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1.
BMC Cardiovasc Disord ; 22(1): 26, 2022 02 02.
Article in English | MEDLINE | ID: covidwho-2153508

ABSTRACT

BACKGROUND: Ethiopia has a high acute rheumatic fever (ARF) and rheumatic heart disease (RHD) prevalence, and to our knowledge, there are no data on the status of secondary prevention in children with RHD. This study describes the status of secondary RHD prevention. METHODS: A multicenter, prospective study was performed on children aged 5-17 years with RHD in Ethiopia. Good adherence was defined as at least 80% completion of benzathine penicillin (BPG) or oral Amoxicillin within the previous year. The primary outcome measure was adherence to prophylaxis, expressed as a proportion. Socio-demographics, severity of RHD, and ARF recurrence were evaluated. RESULTS: A total of 337 children with a mean age of 12.9 ± 2.6 years were included. The majority (73%) had severe aortic/mitral disease. Participants were on BPG (80%) or Amoxicillin (20%) prophylaxis. Female sex (P = 0.04) use of BPG (0.03) and shorter mean duration of prophylaxis in months (48.5 ± 31.5 vs. 60.7 ± 33, respectively, P < 0.008) predicted good adherence. Running out of medications (35%), interrupted follow-up (27%), and the COVID-19 pandemic (26%) were the most common reasons for missing prophylaxis. Recurrence of ARF was higher in participants on Amoxicillin compared with BPG (40% vs. 16%, P < 0.001) and in those with poor adherence compared with good adherence (36.8% vs. 17.9%, respectively, P = 0.005). Type and duration of prophylaxis (OR 0.5, CI = 0.24, 0.9, P = 0.02; OR = 1.1, CI = 1.1, 1.2, P = 0.04, respectively), and sex (OR = 1.9, CI = 1.1, 3.4, P = 0.03) were independent predictors of poor adherence. CONCLUSION: Poor adherence is prevalent in Ethiopian children living with RHD. Amoxicillin is a suboptimal option for prophylaxis as its use is associated with lower adherence and a higher rate of ARF recurrence.


Subject(s)
Amoxicillin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Penicillin G Benzathine/therapeutic use , Rheumatic Heart Disease/prevention & control , Secondary Prevention , Adolescent , Child , Child, Preschool , Ethiopia/epidemiology , Female , Humans , Male , Medication Adherence , Prevalence , Prospective Studies , Recurrence , Rheumatic Heart Disease/diagnosis , Rheumatic Heart Disease/epidemiology , Rheumatic Heart Disease/microbiology , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
2.
BMC Nephrol ; 23(1): 216, 2022 06 21.
Article in English | MEDLINE | ID: covidwho-2139184

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination has become a major part of the strategy to reduce Coronavirus disease 2019 (COVID-19) numbers worldwide. To date, vaccinations based on several mechanisms have been used clinically, although relapse of existent glomerulonephritis presenting as gross hematuria, and occurrence of de novo glomerulonephritis have been reported. CASE PRESENTATION: We report the first sibling cases newly diagnosed as immunoglobulin A (IgA) nephropathy after the second dose of SARS-CoV-2 vaccination. 15- and 18-year-old men presented with gross hematuria following the second dose of SARS-CoV-2 vaccine (Pfizer, BNT162b2) received on the same day. Pathological findings of each kidney biopsy specimen were consistent with IgA nephropathy. Gross hematuria in both cases spontaneously recovered within several days. CONCLUSIONS: These cases indicate that SARS-CoV-2 vaccination might trigger de novo IgA nephropathy or stimulate its relapse, and also highlight the necessity of understanding the immunological responses to the novel mRNA vaccines in patients with kidney diseases.


