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By June 1, 2022, there were 38 prophylactic COVID-19 vaccines approved in 197 countries around the world. The ongoing approval of new vaccines and the accumulation of more than a year's worth of data on their use give particular importance to the consolidation and analysis of information on the safety of such vaccines. The aim of study was to analyse the information on adverse events after immunisation (AEFIs) with coronavirus vaccines in the individual case safety reports entered into the VigiBase database by June 1, 2022. Materials and methods: the author analysed safety reports retrieved from VigiBase through the VigiLyze interface in the expert access mode. The search was carried out using the generic keyword "Covid-19 vaccine” in combination with the trade names of all 38 coronavirus vaccines. Results: the article presents consolidated information on the number and content of the safety reports on COVID-19 vaccines. The author noted that the reports were characterised by a high level of information completeness and quality, which could be due to the fact that the main reporters were the countries with developed pharmacovigilance systems. The analysis of patient complaints showed that the reported symptoms of AEFIs coincided with the manifestations of side effects of the vaccines included in the package leaflets. The author carried out a review of the cases of serious AEFIs and the cases of adverse events of special interest requiring additional monitoring after immunisation. It revealed a positive correlation of individual vaccines with the cases of somnolence in post-COVID-19 patients. Conclusions: the data obtained on the global safety of coronavirus vaccines may be of practical interest to doctors, researchers, developers, and healthcare regulators.
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Latin American clinical researchers had participated in many controlled clinical trials in the 80 s and 90 s sponsored initiated that confirmed the place of calcium channel blockers and RAS blockade in hypertension treatment. Later, non-inferiority or superiority trials like ONTARGET, Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial and VALUE, Valsartan Antihypertensive Long-term Use Evaluation were performed worldwide including Latin-American countries. In the last decade, the absence of new drugs in the pipeline and sponsors portfolios at one side, and the recommendation of fixeddose combination as initial treatment tool at the other could be supposed as main causes of a dramatic reduction in sponsored hypertension research. At the same time, a huge increase in investigator initiated research was observed. Scientific national and regional societies in many cases fueled this increase. In this scenario, the Cardiovascular Risk Factor Multiple Evaluation in Latin America, CARMELA study was the first large-scale population-based study that assessed cardiovascular risk factor prevalence in 7 Latin American cities and its relationship to hypertension mediated organ damage. CARMELA is an example of an epidemiological study investigator initiated supported by a sponsor in Latin America The FOCUS study, Fixed-Dose Combination Drug for Secondary Cardiovascular Prevention was another example of an investigator initiated research supported by a private company. FOCUS was funded by the 7th Framework Programme European Commission Consortium with the participation of the Centro Nacional De Investigaciones Cardiovasculares CNIC Madrid, Spain, World Heart Federation, Federación Argentina De Cardiología, and some European research organizations, supported by FERRER Internacional. FOCUS help to understand the reasons of treatment non-adherence in Latin American countries and also to recognize the potential benefits of fixed-dose combinations in secondary prevention. More recently, the Interamerican Society of Cardiology SIAC developed the CorCOVID Latam study which aim was to study changes in lifestyle habits, treatment adherence, and mental health status in patients with cardiometabolic disease, but no clinical evidence of COVID-19 during the pandemic. This study is a good example of the feasibility of non-sponsored research in Latam supported by a regional scientific society structure and members. Five publications related to gender differences in the impact of the pandemic in Latam, Influenza and Pneumococcal vaccination during the pandemic, and the psychological impact in more than 4 thousand patients were the fruit of this society research initiative.
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Background: Vaccinations are of paramount importance in eradicating various diseases. Currently, there have been numerous reports on the development of new-onset autoimmune phenomena and disease flares following COVID-19 vaccination. The etiology and vaccine trigger mechanism of autoimmune disease still remains unclear. Molecular mimicry, by-stander activation and role of vaccine adjuvants are the main pathogenic mechanisms linked to an autoimmune phenomenon. However, vaccines as inducers of an autoimmunity is still an arguable subject. Case: We report a case series of six patients who developed new onset autoimmune reaction and disease flares following SARS-COV 2 vaccine. The patients received viral vector vaccine, inactivated vaccine and mRNA vaccine who developed symptoms in an average of 7-28 days following inoculation. A 27 year old male, previously healthy developed new onset of clinical amyopathic dermatomyositis after a week of 1st and 2nd dose of a viral vector vaccine. Two patients with systemic lupus erythematous developed severe cutaneous, hematologic and renal flare 14 and 28 days following vaccination. Two rheumatoid arthritis patients in long remission, developed atypical arthritis and disease flares after 10 and 14 days of inactivated and mRNA vaccine inoculation. One patient with spondylarthritis in remission experienced disease flare 7 days following inactivated SARS-COV- 2 vaccination. The patient age ranges from 19-72 years old of whom two are males and four are females. The management was individualized which includes oral corticosteroid and disease modifying anti-rheumatic drugs which showed improvement of symptoms. Conclusion: Development of an autoimmune reaction following SARS-COV 2 vaccination is of scientific and public importance. Vaccination might potentially trigger an autoimmune disease, however further investigations need to be established. The causative link between vaccination and autoimmunity needs to be studied. Susceptibility to a vaccine-induced autoimmunity might be triggered by the individual's genetic predisposition and several pathomechanisms.
