ABSTRACT
BackgroundPrevious studies have shown that using a finger prick as the primary method for blood withdrawal is an efficient way to collect blood samples remotely, and data on blood levels from a finger prick are directly comparable to that obtained by a venepuncture. During the COVID-19 pandemic, we therefore complemented our large digital research platform with serum collection via a home finger prick testing in order to collect samples without the need of visits to a hospital. This repeatedly enabled us to rapidly answer new and relevant clinical research questions about COVID-19, thereby showing the potential of the finger prick for research purposes. However, the use of finger pricks in a research or clinical practice setting is still uncommon, and not yet tested on a large scale. In addition, there is limited data on peoples' willingness and ability to successfully use the finger prick at home, especially in patients with inflammatory rheumatic diseases (iRD) who may have impaired hand function.ObjectivesTo investigate the feasibility of finger prick testing in combination with a digital research platform by evaluating the success rate and patients' perspective towards the use of the finger prick.MethodsData were collected from an ongoing prospective cohort study including patients with iRD from the Amsterdam Rheumatology & immunology Center and healthy controls. Serum samples were collected up to eight times during follow-up via blood withdrawal by venepuncture at the local research institute or via a finger prick that could be performed at home. For the latter option, participants were instructed to collect three drops of blood, which would yield approximately 40-80 µL of serum after clotting. All study participants were questioned about their preference for a particular sampling method for individual healthcare and for scientific research. Participants who received a finger prick test before June 26, 2021, were asked to complete a digital evaluation questionnaire of the finger prick after their attempt. The finger prick was defined as failed when less than 10 µL of serum could be recovered from the collection device, or if no sample was returned to the laboratory and participants indicated in the questionnaires that they did not succeed in collecting the required amount of serum.ResultsA total of 3080 patients with iRD and 1102 healthy controls were included in the study. Of these, 2135 (69%) patients and 899 (82%) controls attempted to execute at least one finger prick, and 1439 (67%) patients and 712 (21%) controls executed multiple finger pricks. The first finger prick was successfully done by 92% (CI 90 – 93) of iRD patients, 94% (CI 92 – 95) of healthy controls, 93% (CI: 92 – 94) of all participants aged 70 years or younger, and 89% (CI 86 – 92) of all participants aged above 70 years (Table 1). Sex did not impact these success rates. Repeated failure occurred in 11 of 1439 (0.8%) patients and 4 of 712 (0.6%) controls. The two most common reasons for perceived failure of the finger prick were related to insufficient blood yield when applying the finger prick. Finally, both patients and controls were less willing to perform a finger prick for individual healthcare compared to scientific research;31% of patients and 61% of controls were willing to perform a finger prick for scientific research compared to 19% of patients and 39% of controls for healthcare. The most important reason for this was lower confidence in the execution and laboratory measurements when blood was drawn via a venepuncture compared to a finger prick.ConclusionIn this study, we demonstrated that the vast majority of participants, among which elderly and patients of whom hand function may be impaired by an underlying rheumatic disease, were able to successfully draw the required amount of blood for serological analyses. This shows that the finger prick testing is suitable for a high-throughput implementation to monitor patients remotely, which will likely contribute to improving the efficiency and cost-effectiveness of b th healthcare and scientific research.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
ABSTRACT
Coronavirus disease 2019 (COVID-19) pandemic has been an important global interest that affected millions of people, and it requires a deep investigation of the disease immunology for developing further therapeutic applications. Adoptive T cell therapy promises to address T cell-dependent immune dysregulation in COVID-19 patients by the generation of specific T cell clones against virus-specific antigens. Additionally, targeting B cell-dependent protection through COVID-19 vaccines, which have been developed in the recent year, possessed sufficient prevention for spreading the virus, since the cases and deaths related to COVID-19 tend to decrease after the vaccination. However, adoptive cell therapies are now encouraging scientists to deal with pathological challenges like inadequate T cell-dependent immune response or lymphopenia, since they are the most frequent outcome of severe infection, especially in immunocompromized patients. In this review, the current knowledge of immunopathology of COVID-19 was aimed to be highlighted along with the T cell responses against SARS-CoV-2 to comprise a basis for therapeutics. Moreover, current therapeutics and treatment strategies for COVID-19 were discussed to evaluate possible agents. Furthermore, the use of adoptive T cell therapy representing an emerging therapeutic approach was purposed to be presented comprehensively against SARS-CoV-2 infection. Even though further studies are needed to fully understand T cell response against SARS-CoV-2 in order to develop therapies to provide long term and efficient protection, adoptive cell therapies now meet the demand for a large population of people who suffer immunocompromization, considering the previous usage of the technique for different infectious diseases.