Subject(s)
COVID-19 , Glomerulonephritis, IGA , Glomerulonephritis , Adolescent , BNT162 Vaccine , COVID-19/diagnosis , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Chronic Disease , Glomerulonephritis, IGA/diagnosis , Glomerulonephritis, IGA/pathology , Hematuria/etiology , Humans , Male , Recurrence , SARS-CoV-2 , Siblings , Vaccination/adverse effects
3.
BMC Neurol ; 22(1): 427, 2022 Nov 14.
Article in English | MEDLINE | ID: covidwho-2115832

ABSTRACT

BACKGROUND: Vaccination is an important public health strategy; however, many neurological adverse effects are associated with COVID-19 vaccination, being encephalitis a rare manifestation. CASE PRESENTATION: We present the case of a 33-year-old woman who received the first dose of the BBIBP-CorV vaccine against COVID-19 on April 4 and the second dose on April 28, 2021. Three days after receiving the second dose, she experienced a subacute episode of headache, fever, insomnia, and transient episodes of environment disconnection. We obtained negative results for infectious, systemic, and oncological causes. Brain magnetic resonance imaging showed lesions in the bilateral caudate nucleus and nonspecific demyelinating lesions at the supratentorial and infratentorial compartments. The results of the neuronal autoantibodies panel were negative. She had an adequate response to immunoglobulin and methylprednisolone; however, she experienced an early clinical relapse and received a new cycle of immunosuppressive treatment followed by a satisfactory clinical evolution. CONCLUSIONS: We report the first case of severe encephalitis associated with BBIBP-CorV (Sinopharm) vaccination in Latin America. The patient had atypical imaging patterns, with early clinical relapse and a favorable response to corticosteroid therapy.


Subject(s)
COVID-19 Vaccines , COVID-19 , Encephalitis , Adult , Female , Humans , COVID-19 Vaccines/adverse effects , Encephalitis/drug therapy , Encephalitis/etiology , Encephalitis/pathology , Recurrence , Vaccination
4.
Iran J Med Sci ; 47(6): 588-593, 2022 11.
Article in English | MEDLINE | ID: covidwho-2100905

ABSTRACT

Background: Previous studies have shown that patients with epilepsy (PWE) perceived significant disruption in the quality and provision of care due to the coronavirus disease 2019 (COVID-19) pandemic. The present study aimed to investigate the effect of this pandemic on seizure control status and changes in seizure frequency in PWE. Methods: A consecutive sample of adult PWE registered in the database of Shiraz Epilepsy Center (Shiraz, Iran) was included in the study. In July 2021, phone interviews were conducted with all selected patients. Information such as age, sex, last seizure, seizure type, and frequency during the 12 months before the study, and history of COVID-19 contraction was extracted. The seizure control status of the patients in 2019 (pre-pandemic) was compared with that during the COVID-19 pandemic. Data were analyzed using SPSS software with the Fisher's exact test and Pearson's Chi squared test. P<0.05 was considered statistically significant. Results: A total of 158 patients were included in the study, out of which 62 (39.2%) patients had a stable seizure control status, 47 (29.7%) had fewer seizures, and 50 (31.6%) had more seizures. Breakthrough seizures were reported by 32 (34.4%) patients. Seizure frequency increased in 18 (27.7%) and decreased in 46 (70.7%) patients. Conclusion: Overall, the COVID-19 pandemic has not been a major precipitating factor nor has it affected the seizure control status of PWE. In treated epilepsy, a fluctuating course with periods of seizure freedom followed by relapses is part of its natural history.


Subject(s)
COVID-19 , Epilepsy , Adult , Humans , Infant , Pandemics , COVID-19/epidemiology , Seizures/epidemiology , Epilepsy/complications , Epilepsy/epidemiology , Recurrence
5.
JAMA Netw Open ; 5(10): e2238867, 2022 Oct 03.
Article in English | MEDLINE | ID: covidwho-2084947

ABSTRACT

This cohort study of US adults with untreated COVID-19 examines the types and length of symptoms experienced following symptom recurrence.


