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INTRODUCTION. The aetiology of Kawasaki disease (KD) remains unknown. Changes in infectious exposure during the COVID-19 pandemic owing to infection prevention measures may have affected the incidence of KD, supporting the pathogenic role of an infectious trigger. The purpose of this study was to evaluate the incidence, phenotype and outcome of KD before and during the COVID-19 pandemic in Denmark. METHODS. This was a retrospective cohort study based on patients diagnosed with KD at a Danish paediatric tertiary referral centre from 1 January 2008 to 1 September 2021. RESULTS. A total of 74 patients met the KD criteria of whom ten were observed during the COVID-19 pandemic in Denmark. Alof these patients were negative for SARS-CoV-2 DNA and antibodies. A high KD incidence was observed during the first six months of the pandemic, but no patients were diagnosed during the following 12 months. Clinical KD criteria were equally met in both groups. The fraction of intravenous immunoglobulin (IVIG) non-responders was higher in the pandemic group (60%) than in the in the pre-pandemic group (28.3%), although the rate of timely administered IVIG treatment was the same in both groups (>= 80%). Coronary artery dilation was observed in 21.9% in the pre-pandemic group compared with 0% in KD patients diagnosed during the pandemic. CONCLUSION. Changes in KD incidence and phenotype were seen during the COVID-19 pandemic. Patients diagnosed with KD during the pandemic had complete KD, higher liver transaminases and significant IVIG resistance but no coronary artery involvement.Copyright © 2023, Almindelige Danske Laegeforening. All rights reserved.
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Introduction: Automatic drug dispensers are now widely used in critical care.1-2 They can provide information about dispensed drugs. Good practice in sedation restricts the use of sedatives and titrates doses to defined responses.3-4 Objectives: To extract drug dispenser issuing records for sedatives and link these to patient records to evaluate sedative use. Method(s): in October 2019, we introduced two Omnicell XT automated dispensing cabinets (Omnicell inc. CA, USA) into a 42 bedded general/neurological unit. ICNARC (Intensive care national audit and research centre) and CCMDS (Critical care minimum data set) data was collected using the Ward Watcher program. Dispenser issuing records for alfentanil, propofol and midazolam were obtained as Excel files for 13 months from January 2020. Output time stamps were converted to dates and times. Outputs were linked to outputs of the ICNARC and CCMDS records for the patients that the drugs were issued to. All the outputs had patients identified by their unique hospital numbers. These were used in Excel "power queries" to produce a spread sheet with a single row per patient. Multiple admissions used the first diagnosis, the final outcome and the total length of stay. The total dose of sedatives was calculated from ampoule dose and number. The duration of treatment was calculated from the first and last issues of the drug. ICNARC codes were used to identify the primary system in the admission diagnostic code and those patients admitted for COVID-19. Variables were compared using Chi Squared, Mann-Whitney U and Kruskal Wallis Tests. The significance of associations was established using Spearman's Rho. Linear regression was used to define relationships more clearly. Result(s): Table one summarises the patient characteristics with respect to all admissions during the study period and for patients who had had the studied drugs issued to them. Midazolam was used in fewer patients, they were more likely to be male, heavier (p>0001) and to die than patients receiving Propofol or Alfentanil (p>0.001). With respect to diagnostic groups, all the sedatives, particularly Midazolam (p<0.001), were more likely to be used in patients with COVID-19. The relationship between the dose of sedative drugs and patient age and weight was explored using the dose per advanced respiratory day. All three drugs had a significant but weak negative relationship with age, lower doses being given to older people (Propofol r2 = 0.02, p=0.01. Alfentanil r2 = 0.04, p=0.00. Midazolam r2 = 0.07, p=0.00.). There was also a weak but significant relationship between increasing dose of Propofol with patient weight (r2 = 0.02, p=0.01), but there was no relation between weight and doses of the other drugs. Conclusion(s): Information from automatic drug dispensers can be interpreted and combined with other datasets to produce clinically relevant information. The limited weak relationships between drug dose and age and weight suggests that sedative drugs could have been better titrated to response.
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Lung cancer is the leading cause of cancer related deaths worldwide, with a relatively low 5-year survival rate. Although there are some therapies against lung cancer, new effective treatment options are urgently required. Recently during the COVID-19 pandemic, we have seen that SARSCoV-2 binds to its receptor angiotensin-converting enzyme 2 (ACE2) via spike S1 to enter the cells. This study underlines the importance of SARS-CoV-2 spike S1 in inducing death in human lung cancer cells. Interestingly, we have seen that recombinant spike S1 treatment at very low doses led to death of human A549 lung cancer cells. On the other hand, boiled recombinant SARS-CoV-2 spike S1 remained unable to induce death, suggesting that the induction of cell death in A549 cells was due to native SARS-CoV-2 spike S1 protein. SARS-CoV-2 spike S1-induced A549 cell death was also inhibited by neutralizing antibodies against spike S1 and ACE2. Moreover, our newly designed wild type ACE2-interacting domain of SARS-CoV-2 (wtAIDS), but not mAIDS, peptide also attenuated SARS-CoV-2 spike S1-induced cell death, suggesting that SARS-CoV-2 spike S1- induced death in lung cancer cells depends on its interaction with ACE2 receptor. Similarly, recombinant spike S1 treatment also led to death of H1299 and H358 human lung cancer cells. Finally, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) intoxication led to the formation tumors in lungs of A/J mice and alternate day intranasal treatment with low dose of recombinant SARS-CoV-2 spike S1 from 22-weeks of NNK insult (late stage) led to induced apoptosis and tumor regression in the lungs. These studies indicate that recombinant SARS-CoV-2 Spike S1 protein may have implications in the treatment of lung cancer.
