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1.
JMIR Res Protoc ; 13: e56271, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842925

RESUMO

BACKGROUND: Globally, there are marked inconsistencies in how immunosuppression is characterized and subdivided into clinical risk groups. This is detrimental to the precision and comparability of disease surveillance efforts-which has negative implications for the care of those who are immunosuppressed and their health outcomes. This was particularly apparent during the COVID-19 pandemic; despite collective motivation to protect these patients, conflicting clinical definitions created international rifts in how those who were immunosuppressed were monitored and managed during this period. We propose that international clinical consensus be built around the conditions that lead to immunosuppression and their gradations of severity concerning COVID-19. Such information can then be formalized into a digital phenotype to enhance disease surveillance and provide much-needed intelligence on risk-prioritizing these patients. OBJECTIVE: We aim to demonstrate how electronic Delphi objectives, methodology, and statistical approaches will help address this lack of consensus internationally and deliver a COVID-19 risk-stratified phenotype for "adult immunosuppression." METHODS: Leveraging existing evidence for heterogeneous COVID-19 outcomes in adults who are immunosuppressed, this work will recruit over 50 world-leading clinical, research, or policy experts in the area of immunology or clinical risk prioritization. After 2 rounds of clinical consensus building and 1 round of concluding debate, these panelists will confirm the medical conditions that should be classed as immunosuppressed and their differential vulnerability to COVID-19. Consensus statements on the time and dose dependencies of these risks will also be presented. This work will be conducted iteratively, with opportunities for panelists to ask clarifying questions between rounds and provide ongoing feedback to improve questionnaire items. Statistical analysis will focus on levels of agreement between responses. RESULTS: This protocol outlines a robust method for improving consensus on the definition and meaningful subdivision of adult immunosuppression concerning COVID-19. Panelist recruitment took place between April and May of 2024; the target set for over 50 panelists was achieved. The study launched at the end of May and data collection is projected to end in July 2024. CONCLUSIONS: This protocol, if fully implemented, will deliver a universally acceptable, clinically relevant, and electronic health record-compatible phenotype for adult immunosuppression. As well as having immediate value for COVID-19 resource prioritization, this exercise and its output hold prospective value for clinical decision-making across all diseases that disproportionately affect those who are immunosuppressed. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/56271.


Assuntos
COVID-19 , Técnica Delphi , Terapia de Imunossupressão , Humanos , COVID-19/imunologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Terapia de Imunossupressão/métodos , Hospedeiro Imunocomprometido/imunologia , Consenso , Medição de Risco/métodos , SARS-CoV-2/imunologia , Adulto , Projetos de Pesquisa/normas
3.
Curr Microbiol ; 81(7): 208, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833191

RESUMO

Diabetes mellitus (DM) leads to impaired innate and adaptive immune responses. This renders individuals with DM highly susceptible to microbial infections such as COVID-19, tuberculosis and melioidosis. Melioidosis is a tropical disease caused by the bacterial pathogen Burkholderia pseudomallei, where diabetes is consistently reported as the most significant risk factor associated with the disease. Type-2 diabetes is observed in 39% of melioidosis patients where the risk of infection is 13-fold higher than non-diabetic individuals. B. pseudomallei is found in the environment and is an opportunistic pathogen in humans, often exhibiting severe clinical manifestations in immunocompromised patients. The pathophysiology of diabetes significantly affects the host immune responses that play a critical role in fighting the infection, such as leukocyte and neutrophil impairment, macrophage and monocyte inhibition and natural killer cell dysfunction. These defects result in delayed recruitment as well as activation of immune cells to target the invading B. pseudomallei. This provides an advantage for the pathogen to survive and adapt within the immunocompromised diabetic patients. Nevertheless, knowledge gaps on diabetes-infectious disease comorbidity, in particular, melioidosis-diabetes comorbidity, need to be filled to fully understand the dysfunctional host immune responses and adaptation of the pathogen under diabetic conditions to guide therapeutic options.


