Implication of IL-12A, IL-12B, IL-6, and TNF single-nucleotide polymorphisms in severity and susceptibility to COVID-19.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) pandemic has led to significant global morbidity and mortality. Understanding the genetic factors that influence disease outcomes can provide critical insights into pathogenesis and potential therapeutic targets. OBJECTIVE: This study aimed to investigate the potential correlation between single nucleotide polymorphisms (SNPs) in Interleukin 12 Subunit Alpha (IL-12A), Interleukin 12 Subunit Beta (IL-12B), Interleukin 6 (IL-6), and Tumor Necrosis Factor (TNF) genes and the severity as well as susceptibility to COVID-19 among Moroccan patients. PATIENTS AND METHODS: Next-Generation sequencing (NGS) was conducted on 325 Moroccan participants, 207 patients with PCR-confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and 118 controls. Among these patients, 51% presented moderate to severe symptoms requiring hospitalization, while 49% were asymptomatic or experienced mild symptoms and did not require hospitalization. Statistical analysis was performed using codominant, dominant, and recessive logistic regression models to assess correlations with the severity and susceptibility to COVID-19 infection. RESULTS: No association was found between SNPs of IL-12A, IL-12B, IL-6 or TNF and COVID-19 severity and susceptibility. However, our results unveiled a noteworthy association with IL-6 rs2069840, which exhibited a negative correlation (OR = 0.21, 95% CI = 0.07-0.69, p = .006), suggesting a protective effect against SARS-CoV-2 infection. CONCLUSION: Polymorphisms in IL-12A, IL-12B, IL-6, and TNF genes are not correlated to the severity and susceptibility of COVID-19.

TYK2, IFITM3, IFNAR2 and OAS3 single-nucleotide polymorphisms among severe COVID-19 ICU patients in Morocco.

OBJECTIVES: This study aimed to explore the potential correlation between specific single nucleotide polymorphisms (TYK2, IFITM3, IFNAR2, and OAS3 variants) and the severity of COVID-19 in Moroccan patients. METHODS: A genetic analysis was conducted on 109 patients with PCR-confirmed SARS-CoV-2 infection in Morocco. Among these patients, 46% were hospitalized in the intensive care unit, while 59% were not hospitalized. Importantly, all patients lacked known risk factors associated with COVID-19 severity. Genotyping was performed to identify variations in TYK2 rs74956615, IFITM3 rs12252, IFNAR2 rs2236757, and OAS3 rs10735079. Statistical analysis was applied using codominant, dominant and recessive logistic regression models to assess correlations with COVID-19 severity. RESULTS: Our findings revealed no significant correlation between TYK2 rs74956615, IFITM3 rs12252, IFNAR2 rs2236757, and OAS3 rs10735079 with COVID-19 severity in Moroccan patients, as indicated in logistic regression models (p > .05). Interestingly, these results may offer insights into the mitigated impact of the COVID-19 pandemic and the reduced severity observed in SARS-CoV-2 infected patients in Morocco. Age, however, exhibited a significant correlation with severity (p < .001), with a trend towards increased likelihood of ICU admission with advancing age. Additionally, In the severe group, a higher proportion of patients were females (54%), indicating a statistically significant correlation with disease severity (p = .04). Nevertheless, female ICU patients aged above 60 years accounted for 37%, compared to 17% for males. CONCLUSION: This study underscores the absence of a genetic association between the selected polymorphisms and COVID-19 severity in Moroccan patients. Advanced age emerges as the primary factor influencing the severity of COVID-19 patients without comorbidities. We recommend setting the threshold for advanced age at 60 years as a risk factor for severe forms of COVID-19.

C-Reactive Protein, Ferritin, and Procalcitonin in 300 Moroccan Patients with COVID 19.

