Absent immune response to SARS-CoV-2 in a 3-month recurrence of coronavirus disease 2019 (COVID-19) case.

BACKGROUND: The viral persistence in patients with Coronavirus Disease 2019 (COVID-19) remains to be investigated. METHODS: We investigated the viral loads, therapies, clinical features, and immune responses in a 70-year patient tested positive for SARS-CoV-2 for 3 months. FINDINGS: The patient exhibited the highest prevalence of abnormal indices of clinical features and immune responses at the first admission, including fever (38.3 â„ƒ), decreased lymphocytes (0.83 × 109/L) and serum potassium (3.1 mmol/L), as well as elevated serum creatinine (115 µmol/L), urea (8.6 mmol/L), and C-reactive protein (80 mg/L). By contrast, at the second and the third admission, these indices were all normal. Through three admissions, IL-2 increased from 0.14 pg/mL, 0.69 pg/mL, to 0.91 pg/mL, while IL-6 decreased from 11.78 pg/mL, 1.52 pg/mL, to 0.69 pg/mL, so did IL-10 from 5.13 pg/mL, 1.85 pg/mL, to 1.75 pg/mL. The steady declining trend was also found in TNF-α (1.49, 1.15, and 0.85 pg/mL) and IFN-γ (0.64, 0.42, and 0.27 pg/mL). The threshold cycle values of RT-PCR were 26.1, 30.5, and 23.5 for ORFlab gene, and 26.2, 30.6, and 22.7 for N gene, showing the patient had higher viral loads at the first and the third admission than during the middle term of the disease. The patient also showed substantially improved acute exudative lesions on the chest CT scanning images. CONCLUSIONS: The patient displayed declining immune responses in spite of the viral shedding for 3 months. We inferred the declining immune responses might result from the segregation of the virus from the immune system.

Progressive multifocal leukoencephalopathy despite immune recovery in a HIV/HCV co-infected patient.

In HIV patients, HCV co-infection has been associated with an increased risk of progressive multifocal leukoencephalopathy (PML). Furthermore, PML has also been described in patients with cirrhosis, whether related to HCV infection or not. We describe here the case of a HIV/HCV co-infected patient with cirrhosis who developed PML despite HIV suppression and CD4 cell count above 250/mm3 for 2 years. Immunological studies performed at onset of PML and before HCV therapy showed a decrease in naïve CD4 cells (CD45RA+CCR7+CD27+ CD4+ T cells - 23% cells, i.e. 75/mm3) and NK lymphopenia with abnormal and activated NK cells (CD3- CD16+ and/or CD56+) (5% lymphocytes, i.e. 58/mm3, CD69 91%, NKp30 26%). This impaired immunity, possibly related to HIV infection, or HCV infection or cirrhosis, or a combination thereof, could have led to the development of PML.

Progressive multifocal leukoencephalopathy in idiopathic CD4+ lymphocytopenia: A case report and review of literature.

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease due to a lytic infection of oligodendrocytes caused by polyoma virus (JC virus) infection. PML usually occurs in a setting of severe immunosuppression and is most commonly associated with human immunodeficiency virus (HIV) infection. Idiopathic CD4+ lymphocytopenia is a very rare cause of PML and only a few cases have been reported in the literature. We present a case of a 45-year-old man who presented with behavioral alteration followed by progressive weakness of right side of the body. Contrast-enhanced magnetic resonance imaging of the brain revealed confluent irregular areas of T2-weighted/fluid-attenuated inversion recovery hyperintensities in left frontoparietal and right temporoparietal regions. His hematological work up showed a decreased absolute CD4+ count of 217 per microliter, but was negative for HIV serology. Keeping a differential diagnoses of central nervous system lymphoma, brain biopsy was performed. Histopathology revealed demyelination with presence of intranuclear inclusions in the oligodendrocytes, which were positive for SV40 immunostain. Adjacent areas showed reactive gliosis with hypertrophic astrocytes, hence a diagnosis of PML was made. The patient died due to aspiration pneumonia. PML can occur very rarely in association with idiopathic CD4+ lymphocytopenia in the absence of other immunosuppressive illnesses. This report highlights the importance of high index of clinical suspicion and need for a careful histological examination for diagnosis of PML to facilitate adequate patient management.

Massive splenomegaly and lymphopenia: a unique case of obstructive shock.

We present a patient with intravascular large B-cell lymphoma (IVLBCL)-induced obstructive shock. This case represents a unique presentation of the disease, while highlighting the difficulty of establishing the diagnosis. Although there was a high clinical suspicion for a lymphomatous process, the obstructive shock component of the patient's presentation was perplexing. It was not until the autopsy reports demonstrated lymphocytes within the pulmonary vasculature that the clinical picture of altered mental status, weight loss and obstructive shock were unified to the diagnosis of intravascular large B-cell lymphoma.

Relationship between lymphocytopenia and circulating tumor cells as prognostic factors for overall survival in metastatic breast cancer.

INTRODUCTION: Lymphocytopenia and circulating tumor cells (CTCs) have been reported as independent prognostic factors for overall survival (OS) in metastatic breast cancer (MBC), and both have been associated with bone metastases. Our objective was to compare the prognostic significance of lymphocytopenia, CTC count, and extensive bone metastases (> 2 lesions) assessed by fluorine-18 ((18)F) fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in patients with MBC. PATIENTS AND METHODS: This is a retrospective study that included patients with MBC who were starting a new line of systemic therapy. The study population consisted of patients treated at the University of Texas MD Anderson Cancer Center between 2004 and 2008 for whom baseline CTC count, lymphocyte counts, and FDG-PET/CT scans were available. Patients were stratified according to estrogen receptor status (positive vs. negative), human epidermal growth factor receptor 2 (HER2) status (amplified vs. constitutive), baseline CTC counts per 7.5 mL of blood (< 5 CTCs/7.5 mL of blood vs. ≥ 5 CTCs/7.5 mL of blood), lymphocytopenia (< 1000 vs. ≥ 1000/µL), and extensive bone metastases (> 2 vs. ≤ 2 lesions). RESULTS: In 195 assessable patients, the median OS was 27 months (range, 1 to > 45 months). In multivariate analysis, lymphocytopenia, ≥ 5 CTCs/7.5 mL of blood, estrogen receptor status, and line of therapy were the only predictive factors for progression-free survival (PFS) (2P = .001, 2P = .032, 2P = .029, and 2P = .002, respectively) and OS (2P = .001, 2P = .009, 2P = .004, and 2P = .024, respectively). CONCLUSION: CTC measurement and lymphocytopenia are independent prognostic factors for PFS and OS in patients with MBC.