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Background. Patients with autoimmune and inflammatory rheumatic diseases (AIRDs) are at high risk of developing COVID-19. Vaccination is an effective method of preventing this disease, which may be unsafe for patients with AIRDs. The aim of the study is to assess the safety of Gam-COVID-Vac in patients with IVRD in real clinical practice. Material and methods. A cross-sectional study was carried out. The main group consisted of patients with AIRDs, the control group consisted of individuals without AIRDs. All participants were interviewed by the research physician using a unified questionnaire, additional information was obtained from medical records. Results. The study included 222 patients with AIRDs (119 with rheumatoid arthritis, 36 with ankylosing spondylitis, 17 with psoriatic arthritis, 17 with Sjögren's disease, 10 with undifferentiated spondyloarthritis, 8 with systemic lupus erythematosus, 4 with metabolic arthritis, 3 with systemic scleroderma, 3 with systemic vasculitis, 2 with polymyalgia rheumatica, 2 with undifferentiated systemic connective tissue disease, 1 with adult Still's disease) and 111 patients without AIRDs. The number of patients with AIRDs who had a combination of local and systemic adverse events (AE) on the introduction of the first component of the vaccine was significantly less than in the control group (22.1 and 44.1%, respectively, P<0.001). Similar differences were also noted after the introduction of the second component (14.0 and 29.7%, respectively, P<0.001). AEs such as pain at the injection site without restriction of movement, weakness, fever, arthralgia/myalgia, headache, and chills were significantly more common in the control group after the introduction of the first component of the vaccine. After complete immunization, AEs were absent in 35.6% of patients with AIRDs and in 21.6% of control group patients (P=0.01). Exacerbations of AIRDs and new autoimmune phenomena were not registered in any cases. Conclusions. According to preliminary data, immunization of patients with AIRDs with the Gam-COVID-Vac combined vector vaccine appears to be quite safe.
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The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disorders;gastrointestinal disorders, neurological disorders, and allergic reactions;and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia;neutropenia is also characteristic of a number of interleukin inhibitors. Haemostatic adverse reactions to anticoagulants depend on the patient's dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions.
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Interferons (IFN) have antiviral activity against many viruses, including SARS-CoV-2. A combination of IFN-a2b and the antioxidant taurine is widely used in the Russian Federation, and its antiviral activity has not been studied before. The aim of this study was to determine the antiviral activity of interferon drugs, in combination with taurine and without it. The study included cytotoxicity and antiviral activity assays of IFN-a2b preparations, when stored according to the instructions at 2-8°C, and after 1 month storage at the temperature of 20-26°C in a pre-opened state. The combination of IFN alpha-2b with taurine has a higher antiviral activity compared to IFN alpha-2b mono-preparation by more than 25% at a «low» and 85% at a «high» multiplicity of infection. Selectivity index for combinations of IFN-a2b (50,000 IU/dose) + taurine (1 mg/ml) and IFN-a2b (10,000 IU/ml) + taurine (0.8 mg/ml) was more than 600 units, whereas for the IFN-a2b (10,000 IU/ml) it was 200 units. Antiviral activity does not change after one month at room temperature. The combination of interferon with taurine at high concentrations was less toxic than interferon. The results obtained demonstrate practicability of interferon alpha-2b and taurine combination use for treatment and prevention of COVID-19.
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Introduction. The tactics of managing and treating patients with chronic recurrent bacterial prostatitis (CRBP) in some cases is a difficult-to-treat condition for a practicing urologist. This circumstance occurs because the disease has several predisposing factors, a complex and multifaceted pathogenesis, and certain difficulties in diagnosis and treatment. Objective. To study the effectiveness of recombinant interferon α-2b medications in post-COVID-19 patients with chronic recurrent prostatitis against the background of antibiotic multi-drug resistance of microorganisms verified in prostate secretion. Materials and methods. The treatment of 52 post-COVID-19 patients with CRBP was analyzed, divided into three therapy-dependent groups. Group 1 patients (n = 18) received antibiotic therapy (ABT): Levofloxacin 500 mg q.d. PO for 28 days. Group 2 patients (n = 18) underwent combined therapy: ABT supplemented with recombinant interferon α-2b with an antioxidant complex of vitamins E and C ("Viferon®” rectal suppositories) 3.000.000 IU b.i.d. PR q12h for 28 days. Group 3 patients (n = 16) received monotherapy with recombinant interferon α-2b with an antioxidant complex of vitamins E and C ("Viferon®”rectal suppositories) 3.000.000 IU b.i.d. PR q12h for 28 days. The follow-up period was 6 months with monitoring of clinical and laboratory parameters assessed before treatment, after 1, 3 and 6 months from the start of therapy. Results. Based on the monitoring of the clinical picture and laboratory parameters, after 1 follow-up month, there was a significant decrease in the symptoms of the disease in all study groups. However, after 3 and 6 follow-up months, this trend was observed only in patients of groups 2 and 3 receiving recombinant interferon alfa-2b with an antioxidant complex (vitamins E and C). Conclusions. Strengthening the standard CRBP-therapy with recombinant interferon α-2b with an antioxidant complex of vitamins E and C makes it possible to normalize both clinical and laboratory parameters in most patients.