Subject(s)
COVID-19 , Humans , Symptom Assessment , Recurrence
6.
Arch Iran Med ; 25(7): 450-455, 2022 Jul 01.
Article in English | MEDLINE | ID: covidwho-2067652

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) continues to be a worldwide healthcare problem. While our knowledge of the interaction of cancer and its management with COVID-19 mortality is gradually evolving, there are still many unanswered questions regarding the impact of COVID-19 on cancer and its prognosis. Several factors activated during COVID-19 have been implicated in tumorigenesis and the development of metastasis. Inflammation, hypoxia, reduced levels of angiotensin converting enzyme 2, elevated levels of Interleukin 6 and some other cytokines that are hallmarks of COVID-19 are capable of inducing tumor relapse and metastasis. On the other hand, there are reports that COVID-19 has been associated with cancer cure. Understanding the interaction between COVID-19 and tumor cells is essential for evaluating the potential long-term risks of COVID-19 in cancer patients, and for scheduling necessary preventive and therapeutic interventions. In this review, we briefly overview the potential impacts that COVID-19 might have on tumorigenesis and cancer relapse, as well as the role that COVID-19 might play in cancer remission and cure.


Subject(s)
COVID-19 , Lung Diseases , Humans , SARS-CoV-2 , Recurrence , Carcinogenesis
7.
Viruses ; 14(10)2022 09 28.
Article in English | MEDLINE | ID: covidwho-2066545

ABSTRACT

Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak and COVID-19 vaccination, new-onset and relapsed clinical cases of membranous nephropathy (MN) have been reported. However, their clinical characteristics and pathogenesis remained unclear. In this article, we collected five cases of MN associated with SARS-CoV-2 infection and 37 related to COVID-19 vaccination. Of these five cases, four (4/5, 80%) had acute kidney injury (AKI) at disease onset. Phospholipase A2 receptor (PLA2R) in kidney tissue was negative in three (3/5, 60%) patients, and no deposition of virus particles was measured among all patients. Conventional immunosuppressive drugs could induce disease remission. The underlying pathogenesis included the subepithelial deposition of viral antigens and aberrant immune response. New-onset and relapsed MN after COVID-19 vaccination generally occurred within two weeks after the second dose of vaccine. Almost 27% of patients (10/37) suffered from AKI. In total, 11 of 14 cases showed positive for PLA2R, and 20 of 26 (76.9%) presented with an elevated serum phospholipase A2 receptor antibody (PLA2R-Ab), in which 8 cases exceeded 50 RU/mL. Conventional immunosuppressive medications combined with rituximab were found more beneficial to disease remission for relapsed patients. In contrast, new-onset patients responded to conservative treatment. Overall, most patients (24/37, 64.9%) had a favorable prognosis. Cross immunity and enhanced immune response might contribute to explaining the mechanisms of MN post COVID-19 vaccination.


Subject(s)
COVID-19 Vaccines , COVID-19 , Glomerulonephritis, Membranous , Humans , Acute Kidney Injury , Antigens, Viral , Autoantibodies , COVID-19/complications , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Glomerulonephritis, Membranous/epidemiology , Receptors, Phospholipase A2 , Rituximab/therapeutic use , SARS-CoV-2 , Vaccination/adverse effects , Recurrence
8.
Continuum (Minneap Minn) ; 28(4): 1025-1051, 2022 08 01.
Article in English | MEDLINE | ID: covidwho-2065056