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Among the longstanding problems made vivid by the COVID-19 pandemic are challenges in gathering data to inform the use of vaccines in pregnancy. Although it was known early on that pregnant persons and their offspring faced greater risks of morbidity and mortality from COVID-19 infection, they were excluded from all trials that led to authorization of vaccines. And while reassuring evidence has since been gathered, delays, as well as mixed public health messaging, have led to low uptake of vaccines among pregnant populations, as well as disproportionate burdens for pregnant persons. Dr. Lyerly will consider key ethical issues foregrounded by the COVID-19 response in pregnancy, including the distortions of risk, misaligned incentives, and regulatory challenges. Drawing on results of the NIH-funded PHASES Project, she will describe key conceptual shifts and ethical frameworks that have recently been advanced to better serve the interests of pregnant persons and their offspring facing illness in pandemic and other contexts, as well as specific recommendations for responsible and timely research with this population.
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Background: Only recently studies have been able to demonstrate the safety and efficacy of purification therapies in inflammatory diseases. Here we present the management of a young (21y) male patient in severe cardiogenic shock due to COVID-19 perymyocarditis admitted to the ICU at Bolzano Central Hospital. November 30th 2020 the patient developed high fever (>40 C) and diarrhea. After unsuccessfully being treated orally with a macrolide he was admitted to a peripheral hospital the 4th of December. The day after he deteriorated, required transfer to the ICU, endotracheal intubation and pharmacological cardiovascular support (Norepinephrine, Levosimendan). Antimicrobial treatment was started with piperacillin/tazobactam, linezolid and metronidazole. Despite multiple radiological and microbiological diagnostic attempts the origin of this severe septic shock remained unclear. December 6th the patient was transferred to Bolzano Central Hospital for VA-ECMO evaluation. Method(s): The transesophageal echocardiography revealed 15-20% of EF, lactate (5,2 mmol/l), cardiac enzymes (TropT 1400 mcg/l) and inflammatory parameters (PCT 35 ng/ml, IL-6 685 pg/ml) were elevated. We performed cardiac monitoring via Swan-Ganz catheter. The cardiac index was 1,6 l/min/m2. The peak dosage for Norepinephrine reached 7,5mg/h (1,47 mcg/kg/min). At Bolzano ICU we facilitate the pharmacological therapy with milrinone, vasopressin and low dose epinephrine. Furthermore, we impost continuous hemodiafiltration with CytoSorb filter. Result(s): Only hours after the start of filtration therapy the patient improved and we were able to gradually reduce catecholamine therapy, lactate values decreased. A VA-ECMO implantation was no more necessary. December 10th, we saw a stable patient without ventilatory or cardiovascular support, at echocardiography we revealed a normal EF. Conclusion(s): Clinically we saw a young patient in severe septic/cardiogenic shock due to perimyocarditis. Yet diagnostic attempts (CT-scan, multiple blood/urinary/liquor cultures) remained negative. Despite multiple negative PCR tests for SARS-CoV2 infection we performed specific immunoglobulin analysis and received a positive result for IgM. We therefore conclude on a COVID-19 associated perymyocarditis. Furthermore, this case illustrates the potential benefit of cytokine filtration and elimination in COVID-19 patients with altered IL6 levels.
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Background & Aim: Liposomes are spherical-shaped vesicles composed of one or more lipid bilayers. The ability of liposomes to encapsulate hydro- or lipophilic drugs allowed these vesicles to become a useful drug delivery system. Natural cell membranes, such as Bioxome, have newly emerged as new source of materials for molecular delivery systems. Bioxome are biocompatible and GMP-compliant liposome-like membrane that can be produced from more than 200 cell types. Bioxome self-assemble, with in-process self-loading capacity and can be loaded with a variety of therapeutic compounds. Once close to the target tissue, Bioxome naturally fuse with the cell membrane and release the inner compound. Orgenesis is interested in evaluating the potential of Bioxome as new drug delivery system for treatment of several diseases, including skin repair, local tumour or COVID19. Methods, Results & Conclusion(s): Bioxome were obtained from adipose- derived Mesenchymal Stem Cells, with a process of organic- solvent lipid extraction, followed by lyophilization and sonication assemblage. During the sonication process, Bioxome were charged or not with several cargos. Size distribution of empty Bioxome was detected by Particle Size Analyzer (NanoSight). Electron Microscopy (EM) was performed to assess Bioxome morphology. Lipid content was evaluated by electrospray ionization system. Dose response in vitro test on human lung fibroblasts treated or not with Bioxome encapsulating a specific cargo (API) against COVID19 were performed. NanoSight analysis showed that nanoparticle size in Bioxome samples ranged between 170+/-50 nm, with a concentration ranging between 109-1010+/-106 particles/mL. EM clearly showed the double phospholipid layers that composes the Bioxome. Stability study demonstrated that Bioxome are stable in size and concentration up to 90 days at +4Cdegree or even at RT. No change in size between encapsulated Bioxome with small size (~340 Da) cargo vs empty Bioxome was observed up to 30 days storage. Lipidomic analysis approach revealed that the yield of lipids and their composition are satisfactory for a therapeutic product using Bioxome. Lastly, in the in vitro model of COVID19, Bioxome encapsulating API effectively saved cells from death (20x vs untreated cells) and at lower doses of API than these of non-encapsulated cargo (0.005 microM vs 0.1 microM). Bioxome seems to be an excellent candidate for liposome mimetic tool as drug delivery system for targeting specific organs and diseases treatment.Copyright © 2023 International Society for Cell & Gene Therapy