Assuntos
Burkholderia pseudomallei , Melioidose , Melioidose/microbiologia , Melioidose/imunologia , Humanos , Burkholderia pseudomallei/imunologia , Complicações do Diabetes/microbiologia , Diabetes Mellitus/imunologia , Diabetes Mellitus/microbiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/microbiologia , Hospedeiro Imunocomprometido
4.
BMC Infect Dis ; 24(1): 564, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844861

RESUMO

This single-centre retrospective cohort study reports on the results of a descriptive (non-comparative) retrospective cohort study of early initiation of antivirals and combined monoclonal antibody therapy (mAbs) in 48 severely immunocompromised patients with COVID-19. The study assessed the outcomes and the duration of viral shedding. The patients started early combined therapy (ECT) a median of 2 days (interquartile range [IQR]: 1-3 days) after the diagnosis of SARS-CoV-2 infection. Except for 1 patient who died due COVID-19-related respiratory failure, patients had their first negative nasopharyngeal swab result after a median of 11 days (IQR: 6-17 days) after starting combined therapy. There were no reports of severe side effects. During a follow-up period of 512 days (interquartile range [IQR]: 413-575 days), 6 patients (12.5%) died and 16 (33.3%) were admitted to hospital. Moreover, 12 patients (25%) were diagnosed with SARS-CoV-2 reinfection a median of 245 days (IQR: 138-401 days) after starting combined treatment. No relapses were reported. Although there was no comparison group, these results compare favourably with the outcomes of severely immunocompromised patients with COVID-19 reported in the literature.


Assuntos
Antivirais , Tratamento Farmacológico da COVID-19 , COVID-19 , Hospedeiro Imunocomprometido , SARS-CoV-2 , Humanos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , COVID-19/imunologia , COVID-19/mortalidade , Antivirais/uso terapêutico , Antivirais/administração & dosagem , SARS-CoV-2/imunologia , Idoso , Eliminação de Partículas Virais/efeitos dos fármacos , Quimioterapia Combinada , Adulto , Resultado do Tratamento , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/administração & dosagem
5.
Virol J ; 21(1): 130, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840177

RESUMO

BACKGROUND: Limited data is available regarding the severity and mortality of Mpox in individuals with immunocompromised conditions. Therefore, we performed this meta-analysis to understand the impact of HIV- or non-HIV-associated immunosuppression on the severity of Mpox requiring hospitalization and mortality. METHODS: A thorough literature search was performed from 2022 up to January 2024. The results were presented as odds ratios (ORs). We only included patients who required hospitalization for severity rather than isolation. RESULTS: A total of 34 studies were included in this analysis. Our analysis did not find a significant difference in the hospitalization risk between HIV-positive individuals and those who were HIV-negative (OR = 1.03; P = 0.85; 7 studies; CD4 count of fewer than 200 cells/µL was less than 0.5% across all studies). Patients with a CD4 count lower than 200 cells/µL or an unsuppressed RNA viral load (> 200 copies/ml) had a significantly higher hospitalization risk (OR = 5.3, P < 0.001) and (OR = 3, P < 0.001), respectively. Most of the reported deaths were reported in patients with HIV with CD4 counts below 200 cells/µL, with some fatal cases occurring in non-HIV immunosuppressed patients, particularly organ transplant recipients. Based on the autopsy findings, Mpox was confirmed in multiple organs, particularly the digestive tract, lung, and testes. Furthermore, some studies documented cases of death that were suspected to be related to hemophagocytic lymphohistiocytosis (HLH) and immune reconstitution inflammatory syndrome (IRIS). Most of the death reports showed concomitant non-Mpox infections at the time of hospitalization and death CONCLUSIONS: Our finding shows that Mpox acts as an opportunistic pathogen in immunocompromised individuals. These individuals should be prioritized for early care and closely monitored for signs of deteriorating clinical conditions. Clinical manifestations and autopsy findings strongly suggest Mpox dissemination to multiple organs, particularly the digestive tract, and lungs. However, the presence of concomitant non-Mpox infections complicates the assessment of the attribution of Mpox to death. Caution should be exercised when interpreting data suggesting poorer outcomes in individuals with non-HIV immunosuppression, as current evidence is scarce and further research is needed.


Assuntos
Infecções por HIV , Hospitalização , Hospedeiro Imunocomprometido , Mpox , Humanos , Hospitalização/estatística & dados numéricos , Infecções por HIV/mortalidade , Infecções por HIV/complicações , Infecções por HIV/imunologia , Contagem de Linfócito CD4 , Mpox/epidemiologia , Mpox/mortalidade , Surtos de Doenças , Terapia de Imunossupressão/efeitos adversos , Carga Viral
6.
BMC Med ; 22(1): 237, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858672