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Introduction: Neutralising monoclonal antibodies (mABs) have been proposed and developed for the treatment of Coronavirus Disease-2019 (COVID-19) patients with mild to moderate diseases and to prevent further progression. The combination of Casirivimab and Imdevimab blocks the entry of virus into cells by attaching to receptor binding domain of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) spike glycoprotein. The mABs are utilised as a pre-emptive strategy in certain high-risk groups such as those suffering from chronic liver, kidney and respiratory disease, malignancies and other immunocompromised states where efficacy of vaccines may be suboptimal. Aim: To evaluate the clinical outcomes in COVID-19 patients who were treated with Antibody Cocktail drug (casirivimab and imdevimab). Materials and Methods: A retrospective observational study was conducted in patients confirmed positive for SARS-CoV-2 from June 2021 to January 2022 and subsequently, the collected data was analysed from May 2022 to June 2022. The study was conducted in a tertiary care referral hospital in eastern India. All eligible patient subsequently received casirivimab and imdevimab at COVID-19 facility. Monitoring of patients was done upto 12 hour postinfusion. Demographic parameters, routine investigations and clinical outcomes were assessed. Data entry was done using Microsoft Excel. Data was entered, coded and analysed using International Business Machines (IBM) Statistical Package for the Social Sciences (SPSS) version 21.0. All analysis was done at a preset alpha error of 5% and results expressed at confidence levels of 95%. Results: Total 104 eligible cases were taken in present study. Nearly, 93% of those patients who had not been vaccinated were at higher risk for having severely elevated levels of C-Reactive Protein (CRP) as compared to 48% of those with COVID-19 vaccination. Nearly, 9 out of 10 patients with moderate-severe CRP levels were at nine times more risk for longer duration of hospitalisation as compared to normal levels of CRP. All patients having moderate-severe CRP levels required mechanical ventilation in comparison to mild CRP levels. Patients with comorbidities were more likely to get severe COVID-19 infections (p-value ≤0.05). Unvaccinated subjects were more likely to have severe infections than vaccinated subjects. (p-value ≤0.05). Prolonged hospitalisation (>7 days) was statistically significant in severe COVID-19. Unvaccinated subjects had a statistically significant rise in CRP over vaccinated subjects. The majority of the patients receiving antibody cocktail did not require prolonged hospitalisation while a minor fraction required invasive ventilation. Antibody cocktail was safe, well tolerated and had good efficacy and low mortality rate as compared to other modalities of treatment in this study. Conclusion: The duration of hospitalisation and outcomes were superior in patients having mild to moderate COVID-19 who received antibody cocktail without any serious side-effects.
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Objective: The role of angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) in the pandemic context of coronavirus disease 2019 (COVID-19) continues to be debated. Patients with hypertension, diabetes mellitus, chronic renal failure, cerebro-cardiovascular disease, or chronic obstructive pulmonary disease (COPD), who often use ACEi/ARB, may affect risk of severe COVID-19. However, there are no data available on the association of ACEi/ARB use with COVID-19 severity in this population. Design and method: This study is an observational study of patients with a positive SARS-CoV-2 test and inpatient treatment at a healthcare facility, using the registry information of COVIREGI-JP. Our primary outcomes were consisting of in-hospital death, ventilator support, extracorporeal membrane oxygenation support, and ICU admission. Out of the 6,055 patients, 1,921 patients with preexisting hypertension, diabetes mellitus, chronic renal failure, cerebro-cardiovascular disease, or COPD were enrolled. We also evaluated 1,097 patients with hypertension. Results: Factors associated with an increased risk of the primary outcomes were aging, male sex, COPD, severe renal impairment, and diabetes mellitus. No correlations were observed with ACEi/ARB, cerebro-cardiovascular diseases, or hypertension. Associated factors in male patients were aging, renal impairment, hypertension, and diabetes. In female patients, factors associated with an increased risk were aging, ACEi/ARB, renal impairment, and diabetes, whereas hypertension was associated with a lower risk of the primary outcomes. In patients with hypertension, factors associated with an increased risk of the primary outcomes were aging, male sex, severe renal impairment, and diabetes mellitus, but not ACEi/ ARB, cerebro-cardiovascular diseases, or COPD. Conclusions: Independent factors for the primary outcomes were aging, male sex, COPD, severe renal impairment, and diabetes, but not ACEi/ARB, in the COVID-19 patients with preexisting hypertension, diabetes mellitus, chronic renal failure, cerebro-cardiovascular disease or COPD. Based on this registry data analysis, more detailed data collection and analysis is needed with the cooperation of multiple healthcare facilities.