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Objectives: According to the CDC, as of December 2022, almost one in three Americans had confirmed COVID-19 infection;yet only a small portion generated healthcare claims related to COVID-19. Higher burden of COVID-19 cases in Northeastern states compared to other US regions has been documented. This study examined the regional variation in demographic characteristics and treatment patterns among patients with a claim for COVID-19 in a nationwide US claims database. Method(s): Analysis of data from over 277 million patients in IQVIA's longitudinal medical and pharmacy claims databases resulted in a cohort of 17,682,111 patients with COVID-19 diagnosis between 4/1/2020 and 4/30/2022. Demographic characteristics and treatment rates for key approved and un-approved COVID-19 therapies were assessed and stratified by region. Result(s): Among patients in the database, 6.4% had a COVID-19 diagnosis. The proportion was higher in the Northeast (7.1%) and South (6.9%) compared with the West (4.8%). The highest proportion of patients were aged 18-44 years (32.7% in South to 35.2% in West). Over a fifth of the patients were >= 65 years old (US overall= 23.7%;22.5% in Northeast to 25.8% in Midwest). Approximately 57% of the patients nationally and within each region were women. For approved medications, utilization ranged from 1.7% in Northeast to 2.7% in Midwest (overall:2.2%) for remdesivir;0.7% in Northeast to 2.2% in South (overall: 1.5%) for casirivimab/imdevimab. For unapproved medications, utilization ranged from 0.9% in Northeast to 1.6% in South (overall:1.3%) for hydroxychloroquine and 0.4% in Northeast to 1.8% in South (overall:1.1%) for ivermectin. Conclusion(s): Less than one in five US cases of COVID-19 had a claim with diagnosis of COVID-19. Use of COVID-19 specific medications remained low throughout the pandemic. Despite the higher disease burden, proportion of patients with claims and receiving COVID-19 treatment were low nationally, particularly in the northeast US region.Copyright © 2023
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Objective: Humoral and cellular immune responses to SARS-CoV-2 vaccination are reduced in adult kidney recipients. After pediatric kidney transplantation there are only few data available - mostly limited to monitoring of SARS-CoV-2 antibodies. Method(s): Cellular and humoral immune responses have been monitored before and after SARS-CoV-2 vaccination in pediatric kidney recipients. After in vitro stimulation with SARS-CoV-2 antigen (spike glycoprotein) virus-specific CD4 and CD8 T cells (SARS-CoV-2-Tvis) have been identified by cytokine flow cytometry. SARS-CoV-2 IgG was measured by CMIA. Result(s): Immune response after SARS-CoV-2 vaccination was analyzed in a total of 30 pediatric kidney recipients (age at 1st vaccine dose 5.2 - 17.8 years, median 14.8 years;43% male;30/30 2 vaccine doses;23/30 3 vaccine doses). At time of vaccination 22 patients (73%) received a tacrolimus (Tac)-based immunosuppression combined with mycophenolate mofetil (MMF;n = 15) or everolimus (n = 6) or neither of them (n = 1);3 patients were exposed to cyclosporine A and 5 patients to a calcineurin inhibitor (CNI)- free immunosuppression. MMF was used in 18/30 patients. After 1st dose of mRNA vaccine SARS-CoV-2 antibodies were detectable in 50% of pediatric kidney recipients, after 2nd dose in 78% and after 3rd dose in 88%. After the 2nd vaccine dose absence of humoral immune response (< 33.8 BAU/ml) was only found in case of MMF use (predominately combined with Tac). Peak IgG values (> 2,080 BAU/ml) were only detected in MMF-free regimens (6/7). Cellmediated response partially differed from humoral response, e. g., in some patients SARS-CoV2-Tvis were found despite lack of virus-specific antibodies. After 1st vaccine dose SARS-CoV-2-Tvis were detectable in 50% of pediatric kidney recipients, after 2nd dose in 92%. After 2nd vaccine dose absence or very low levels of SARS-CoV-2-Tvis (< 0.3 cells/mul) were only found in Tac-based immunosuppressive regimens, whereas higher levels (> 1.3 cells/mul) were exclusively detected in patients with MMFfree medication. Conclusion(s): After pediatric kidney transplantation humoral and cellular immune responses to SARS-CoV-2 vaccination were suboptimal, but more pronounced than in adult kidney recipients. Use of Tac and MMF was associated with impaired immune response to vaccination. SARS-CoV-2-specific humoral response corresponded only partially to cell-mediated response. Additional monitoring of SARS-CoV- 2-Tvis might be recommendable to improve assessment of the individual vaccine response and thereby to personalize the decision on the necessity of further vaccine doses.
