COVID-19 infection and/or vaccination. Veterans successfully collected their own specimens with no strong preference for either device.