ABSTRACT

PURPOSE OF REVIEW: Given the expansion of options for the treatment of relapsing multiple sclerosis, this review outlines the framework for developing a treatment strategy, with consideration of when to switch or discontinue therapies, and a comprehensive elaboration of the mechanisms of action, efficacy, and safety considerations for each of the therapeutic classes. RECENT FINDINGS: The armamentarium of immunotherapies has grown rapidly, to encompass 19 US Food and Drug Administration (FDA)-approved immunotherapies available in 2021, which are addressed in the review. The coronavirus pandemic that began in 2020 underscored existing concerns regarding vaccine efficacy in those treated with immune-suppressing immunotherapies, which are also addressed here. SUMMARY: By choosing a treatment strategy before exploring the individual medications, patients and providers can focus their efforts on a subset of the therapeutic options. Although the mechanisms of action, routes of administration, efficacy, safety, and tolerability of the described agents and classes differ, all are effective in reducing relapse frequency in multiple sclerosis (MS), with most also showing a reduction in the accumulation of neurologic disability. These powerful effects are improving the lives of people with MS. Pharmacovigilance is critical for the safe use of these immune-modulating and -suppressing agents, and vaccine efficacy may be reduced by those with immune-suppressing effects.


Subject(s)
Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Humans , Immunosuppressive Agents , Immunotherapy , Multiple Sclerosis/drug therapy , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Recurrence , United States , United States Food and Drug Administration
9.
Mult Scler ; 28(12): 1944-1962, 2022 10.
Article in English | MEDLINE | ID: covidwho-2064612

ABSTRACT

BACKGROUND: Ozanimod, an oral sphingosine 1-phosphate receptor 1 and 5 modulator, is approved in multiple countries for treatment of relapsing forms of MS. OBJECTIVE: To characterize long-term safety and efficacy of ozanimod. METHODS: Patients with relapsing MS who completed a phase 1‒3 ozanimod trial were eligible for an open-label extension study (DAYBREAK) of ozanimod 0.92 mg/d. DAYBREAK began 16 October 2015; cutoff for this interim analysis was 2 February 2021. RESULTS: This analysis included 2494 participants with mean 46.8 (SD 11.9; range 0.033‒62.7) months of ozanimod exposure in DAYBREAK. During DAYBREAK, 2143 patients (85.9%) had treatment-emergent adverse events (TEAEs; similar in nature to those in the parent trials), 298 (11.9%) had a serious TEAE, and 75 (3.0%) discontinued treatment due to TEAEs. Serious infections (2.8%), herpes zoster infections (1.7%), confirmed macular edema cases (0.2%), and cardiac TEAEs (2.8%) were infrequent. Adjusted annualized relapse rate was 0.103 (95% confidence interval, 0.086‒0.123). Over 48 months, 71% of patients remained relapse free. Adjusted mean numbers of new/enlarging T2 lesions/scan and gadolinium-enhancing lesions were low and similar across parent trial treatment subgroups. CONCLUSIONS: This long-term extension of ozanimod trials confirmed a favorable safety/tolerability profile and sustained benefit on clinical and magnetic resonance imaging measures of disease activity.


Subject(s)
Indans , Multiple Sclerosis, Relapsing-Remitting , Oxadiazoles , Follow-Up Studies , Humans , Indans/adverse effects , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Oxadiazoles/adverse effects , Recurrence , Sphingosine-1-Phosphate Receptors
10.
Allergol Immunopathol (Madr) ; 50(S Pt 2): 1-7, 2022.
Article in English | MEDLINE | ID: covidwho-2056550