BACKGROUND: COVID-19 is a true global pandemic since March 2020, and it is responsible in the majority of patients mild symptoms; however, a small number of patients progress to the severe form with acute respiratory distress syndrome (ARDS) and some of them progress to the very severe form which can be fatal when it comes to multiorgan failure. Thus, it is important to identify as early as possible patients at high risk of progressing to severe forms requiring early and specialized management in order to reduce mortality. METHODS: Our five-month retrospective study (May 2020 - October 2020) included 300 SARS-CoV-2 patients confirmed by RT-PCR and hospitalized in the Infectious and Tropical Diseases Center (CMIT), and in the Intensive Care Unit of the Military Hospital of instructions Mohamed V of Rabat (Morocco). Our objective was to compare the levels of C-reactive protein (CRP), ferritin, and procalcitonin (PCT) according to the clinical state and prog-nosis of patients. RESULTS: In our series of results, very significantly elevated levels of C-reactive protein, ferritin, and procalcitonin were associated with severe and very severe forms of COVID-19 disease as well as a poor prognosis. CONCLUSIONS: In the absence of international recommendations, the validation of clinical-biological scores involving different biological parameters in COVID-19 patients would allow a standardization of practices, a correct prescription of biological analyses and a risk stratification allowing to palliate the lack of medical resources and thus to reduce mortality.

Relapsing fever in a Moroccan man.

Tick-borne relapsing fever is a zoonosis caused by spirochetes of the genus Borrelia, transmitted by hematophagous ticks. This life-threatening condition is still misdiagnosed. We report a case of tick-borne relapsing fever in a 54 year-old man in Morocco with a history of hiking, who was hospitalized for an isolated fever. On admission, the clinical examination showed no specific signs. The laboratory assessment showed inflammatory syndrome with disturbance of the liver function. The blood culture was sterile. Serology was negative for HIV and Lyme disease, as were all the rest of the paraclinical tests. The patient's course was marked by spontaneous resolution of the fever and then, seven days later, the onset of a new episode of fever. Malaria was suspected and a blood sample was sent to the parasitology department. The thick smear and blood smear stained with May-Grünwald Giemsa showed the presence of spirochetes. Tick-borne relapsing fever was diagnosed and the patient responded favorably to treatment by cycline drugs. This disease is poorly known and should be considered in cases of presence of intermittent fever without a specific clinical-laboratory picture, according to epidemiological context. The diagnosis is confirmed by the presence of spirochetes on thick smear and blood or cerebrospinal fluid smear stained with MGG.

Pulmonary hypertension and von Recklinghausen's disease: association and therapeutic difficulties.

The neurofibromatosis type 1 (NF1) or Von Recklinghausen's disease is a genetic disorder. The café-au-lait spots and neurofibromas are the most common manifestations. Respiratory symptoms are rare in this disease, described as neurofibromas, infiltrative lesions, cysts, bubbles or emphysema. Pulmonary hypertension is rarely reported. It is due to the plexiform lesions in pulmonary arterioles or to parenchymal lung lesions reducing the vascular bed. We report a case of idiopathic precapillary pulmonary hypertension in a young patient with Von Recklinghausen's disease.

[Pulmonary nocardiosis and sarcoidosis]. / Nocardiose pulmonaire et sarcoïdose.

Infectious complications are rarely observed in the course of sarcoidosis. Only small series or cases reports of infection are described in sarcoidosis. Corticosteroids-induced immune suppression, pulmonary fibrosis and T-CD4 lymphopenia, are often present. Pulmonary nocardiosis is an important cause of opportunistic infection in immunosuppressed patients, and the incidence of this infection is increasing. Pulmonary nocardiosis manifests as an acute, subacute or chronic infection with a marked tendency towards remissions and exacerbations. We report a case of pulmonary nocardiosis in a patient with sarcoidosis followed for pulmonary fibrosis receiving corticosteroids. During the investigation of pyrexia and dyspnea, evidence of Nocardia spp. infection was found in the bronchial secretions. Six months of trimethoprim/sulfamethoxazole therapy ensured further resolution of this pleuropulmonary infection. Pulmonary nocardiosis is exceptional in sarcoidosis and mainly occur, in patients receiving corticosteroids, and with CD4+ T-lymphocytopenia. Sarcoidosis by itself does not appear to be a risk factor of opportunistic infection.

[Malaria in the United Nations troops in the Democratic Republic of the Congo during 2005]. / Importance du paludisme au sein des troupes Onusiennes en République Démocratique du Congo, 2005.