RESUMO

BACKGROUND: Immunocompromised individuals are at increased risk of severe COVID-19 outcomes, underscoring the importance of COVID-19 vaccination in this population. The lack of comprehensive real-world data on vaccine uptake, effectiveness and safety in these individuals presents a critical knowledge gap, highlighting the urgency to better understand and address the unique challenges faced by immunocompromised individuals in the context of COVID-19 vaccination. METHODS: We analysed data from 12,274,946 people in the UK aged > 12 years from 01/12/2020 to 11/04/2022. Of these, 583,541 (4.8%) were immunocompromised due to immunosuppressive drugs, organ transplants, dialysis or chemotherapy. We undertook a cohort analysis to determine COVID-19 vaccine uptake, nested case-control analyses adjusted for comorbidities and sociodemographic characteristics to determine effectiveness of vaccination against COVID-19 hospitalisation, ICU admission and death, and a self-controlled case series assessing vaccine safety for pre-specified adverse events of interest. RESULTS: Overall, 93.7% of immunocompromised individuals received at least one COVID-19 vaccine dose, with 80.4% having received three or more doses. Uptake reduced with increasing deprivation (hazard ratio [HR] 0.78 [95%CI 0.77-0.79] in the most deprived quintile compared to the least deprived quintile for the first dose). Estimated vaccine effectiveness against COVID-19 hospitalisation 2-6 weeks after the second and third doses compared to unvaccinated was 78% (95%CI 72-83) and 91% (95%CI 88-93) in the immunocompromised population, versus 85% (95%CI 83-86) and 86% (95%CI 85-89), respectively, for the general population. Results showed COVID-19 vaccines were protective against intensive care unit (ICU) admission and death in both populations, with effectiveness of over 92% against COVID-19-related death and up to 95% in reducing ICU admissions for both populations following the third dose. COVID-19 vaccines were generally safe for immunocompromised individuals, though specific doses of ChAdOx1, mRNA-1273 and BNT162b2 raised risks of specific cardiovascular/neurological conditions. CONCLUSIONS: COVID-19 vaccine uptake is high in immunocompromised individuals on immunosuppressive drug therapy or who have undergone transplantation procedures, with documented disparities by deprivation. Findings suggest that COVID-19 vaccines are protective against severe COVID-19 outcomes in this vulnerable population, and show a similar safety profile in immunocompromised individuals and the general population, despite some increased risk of adverse events. These results underscore the importance of ongoing vaccination prioritisation for this clinically at-risk population to maximise protection against severe COVID-19 outcomes.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Hospedeiro Imunocomprometido , Imunossupressores , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , COVID-19/prevenção & controle , COVID-19/epidemiologia , Adulto , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/administração & dosagem , Idoso , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Estudos de Coortes , Inglaterra/epidemiologia , Adolescente , Adulto Jovem , SARS-CoV-2/imunologia , Estudos de Casos e Controles , Eficácia de Vacinas , Vacinação , Criança , Idoso de 80 Anos ou mais
7.
Artigo em Inglês | MEDLINE | ID: mdl-38865572

RESUMO

Hyalohyphomycosis and phaeohyphomycosis are groups of mycoses caused by several agents and show different clinical manifestations. We report a case of an immunocompromised patient who presented rare manifestations of opportunistic mycoses: mycetoma-like hyalohyphomycosis on his right foot caused by Colletotrichum gloeosporioides, followed by cutaneous phaeohyphomycosis on his right forearm caused by Exophiala oligosperma. Further to the rarity of this case, the patient's lesion on the foot shows that the clinical aspects of mycetomas could falsely appear in other fungal infections similar to hyalohyphomycosis. We also show that the muriform cells that were seen in the direct and anatomopathological examination of the skin are not pathognomonic of chromoblastomycosis, as observed in the lesion of the patient's forearm.


Assuntos
Cromoblastomicose , Micetoma , Humanos , Masculino , Cromoblastomicose/patologia , Cromoblastomicose/diagnóstico , Cromoblastomicose/microbiologia , Cromoblastomicose/tratamento farmacológico , Micetoma/patologia , Micetoma/microbiologia , Micetoma/diagnóstico , Micetoma/tratamento farmacológico , Diagnóstico Diferencial , Hospedeiro Imunocomprometido , Hialoifomicose/patologia , Hialoifomicose/microbiologia , Hialoifomicose/diagnóstico , Exophiala/isolamento & purificação , Pessoa de Meia-Idade
10.
BMJ Case Rep ; 17(6)2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890117

RESUMO

Actinomycosis is a rare endogenous infection characterised by indolent progression, contiguous spreading, abscess formation and draining sinuses. Here, we present a case of Schaalia odontolytica causing a mediastinal abscess that is unique in its acuity and location. Our patient presented with worsening dysphagia, and CT of her chest revealed a new mass in the posterior mediastinum displacing the oesophagus. Oesophagram revealed mild motility disorder, but no masses or ulcers within the oesophagus. Oesophagogastroduodenoscopy with endoscopic ultrasound revealed extrinsic compression of the oesophagus. Fine-needle aspiration of the mass yielded purulent fluid, which was cultured. A single colony of S. odontolytica was isolated. Initially, medical treatment was favoured, but as she developed worsening dysphagia, the abscess was drained. She continued on long-term antibiotic therapy after drainage and had complete resolution of the abscess at 1 year.