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Despite the development of new antigens and adjuvants in conventional vaccine studies, different approaches are required in vaccine formulations due to the poor immunogenicity, in vivo intrinsic instability, toxicity, and the need for multiple administrations of conventional vaccines. To overcome these problems, nanotechnology approaches have recently been incorporated into vaccine formulations. As the development of vaccines is directed towards "minimal” compositions with low immunogenicity, there is an increasing need for new formulations that enhance the efficacy of antigens and adjuvants. There is an urgent need to regulate existing advanced treatment options for the global health threat posed by COVID-19, as well as to accelerate the development of new vaccines and drugs. Nano-sized carrier systems developed for the diagnosis and treatment of many diseases, especially cancer, continue to maintain their importance in the COVID-19 pandemic. The use of nanoparticles in medicine started about 30 years ago, but gained momentum with the pandemic and reached many people in a short time with vaccine formulation. The rapid development, approval and delivery of SARS-CoV-2 vaccines is one of the most important achievements in the history of medicine, and nanomedicine is part of that history. Within the scope of the review, up-to-date information was given about the use of nanotechnology and nanoparticles in COVID-19 vaccine development studies.
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Introduction: Favipiravir and remdesivir are antiviral drugs being used in the present pandemic and were also used previously for other viral infections in the past. Monoclonal antibody (Mab) Casirivimab-Imdevimab is a Coronavirus Disease 2019 neutralising antibody approved in the last one year. Therefore, a clinical comparison with the existing treatment modalities is imperative. Aim: To compare Mab with remdesivir and favipiravir for mild to moderate COVID-19 disease. Materials and Methods: A retrospective, observational and single-centre study was conducted at a COVID-19 infection facility and private tertiary care hospital, Mumbai, Maharashtra, India. Data of patients admitted during the period of 1st June 2021 to 31st August 2021 was collected and analysed in the months of September 2021 and October 2021. Adults participants diagnosed to have COVID-19 infection, not requiring critical care or oxygen therapy were included in the study. Time to recovery from treatment onset and the need for treatment escalation were the primary outcome measures. Data was entered into Microsoft Excel spreadsheet version 16 and analysed. Statistical analysis was carried out using Chi-square test for the significance of association between tabulated values of data for qualitative and categorical data. Two-tailed unpaired t-test and Analysis of Variance (ANOVA) was used for quantitative tabulated data. Results: This study included 158 participants, grouped into remdesivir(n=63),favipiravir(n=30)andMab(n=65)treatmentgroups. Gender distribution was comparable in all groups (p-value=0.08). The three groups were compared for need of treatment escalation and time of recovery. The Mab treatment group (on comparing with other treatment arms) had earlier symptom recovery when given to patients with mild COVID-19 disease (p-value=0.006 for major symptoms) or when treatment was started within five days of symptom onset (p-value <0.001). Patients in Mab treatment group with mild illness required no treatment escalation compared to other groups (p-value=0.011). However, time to recovery patients in all treatment groups was comparable in case of patients with moderate COVID-19 illness (p-value=0.7381). In patients with moderate COVID-19 illness Mab treatment group required more frequent treatment escalation compared to remdesivir treatment group (p-value=0.044), when treatment was started within 5 days of symptom onset remdesivir and mab were comparable for treatment escalation (p=0.144). Vaccination status of the three groups differed significantly (p-value=0.033) hence a further subanalysis was done. On further analysis, non-vaccinated patients receiving Mab recovered from minor symptoms (p-value=0.0006) earlier than those receiving Remdesivir. Amongst the participants of the Mab treatment-group, vaccinated and non-vaccinated patients had comparable recovery time and need for treatment escalation (p-value=0.57 and p-value=0.76, respectively). Participants who received Mab-treatment within five days of symptom onset;recovered earlier compared to those who received Mab treatment after five days (p-value=0.019). Conclusion: Monoclonal antibody treatment group compared to the other treatment groups had earlier recovery in non vaccinated patients, mild COVID-19 disease, and when treatment was started before or on the 5th day of symptom onset.