This prospective study examined malaria among United Nations troops participating in Operation MONUC in the town of Bunia in the Democratic Republic of Congo from April through October, 2005. Of 245 soldiers hospitalized, 105 were diagnosed with malaria, 93.6% with Plasmodium falciparum. All but one were men, and their median age was 43.5 years (range:29-52 years). South African (40/105) and Moroccan (22/105) soldiers accounted for the majority. Cases were collected mainly from May through July.

[Adult refractory Still disease with atypical articular manifestations: efficacity of interleukin-6 antagonists (tocilizumab)]. / Atteintes articulaires atypiques au cours d'une maladie de Still de l'adulte réfractaire : efficacité des antagonistes de l'interleukine-6 (tocilizumab).

INTRODUCTION: Tocilizumab is a humanized monoclonal antibody directed against interleukin-6 receptor and is beginning to be reported as effective in some cases of Still's disease refractory in adults (ASD). ASD is rare, heterogeneous, with unpredictable evolution. The distal destructive arthritis represents a possible complication. PATIENT: We report an unusual case of adult-onset Still's disease with severe distal interphalangeal destructive arthritis with refractory early and prolonged remission after the first tocilizumab infusion. CONCLUSION: Tocilizumab can be used in patients with refractory ASD after failure or intolerance of conventional treatments.

Pandemic influenza A(H1N1)2009 in Morocco: experience of the Mohammed V Military Teaching Hospital, Rabat, 12 June to 24 December 2009.

On 12 June 2009, Morocco was the first country in North Africa to report a laboratory-confirmed case of influenza A(H1N1)2009 virus infection. This study describes the epidemiological and clinical characteristics of 240 laboratory-confirmed cases among 594 outpatients with influenza-like illness at the Mohammed V Military Teaching Hospital, Rabat, from 12 June to 24 December 2009. Real-time reverse transcription-PCR was used to confirm the infection. The epidemic peaked in weeks 47 to 49 (16 November to 6 December 2009). The mean age of cases was 23 years (standard deviation: 14 years). Cough was the most common symptom in 200 cases (83%), followed by fever (≥38 °C) in 195 (81%). Diarrhoea or vomiting was reported in 12 (5%) patients. None of the cases developed any complications and no deaths occurred during the study period.

[Functional somatic syndromes]. / Les syndromes somatiques fonctionnels.

Functional somatic syndromes are a diagnostic and therapeutic challenge to the medical community. In this article, we review the definition, epidemiology, classification, etiology, and common determinants of natural history and management of functional somatic syndromes. Functional somatic syndromes are characterized by high morbidity due to various, fluctuating symptoms without objective somatic findings. They are common in medical care and the general population. Predisposing, precipitating and perpetuating factors influence the natural history of the functional somatic syndromes. Recent proposals to improve their classification tend to discard the traditional separation of symptoms into medical or psychiatric clusters. Moreover, interest in the psychological nature and treatment of functional somatic syndromes has expanded, culminating in the development of tailored psychological interventions for these conditions. The future classification of functional somatic syndromes should reflect the need for a balance between organic and psychological approaches. At present, patients with functional somatic syndromes are often dissatisfied with the care they receive, so training of medical students and doctors is mandatory to improve their skills regarding these conditions.

[Nodular liver lesions with fever in a Moroccan man: hepatic brucelloma]. / Nodules hépatiques fébriles chez un marocain.

Hepatic brucelloma is an exceptional localization in brucellosis. The purpose of this report is to describe an uncommon case involving a 42-year-old man hospitalized for febrile hepatic cytolysis. Diagnosis was established based on positive rose bengal test results, positive blood culture, hypoechogenic masses on ultrasound, and hypodense enhancing masses on CT scan. Hepatic brucelloma is a focal suppurative lesion occurring after undetected acute brucellosis or undertreated brucellosis. Diagnosis is based on the association of imaging showing characteristic features (hepatic calcifications) and on positive blood culture and serology. First-line treatment should consist of doxycyclin and rifampicin for 2 to 12 months. If medical treatment fails, surgical drainage should be performed.

Phenotypic expression of ferroportin disease in a family with the N144H mutation.