Assuntos
Actinomicose , Transtornos de Deglutição , Hospedeiro Imunocomprometido , Doenças do Mediastino , Humanos , Feminino , Actinomicose/diagnóstico , Actinomicose/complicações , Actinomicose/tratamento farmacológico , Transtornos de Deglutição/etiologia , Doenças do Mediastino/diagnóstico , Diagnóstico Diferencial , Abscesso/diagnóstico , Abscesso/microbiologia , Antibacterianos/uso terapêutico , Tomografia Computadorizada por Raios X , Drenagem , Pessoa de Meia-Idade , Mediastino
11.
PLoS Negl Trop Dis ; 18(6): e0012232, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38843299

RESUMO

BACKGROUND: Ocular toxoplasmosis (OT) is the most common cause of infectious uveitis worldwide, including Thailand. This study describes the clinical presentation, visual acuity (VA) outcomes, and factors associated with VA loss in patients with active OT following antiparasitic treatment. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective chart review of patients with active OT treated with antiparasitic drugs between 2010 and 2020 was performed. Outcome measures included clinical characteristics, interval VA, and predictive factors associated with loss of VA ≤ 20/50 at 6 months post-treatment. Ninety-two patients (95 eyes) were enrolled. The median follow-up time was 10.9 months (IQR 4.9-31.8 months). The median age at presentation was 35.9 years, 51% were male, and 92.4% had unilateral OT. Eleven patients (12%) were immunocompromised (HIV infection, eight patients; receiving immunosuppressive agents, three patients). Patients mainly presented with primary retinitis without previous scar (62%), posterior pole lesion (56%), and lesion size of ≤ 2-disc area (75%). Immunocompromised patients showed a significantly larger size of retinitis than immunocompetent patients. Oral trimethoprim/sulfamethoxazole monotherapy was the primary short-term antiparasitic drug prescribed (85%). At the final visit, 21% of all affected eyes suffered VA ≤ 20/200. The cumulative incidence of recurrent OT at three years was 33.9% (95% CI, 19.7%-54.2%). Immunocompromised patients [adjusted odds ratio (aOR) 4.9, p = 0.041], macular lesion (aOR 5.4, p = 0.032), and initial VA ≤ 20/200 (aOR 9.1, p = 0.014) were predictive of having VA ≤ 20/50 at 6 months post-treatment. CONCLUSIONS: Ocular toxoplasmosis mainly presents as unilateral primary retinitis within the posterior pole. Severe VA loss was observed in one-fifth of eyes following treatment with lesion resolution. Immunocompromised patients, eyes with macular lesions, and poor initial VA were associated with poor VA outcomes.


Assuntos
Centros de Atenção Terciária , Toxoplasmose Ocular , Acuidade Visual , Humanos , Toxoplasmose Ocular/tratamento farmacológico , Toxoplasmose Ocular/fisiopatologia , Toxoplasmose Ocular/complicações , Toxoplasmose Ocular/epidemiologia , Masculino , Estudos Retrospectivos , Adulto , Feminino , Tailândia/epidemiologia , Pessoa de Meia-Idade , Centros de Atenção Terciária/estatística & dados numéricos , Adulto Jovem , Hospedeiro Imunocomprometido , Antiparasitários/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Adolescente , Resultado do Tratamento , População do Sudeste Asiático
12.
BMC Infect Dis ; 24(1): 605, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898444