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Background: Necrotizing myopathy has been previously described but was not included in the Peter and Bohan criteria until 2004, when immune-mediated necrotizing myopathy (IMNM) was distinguished from polymyositis (PM) based on immunologic and histopathologic differences. IMNM is currently a well-recognized autoimmune myopathy and represents up to 20% of these cases. Case: A 60-year- old female with biopsy-proven PM achieved sustained clinical remission with Rituximab. Her co-morbid conditions include hypertension, diabetes mellitus, and dyslipidemia. The patient noted a recurrence of gradual progressive, proximal muscle weakness and easy fatigability after receiving her first mRNA Covid-19 vaccine. Four months after onset of symptoms, CK Total was 9600 U/L. Rituximab was administered and muscle weakness and total CK levels (1247 U/L) improved within 10 days. She was prescribed rosuvastatin and fenofibrate for dyslipidemia within 7 days of completing the rituximab course. Two weeks later, proximal muscle weakness recurred. She became wheelchair-bound and experienced dysphonia. MMT score was 2/5 in proximal muscles and total CK total increased to 19,935 U/L. The patient received Methylprednisolone 500 mg IV once a day for 3 days. She had a good response with resolution of dysphonia and improvement of MMT to 4/5 on shoulder abduction and hip flexion on the 6th hospital day. She was discharged on oral methylprednisolone at 1 mg/kg/day. Muscle biopsy was consistent with an immune-mediated necrotizing myopathy, revealing necrotic fibers, intracellular macrophages, fatty infiltrates, irregular staining patterns on NADH stain with no evidence of endomysial inflammation, perifascicular atrophy, ragged red fibers, or rimmed vacuoles. Antibodiy against 3-hydoxy- 3- methylglutarylcoenzymeA reductase (HMGCR) result is pending but the other myositis-specific antibodies are negative.(including anti-SRP). Conclusion(s): IMNM is an autoimmune myopathy associated with anti-HMGCR and anti-SRP antibodies that clinically present similarly to polymyositis. The temporal occurrence of worsening muscle weakness with initiation of statin therapy make statin toxic myopathy or immune mediated necrotizing myopathy as diagnostic considerations. This case emphasizes the need to re-evaluate the etiology of new onset muscle weakness in patients with idiopathic inflammatory myopathy and highlights the role of myositis-specific antibodies and muscle biopsy in confirming the diagnosis.
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Case Report: Acute transverse myelitis (TM) is a rare inflammatory disease that typically presents asweakness, sensory alterations, and bowel or bladder dysfunction. Among the causes of TM are infections, paraneoplastic syndromes, or autoimmune conditions of CNS. Postinfectious TM can develop secondary to a viral or bacterial infection. SARS-CoV-2 is a recently discovered viral illness, and sequelae due to COVID-19 infection are still being studied. There is scarce literature relating the two conditions, and it is imperative to raise awareness. A 72-year-old man with hypertension and GERD, completely independent in ADL, was brought to the ED with sudden onset of bilateral lower extremity weakness. He reported symptoms started with difficulty climbing stairs that rapidly progressed to inability to ambulate independently and were associated with bilateral thigh soreness. Nine days prior, he developed fever and generalized malaise, and two days later, SARS-CoV-2 PCR and Ag tests were positive. He received azithromycin, Paxlovid, and dexamethasone as treatment. Upon evaluation, the patient was afebrile and hemodynamically stable. Neurological examination was remarkable for spasticity and hyperreflexia at bilateral lower limbs, clonus, preserved motor strength with adequate sensation to soft touch, and intact vibration and proprioception in all extremities. Cranial nerves were intact. These findings were consistent with an upper motor neuron lesion. On imaging, the Head CT scan was unremarkable. Thoracic/Lumbar Spine MRI was significant for distal thoracic and conus areas with central homogeneous brightness compatible with nonspecific myelitis. Laboratories showed leukocytosis without neutrophilia or bandemia, thrombocytosis, and elevated CRP. HIV and RPR tests were negative. A lumbar puncture for CSF analysiswas remarkable for mild monocytic pleocytosis (7 cell/muL), an increased level of total proteins (56 mg/dL), and normal glucose (57 mg/dL). CSF culture and gram stain were negative. CSF cytology yielded few lymphocytes and few monocytes and was negative for malignant cells. The meningoencephalitis panel was negative. Based on these findings, a clinical diagnosis of postinfectious myelitis secondary to COVID-19was made. The patient was treated with intravenous Methylprednisolone 1 g daily for five days. On follow-up, lower extremity weakness resolved completely, and he resumed his daily physical activities. Patients with COVID-19 infection can present with neurologic manifestations such as headache, myalgias, dizziness, dysgeusia, and anosmia. This case hopes to raise awareness of less commonly known neurological manifestations of SARS-CoV-2 infection and how the early recognition of symptoms can help expedite the diagnosis and treatment of the condition to avoid long-term sequelae. [Figure presented] Copyright © 2023 Southern Society for Clinical Investigation.