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Background/Aims Research has shown nurse-led gout clinics provide better outcomes compared to usual care. This District General Hospital set up a pilot nurse-led gout clinic in autumn 2019. This aimed to improve patients' understanding of their condition, achieve better control of serum uric acid levels (SUA), reduce flares and prevent Emergency Department attendances. Methods A modified clinic protocol, closely modelled on BSR guidance was agreed within the department. With consultant supervision, one nurse specialist provided a mix of in-person and telephone appointments. Targets were set aiming for SUA <360mumol/L for most patients and <300mumol/L for those with erosive change or tophi. All patients were offered prophylaxis. Patients required a rheumatologist's diagnosis of gout or crystal confirmation for enrolment. Exclusion criteria were significant renal or hepatic derangement. Within 3 months of the service starting SARS-CoV-2 impacted the operation of healthcare worldwide and led to the closure of routine outpatient clinics in Northern Ireland. A decision was made to switch the gout clinic to run entirely by telephone. Blood testing was facilitated through primary care and phlebotomy hubs. Results Over a 19-month period, 78 patients were treated and audited through this clinic: 69 men and 9 women. Average age was 57, mean SUA 509 mumol/L at referral and 322 mumol/L on discharge. 69 patients received allopurinol and 9 received febuxostat. No patients required uricosuric drugs. All patients were offered and agreed to take prophylaxis with a majority (85.8%) remaining on it for 3-6 months. Patients required a mean of 3.38 appointments prior to discharge from the clinic. The mean dose of urate lowering therapy on discharge was 315.9mg allopurinol and 93.3mg febuxostat. 95% experienced >=2 flares during their enrolment in the clinic with no patients requiring Emergency Department attendance due to gout flare. Conclusion The nurse-led gout clinic was well received by patients and was effective as a telephone service during the pandemic when so many services were stood down. The clinic was able to continue to provide education, deliver effective reductions in uric acid as well as reduce incidence of flares and Emergency Department attendances. Lower doses of urate lowering therapy than expected were needed to achieve target. A small number of patients were discharged prior to enrolment for initial non-engagement which may have been exacerbated by the lack of face-to-face appointments. Our COVID-19 model did struggle with those patients needing an interpreter. In-person initial appointments have since been restarted;however, a greater proportion of reviews will continue to be offered by telephone given the unexpected success of the model. This audit showed that a nurse-led gout clinic can run successfully, even during a pandemic with a significant reliance on telephone consultations.
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Background/Aims When the COVID-19 pandemic began, steps were taken to minimise risk to those vulnerable to severe outcomes. For immunosuppressed patients with rheumatoid arthritis (RA), consideration was given to reducing risk whilst mindful of compromising control of their underlying condition. At Leeds Teaching Hospitals NHS Trust, patients receiving rituximab (RTX) were considered for a reduced dose regimen. A retrospective study, using real-world data, was undertaken to assess the impact of lower doses of RTX on response to treatment. Methods The clinical records of all patients with RA who had received RTX between March 2020 and March 2021 were reviewed. Demographics and previous RTX exposure were recorded. The dose of RTX given during the specified period was noted. Response to treatment was recorded pragmatically by physicians as good, partial or none, based on patient reported VAS for disease activity and swollen and tender joint counts, given the limitations placed on face-to-face patient review due to the pandemic. The time to subsequent RTX treatment and the need for steroid treatment for flares was also studied. Results The number of patients treated with RTX was 282, of whom 89 patients received full dose (1g x 2 infusions), 192 patients received half dose (500mg x 2 infusions). The mean age was 61 years. 77% were female. 9% were RTX-naive, 80% had previously had full dose. Follow-up data were available for 185/192 of the group receiving 1g and 88/89 of the group receiving 2g. Clinical outcomes were as follows for the two groups (1g RTX vs 2g RTX): no response 10.3% vs 9.1%;partial response:34.9% vs 20% %;good response: 54.8% vs 70.9%. The mean length of response was 7.5 months in the patients receiving 1g of RTX compared to 8.6 months in the group receiving 2g of RTX. Similar number of patients required steroid for a flare after receiving Ig of RTX (23.9%) compare to those receiving 2g of RTX (25.8%). Conclusion A majority of patients receiving RTX for RA at either standard or reduced dose reported clinical response. Those receiving lower dose RTX were more likely to report a partial response whilst those receiving full dose were more likely to report a good response. Duration of response and need for steroid therapy for flare of RA between treatments did not significantly differ between groups. Further analysis of factors that may influence clinical response to lower dose RTX is ongoing, which could guide tailored therapy regimens should the need arise again.