RESUMO

BACKGROUND PAECILOMYCES: and Penicillium are considered as rare opportunistic pathogens in immunocompromised hosts, and pneumonia caused by Paecilomyces and Penicillium is rare. In this study, we present first case of severe pneumonia with pleural effusion caused by co-infection of Paecilomyces variotii (P. variotii) and Penicillium oxalicum (P. oxalicum) in a 66-year-old female with poorly controlled type 2 diabetes. CASE PRESENTATION: A 56-year-old woman patient presented to hospital for nausea, poor appetite, and vomiting for one day. On the second day of admission, blood culture and renal puncture fluid culture grew multidrug-resistant Escherichia coli (imipenem/cilastatin sensitive), and she received combination therapy with imipenem/cilastatin (1 g, every 8 h) and vancomycin (0.5 g, every 12 h). On the fourth day, she developed symptoms of respiratory failure. Pulmonary computed tomography (CT) showed an increase in pneumonia compared to before, with minor pleural effusion on both sides. Two fungi were isolated repeatedly from BALF culture, which were confirmed as P. variotii and P. oxalicum by Internal transcribed spacer (ITS) sequencing. Her pleural effusion was completely absorbed, pneumonia symptoms have significantly improved and discharged with receiving liposomal amphotericin B treatment for four weeks. CONCLUSIONS: It is worth noting that clinicians and laboratory personnel should not simply consider Paecilomyces and Penicillium species as contaminants, especially in immunocompromised patients. Early fungal identification and antifungal drug sensitivity are crucial for clinical drug selection and patient prognosis.


Assuntos
Coinfecção , Diabetes Mellitus Tipo 2 , Paecilomyces , Penicillium , Derrame Pleural , Humanos , Feminino , Penicillium/isolamento & purificação , Derrame Pleural/microbiologia , Derrame Pleural/tratamento farmacológico , Pessoa de Meia-Idade , Idoso , Diabetes Mellitus Tipo 2/complicações , Coinfecção/microbiologia , Coinfecção/tratamento farmacológico , Paecilomyces/isolamento & purificação , Pneumonia/microbiologia , Pneumonia/tratamento farmacológico , Micoses/microbiologia , Micoses/tratamento farmacológico , Hospedeiro Imunocomprometido , Antibacterianos/uso terapêutico , Antifúngicos/uso terapêutico
13.
BMJ Case Rep ; 17(6)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38901854

RESUMO

Non-hepatic causes of hyperammonaemia are uncommon relative to hepatic aetiologies. An adolescent female was admitted to the hospital with a diagnosis of very severe aplastic anaemia. During her treatment with immunosuppressive therapy, she developed neutropenic enterocolitis, pseudomonal bacteraemia and hyperammonaemia. A combination of intermittent haemodialysis and high-volume continuous veno-venous haemodiafiltration (CVVHDF) was required to manage the hyperammonaemia. Despite a thorough investigation, there were no hepatic, metabolic or genetic aetiologies identified that explained the hyperammonaemia. The hyperammonaemia resolved only after the surgical resection of her inflamed colon, following which she was successfully weaned off from the renal support. This is a novel case report of hyperammonaemia of non-hepatic origin secondary to widespread inflammation of the colon requiring surgical resection in an immunocompromised patient. This case also highlights the role of high-volume CVVHDF in augmenting haemodialysis in the management of severe refractory hyperammonaemia.


Assuntos
Hiperamonemia , Hospedeiro Imunocomprometido , Humanos , Feminino , Hiperamonemia/terapia , Hiperamonemia/etiologia , Adolescente , Enterocolite/terapia , Enterocolite/diagnóstico , Diálise Renal , Encefalopatias/etiologia , Enterocolite Neutropênica/complicações
14.
J Infect Public Health ; 17(7): 102473, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38865774

RESUMO

BACKGROUND: Cancer patients often have weakened immune systems, resulting in a lower response to vaccines, especially those receiving immunosuppressive oncological treatment (OT). We aimed to assess the impact of OT on the humoral and T-cell response to the B.1 lineage and Omicron variant following COVID-19 vaccination in patients with solid and hematological neoplasms. METHODS: We conducted a prospective study on cancer patients, stratified into OT and non-OT groups, who received a two-dose series of the COVID-19 mRNA vaccine and a booster six months later. The outcomes measured were the humoral (anti-SARS-CoV-2 S IgG titers and ACE2-S interaction inhibition capacity) and cellular (SARS-CoV-2 S-specific T-cell spots per million PBMCs) responses against the B.1 lineage and Omicron variant. These responses were evaluated four weeks after the second dose (n = 98) and eight weeks after the booster dose (n = 71). RESULTS: The humoral response after the second vaccine dose against the B.1 lineage and Omicron variant was significantly weaker in the OT group compared to the non-OT group (q-value<0.05). A booster dose of the mRNA-1273 vaccine significantly improved the humoral response in the OT group, making it comparable to the non-OT group. The mRNA-1273 vaccine, designed for the original Wuhan strain, elicited a weaker humoral response against the Omicron variant compared to the B.1 lineage, regardless of oncological treatment or vaccine dose. In contrast, T-cell responses against SARS-CoV-2, including the Omicron variant, were already present after the second vaccine dose and were not significantly affected by oncological treatments. CONCLUSIONS: Cancer patients, particularly those receiving immunosuppressive oncological treatments, should require booster doses and adapted COVID-19 vaccines for new SARS-CoV-2 variants like Omicron. Future studies should evaluate the durability of the immune response and the efficacy of individualized regimens.