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Background: We report a 40-year- old female with co-existent lupus nephritis and thymoma who developed severe lupus flare (worsening nephritis, new onset hemolytic anemia) following SARS-CoV- 2 vaccine. Case: This 40 year old female has had stable lupus nephritis (LN) while maintained on mycophenolate mofetil and hydroxychloroquine for several years. A co-existent thymoma was likewise stable and did not require any added therapy apart from the management of the LN. She received the first dose of inactivated vaccine for SARS-CoV- 2 without event. Two weeks following the second dose, she developed Coombs positive hemolytic anemia (hemoglobin 64 g/L) with leukopenia (WBC 2.3 x 109/L), worsening nephritis (3+ proteinuria with uPCR 1.0, active urine sediments), hypocomplementemia, and elevated anti-dsDNA. She received methylprednisolone pulse therapy then maintained on prednisone 40mg/day with clinical improvement. Two weeks thereafter, she was admitted due to severe COVID-19 pneumonia accompanied by severe anemia requiring blood transfusion;she received a regimen of bevacizumab, dexamethasone, and remdesivir and was discharged recovered, without overt sequelae at the time of this report. Discussion(s): Vaccines are highly effective in reducing hospitalization and death attributable to SARS-CoV- 2 infection. There are concerns however regarding autoimmune disease flares following SARS-CoV- 2 vaccine, reported to occur in about 4% patients with autoimmune disorders. It is also possible that this patient's reaction may have been further aggravated by the co-existent thymoma. While there was apparent sub-optimal protection of the vaccine against moderate to severe COVID-19 infection in this patient, it may be conjectured that her significant recovery and response to the anti-viral combined with immunosuppressive regimen may be due to the high dose steroid treatment given for the post-vaccine autoimmune reaction.
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Introduction: An unusual case presentation of MOG-positive Acute Disseminated Encephalomyelitis (ADEM) in a preschool child following meta-pneumo viral infection responded to the combination of immune modulatory treatment with a favourable outcome. Material: Three-year-old female child presented with acute encephalopathy, high fever, vomiting, starring episodes, floppiness, and left abducent nerve palsy with rapid deteriorating GCS necessitating intubation and ventilation. Two weeks earlier, she was treated for suspected CNS infection with 10 days of antibiotics in the PICU with a positive meta-pneumo-virus. On admission, she had a GCS score of 6 with left-sided increased tone, bilateral hyperreflexia, and bilateral extensor response and on Day 14 demonstrated hyperkinetic movements of the upper and lower limbs. Method(s): Serum MOG antibody positive, CSF MOG low positive, metabolic investigations, Mycoplasma, EBV, Influenza, corona PCR, SARS-COV-2 Antibody, viral CSF panel unremarkable. MRI brain demonstrated T2 hyperintense signal in bilateral medial thalami and brain stem with a normal spine. Progressive changes were shown on repeated MRI Brains on day 4 and day 14 suggestive of multifocal changes involving deep cortical and subcortical white matter bilaterally with a new short segment of the spinal lesion at the T8 level. Repeated EEG and ambulatory EEG showed a diffusely slow background with intermittent slow runs of slow waves suggestive of generalized cerebral dysfunction. Result(s): After receiving the combination of high pulse steroids with a taper over 10 weeks, IVIG and 10 cycles of plasmapheresis she demonstrated gradual and remarkable clinical improvement over 10-12 weeks with a minimal focal neurological deficit. Conclusion(s): Initial differentiating CNS infection, metabolic disease and ADEM may be clinically challenging. Her clinical presentation, investigations and imaging were in keeping with the diagnosis of MOG-positive ADEM. Previous CNS infection may be related. MOG-positive ADEM treated with the early combination of immunomodulation may lead to positive clinical outcomes.