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Background/Aims Intraarticular corticosteroid injections (CSI) are used as a short-term treatment for inflammatory arthritis and osteoarthritis. At the outset of the COVID-19 pandemic there was concern regarding the immunosuppressive effect of steroids and the potential risk of COVID-19 infection in patients treated with CSI. There is no universal evidencebased consensus on the optimum dosing of CSI. Nationally there was a mixed response to CSI use during the COVID- 19 pandemic. Early during the pandemic, our Trust advised using only the lowest BNF indicated steroid dose to minimize any potential side effects. Large joints (knees and shoulders) were injected with 40mg of Kenalog compared to 80mg pre pandemic. No previous survey has reported the incidence of covid infection post CSI. The primary aim of this project was to address this gap. A secondary aim was to review the clinical effectiveness of a 'larger' versus 'smaller' steroid dose in CSI. Methods Retrospective data collection was carried out for 107 patients who received CSI during the pandemic. All patients who received CSI within the Trust rheumatology department were followed up with a sixweek phone call. During this consultation the effectiveness of the CSI was considered by asking them to score the effectiveness of the CSI out of 10 (10 being maximum improvement). The incidence of COVID- 19 infection was also recorded. This data was compared to the same data from a group of patients injected with a larger dose of CSI pre-pandemic (n=114). Results The patient reported incidence of COVID-19 infection within 6 weeks of CSI was 1.87%. Patient reported outcomes showed a mean improvement in joint symptoms of 6.97 using 80mg of kenalog, versus 5.02 improvement using the smaller 40mg dose at six week follow up. Interestingly 56% of people injected with a larger dose reported a minimum 8/10 improvement compared to 22% of patients injected with a smaller dose. Conclusion The low incidence of COVID-19 infections following CSI indicates that there is no significant correlation with increased in risk of contracting COVID-19. This study did not collect any data on outcomes of infection but at the time of the phone calls no patients had been hospitalized or died. The incidence of COVID-19 infection was below the national average. Some of the Rheumatology patients injected may have been advised to shield which may have contributed to the lower-than-expected figure. The significantly increased benefit consistently reported by patients supports the use of a higher dose steroid (Kenalog 80mg) versus lower dose (40mg) when injecting large joints in patients with arthritis. It is important to weight up the risks and benefits of CSI but this suggests that we should use the higher dose in clinical practice.
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Various guidelines recommend steroid in only severe COVID-19 patients. But in hospitals steroids are being rampantly used even at the beginning of symptom onset. Some studies indicate starting steroid only in severe and/or patients on mechanical ventilation while some suggest starting in first 5-7 days to stave off cytokine storm. Hence this study was undertaken with the aim to study the relationship between initiation of steroid therapy and clinical outcome in hospitalized COVID-19 patients. The data for this study was collected from the medical records of patients diagnosed with COVID-19 in a tertiary care hospital. Evaluation of relationship between day of initiating steroid therapy and dose with the clinical outcome was done in terms of all-cause mortality, duration of hospital stay, requirement of assisted ventilation, requirement of ICU and requirement of oxygen therapy. Patients were categorized according to the day of initiating steroid after symptom onset or RTPCR or RAT positivity date, whichever was earlier in 4-7 days group, 8-10 days group and 11-14 days group. And according to dose given of methylprednisolone per day in 40 mg and 80 mg groups. All-cause mortality was significantly less in 8-10 days group (25.78%) compared to 4-7 days (38%) and 11-14 days group (39.68%) and significantly less in 40 mg group (26.67%) compared to 80 mg group (38.46%). Starting steroid between 8-10 days and in low dose (40 mg) is more beneficial in terms of all-cause mortality.Copyright © 2023, Global Research Online. All rights reserved.
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Background: The infection caused by the SARS-CoV-2 continues affecting millions of people worldwide and vaccines to prevent the coronavirus disease (COVID-19) are considered the most promising approach for curbing the pandemic. Otherwise, cardiovascular and neurological complications associated with the vaccines were speculated and some few case reports were published. Objective(s): We describe a case of postural orthostatic tachycardia syndrome (POTS) after viral vector COVID-19 vaccination and the possible autoimmune process of the syndrome. Method(s): A 35-year-old female, without previous symptoms or comorbidities, developed intermittent palpitation, intense fatigue and dyspnea, compromising her daily activities, triggered by upright position, seven days following the second dose of the Oxford vaccine. Physical examination was normal, except for a heart rate (HR) increase of 33 beats/min from supine to standing position, with no significant change in blood pressure and reproduction of symptoms. Result(s): A 24-hour Holter monitoring revealed episodes of spontaneous sinus tachycardia correlated with palpitation and fatigue. Extensive diagnostic investigations excluded primary cardiac, endocrine, infectious and rheumatologic etiologies. The patient underwent an autonomic function test which