Assuntos
Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Neoplasias , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , Estudos Prospectivos , Masculino , COVID-19/imunologia , COVID-19/prevenção & controle , Feminino , Pessoa de Meia-Idade , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Glicoproteína da Espícula de Coronavírus/imunologia , SARS-CoV-2/imunologia , Idoso , Neoplasias/imunologia , Anticorpos Antivirais/sangue , Linfócitos T/imunologia , Imunização Secundária , Vacinação , Adulto , Imunidade Humoral , Imunoglobulina G/sangue , Hospedeiro Imunocomprometido , Imunidade Celular
15.
Viruses ; 16(5)2024 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-38793590

RESUMO

Due to immunosuppression, transplant recipients are at higher risk of infections with SARS-CoV-2 and worse clinical outcomes than immunocompetent hosts. Furthermore, lung transplant patients represent a special group among solid organ recipients, since pneumonia is the main manifestation of COVID-19. However, data on the course of disease and the changes in morbidity and mortality during the course of the pandemic are limited. In our pulmonary rehabilitation clinic, we treat patients shortly after lung transplant as well as long-term transplant patients. Over the last almost 4 years of pandemic, we witnessed several COVID-19 infections in lung transplant patients in our clinic as well as patients who acquired an infection beforehand. In this paper, we aim at retrospectively describing a series of recent COVID-19 cases in our clinic, looking at the clinical course of disease and outcomes in lung transplant patients.


Assuntos
COVID-19 , Transplante de Pulmão , SARS-CoV-2 , Transplantados , Humanos , COVID-19/epidemiologia , Transplante de Pulmão/efeitos adversos , Pessoa de Meia-Idade , Masculino , Feminino , Estudos Retrospectivos , Idoso , Adulto , Hospedeiro Imunocomprometido
16.
Viruses ; 16(5)2024 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-38793600

RESUMO

Although the coronavirus disease 2019 (COVID-19) pandemic is coming to an end, it still poses a threat to the immunocompromised and others with underlying diseases. Especially in cases of persistent COVID-19, new mutations conferring resistance to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) therapies have considerable clinical implications. We present a patient who independently acquired a T21I mutation in the 3CL protease after nirmatrelvir exposure. The T21I mutation in the 3CL protease is one of the most frequent mutations responsible for nirmatrelvir resistance. However, limited reports exist on actual cases of SARS-CoV-2 with T21I and other mutations in the 3CL protease. The patient, a 55 year-old male, had COVID-19 during chemotherapy for multiple myeloma. He was treated with nirmatrelvir early in the course of the disease but relapsed, and SARS-CoV-2 with a T21I mutation in the 3CL protease was detected in nasopharyngeal swab fluid. The patient had temporary respiratory failure but later recovered well. During treatment with remdesivir and dexamethasone, viruses with the T21I mutation in the 3CL protease showed a decreasing trend during disease progression while increasing during improvement. The impact of drug-resistant SARS-CoV-2 on the clinical course, including its severity, remains unknown. Our study is important for examining the clinical impact of nirmatrelvir resistance in COVID-19.


Assuntos
Antivirais , COVID-19 , Farmacorresistência Viral , Hospedeiro Imunocomprometido , SARS-CoV-2 , Humanos , Pessoa de Meia-Idade , Masculino , SARS-CoV-2/genética , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/imunologia , Farmacorresistência Viral/genética , Antivirais/uso terapêutico , Antivirais/farmacologia , COVID-19/imunologia , COVID-19/virologia , Mutação , Mieloma Múltiplo/tratamento farmacológico , Proteases 3C de Coronavírus/genética , Tratamento Farmacológico da COVID-19 , Alanina/análogos & derivados , Alanina/uso terapêutico
17.
Lupus ; 33(8): 797-803, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38709545