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Background: Blockade of JAK, preferably JAK1, by upadacitinib is a feasible approach to achieve erosion repair as it (1) is approved for the treatment of rheumatoid arthritis (RA), (2) effectively controls the inflammation and (3) targets pathogenic pathways that influence local bone homeostasis in the joint. To address the question whether inhibition of JAK1 could lead to erosion repair in patients with active RA, we performed a pilot non-randomized study comparing the changes in bone erosions on high-resolution peripheral quantitative computer tomography (HR-pQCT) before and after upadacitinib. Method(s): This is a 24-week, single-centered, prospective, non-randomized pilot study. We enrolled 20 adult patients with active RA (Disease activity score 28-C- reactive protein [DAS28-CRP] > 3.2) and >=1 bone erosion on HR-pQCT. They were given upadacitinib 15mg once daily for 6 months. HR-pQCT of the 2-4 metacarpophalangeal (MCP) head was done at baseline and 6 months. The primary outcome was the change of erosion volume on HR-pQCT. Secondary outcomes included change in RA disease activity and predictors of response to treatment. Erosion regression was defined as decrease in volume exceeding the smallest detectable change. Result(s): The baseline clinical characteristics of the recruited patients were shown in Table 1. Of the 20 patients, 11 (55%) patients failed to respond to 3 or more csDMARDs. At 24-week, there was significant improvement in mean DAS28 (-1.75, P < 0.001). Erosion regression was seen in 8 (40%) patients on HR-pQCT (Figure 1). Although no significant change in overall median erosion volume before and after upadacintinib (0.07 [-0.90 to 0.76 mm3] mm3, P = 0.904) was noted, the deterioration was less obvious compared to a historic cohort of 20 patients with similar age and disease activity on csDMARDs (median erosion volume change in 6 months: 0.67 mm3). When patients were stratified according to whether or not they had failed multiple csDMARDs, significantly high proportion of patients in the non-multiple- DMARDs failure group had volume regression in at least one erosion compared to those in the failure group (75% vs 25%, P = 0.04). There was improvement in mean total erosion volume in the non-failure group (-0.33 +/- 1.33 mm3), whereas mean erosion volume in the failure group worsened (2.09 +/- 7.62 mm3). One patient developed chest infection requiring hospitalization and withdrew from the study. No other serious adverse event was noted. Conclusion(s): The results of the study suggest upadacitinib is clinically efficacious in refractory RA disease and can retard erosion progression. Regression of erosion is possible, particularly in those with limited csDMARDs exposure. Whether early JAK1 inhibition could lead to better structural outcome warrants further investigations. (Figure Presented).
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Guduchi (Tinospora cordifolia) is an essential drug of the Ayurvedic medicine system used in different Ayurvedic formulations to treat a variety of ailments. Guduchi is a member of the Menispermaceae family and is widely produced in tropical and sub-tropical countries such as India, Sri Lanka, China, Myanmar, Philippines, South Africa, Thailand, Bangladesh, and several south-east Asian continents such as Indonesia, Malaysia. All parts of Guduchi have nutritional value and medicinal importance, including the roots, stem, bark, and leaves. A different class of phytochemicals like alkaloids, glycosides, aliphatic compounds, diterpenoids, sesquiterpenoids, phenolic compounds, steroid and polysaccharides, etc., are found in Guduchi. Tinosporaside, tinosporine, magnosporine, berberine, choline, Jatrorrhizine, palmatine, beberine, giloin, giloinsterol, and other beneficial biomarkers are present in this herb. Guduchi is used to treat cold, fever, headache, jaundice, digestive disorder, among other things, and it shows several proven pharmacological activities such as anti-oxidant, anti-inflammatory, antidiabetic, immunomodulatory activity, anti-toxic, hepatoprotective, anticancer, cardioprotective activity, radioprotective, antimicrobial, anti-stress, anti-HIV and many more. This review article majorly highlights the phytochemical present in Guduchi, analytical works and pharmacological activities of Guduchi. Copyright © 2022 are reserved by International Journal of Pharmaceutical Sciences and Research.
ABSTRACT
Background: A 54-year- old male presented to our centre with a chronic non-productive cough and breathlessness. Recent history of COVID treated and resolved few months back. He had a history of brain surgery performed five years back but details not known. Physical examination revealed no oedema and bilateral coarse creps with bronchiolar breathing. Laboratory findings indicated neutrophilic leucocytosis, elevated inflammatory markers, with elevated troponin I and D dimers. Urine analysis suggested microscopic haematuria with sediments. While 24 hour quantification revealed sub nephrotic proteinuria. As auto immune workup and vasculitis profile was negative and patient has not improved in spite of standard of therapy hence we went ahead with CT-Chest indicating ground-glass opacities in bilateral lung parenchyma and prominent interlobular/intralobular septal thickening. Then Bronchoscopy done which revealed the blood-stained secretions in the main stem bronchi and diffuse alveolar haemorrhage in bilateral bronchial segments indicating an inflammatory study, while tuberculosis diagnostic panel and infective bio fire panel in BAL was negative. Meanwhile, his repeat BAL culture suggested Carbapenem resistant Acinetobacter baumannii complex infection. As the patient did not respond to the standard of care for vasculitis. Probability considered was a small vessel vasculitis (namely Granulomatous polyangiitis) was considered due to lung manifestation involving upper respiratory tract with epistaxis, neutrophilic leucocytosis, elevated acute reactive protein, and renal manifestation including microscopic haematuria and proteinuria. However he responded poorly to conventional standard of treatment including pulse steroids and IVIG. Hence after MDT discussion we proceeded with lung biopsy which showed linear cores of lung tissue infiltrated by a malignant neoplasm and acinar pattern suggesting Invasive mucinous adenocarcinoma. Hence we went ahead with the biopsy diagnosis for the treatment plan. As he was to be started on chemotherapy, but he suddenly collapsed and went into hypotension, bradycardia, and cardiac arrest. In spite of high supports and post 4 cycles of CPR, was unable to revive and sadly succumbed to his illness. Discussion(s): In this rare case, the original diagnosis pointed to the pulmonary-renal syndrome, an autoimmune disease characterized by diffuse pulmonary haemorrhage and glomerulonephritis. However, negative autoimmune antibodies and vasculitis profile along with lung biopsy results indicated an unusual case of malignant lung adenocarcinoma presented with pulmonary renal syndrome. Conclusion(s): In cases suggesting pulmonary-renal syndromes, if autoimmune work up is negative and response is suboptimal relook the diagnosis.