ABSTRACT

BACKGROUND: Chronic urticaria (CU), characterized by daily wheals and/or angioedema lasting more than 6 weeks, is a common skin disease. CU is classified as spontaneous or inducible. Because of Coronavirus Disease-19 (COVID-19) pandemic, face-to-face visits were reduced, and many centers started remote consultations to minimize hospital admissions and risk for viral diffusion. Telemedicine became a valuable tool for evaluating and monitoring patients with chronic diseases, such as CU. This study aims to evaluate the effectiveness of telemedicine as a means for the follow-up of patients with chronic spontaneous urticaria (CSU) during the COVID-19 pandemic. In particular, we collected data related to CSU evolution and treatment by remote consultation. Moreover, we specifically investigated the impact of SARS-CoV-2 infection or vaccination on CSU in relapsing or worsening of such a disease. METHODS: The electronic charts were reviewed for patients diagnosed with CSU, who were referred to the allergy unit of Meyer Children's Hospital, Florence. For each patient, a review of demographic characteristics, diagnostic workup, efficacy, and tolerability of the treatment was performed. Patients with a physical agent triggering CU were excluded from the study. Disease activity was monitored using the Urticaria Activity Score (UAS7). In addition, when the COVID-19 pandemic started, follow-up continued through telemedicine after an initial face-to-face visit when possible. Approximately 1 year after the diagnosis of CSU, patients were recontacted to investigate whether they had experienced a relapse or worsening of urticaria during a possible COVID-19 or immediately after receiving a COVID-19 vaccine. RESULTS: From January 2020 to March 2021, 84 cases of CSU were identified, with 71 (84.5%) of these being evaluated via televisit (remote consultation). During the remote follow-up period, 38/71 (53.5%) patients who were evaluated via televisit recovered completely from CSU, while 24 (33.8%) made therapy adjustments, and 9 (12.7%) had to discontinue follow-up through remote visits and return to face-to-face visits. In February 2022, we recontacted the 71 patients with CSU, and 50 (70.4%) of them answered by phone call interview. Four (19.2%) of the 26 patients who had COVID-19 showed CSU relapse, while 1 (3.8%) had a CSU worsening. Instead, 1 (3.8%) patient of the 26 who were vaccinated had a relapse of CSU, and 1 (3.8%) had a worsening of CSU, both after the first dose. CONCLUSION: Our data showed that telemedicine can be an effective tool for the follow-up of patients with CSU. Moreover, COVID-19, as well as COVID-19 vaccination, may trigger CSU relapse or worsening, but both are unspecific triggers, and urticaria shows a very short duration in most cases.


Subject(s)
COVID-19 Vaccines , COVID-19 , Chronic Urticaria , Telemedicine , Urticaria , COVID-19/complications , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Child , Chronic Disease , Copper/therapeutic use , Follow-Up Studies , Humans , Pandemics , Recurrence , SARS-CoV-2
11.
Front Cell Infect Microbiol ; 12: 932556, 2022.
Article in English | MEDLINE | ID: covidwho-2054966

ABSTRACT

Therapeutic advances in the 20th century significantly reduced tuberculosis (TB) mortality. Nonetheless, TB still poses a massive global health challenge with significant annual morbidity and mortality that has been amplified during the COVID-19 pandemic. Unlike most common bacterial infectious diseases, successful TB treatment requires months-long regimens, which complicates the ability to treat all cases quickly and effectively. Improving TB chemotherapy by reducing treatment duration and optimizing combinations of drugs is an important step to reducing relapse. In this review, we outline the limitations of current multidrug regimens against TB and have reviewed the genetic tools available to improve the identification of drug targets. The rational design of regimens that sterilize diverse phenotypic subpopulations will maximize bacterial killing while minimizing both treatment duration and infection relapse. Importantly, the TB field currently has all the necessary genetic and analytical tools to screen for and prioritize drug targets in vitro based on the vulnerability of essential and non-essential genes in the Mtb genome and to translate these findings in in vivo models. Combining genetic methods with chemical screens offers a formidable strategy to redefine the preclinical design of TB therapy by identifying powerful new targets altogether, as well as targets that lend new efficacy to existing drugs.