Ferroportin is a putative transmembrane channel involved in the exit of iron out of the enterocytes, the macrophages and the hepatocytes. Mutations in the human gene coding ferroportin have been linked to an unusual form of iron overload, now referred to as "hemochromatosis type IV" or "ferroportin disease" characterized by a prevalent iron overload of macrophages and liver Küpffer cells. We report four patients from a same family with ferroportin disease associated with the N144H mutation. We show that in this family the mutation which is fully penetrant, may act through an increased iron export from macrophages as suggested by the unexpected absence of iron overload in the spleen and bone marrow detected by magnetic resonance imaging, that it co-segregates with a phenotype close to the classical form of HFE-associated hemochromatosis and was associated, in the oldest patient, with the development of hepatocellular carcinoma in a non cirrhotic liver. Our findings illustrate the existence of a genotype-phenotype relationship in "ferroportin disease", suggest that MRI may be useful in determining this phenotype and show that hepatocellular carcinoma may occur in these patients even without cirrhosis. This observation justifies careful follow-up of this subgroup of patients.

[Acquired ichthyosis revealing an Hodgkin's disease]. / Ichtyose acquise révélant une maladie de Hodgkin. Une nouvelle observation.

INTRODUCTION: Acquired ichthyosis is a rare condition that usually reveals malignant diseases. CASE REPORT: A 70-year-old man was admitted with weight loss, diffuse ichthyosis, lymphadenopathy of the inguinal lymph nodes and elevated inflammatory markers in peripheral blood. Histology of the lymph node revealed mixed-cellularity Hodgkin disease. The evolution was fatal in spite of the chemotherapy. DISCUSSION: Acquired ichthyosis is a cutaneous paraneoplastic syndrome, generally related to hematologic malignancies. A possible pathomecanism is the stimulation of epidermal growth secondary to the production of epidermal growth factor (EGF) by tumour cells. Acquired ichtyosis can rarely reveal systemic or infectious diseases. It can also be drug-induced or idiopathic.

[Primary gastric lymphoma: a retrospective series of 35 cases]. / Le lymphome gastrique primitif (etude rétrospective d'une série de 35 patients).

BACKGROUND: Primary gastric non Hodgkin's lymphoma (PGNHL) is the most common site of extranodal malignant lymphoma. It is a rare subtype of malignancy, for which no consensus exists about treatment. AIM: The purpose of This paper was to assess the managemnt of PGNHL. METHODS: Between January 1992 and December 2001, 35 patients were retrospectively evaluated. RESULTS: Of the 35 patients, with a mean age of 44 years old Signs and symptoms are unspecific. 20 (57.1%) were in stage IE/IIE1. 15 patients (42.8%) were in stage IIE2,IIIE,IVE. These patients were treated with primary surgery with or without chemotherapy (11; 31.4%); primary chemotherapy (CT) alone with surgery in one patient (21; 60%) and three patients with gastric MALT lymphoma were treated by Helicobacter pylori eradication. The 5 year survival rates of the 35 patients are 62, 86%. There was no significant difference in the 5 year survival rate between the patients with low grade lymphoma and the patients with large grade lymphoma (75% versus 60%, P = 0.467). The 5-year survival rates for stage I/IIE1 and IIE2/III/IV patients were 80%, 53.3% respectively (p < 0.144). Of the 11 primary surgical groups with or without chemotherapy, the 5 year survival rate is 90.9%. Of the 21 patients who received CT, alone or combined with surgery, the survival rate is 52.4%. There was significant difference between the two groups (P = 0.05). Of the 3 patients with low-grade mucosa-associated lymphoid tissue (MALT) lymphoma with only oral anti-Helicobacter pylori regimen remained disease-free after a median follow-up of two years. CONCLUSIONS: This study suggested that primary surgical resection may be important factor predicting the long-term survival of patients with primary gastric NHL. H. pylori eradication therapy was an effective first-line treatment for patients with gastric MALT lymphoma.

[Hodgkin's disease presenting with spinal cord compression]. / Epidurite révélatrice d'une maladie de Hodgkin.