ABSTRACT
Shoulder injury related to vaccine administration (SIRVA) is a term given to describe shoulder pain and dysfunction arising within 48 hours after vaccine administration and lasting for more than one week. While SIRVA is most commonly seen after influenza and tetanus vaccines, there have been a few recent case reports describing SIRVA-like symptoms after COVID-19 vaccine administration. Two patients presented to the shoulder surgeon's practice center with complaints of shoulder stiffness and pain following the COVID-19 vaccine. The first patient was a 33-year-old man;he presented within 2 days of onset of the pain and 14 days from the vaccine date. He had a complete restriction of shoulder motion (0degree flexion, and no external or internal rotation) at presentation. This patient was treated with non-steroidal anti-inflammatory drugs (NSAID) and rested in a sling for a week. The second patient was a 53-year-old woman;she presented with a 6-week duration of mild restriction of active shoulder motion and shoulder pain. Her magnetic resonance imaging (MRI) revealed the presence of subacromial-subdeltoid bursitis. She was treated with subacromial steroid injection and range of motion shoulder exercises. Both patients recovered a near-normal range of motion recovery within a month, and their pain improved significantly. The main lessons from this case report were: (1) patients presenting with a recent increase in pain and acute loss of shoulder movements after vaccination may be managed conservatively with rest and NSAID medications and (2) in case of a subacromial-subdeltoid bursitis in the MRI, subacromial injection of steroid may provide good pain relief. Copyright © 2022, Yale Journal of Biology and Medicine Inc. All rights reserved.
ABSTRACT
Case Report: Tsukamurella species are aerobic, partially acid fast saprophytes commonly isolated from soil and water. They are opportunistic pathogens known to infect multiple organs and can contribute to significant pathologies such as bacteremia, peritonitis, and respiratory tract infections. Moreover, Tsukamurella shares certain characteristic properties to Mycobacterium tuberculosis and Actinomyces species, including the acid fast stain, which can contribute to misdiagnosis of patients. A 68 year old female patient presented to the ED for shortness of breath, fatigue, and weight loss for 6 months. The patient's past medical history includes pulmonary fibrosis, type 2 diabetes, coronary artery disease with stent, hyperlipidemia, hypertension, and M. tuberculosis infection when she was 3 years old in Finland. On admission, labs revealed thrombocytosis (reactive 555 000/microL), leukocytosis (14 450/microL), and microcytic anemia (9.4 microg/dl). Moreover, C reactive protein was elevated and procalcitonin was normal (0.06 microg/l);a COVID-19 PCR was negative. An X-ray revealed severe patchy and interstitial infiltrates throughout both lungs with parenchymal scarring and pleural thickening in the periphery of the left mid-lung zone with multifocal pneumonia. Blood and sputum cultures were performed under the impression of pneumonia, and treatment with azithromycin and ceftriaxone was started. A M. tuberculosis infection was suspected due to a positive AFS. Further chest CT suggested multifocal pneumonia within the left lung in addition to apparent cavitary lesions versus bulla, a chronic interstitial lung disease with traction bronchiectasis, calcified right lower lung nodule, and calcified hilar lymph nodes suggesting a history of granulomatosis diseases. A bronchoscopy with Bronchoalveolar lavage was performed. The initial sputum specimen direct smear showed acid-fast stain positive with Actinomyces growth, and Penicillin G was added to the treatment. Samples were sent to the state department lab, and biopsy revealed granulomatous inflammation negative for malignant cells. One month later, the patient's sputum culture showed Tsukamurella for High-performance liquid chromatography (HPLC). Moreover, a rifampicin sensible M. tuberculosis complex by NAA was also positive six weeks later. The patient was started on a complete TB regimen and continued in the outpatient pulmonology clinic with the addition of levofloxacin for three months and rifampicin substituted for rifabutin. As demonstrated in the case above, a Tsukamurella infection can present similarly to a Mycobacterium infection. Patients may be misdiagnosed or potentially be co-infected. Our patient was further tested and appropriately treated for Tsukamurella after further extensive diagnostic screenings. Due to a high rate of missed cases, it is important to keep Tsukamurella infection on the differential diagnosis as the patient presentation may initially appear to be a Mycobacterium or other pulmonary infection. Copyright © 2023 Southern Society for Clinical Investigation.