demonstrated normal baroreflex sensitivity, as well as normal cardiovagal and adrenergic scores. Head-up tilt test showed persistent orthostatic tachycardia (HR increase from a medium of 84 beats/min in supine position to 126 beats/min during upright tilt), without hypotension, consistent with the diagnostic criteria for POTS. According to the current guidelines, general behavior recommendations, pharmacotherapy with low dose of propranolol associated with the autonomic rehabilitation were oriented. Along three months of follow-up, the patient reported a gradually improvement in her symptoms. Conclusion(s): POTS is a heterogeneous disorder of the autonomic nervous system characterized by orthostatic tachycardia associated with symptoms of orthostatic intolerance. Although the physiopathology of COVID-19 vaccine and autonomic disorders remains speculative, autoimmune response is one of the possible mechanisms. Based on clinic presentation, the time frame of symptom onset is consistent with other well-known post-vaccination syndromes, which may be an indicator of an autoimmune process induced by immunization. Further studies are needed to assess causal relationship between immunization and autonomic dysfunction.Copyright © 2023
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Objectives: Patients with immune-mediated diseases achieve lower seroconversion rates to COVID19 vaccines compared to healthy controls. The aim of this study was to assess the SARS-CoV-2-specific humoral and T-cell responses after a two-dose regimen of SARS-CoV-2 vaccine in patients with rheumatoid arthritis (RA). Method(s): Observational study. Patients with RA, >=18 years of age, who were vaccinated according to the Argentine National Health Ministry's vaccination strategy were included. Anti-SARS-CoV-2 IgG antibodies, neutralizing activity and specific T-cell responses were assessed after the first and second doses. Result(s): A total of 120 RA patients were included. Mostly, homologous regimens were used, including Gam-COVID-Vac (27.5%), ChAdOx1 (24.2%), BBIBP-CorV (22.5%) and BNT162b2 (0.8%), while the most frequent combination of vaccines was Gam-COVID-Vac/mRNA-1273 (21.7%). After the second dose 81.7% presented anti-SARS-CoV-2 antibodies, 70.0% neutralizing activity and 65.3% specific T-cell response. The use of BBIBP-CorV, treatment with abatacept (ABA) and rituximab (RTX) were associated with undetectable antibodies and no neutralizing activity after two doses of vaccine. BBIBP-CorV was also associated with the absence of T-cell response. The total incidence of adverse events was 357.1 events/1000 doses: significantly lower with BBIBP-CorV (166.7 events/1000 doses, p alpha 0.02). Conclusion(s): In this cohort of patients with RA who received 2 doses of COVID-19 vaccine, according to the Argentine strategic vaccination planwhich included homologous and heterologous regimens, two of ten did not develop IgG anti-SARS-CoV-2, 70% presented neutralizing activity and 65% specific T-cell response. The use of BBIBP-CorV was associated with deficient humoral and cellular response, while treatment with ABA and RTXaffected the development of IgG anti-SARS-CoV-2 and neutralizing activity.
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Objectives: As of March 5th, 2022, around 1.585 cases of MIS-C and 98 deaths (6,4%) were reported in Brazil. The state of Rio de Janeiro State (RJ) having 94 cases (5,9%) and 4 deaths (4,2%)1.Our aim was to evaluate clinical and laboratory features, and management of MIS-C in seven pediatric hospitals in RJ, Brazil. Method(s): Multicenter, observational, ambidirectional cohort study in seven tertiary hospitals in RJ(Brazil), assessing medical charts of pediatric inpatients (0-18 years) diagnosed with MIS-C according to WHO/CDC criteria, from August, 2020 to February, 2022. Descriptive statistics were used to analyze distributions of continuous variables, frequencies, and proportions. Result(s): A total of 112 cases of MIS-C were enrolled. The mean age was 4.2 years and thre was male predominance (59,8%). All cases had a SARS-CoV-2 contact (29.5% close contact;31.3%:positive PCR;serology:43.8%).Only 12.5% had comorbidities. Length of stay (LOS) was 7 days.Median duration of fever was 8 days. Most common symptoms were: rash(67%);gastrointestinal (67%);conjunctivitis (42%);neurological(39.6%);cardiovascular(37.5%);cervical lymphadenopathy (36.6%), and shock/hypotension(28.6%).Co-infection occurred in 3 patients. Forty-four patients fulfilled criteria for Kawasaki disease. Most patients were admitted to PICU(12;62,5%) for amedian of 2 days. Respiratory distress was seen in 18,7%;hypotension:28,6%, and shock in 23,2%. Main laboratory findings were: high C-reactive protein in 95%;D-dimer:77%, anemia:77%, thrombocytosis:63%;transaminitis:43.8%, lymphopenia:38%;hypoalbuminemia:34%;thrombocytopenia: 29%;hypertriglyceridemia:28%, and high pro-BNP in 27%. Echocardiogram was performed in 91/112 patients;abnormal in 70,3%;exhibiting myocardial dysfunction( 25%);pericardial effusion(21%);coronary dilation/aneurysms(11%) and, valvulitis (14.5%). IVIG+corticosteroids (CTC) were administered in 59.8%(67/ 112);18.6%(18/112) IVIG only;10.7%(12/112) CTC only;3.4%(4/112)biologics, and 15(13.3%) received no treatment. ASA low dose in 77.7% (87/112) and moderate/high dose in 34.8%. Oxygen support was needed in 27,7%;vasoactive amines:18,7%;dialysis:5,3%, and transfusion:18,7%.One patient died from a cytokine storm syndrome. Conclusion(s): Our study reports a higher number of MIS-C cases in RJ than the number reported to Brazilian authorities, highlighting underreporting. Our patients were younger, had fewer comorbidities, cardiovascular/gastrointestinal/renal involvement, shortest LOS in ICU, and a higher frequency of myopericarditis.
