Lymphopenia in patients affected by SARS-CoV-2 infection is caused by margination of lymphocytes in large bowel: an [18F]FDG PET/CT study.

BACKGROUND: To investigate the cause of lymphopenia in patients with newly diagnosed COVID-19, we measured [18F]FDG uptake in several tissues, including the ileum, right colon, and caecum at diagnosis and after recovery and correlated these measurements with haematological parameters. METHODS: We studied, by [18F]FDG PET/CT, 18 newly diagnosed patients with COVID-19. Regions of interest were drawn over major organs and in the terminal ileum, caecum, and right colon, where the bowel wall was evaluable. Five patients were re-examined after recovery, and three of them also performed a white blood cell scan with 99mTc-HMPAO-WBC on both occasions. Complete blood count was performed on both occasions, and peripheral blood lymphocyte subsets were measured at diagnosis. Data were analysed by a statistician. RESULTS: Patients had moderate severity COVID-19 syndrome. Basal [18F]FDG PET/CT showed focal lung uptake corresponding to hyperdense areas at CT. We also found high spleen, ileal, caecal, and colonic activity as compared to 18 control subjects. At recovery, hypermetabolic tissues tended to normalize, but activity in the caecum remained higher than in controls. Regression analyses showed an inverse correlation between CD4 + lymphocytes and [18F]FDG uptake in the caecum and colon and a direct correlation between CD8 + lymphocytes and [18F]FDG uptake in lungs and bone marrow. WBC scans showed the presence of leukocytes in the caecum and colon that disappeared at recovery. CONCLUSIONS: These findings indicate that lymphopenia in COVID-19 patients is associated with large bowel inflammation supporting the hypothesis that CD4 + lymphocytes migrate to peripheral lymphoid tissues in the bowel.

Lymphopenia and lung complications in patients with coronavirus disease-2019 (COVID-19): A retrospective study based on clinical data.

A rapid outbreak of novel coronavirus, coronavirus disease-2019 (COVID-19), has made it a global pandemic. This study focused on the possible association between lymphopenia and computed tomography (CT) scan features and COVID-19 patient mortality. The clinical data of 596 COVID-19 patients were collected from February 2020 to September 2020. The patients' serological survey and CT scan features were retrospectively explored. The median age of the patients was 56.7 ± 16.4 years old. Lung involvement was more than 50% in 214 COVID-19 patients (35.9%). The average blood lymphocyte percentage was 20.35 ± 10.16 (normal range, 20%-50%). Although the levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were high in more than 80% of COVID-19 patients; CRP, ESR, and platelet-to-lymphocyte ratio (PLR) may not indicate the in-hospital mortality of COVID-19. Patients with severe lung involvement and lymphopenia were found to be significantly associated with increased odds of death (odds ratio, 9.24; 95% confidence interval, 4.32-19.78). These results indicated that lymphopenia < 20% along with pulmonary involvement >50% impose a multiplicative effect on the risk of mortality. The in-hospital mortality rate of this group was significantly higher than other COVID-19 hospitalized cases. Furthermore, they meaningfully experienced a prolonged stay in the hospital (p = .00). Lymphocyte count less than 20% and chest CT scan findings with more than 50% involvement might be related to the patient's mortality. These could act as laboratory and clinical indicators of disease severity, mortality, and outcome.

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.

Severe multiple sclerosis reactivation during prolonged lymphopenia after dimethyl fumarate discontinuation.

BACKGROUND: Delayed-release dimethyl fumarate (DMF) treatment can be associated with reduced lymphocyte and leucocyte counts, which might persist after DMF discontinuation. CASE PRESENTATION: We report the case of a patient with severe disease reactivation despite prolonged lymphopenia after DMF discontinuation. We describe the frequency and impact of prolonged lymphopenia after DMF discontinuation at two tertiary MS centres. A 36-year-old female patient with multiple sclerosis was switched to DMF after 14 years of treatment with interferon beta-1a. DMF was suspended after 4 months because of persistent lymphopenia for 3 months. Six months later, the patient had a severe relapse with multiple enhancing brain lesions at MRI although lymphopenia was still persistent. Haematological assessment excluded other causes of lymphopenia, which was evaluated as a probable iatrogenic complication of DMF. The patient was treated with i.v. methylprednisolone 1 gr daily for 3 days with clinical recovery. CONCLUSIONS: Prolonged lymphopenia after DMT discontinuation does not protect against disease reactivation. Starting a new immune therapy should be balanced against the option of a "wait and see." A different immunotherapeutic strategy such as an anti-B therapeutic approach could be considered.

Zellweger syndrome with severe malnutrition, immunocompromised state and opportunistic infections.

Peroxisome biogenesis disorders are related to a spectrum of genetic diseases that range from severe Zellweger syndrome to milder infantile Refsum disease. Zellweger syndrome is characterised by dysmorphic features, severe hypotonia, seizures, failure to thrive, liver dysfunction and skeletal defects. Increased levels of very long chain fatty acids are the biochemical hallmark and the most common mutations found in the PEX1 gene. We report an unusual presentation of Zellweger syndrome in a 2-month-old female infant with severe malnutrition, opportunistic infections, lymphopaenia and a small thymic shadow on chest radiography. With this clinical picture, an initial hypothesis of primary immunodeficiency was considered. It was later confirmed to not be the case. On follow-up, global developmental delay, bilateral optic nerve atrophy and moderate bilateral sensorineural deafness grade II were documented. There were no further infectious complications and we concluded malnutrition was the cause of the infant's immunocompromised state.