ABSTRACT
Context: Diabetes mellitus is a well known risk factor for COVID-19 patients. However, There is limited data to investigate the association between prediabetes and COVID-19. Objective: We aimed to evaluate the effect of prediabetes and mechanical ventilation on the course of COVID-19 and determine whether patients who recover from COVID-19 infection show changes in cardiac function and laboratory findings during follow-up. Patients and Methods: This study included 87 adult patients who were diagnosed with COVID-19 according to the WHO definition and were admitted for inpatient treatment between April 2021 and August 2021. They were classified into 3 groups, normoglycemia (n=40), prediabetes (n=25), and diabetes (n=22), and then divided into groups according to need for mechanical ventilation. Statistical analyses were performed to compare laboratory, echocardiographic findings and COVID-19 outcomes among the groups. Results: The need of mechanical ventilation was significantly higher in both diabetes and prediabetes groups than the normoglycemic group. Patients with diabetes and prediabetes had significantly higher LV E/Em (p=0.003, p=0.045) and RV MPI (p=0.032, p=0.021) and significantly shorter PAT (p=0.001, p=0.036) and significantly longer RV IVRT (p=0.021, p=0.017), respectively, compared to the normoglycemia group. Patients who required mechanical ventilation had significantly higher CRP (p=0.043), troponin (p<0.001), ferritin (p<0.001), HBA1C (P<0.001), glucose (p=0.019), monocytes (p<0.001), and monocytes-HDL ratio (MHR) (p<0.001) and significantly lower levels of HDL-C (p<0.001). Glucose, HDL-C, troponin, MPV, NLR, PLR level and RV and E/Em were found independently associated with the RVMPI. Conclusion: Prediabetes was associated with more impaired LV and RV diastolic functions compared to normoglycemic patients, comparable to those seen in diabetes. Our observations suggest that prediabetes should be considered as diabetes in the risk stratification of patients with COVID-19.
ABSTRACT
Background: Concerns have been raised regarding risks of COVID-19 breakthrough infections in vaccinated patients with immune-mediated infammatory diseases (IMIDs) treated with immunosuppressants, but data on COVID-19 breakthrough infections in these patients are still scarce. Objectives: The primary objective was to compare the incidence and severity of COVID-19 breakthrough infections with the SARS-CoV-2 delta variant between fully vaccinated IMID patients with immunosuppressants, and controls (IMID patients without immunosuppressants and healthy controls). The secondary objective was to explore determinants of breakthrough infections. Methods: In this study we pooled data collected from two large ongoing prospective multi-center cohort studies (Target to-B! [T2B!] study and ARC study). Clinical data were collected between February and December 2021, using digital questionnaires, standardized electronic case record forms and medical files. Post-vaccination serum samples were analyzed for anti-RBD antibodies (T2B! study only) and anti-nucleocapsid antibodies to identify asymptomatic breakthrough infections (ARC study only). Logistic regression analyses were used to assess associations with the incidence of breakthrough infections. Multivariable models were adjusted for age, sex, cardiovascular disease, chronic pulmonary disease, obesity and vaccine type. Results: We included 3207 IMID patients with immunosuppressants and 1810 controls (985 IMID patients without immunosuppressants and 825 healthy controls). The incidence of COVID-19 breakthrough infections was comparable between patients with immunosuppressants (5%) and controls (5%). The absence of SARS-CoV-2 IgG antibodies after COVID-19 vaccination was independently associated with an increased incidence of breakthrough infections (P 0.044). The proportion of asymptomatic COVID-19 breakthrough cases that were additionally identifed serologically in the ARC cohort was comparable between IMID patients with immunosuppressants and controls;66 (10%) of 695 patients vs. 64 (10%) of 647 controls. Hospitalization was required in 8 (5%) of 149 IMID patients with immunosuppressants and 5 (6%) of 86 controls with a COVID-19 breakthrough infection. Hospitalized cases were generally older, and had more comorbidities compared with non-hospitalized cases (Table 1). Hospitalization rates were signifcantly higher among IMID patients treated with anti-CD20 therapy compared to IMID patients using any other immunosuppres-sant (3 [23%] of 13 patients vs. 5 [4%] of 128 patients, P 0.041;Table 1). Conclusion: The incidence of COVID-19 breakthrough infections in IMID patients with immunosuppressants was comparable to controls, and infections were mostly mild. Anti-CD20 therapy might increase patients' susceptibility to severe COVID-19 breakthrough infections, but traditional risk factors also continue to have a critical contribution to the disease course of COVID-19. Therefore, we argue that most patients with IMIDs should not necessarily be seen as a risk group for severe COVID-19, and that integrating other risk factors should become standard practice when discussing treatment options, COVID-19 vaccination, and adherence to infection prevention measures with patients.