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Background/Aims Since the COVID-19 outbreak the rheumatology community have been concerned about the risk of SARS-CoV-2 infection in patients prescribed immunosuppressing medications. Data suggests that patients receiving Rrtuximab are at increased risk of developing severe outcomes from COVID-19 (1). In our unit all patients receiving rituximab were selected to receive a targeted vaccination and booster programme with all patients receiving at least 2 vaccinations and up to 3 booster vaccinations. We studied the efficacy of the COVID-19 vaccines in rituximab patients, by checking the the Roche Elecsys Anti-SARS-CoV-2-S (Spike) IgG/IgM total antibody levels post vaccination. Our aim was to assess the vaccination response in patients receiving rituximab and to offer advice on continued shielding or alternatively passive immunization with tixagevimab/cilgavimab in those patients who did not mount a response. Methods Taking 39 patients currently on rituximab therapy, we measured Anti- SARS-CoV-2-S (Spike) antibody levels post vaccination. We recorded whether the test was positive or negative, and the numerical result. We recorded rituximab dates of administration and dates of vaccines. We also recorded diagnosis, co-prescribed DMARDs, immunoglobulin levels, white cell and lymphocyte counts. We took record of whether or not the patient subsequently contracted COVID-19, required a hospital admission, ICU or died. Results Of our 39 patients, 21 had Anti-SARS-CoV-2-S (Spike) antibody levels checked. Of these patients, 7 (33%) had a negative spike protein result. Of the patients with a positive result, 8 (38%) had an antibody level between 0-250U/ML, and only 6 (28.6%) had a level >250U/ML (The manufacturer advises that a level above 0.8U/ML is a positive result). Of patients with a negative result, 1 patient had received 3 vaccines, 5 patients had received 4, and 1 patient had 5. All of the patients had received a vaccine >4 weeks prior to receiving the drug. Two patients were co-prescribed Belimumab, 3 were co-prescribed low-dose methotrexate and 2 were not on additional disease modifying agents. The diagnoses of these patients were, 2 patients with SLE, 4 with SPRA, and 1 MPO Vasculitis. There were no significant findings in lymphocyte count, white cell count or immunoglobulin levels. Conclusion These findings suggest that our current COVID-19 vaccination and booster programme may not provide adequate response in patients receiving rituximab therapy. Despite this being a small cohort, these results show that 33% of patients have not mounted a vaccine response and this is concerning. We suggest that vaccine response should be checked in all patients receiving rituximab therapy and those patients who do not mount a vaccine response should be offered passive immunity and advised of possible additional risks regarding COVID-19 exposure.
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Intro: Children and Young people were the last group in England be offered COVID-19 vaccination (from September 2021), thus were the largest susceptible group when SARS-CoV-2 Omicron variants emerged. We monitored vaccine and naturally-derived antibodies in schools between November 2021 and March 2022. Method(s): We conducted three large surveys (November 2021, January and March 2022) in a nationally representative random sample of primary and secondary schools, stratified by regions. Oral fluid samples were tested for IgG antibodies against SARS-CoV-2 nucleocapsid (anti-NP) and spike (anti-S1) proteins using novel validated ELISAs;vaccines used in England elicit anti-S1 antibodies only. We calculated weighted prevalences for each survey, and used multilevel logistic regression to investigate associations with socio-demographic factors. Finding(s): Overall 11311 students contributed 22478 biological samples (respectively 4840, 7549 and 10089 in rounds 1, 2 and 3, with similar socio- demographic characteristics). In 4-11 year olds, not eligible for vaccination, anti- S1 and anti-NP antibody prevalences were 31.3% and 26.6%, 46.2% and 43.8%, and 53.4% and 58.7% respectively over the three rounds. The corresponding estimates in 12 to 18 year olds) were 70.7% and 34.6%, 85.6% and 45.9%, 89.0 and 53.9%. In November 2021 (before Omicron dominance), higher anti-S1 antibody positivity was associated with older age and Black ethnicity, and non- eligibility for free school meals in 4-11 year olds. In 12-18 years it was associated with non-eligibility for free school meals. In March 2022 when Omicron dominated, these associations remained, together with urban location in 4-11 years old. Conclusion(s): The steep increase in 4-11 year olds in both sets of antibodies reflected the emergence and spread of highly infectious Omicron variants whilst high and increasing anti-S1 prevalence in secondary students was consistent with greater vaccine uptake. Socioeconomically deprived 12-18 year olds had lower odds of anti-S1, suggesting lower vaccine uptake or access.Copyright © 2023
ABSTRACT
Introduction: Mucosa-associated lymphoid tissue (MALT) lymphomas are extra-nodal marginal zone B-cell lymphomas, most commonly found in the stomach, associated with Helicobacter pylori infections, and generally not linked with inflammatory bowel disease. Rectal MALT lymphoma is very uncommon and often associated with painful defecation, change in bowel habits, or rectal pressure/prolapse. Here, we present a rare case of an asymptomatic female with ulcerative colitis (UC) found to have benign-appearing rectal polyps during a routine screening colonoscopy. Case Description/Methods: The patient is a 56-year-old female with a history of left-sided UC, diagnosed in 1993, with one flare after receiving the 2nd dose of the Moderna COVID-19 vaccine, taking oral Olsalazine 500 mg twice daily, low-dose Prednisone, and mesalamine suppositories as needed presenting for screening colonoscopy. The patient was asymptomatic, citing regular non-bloody bowel movements and normal stool consistency. Colonoscopy revealed two 7 mm sessile, non-bleeding rectal polyps, surrounded by congested, erythematous, friable, and ulcerated mucosa in the rectosigmoid colon. Cold forceps biopsies were taken. Hematopathology evaluation of the routine colon biopsy samples revealed chronic nonspecific colitis while pathology of the rectal polyps showed marked lymphoplasmacytic infiltrate and extra-nodal marginal zone lymphoma of MALT. Ancillary studies, immunohistochemistry, and molecular studies for B-cell gene rearrangement confirmed extra-nodal marginal zone lymphoma of MALT with prominent plasmacytic differentiation. The patient was informed and close follow-up in Gastroenterology clinic was arranged. (Figure) Discussion: Rectal MALT lymphoma is rare with unclear management options. Treatments of UC include watchful waiting, surgical resection, endoscopic mucosal resection, radiation, and/or chemotherapy. Helicobacter pylori infections, though strongly linked with gastric MALT lymphoma, have not been shown to be strongly correlated with rectal MALT lymphoma. Given that patients with UC have chronic UCassociated colonic inflammation, lymphoma is often difficult to distinguish visually during colonoscopy, frequently masked by ulcerations and pseudo-polyps. In cases like these, more definitive treatments such as surgical resection could therefore be warranted. Long-term follow-up data is sparse and definitive management remains a clinical conundrum, thus these patients require reliable long-term multidisciplinary close follow-up. (Figure Presented).