Persistence of lymphocytopenia with CT abnormalities among patients with critical H7N9 swine-origin influenza A virus infection.

PURPOSE: H7N9 is an emerging pathogen with associated morbidity and mortality, and a broader understanding of the chest radiographic characteristics associated with human H7N9 infections is needed. This study was performed to determine the time course of recovery from lymphocytopenia and resolution of pneumonitis of critical H7N9 infection patients. MATERIALS AND METHODS: We performed chest X-ray and computed tomography (CT) for patients with H7N9 influenza. Lesion patterns, distributions, and changes at follow-up chest X-ray and/or CT were investigated. The time to progression on chest CT image, and the time to resolution of the chest CT findings were assessed. RESULTS: Lymphocytopenia was a common laboratory test abnormality. The most common CT findings were lobar consolidation with air bronchogram and ground-glass opacities. For 7 recovering patients, the time to resolution of the chest CT findings was 10-90 days. Fibrosis and traction bronchiectasis were the main features on the CT scans of recovering patients. Interestingly, the time to recovery from lymphopenia was highly consistent with time to resolution of the chest CT findings. CONCLUSIONS: We have shown the presence of radiographic abnormalities among H7N9 patients. Monitoring of the variation of lymphocytes for H7N9 patients has important clinical significance, especially for prediction of the resolution of pneumonitis.

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.

Hypoalbuminemia and lymphocytopenia in patients with decompensated biventricular failure.

BACKGROUND: In patients hospitalized with decompensated biventricular failure having hypoalbuminemia and lymphocytopenia without underlying hepatic or renal disease, we addressed the presence of a protein-losing enteropathy (PLE). METHODS: We studied 78 patients having a dilated cardiomyopathy, who were hospitalized with congestive heart failure (CHF) and hypoalbuminemia of uncertain origin. In the first 19 patients, we investigated the presence of PLE using Tc-Dex scintigraphy together with serum albumin 2 to 4 weeks later when compensation had been restored. In the next 59 patients, presenting with reduced serum albumin and relative lymphocyte count at admission, these parameters were again monitored (2-4 weeks) later when symptoms and signs of CHF had resolved. RESULTS: PLE, documented by Tc-Dex(70) scintigraphy, was found in 10 of 19 patients and whose hypoalbuminemia (2.7 +/- 0.1 g/dL, mean +/- standard error of mean) were corrected (3.3 +/- 0.1 g/dL; P < 0.05) with the resolution of CHF, whereas in the 9 patients without a PLE, reduced baseline serum albumin (2.6 +/- 0.1 g/dL) failed to improve on follow-up (2.6 +/- 0.2 g/dL) in keeping with malnutrition. Relative lymphocyte count was reduced (14.6 +/- 1.5%) in patients with PLE but was normal (21.4 +/- 3.3%; P < 0.05) in those without PLE. Serum albumin and relative lymphocyte count were each reduced at admission (2.8 +/- 0.1 g/dL and 14.4 +/- 1.0%, respectively) in 59 patients and increased (P < 0.05) to normal values (3.5 +/- 0.1 g/dL and 24.9 +/- 1.0%) 2 to 4 weeks after they were compensated. CONCLUSIONS: Enteral losses of albumin and lymphocytes account for the reversible hypoalbuminemia and lymphocytopenia found in patients hospitalized with CHF having splanchnic congestion.

Reversible acute gastrointestinal syndrome associated with active systemic lupus erythematosus in patients admitted to hospital.

Patients with systemic lupus erythematosus (SLE) frequently have gastrointestinal (GI) symptoms. These are usually self-limiting and related to treatment side-effects or concurrent illness. However, abdominal pain may be due to bowel ischaemia which can lead to infarction and perforation. The likelihood of these serious events is increased in individuals with pain severe enough to require assessment in hospital or a SLEDAI score > 5. This paper describes a group of patients with active SLE and GI symptoms severe enough to require admission to hospital using a retrospective review of 52 SLE patients admitted to hospital with acute abdominal symptoms. The results showed that abdominal pain (87%), vomiting (82%) and diarrhoea (67%) had been present for a mean of 4.4 +/- 6.5 days and SLEDAI score was > or = 4 in 83% of patients. CT scanning showed evidence of serositis and bowel involvement in 63% of patients who underwent this investigation. Intravenous (iv) fluids were used in 87%, parenteral steroids in 90% and iv cyclophosphamide in 31%. Most (n = 51) were discharged well. Recurrence of GI symptoms occurred in 12 patients. The conclusions are that active SLE may manifest as an acute gastrointestinal syndrome. Early diagnosis, bowel rest, supportive medical therapy and treatment with corticosteroids and/or immunosupressives can result in a good outcome.