ABSTRACT
Background: Many countries are promoting booster SARS-CoV-2 vaccination campaigns as the COVID-19 pandemic continues. Incremental short-term adverse events after two SARS-CoV-2 vaccinations have been reported in healthy individuals.1,2 However, data on incremental short-term adverse events in patients with various immune-mediated infammatory diseases (IMIDs) after repeated SARS-CoV-2 vaccination is scarce. Objectives: We report risk factors for short-term adverse events in IMID patients after SARS-CoV-2 vaccination. Methods: Self-reported daily questionnaires on adverse events in the frst seven days after SARS-CoV-2 vaccination were obtained from individuals participating in an ongoing prospective multi-arm multicenter cohort study on SARS-CoV-2 vaccination in patients with various IMIDs in the Netherlands (T2B! immunity after SARS-CoV-2). Clinically relevant adverse events were defned as systemic adverse advents lasting longer than two days or hindering daily activities. Adjusted relative risks for developing clinically relevant adverse events were calculated using a logistic mixed-effects model. Results: Data of 2081 patients and 178 healthy controls were obtained. Infammatory bowel disease (N:480), Multiple sclerosis (N:343) and Rheumatoid arthritis (N:266) were the largest disease groups. Adjusted relative risks for relevant adverse events are presented in Figure 1. Third vaccination was not associated with increased risk on adverse events when compared to a second vaccination (aRR: 0.93 95% CI: 0.84-1.02). Patients with IMIDs were at increased risk for developing adverse events after vaccination when compared to controls (aRR: 1.16 95% CI: 1.01-1.34). Female sex (aRR 1.43 95% CI: 1.32-1.56), age below 50 (aRR 1.14 95% CI: 1.06-1.23) and a preceding SARS-CoV-2 infection (aRR: 1.14 95% CI: 1.01-1.29) were also associated with increased risk of adverse events following vaccination. Allergic reactions and hospital admission were uncommon (0.67% and 0.19% respectively);7.4% and 6.8% of patients reported adverse events impacting daily life on day seven after second and third vaccination, respectively. Data on increase in disease activity of the IMID following vaccination are currently being investigated. Conclusion: A third SARS-CoV-2 vaccination was not associated with an increased risk on short-term clinically relevant adverse events when compared to a second vaccination. Although patients with IMIDs may be slightly more at risk to develop adverse events after SARS-CoV-2 vaccination, most adverse events were transient and disappeared within seven days. This message should reassure IMID patients who are hesitant on booster vaccination. Data on potential IMID fare-ups after vaccination will follow.
ABSTRACT
Background The aim of this study was to investigate the effect of various immunosuppressants on the humoral immune responses after vaccination against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs). Methods The Target to B! SARS-CoV-2 study is a multicentre study, taking place in 7 Dutch academic hospitals. Patients with the following IMIDs were recruited: Crohn’s disease (CD), ulcerative colitis (UC), auto-immune hepatitis, rheumatic (e.g. rheumatoid arthritis), neurological (e.g. multiple sclerosis) and dermatological IMIDs (e.g. atopic dermatitis). Patients were recruited based on immunosuppressants (table 1) and previous SARS-CoV-2 infection. The control group consisted of healthy subjects and IMID patients without immunosuppressants. SARS-CoV-2 receptor binding domain (RBD) antibodies were measured 28 days after completed SARS-CoV-2 vaccination. Seroconversion was defined as anti-RBD IgG >4 AU/mL. In this , we focus on therapies relevant for inflammatory bowel diseases (IBD) and present results for these treatments from patients with IBD, but also other IMIDs. Results Numbers of recruited patients with each immunosuppressant are shown in table 1. Amongst these patients, 312 patients had CD and 176 UC, the rest was diagnosed with another IMID. Seroconversion was reduced in patients receiving sphingosine 1-phosphate (S1P) modulators (all multiple sclerosis patients) while seroconversion was similar to controls in the other treatment groups. However, use of Anti-tumour necrosis factor (TNF), methotrexate, janus kinase (JAK) inhibitor monotherapy and all combination therapies (except for corticosteroids combined with other immunosuppressants) were associated with reduced Sars-CoV-2 antibody titres. Patients with a previous SARS-CoV-2 infection had higher median antibody titres after second vaccination than those without a previous SARS-CoV-2 infection. The type of IMID did not affect seroconversion rates. Conclusion No immunosuppressant, registered for IBD, reduced the rates of seroconversion after vaccination against SARS-CoV-2. Some immunosuppressants were associated with lower antibody titres. However, the clinical relevance of lower antibody titres remains unknown. S1P modulators, had a clear negative impact on the humoral response against SARS-CoV-2 after vaccination. This might be relevant in the future as this therapy is currently being approved for UC. Disease aetiology did not impair immunity against SARS-CoV-2 immunity after vaccination. Disclaimer: Absolute numbers of antibody titres and rates of seroconversion will be reported at the conference and are not reported in this as this might negatively impact the current submission process.