ABSTRACT
Purpose of Study: Sickle cell disease (SCD) is a hemoglobinopathy that disproportionately affects the indigenous Tharu population of Nepal, a marginalized ethnic group concentrated in the Dang district. There are significant global disparities in the prognosis of SCD;in low-income countries, which lack screening and management infrastructure, up to 80% of those born with SCD are undiagnosed and less than half survive beyond 5 years of age. Since 2015, University of British Columbia medical student teams have collaborated with a local community partner, Creating Possibilities (CP), to improve SCD awareness, screening, diagnosis, and management for the Tharu population in and around Dang. Community members with SCD have previously expressed numerous challenges in obtaining treatment once diagnosed. This study aims to better understand difficulties in accessing SCD care for this community. Methods Used: The Access to SCD Care Questionnaire was developed from items in existing scales, deductive and inductive item generation, and feedback from expert local partners to ensure it is culturally appropriate, needs-specific, and easily understandable. The questionnaire includes closed-ended questions using a Likert scale and open-ended interview prompts. It centers around five core themes: personal beliefs, community attitudes, finances, transportation, and medical infrastructure. Interviews were conducted in Tharu (local dialect) by CP staff members in January to March 2022. Themes and sub-themes were qualitatively analyzed. Summary of Results: Participants aged from 14 to 42 with an equal sex ratio, a total of 12 interviews were conducted before study saturation was reached. All participants reported at least one minor or major problem with access to SCD care in each of the five core themes of the questionnaire. Inadequate healthcare infrastructure was the most frequently reported barrier, with participants reporting lack of local medication accessibility and low supplies at further district hospitals. Additionally, despite government funding for treatment coverage, participants reported difficulties obtaining the necessary legal documents to prove eligibility. The second largest perceived barrier to care was transportation, which was reported to be costly, time-consuming, and not readily available. Regardless of sub-theme, participants reported that system-wide effects from COVID-19 perpetuated these issues. Conclusion(s): Results from the Access to SCD Care Questionnaire demonstrate that availability and accessibility to medications and transportation services are the primary challenges to receiving SCD care in this indigenous community. Therefore, future interventions for this community should focus on these findings. In contrast with previous literature, community stigma and personal beliefs were not often reported as hindering SCD treatment. This may be attributed to successful education campaigns within this specific community or due to participation bias.
ABSTRACT
Background: Despite the development of safe and effective vaccines and antiviral treatments against COVID- 19, marginalized racial/ethnic groups in the United States continue to be disproportionally burdened by COVID-19. In response to this inequity, public health officials in several states designed, usually in an ad-hoc manner, policies aimed to be more equitable in both access and distribution of COVID-19 interventions. Method(s): We constructed an age- and race-stratified mathematical model of SARS-CoV-2 transmission and COVID-19 vaccination. We fit our model to data from Oregon at the beginning of 2021. Next, we explored counterfactual scenarios where we determined the optimal use of limited amounts of vaccine over the first 4 months of 2021 with the goal of minimizing 1) number of deaths or Years of Life Lost (YLL), 2) the inequity in mortality or YYL between race groups, 3) a combination of both. We compared them to a base-case scenario without vaccination. Result(s): When vaccine supply is very limited (enough to cover 10% of the population), there is a trade-off between minimizing mortality or minimizing inequity (Fig.1). For minimizing mortality, it is optimal to allocate vaccine to the oldest age group, irrespective of race. To minimize inequity, vaccine needs to be allocated first to the marginalized populations in the young- and middle-aged groups, incurring significantly more deaths in all groups, including the marginalized ones, compared to minimizing mortality (Fig.1). When minimizing both deaths and inequity, the optimal vaccination strategy achieved a significant reduction in inequity while preserving most of the reduction in mortality (Fig.1). When minimizing YYL and inequity, the optimal allocation resulted in a more equitable distribution of resources and outcomes across race groups. Once vaccine supply was enough to cover 20% of the population, our results suggest that it is possible to minimize both mortality (or YYL) and inequity, by protecting marginalized communities and the oldest populations at the same time. Conclusion(s): With low vaccine supply, there is a trade-off between being more equitable and reducing mortality. This is true because COVID-19 related mortality is concentrated in the oldest population while marginalized populations are predominately young. This trade-off quickly disappears when more vaccine is available. An interdisciplinary approach is needed to address the inequitable distribution of resources and outcomes in public health. Mortality rate (left), Years of Life Lost (center) and Indices of Disparity (right) with no vaccination (top row), minimizing deaths (2nd row), inequity (3rd row) or both (4th row) with enough vaccine to cover 10% of the population.