Subject(s)
COVID-19 , Mycobacterium tuberculosis , Tuberculosis, Lymph Node , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Humans , Mycobacterium tuberculosis/genetics , Pandemics , Recurrence
12.
Blood Adv ; 6(22): 5857-5865, 2022 11 22.
Article in English | MEDLINE | ID: covidwho-2043101

ABSTRACT

IDH2 (isocitrate dehydrogenase 2) mutations occur in approximately 15% of patients with acute myeloid leukemia (AML). The IDH2 inhibitor enasidenib was recently approved for IDH2-mutated relapsed or refractory AML. We conducted a multi-center, phase I trial of maintenance enasidenib following allogeneic hematopoietic cell transplantation (HCT) in patients with IDH2-mutated myeloid malignancies. Two dose levels, 50mg and 100mg daily were studied in a 3 × 3 dose-escalation design, with 10 additional patients treated at the recommended phase 2 dose (RP2D). Enasidenib was initiated between days 30 and 90 following HCT and continued for twelve 28-day cycles. Twenty-three patients were enrolled, of whom 19 initiated post-HCT maintenance. Two had myelodysplastic syndrome, and 17 had AML. All but 3 were in first complete remission. No dose limiting toxicities were observed, and the RP2D was established at 100mg daily. Attributable grade ≥3 toxicities were rare, with the most common being cytopenias. Eight patients stopped maintenance before completing 12 cycles, due to adverse events (n=3), pursuing treatment for graft-vs-host disease (GVHD) (n=2), clinician choice (n=1), relapse (n=1), and COVID infection (n=1). No cases of grade ≥3 acute GVHD were seen, and 12-month cumulative incidence of moderate/severe chronic GVHD was 42% (20-63%). Cumulative incidence of relapse was 16% (95% CI: 3.7-36%); 1 subject relapsed while receiving maintenance. Two-year progression-free and overall survival were 69% (95% CI: 39-86%) and 74% (95% CI, 44-90%), respectively. Enasidenib is safe, well-tolerated, with preliminary activity as maintenance therapy following HCT, and merits additional study. The study was registered at www.clinicaltrials.gov (#NCT03515512).


Subject(s)
COVID-19 , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Myeloproliferative Disorders , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Leukemia, Myeloid, Acute/therapy , Leukemia, Myeloid, Acute/drug therapy , Recurrence
13.
PLoS One ; 17(9): e0274697, 2022.
Article in English | MEDLINE | ID: covidwho-2039424

ABSTRACT

OBJECTIVES: To investigate the prevalence, associated factors and socioeconomic inequalities in chronic disease relapses (CDR) during 2020 in Peru. METHODS: A secondary analysis was made of the National Household Survey on Living Conditions and Poverty (ENAHO) 2020. Participants older than 18 years who suffered from a chronic disease and with information about the occurrence of a CDR in the last 4 weeks prior to the survey were included. Adjusted prevalence ratios (aPRs) were estimated to determine the associated factors. Socioeconomic inequality in CDR was estimated using concentration curves (CC) and the Erreygers concentration index (ECI). RESULTS: Data from 38,662 participants were analyzed; the prevalence of CDR in the last 4 weeks prior to the survey was 16.5% (95% CI: 15.8-17.2). Being female (aPR 1.29; 95% CI: 1.21-1.37), with regards to being male; being 30-39 (aPR 1.22; 95% CI: 1.05-1.42), 40-49 (aPR 1.29; 95% CI: 1.12-1.48), 50-59 (aPR 1.60; 95% CI: 1.41-1.82), and 60 years or older (aPR 1.80; 95% CI: 1.58-2.04), compared to 18-29; reaching up to primary (aPR 1.18; 95% CI: 1.07-1.31), or secondary education (aPR 1.13; 95% CI: 1.02-1.24), in contrast to tertiary education; presenting some physical, psychological or cognitive limitation (aPR 1.33; 95% CI: 1.21-1.46), with respect to experiencing no limitations; and being affiliated to a health insurance (aPR 1.18; CI 95%: 1.09-1.29), opposed to not having health insurance; were associated with a higher probability of CDR. Residing in the natural region of the coastal area (aPR 0.83; 95% CI: 0.74-0.92) was associated with a lower probability of relapse compared to residing in the jungle area. In people with limitations and residents of the jungle areas, the prevalence of CDR was concentrated in those with higher per capita spending. CONCLUSIONS: Approximately 1 in 6 Peruvians with chronic diseases had a relapse within the last 4 weeks prior to the survey of 2020 and certain geographic and sociodemographic factors were found to be associated with CDR. It was also found that a higher concentration of CDR was observed in the population with the highest per capita spending with some limitations, as well as in residents of the jungle, implying the need for appropriate policy interventions that address CDR with a special focus on these populations.