RESUMO

Cytomegalovirus (CMV) infection and disease is a condition usually described in immunocompromised patients, but among them, those with connective tissue diseases are poorly represented. Here we present the clinical, laboratory characteristics, management and outcomes of systemic lupus erythematosus (SLE) patients who presented with a CMV infection/disease to a high complexity hospital in southwestern Colombia between 2011 and 2020. 16 SLE patients were found to have a CMV infection. SLE was predominantly characterized by renal involvement (10 patients; 62.50%), and 14 patients (87.5%) were receiving steroids previous to the CMV infection. The entire sample required hospital admission, mainly related to acute kidney injury, and nine patients were admitted to the intensive care unit (ICU). Gastrointestinal organ damage was the most common CMV disease manifestation. All patients received ganciclovir, five of them (31.25%) suffered from septic shock, and seven (43.75%) died. Age ≥38 years and the presence of septic shock at admission were correlated to the mortality outcome. To our knowledge, this is the first publication evaluating SLE patients with CMV infection/disease in a Colombian population.


Assuntos
Infecções por Citomegalovirus , Lúpus Eritematoso Sistêmico , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/epidemiologia , Colômbia/epidemiologia , Feminino , Adulto , Masculino , Pessoa de Meia-Idade , Antivirais/uso terapêutico , Adulto Jovem , Ganciclovir/uso terapêutico , Hospedeiro Imunocomprometido , Choque Séptico/etiologia , Estudos Retrospectivos , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/epidemiologia , Hospitalização/estatística & dados numéricos , Unidades de Terapia Intensiva/estatística & dados numéricos
18.
Mycoses ; 67(5): e13749, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38782759

RESUMO

BACKGROUND: Coccidioidomycosis is a systemic fungal disease endemic to arid regions of the Western Hemisphere. In the south-western US, Coccidioides spp. may account for up to 20%-25% of all cases of community acquired pneumonia. Clinical manifestations vary widely, from asymptomatic infection to life-threatening disease, especially in immunocompromised hosts. OBJECTIVES: The primary objective of the study was to characterise cases of coccidioidomycosis in an area of the United States not considered traditionally endemic for the disease. METHODS: We performed a single-centre retrospective study of all cases of coccidioidomycosis from 1 January 2000 to 31 December 2020, in the University of Oklahoma Health Sciences Medical Center. RESULTS: A total of 26 patients were included for analysis. The central nervous system (CNS) and the lungs were the sites most frequently involved. Twenty (77%) had travelled to a coccidioidomycosis endemic region. Most were male (81%) with a median age of 42 years (range: 3-78 years). The majority (46%) were Caucasians, 19% were African American, 19% Hispanic, and 12% Native American. The most common comorbidities were diabetes mellitus and acquired immunodeficiency syndrome, identified in 27% and 23% of patients, respectively. Patients on immunosuppressive therapy accounted for 12% of all cases. CONCLUSION: Our study is one of the largest single-centre case series of coccidioidomycosis from a non-endemic area. Diabetes mellitus was the most frequent comorbidity. Compared to other case series of coccidioidomycosis, our patient population had higher rates of immunosuppression and had both a higher rate of disseminated disease and overall mortality.


Assuntos
Coccidioidomicose , Humanos , Coccidioidomicose/epidemiologia , Coccidioidomicose/microbiologia , Coccidioidomicose/tratamento farmacológico , Estudos Retrospectivos , Oklahoma/epidemiologia , Pessoa de Meia-Idade , Masculino , Feminino , Adulto , Idoso , Adolescente , Adulto Jovem , Criança , Pré-Escolar , Hospedeiro Imunocomprometido , Coccidioides/isolamento & purificação , Comorbidade
19.
J Int Med Res ; 52(5): 3000605241239857, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38757522

RESUMO

Fungal orbital cellulitis is usually seen in immunocompromised individuals, and opportunistic pathogens are the main etiology. We herein report a case of fungal orbital cellulitis due to Aspergillus in a patient with no history of trauma. A 48-year-old man presented to the emergency room of our hospital with a 2-week history of periorbital swelling, conjunctival hyperemia, and chemosis of his right eye. The visual acuity of his right eye was 6/20, and the intraocular pressure was 44 mmHg. The main clinical findings were proptosis of the right ocular globe with conjunctival hyperemia and a palpable infratemporal orbital mass. Laboratory testing failed to detect the presence of a pathogenic infection, and the lesions on computed tomography images resembled those of a malignant tumor of the orbit. The diagnosis was finally confirmed by postoperative pathological examination, and the patient responded favorably to debridement combined with antifungal therapy. Histopathological examination may help to reveal the nature of this disease. Surgical removal of inflammatory lesions can serve as an important diagnostic and treatment method for fungal orbital cellulitis.