ABSTRACT
Coronavirus disease 2019 (COVID-19) pandemic has been an important global interest that affected millions of people, and it requires a deep investigation of the disease immunology for developing further therapeutic applications. Adoptive T cell therapy promises to address T cell-dependent immune dysregulation in COVID-19 patients by the generation of specific T cell clones against virus-specific antigens. Additionally, targeting B cell-dependent protection through COVID-19 vaccines, which have been developed in the recent year, possessed sufficient prevention for spreading the virus, since the cases and deaths related to COVID-19 tend to decrease after the vaccination. However, adoptive cell therapies are now encouraging scientists to deal with pathological challenges like inadequate T cell-dependent immune response or lymphopenia, since they are the most frequent outcome of severe infection, especially in immunocompromized patients. In this review, the current knowledge of immunopathology of COVID-19 was aimed to be highlighted along with the T cell responses against SARS-CoV-2 to comprise a basis for therapeutics. Moreover, current therapeutics and treatment strategies for COVID-19 were discussed to evaluate possible agents. Furthermore, the use of adoptive T cell therapy representing an emerging therapeutic approach was purposed to be presented comprehensively against SARS-CoV-2 infection. Even though further studies are needed to fully understand T cell response against SARS-CoV-2 in order to develop therapies to provide long term and efficient protection, adoptive cell therapies now meet the demand for a large population of people who suffer immunocompromization, considering the previous usage of the technique for different infectious diseases.
ABSTRACT
OBJECTIVE: The objective of this study was to measure humoral responses after SARS-CoV-2 vaccination in MS patients treated with ocrelizumab (OCR) compared to MS patients without disease modifying therapies (DMTs) in relation to timing of vaccination and B-cell count. METHODS: OCR treated patients were divided into an early and a late group (cut-off time 12 weeks between infusion and first vaccination). Patients were vaccinated with mRNA-1273 (Moderna). B-cells were measured at baseline (time of first vaccination) and SARS-CoV-2 antibodies were measured at baseline, day 28, 42, 52 and 70. RESULTS: 87 patients were included (62 OCR patients, 29 patients without DMTs). At day 70, seroconversion occurred in 39.3% of OCR patients compared to 100% of MS patients without DMTs. In OCR patients, seroconversion varied between 26% (early group) to 50% (late group) and between 27% (low B-cells) to 56% (at least 1 detectable B-cell/µL). CONCLUSIONS: Low B-cell counts prior to vaccination and shorter time between OCR infusion and vaccination may negatively influence humoral response but does not preclude seroconversion. We advise OCR treated patients to get their first vaccination as soon as possible. In case of an additional booster vaccination, timing of vaccination based on B-cell count and time after last infusion may be considered.
Subject(s)
COVID-19 , Multiple Sclerosis , Antibodies, Monoclonal, Humanized , COVID-19 Vaccines , Humans , SARS-CoV-2 , VaccinationABSTRACT
Some studies have discovered a connection between prostate cancer and COVID-19. In this study, we evaluated the link between prostate cancer and COVID-19, contributing to elucidate the connection between TMPRSS2 and ACE2. We discovered 209 number of variants in TMPRSS2 gene, and 110 variants represent EA populations and 99 of them represent AA populations. Moreover, we found 23 suspected missense and 3 unknown variants. Then, linked genes to TMPRSS2 and ACE2 were found in our study. We investigated the expression level of TMPRSS2 and the results showed that it was very high in the prostate, colon, lung, kidney, and saliva-secreting gland. Also, the important role of the AR gene was revealed in addition to other oncogenes and tumor suppressor genes for prostate cancer by KEGG Pathway analysis. In conclusion, these results can highlight several molecular mechanisms of SARS-CoV-2, and also TMPRSS2, ACE2, and AR connection explains the high expression level of AR gene found in the male lung.