Subject(s)
COVID-19 , COVID-19/epidemiology , Chronic Disease , Cross-Sectional Studies , Educational Status , Female , Humans , Male , Pandemics , Peru/epidemiology , Recurrence
14.
Br J Haematol ; 199(5): 679-687, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2037915

ABSTRACT

Patients with severe aplastic anaemia (SAA) are often not vaccinated against viruses due to concerns of ineffective protective antibody response and potential for pathogenic global immune system activation, leading to relapse. We evaluated the impact of COVID-19 vaccination on haematological indices and disease status and characterized the humoural and cellular responses to vaccination in 50 SAA patients, who were previously treated with immunosuppressive therapy (IST). There was no significant difference in haemoglobin (p = 0.52), platelet count (p = 0.67), absolute lymphocyte (p = 0.42) and neutrophil (p = 0.98) counts prior to and after completion of vaccination series. Relapse after vaccination, defined as a progressive decline in counts requiring treatment, occurred in three patients (6%). Humoural response was detectable in 90% (28/31) of cases by reduction in an in-vitro Angiotensin II Converting Enzyme (ACE2) binding and neutralization assay, even in patients receiving ciclosporin (10/11, 90.1%). Comparison of spike-specific T-cell responses in 27 SAA patients and 10 control subjects revealed qualitatively similar CD4+ Th1-dominant responses to vaccination. There was no difference in CD4+ (p = 0.77) or CD8+ (p = 0.74) T-cell responses between patients on or off ciclosporin therapy at the time of vaccination. Our data highlight appropriate humoural and cellular responses in SAA previously treated with IST and true relapse after vaccination is rare.


Subject(s)
Anemia, Aplastic , COVID-19 , Humans , Anemia, Aplastic/drug therapy , Cyclosporine/therapeutic use , COVID-19 Vaccines/therapeutic use , SARS-CoV-2 , Immunosuppressive Agents/therapeutic use , COVID-19/prevention & control , Recurrence , Immunity , Vaccination
16.
Int J Environ Res Public Health ; 19(18)2022 Sep 11.
Article in English | MEDLINE | ID: covidwho-2032943

ABSTRACT

Atypical hemolytic uremic syndrome (aHUS) is a life-threatening disease causing systemic thrombotic microangiopathy (TMA) due to the fact of complement dysregulation. Immune activation by viruses, including SARS-CoV-2, can lead to the development of an episode of aHUS against a background of genetic dysregulation in the complement pathway. This paper presents an analysis of two cases of aHUS-siblings diagnosed with familial disease, with a genetic predisposition to aHUS, in whom infection with SARS-CoV-2 was a strong trigger of disease recurrence. The quick recognition and treatment with eculizumab in the early stage of the disease resulted in a rapid improvement in clinical conditions and laboratory parameters.


Subject(s)
Atypical Hemolytic Uremic Syndrome , COVID-19 , COVID-19/complications , Humans , Recurrence , SARS-CoV-2
17.
N Engl J Med ; 387(6): 495-505, 2022 08 11.
Article in English | MEDLINE | ID: covidwho-2031919