Assuntos
Antifúngicos , Aspergilose , Hospedeiro Imunocomprometido , Tomografia Computadorizada por Raios X , Humanos , Masculino , Pessoa de Meia-Idade , Aspergilose/diagnóstico , Aspergilose/complicações , Aspergilose/microbiologia , Aspergilose/imunologia , Antifúngicos/uso terapêutico , Celulite Orbitária/microbiologia , Celulite Orbitária/diagnóstico , Desbridamento , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/microbiologia
20.
Lancet Rheumatol ; 6(6): e339-e351, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38734019

RESUMO

BACKGROUND: The humoral and T-cell responses to booster COVID-19 vaccine types in multidisease immunocompromised individuals who do not generate adequate antibody responses to two COVID-19 vaccine doses, is not fully understood. The OCTAVE DUO trial aimed to determine the value of third vaccinations in a wide range of patients with primary and secondary immunodeficiencies. METHODS: OCTAVE-DUO was a prospective, open-label, multicentre, randomised, controlled, phase 3 trial investigating humoral and T-cell responses in patients who are immunocompromised following a third vaccine dose with BNT162b2 or mRNA-1273, and of NVX-CoV2373 for those with lymphoid malignancies. We recruited patients who were immunocompromised from 11 UK hospitals, aged at least 18 years, with previous sub-optimal responses to two doses of SARS-CoV-2 vaccine. Participants were randomly assigned 1:1 (1:1:1 for those with lymphoid malignancies), stratified by disease, previous vaccination type, and anti-spike antibody response following two doses. Individuals with lived experience of immune susceptibility were involved in the study design and implementation. The primary outcome was vaccine-specific immunity defined by anti-SARS-CoV-2 spike antibodies (Roche Diagnostics UK and Ireland, Burgess Hill, UK) and T-cell responses (Oxford Immunotec, Abingdon, UK) before and 21 days after the third vaccine dose analysed by a modified intention-to-treat analysis. The trial is registered with the ISRCTN registry, ISRCTN 15354495, and the EU Clinical Trials Register, EudraCT 2021-003632-87, and is complete. FINDINGS: Between Aug 4, 2021 and Mar 31, 2022, 804 participants across nine disease cohorts were randomly assigned to receive BNT162b2 (n=377), mRNA-1273 (n=374), or NVX-CoV2373 (n=53). 356 (45%) of 789 participants were women, 433 (55%) were men, and 659 (85%) of 775 were White. Anti-SARS-CoV-2 spike antibodies measured 21 days after the third vaccine dose were significantly higher than baseline pre-third dose titres in the modified intention-to-treat analysis (median 1384 arbitrary units [AU]/mL [IQR 4·3-7990·0] compared with median 11·5 AU/mL [0·4-63·1]; p<0·001). Of participants who were baseline low responders, 380 (90%) of 423 increased their antibody concentrations to more than 400 AU/mL. Conversely, 166 (54%) of 308 baseline non-responders had no response after the third dose. Detectable T-cell responses following the third vaccine dose were seen in 494 (80%) of 616 participants. There were 24 serious adverse events (BNT612b2 eight [33%] of 24, mRNA-1273 12 [50%], NVX-CoV2373 four [17%]), two (8%) of which were categorised as vaccine-related. There were seven deaths (1%) during the trial, none of which were vaccine-related. INTERPRETATION: A third vaccine dose improved the serological and T-cell response in the majority of patients who are immunocompromised. Individuals with chronic renal disease, lymphoid malignancy, on B-cell targeted therapies, or with no serological response after two vaccine doses are at higher risk of poor response to a third vaccine dose. FUNDING: Medical Research Council, Blood Cancer UK.


Assuntos
Vacina BNT162 , Vacinas contra COVID-19 , COVID-19 , Hospedeiro Imunocomprometido , Imunogenicidade da Vacina , SARS-CoV-2 , Humanos , Feminino , Masculino , COVID-19/prevenção & controle , COVID-19/imunologia , Pessoa de Meia-Idade , Hospedeiro Imunocomprometido/imunologia , SARS-CoV-2/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Idoso , Vacina BNT162/imunologia , Vacina BNT162/administração & dosagem , Anticorpos Antivirais/sangue , Estudos Prospectivos , Imunização Secundária , Vacina de mRNA-1273 contra 2019-nCoV/imunologia , Adulto , Linfócitos T/imunologia , Reino Unido , ChAdOx1 nCoV-19/imunologia
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