INTRODUCTION: Hematological neoplasms may be complicated by signs of neurological compression. Most cases reported in the literature have described advanced-stage non-Hodgkin lymphomas. We report a case of spinal cord compression revealing an isolated vertebral localization of Hodgkin lymphoma. CASE REPORT: Magnetic resonance imaging of the thoracic spine in a 54-year-old man who presented with spastic paraplegia revealed a vertebral and extradural mass. After laminectomy, histology and immunohistochemistry showed Hodgkin's disease. Post-operative staging did not reveal any other localization. The patient responded favorably after decompressive surgery and ABVD regimen. CONCLUSION: Spinal cord compression is a rare complication of Hodgkin's disease, occurring in only 5p.cent of cases, usually in the setting of progressive, advanced disease. As the initial symptom of Hodgkin's disease, it is extremely rare, with only a few cases reported in the literature. Significant results may be obtained with decompressive surgery and chemotherapy when the disease is promptly diagnosed. Spinal cord compression by primary Hodgkin's disease is a very infrequent situation. We urge this diagnosis be considered in all patients presenting with spinal cord compression attributed to malignancy.

[Angiolymphoid hyperplasia with eosinophilia]. / Hyperplasie angiolymphoïde à éosinophiles.

INTRODUCTION: Angiolymphoid hyperplasia with eosinophilia is a rare affection. CASE REPORT: A 36 years-old woman presented an angiolymphoid hyperplasia with eosinophilia manifesting by erythematous nodular lesions on the face and the forearms, severe neuropathy, visual loss and eosinophilia. Corticosteroids, immunosuppressive drugs and interferon-alpha were unsuccessful. DISCUSSION: Angiolymphoid hyperplasia with eosinophilia is a dermatological disease with possible systemic features. Differential diagnosis with Kimura disease is based on clinical presentation and histological findings. Etiopathology remains unknown and the treatment is not codified.

[Non-Hodgkin's lymphoma and hepatitis C virus infection]. / Lymphomes non hodgkiniens et infection par le virus de l'hépatite C.

INTRODUCTION: The authors report four cases of non Hodgkin's lymphomas (NHL) among patients infected by the hepatitis C virus (HCV). They discuss the epidemiological, physiopathological and clinical features of this association. CURRENT KNOWLEDGE AND KEY POINTS: The role of the HCV in the development of B-cell NHL is probable but the reported frequency of the association with HCV infection is variable especially in different countries. Most of the reported cases are low-grade NHL with frequent extranodal involvement. FUTURE PROSPECTS AND PROJECTS: New studies will improve the understanding of the physiopathological mechanisms that might explain the occurrence of NHL in the course of HCV infection. The recent evidence that the antiviral treatment is effective in splenic lymphoma with villous lymphocytes leads to reconsider the relationship between HCV and NHL and to think about new therapeutic possibilities.

[Cardiac localization of non Hodgkin's lymphoma: a study on four cases]. / Localisations cardiaques du lymphome non hodgkinien: à propos de quatre cas.

INTRODUCTION: Cardiac localization of non-Hodgkin's lymphoma is rare and usually seen in the latest phase of the disease. However, its frequency is certainly under-estimated because 20% of patients who die of lymphoma have a heart involvement at autopsy. EXEGESIS: We report four cases of cardiac involvement of non-Hodgkin's lymphoma with various revelation modalities. Features of cardiac lymphoma are multiple and not specific. Echocardiography can be helpful in finding cardiac localizations, which can involve every cardiac structure. Histological proof of such an involvement is sometimes difficult to obtain. CONCLUSION: Prognosis of cardiac lymphoma remains poor despite the real progress in the treatment of lymphomas.

[Digestive malacoplakia]. / Malacoplakie digestive.

INTRODUCTION: Malacoplakia, a chronic granulomatous disease, rarely involves the digestive tube and, when it does, takes on a pseudotumoral aspect. OBSERVATION: A 37 year-old man was hospitalized for chronic diarrhea that had progressed over 15 years. He exhibited an edematous-ascitic syndrome and bilateral pleurisy together with, biologically, a malabsorption syndrome. The endoscopic examinations (fibroscopy and colonoscopy) revealed polypoid tumor-like formations. An image of tumoral stenosis of the sigmoid-colic junction was revealed on barite lavage. Histological examination of the surgical sample (wide left colectomy of one third of the transverse) was suggestive of malacoplakia (histiocytes with characteristic Michaelis-Gutmann bodies). DISCUSSION: Malacoplakia is an inflammatory disease predominantly affecting the urogenital tract. Other organs can be involved. Its clinical symptomatology is highly disparate. The interest of this disease is in its pathogenesis, on which, in fact, its treatment is based.