ABSTRACT

BACKGROUND: Teclistamab is a T-cell-redirecting bispecific antibody that targets both CD3 expressed on the surface of T cells and B-cell maturation antigen expressed on the surface of myeloma cells. In the phase 1 dose-defining portion of the study, teclistamab showed promising efficacy in patients with relapsed or refractory multiple myeloma. METHODS: In this phase 1-2 study, we enrolled patients who had relapsed or refractory myeloma after at least three therapy lines, including triple-class exposure to an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody. Patients received a weekly subcutaneous injection of teclistamab (at a dose of 1.5 mg per kilogram of body weight) after receiving step-up doses of 0.06 mg and 0.3 mg per kilogram. The primary end point was the overall response (partial response or better). RESULTS: Among 165 patients who received teclistamab, 77.6% had triple-class refractory disease (median, five previous therapy lines). With a median follow-up of 14.1 months, the overall response rate was 63.0%, with 65 patients (39.4%) having a complete response or better. A total of 44 patients (26.7%) were found to have no minimal residual disease (MRD); the MRD-negativity rate among the patients with a complete response or better was 46%. The median duration of response was 18.4 months (95% confidence interval [CI], 14.9 to not estimable). The median duration of progression-free survival was 11.3 months (95% CI, 8.8 to 17.1). Common adverse events included cytokine release syndrome (in 72.1% of the patients; grade 3, 0.6%; no grade 4), neutropenia (in 70.9%; grade 3 or 4, 64.2%), anemia (in 52.1%; grade 3 or 4, 37.0%), and thrombocytopenia (in 40.0%; grade 3 or 4, 21.2%). Infections were frequent (in 76.4%; grade 3 or 4, 44.8%). Neurotoxic events occurred in 24 patients (14.5%), including immune effector cell-associated neurotoxicity syndrome in 5 patients (3.0%; all grade 1 or 2). CONCLUSIONS: Teclistamab resulted in a high rate of deep and durable response in patients with triple-class-exposed relapsed or refractory multiple myeloma. Cytopenias and infections were common; toxic effects that were consistent with T-cell redirection were mostly grade 1 or 2. (Funded by Janssen Research and Development; MajesTEC-1 ClinicalTrials.gov numbers, NCT03145181 and NCT04557098.).


Subject(s)
Antibodies, Bispecific , Antineoplastic Agents, Immunological , B-Cell Maturation Antigen , CD3 Complex , Multiple Myeloma , Antibodies, Bispecific/administration & dosage , Antibodies, Bispecific/adverse effects , Antibodies, Bispecific/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Antineoplastic Agents, Immunological/administration & dosage , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , B-Cell Maturation Antigen/antagonists & inhibitors , CD3 Complex/antagonists & inhibitors , Humans , Injections, Subcutaneous , Multiple Myeloma/drug therapy , Multiple Myeloma/immunology , Multiple Myeloma/pathology , Neoplasm Recurrence, Local/drug therapy , Recurrence , T-Lymphocytes/drug effects , T-Lymphocytes/immunology
18.
Dermatol Ther ; 35(11): e15838, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2029319

ABSTRACT

Urticaria is a disease characterized by wheals and/or angioedema. Chronic spontaneous urticaria (CSU) occurs for longer than 6 weeks and appears independently of any identifiable exogenous stimulus. During the vaccination campaign for Coronavirus disease 2019 (COVID-19) pandemic, several cutaneous adverse events have been described, among which urticaria lasting less than 6 weeks (acute urticaria, AU). AU due to vaccines can be IgE or non-IgE mediated; the former typically develop within 4 h of drug exposure, the latter occurs later and the mechanism is unclear. In this retrospective study we analyzed the frequency and clinical characteristics of urticaria occurring after COVID-19 vaccine (post-vaccination urticaria relapse) in adult CSU patients treated with antihistamine and omalizumab, and in clinical remission.


Subject(s)
Anti-Allergic Agents , COVID-19 , Chronic Urticaria , Urticaria , Adult , Humans , Omalizumab/adverse effects , Chronic Urticaria/drug therapy , COVID-19 Vaccines/adverse effects , Retrospective Studies , RNA, Messenger , Anti-Allergic Agents/adverse effects , Urticaria/etiology , Urticaria/chemically induced , Histamine Antagonists/adverse effects , Chronic Disease , Recurrence , Treatment Outcome
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