ABSTRACT
Introduction Les formes sévères de COVID-19 comportent à une hyperinflammation systémique intense ;ce qui a justifié des essais thérapeutiques avec des immunomodulateurs régulièrement utilisés chez les patients atteints de maladies systémiques auto-immunes ou inflammatoires Depuis février 2021 où les premières recommandations EULAR sur l’utilisation de thérapeutiques immunomodulatrices dans le COVID-19 ont été publiées [1], de nouveaux essais thérapeutiques ont été réalisés ce qui rend nécessaire une mise à jour ces recommandations. Matériels et méthodes Selon les procédures standardisées de l’EULAR [2], les résultats d’une revue de la littérature systémique réalisée jusqu’au 15 décembre 2020 puis mise à jour jusqu’au 14 juillet 2021 incluant tous types d’études ont été présentés à un groupe de travail multidisciplinaire composé d’experts internationaux comprenant des rhumatologues, des immunologistes translationnels, des hématologues, des pédiatres, des patients et des professionnels de la santé. La mise à jour des recommandations a été discutée et votée par l’ensemble du panel d’experts sur la base des résultats présentés, principalement des essais randomisés contrôlés (ECT) sur différents traitements immunomodulateurs. Résultats La mise à jour comprend deux principes généraux et dix recommandations. Les recommandations concernent uniquement la prise en charge des patients présentant des formes de COVID-19 modérées à sévères ou critiques, faute de preuves suffisantes avec très peu d’ECT concernant les patients asymptomatiques et ceux avec des formes légères de la maladie. Les molécules suivantes ont montré une efficacité dans le traitement de formes modérées à sévères ou critiques du COVID-19. L’association de glucocorticoïdes et de tocilizumab est bénéfique dans les cas de COVID-19 nécessitant une oxygénothérapie et dans les cas critiques de COVID-19. L’utilisation d’inhibiteurs de Janus kinase (baricitinib et tofacitinib) et peut-être d’Ac anti-GM-CSF est prometteuse dans les mêmes populations. Les anticorps monoclonaux anti-SARS-CoV-2 et l’utilisation de plasma convalescent pourraient trouver une application dans les phases précoces de la maladie et dans certains sous-groupes de patients immunodéprimés. D’autres immunomodulateurs comme l’hydroxychloroquine, la colchicine ou l’anakinra n’ont pas démontré leur efficacité sur la mortalité et ou sur l’aggravation clinique (évolution vers une détresse respiratoire), quel que soit le stade de la maladie. Conclusion Un nombre grandissant d’ECT soutiennent l’efficacité de l’association de glucocorticoïdes et d’autres agents immunomodulateurs tels que le tocilizumab dans le traitement de formes modérée à sévère et critique du COVID-19. De plus, certaines études en cours pourraient confirmer l’efficacité potentielle d’autres approches thérapeutiques comme les inhibiteurs de JAK ou les Ac anti-GM-CSF. L’implication des rhumatologues, en tant qu’experts des maladies inflammatoires et auto-immunes systémiques et des traitements immunomodulateurs est nécessaire dans le design des nouveaux essais cliniques et dans l’élaboration de nouvelles recommandations pour la prise en charge du COVID-19.
ABSTRACT
Clinical research projects often use traditional methods in which data collection and signing informed consent forms rely on patients' visits to the research institutes. However, during challenging times when the medical community is in dire need of information, such as the current COVID-19 pandemic, it becomes more urgent to use digital platforms that can rapidly collect data on large numbers of patients. In the current manuscript, we describe a novel digital rheumatology research platform, consisting of almost 5000 patients with autoimmune diseases and healthy controls, that was set up rapidly during the COVID-19 pandemic, but which is sustainable for the future. Using this platform, uniform patient data can be collected via questionnaires and stored in a single database readily available for analysis. In addition, the platform facilitates two-way communication between patients and researchers, so patients become true research partners. Furthermore, blood collection via a finger prick for routine and specific laboratory measurements has been implemented in this large cohort of patients, which may not only be applicable for research settings but also for clinical care. Finally, we discuss the challenges and potential future applications of our platform, including supplying tailored information to selected patient groups and facilitation of patient recruitment for clinical trials.