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Background: Neurocognitive symptoms are common in acute as well as convalescent (post-acute sequelae of COVID-19 [PASC]) COVID-19, but mechanisms of CNS pathogenesis are unclear. The aim of this study was to investigate cerebrospinal fluid (CSF) biomarker evidence of CNS infection, immune activation and neuronal injury in convalescent compared with acute infection. Method(s): We included 68 (35% female) patients >=18 years with CSF sampled during acute (46), 3-6 months after (22) SARS-CoV-2 infection or both (17), and 20 (70% female) healthy controls from longitudinal studies. The 22 patients sampled only at 3-6 months were recruited in a PASC protocol. CSF N-Ag was analyzed using an ultrasensitive antigen capture immunoassay platform (S-PLEX SARS-CoV-2 N Kit, Meso Scale Diagnostics, LLC. Rockville, MD). Additional analyses included CSF beta2-microglobulin (beta2M)], IFN-gamma, IL-6, TNF-alpha neurofilament light (NfL), and total and phosphorylated tau. Log-transformed CSF biomarkers were compared using ANOVA (Tukey post-hoc test). Result(s): Patients sampled during acute infection had moderate (27) or severe (19) COVID-19. In patients sampled at 3-6 months, corresponding initial severity was 10 (mild), 14 (moderate), and 15 (severe). At 3-6 months, 31/39 patients reported neurocognitive symptoms;8/17 patients also sampled during acute infection reported full recovery after 3-6 months. CSF biomarker results are shown in Figure 1. SARS-CoV-2 RNA was universally undetectable. N-Ag was detectable only during acute infection (32/35) but was undetectable in all follow up and control samples. Significantly higher CSF concentrations of beta2M (p< 0.0001), IFN-gamma (p=0.02), IL-6 (p< 0.0001) and NfL (p=0.04) were seen in acute compared to post-infection. Compared to controls, beta2M (p< .0001), IL-6 (p< 0.0001) and NfL (p=0.005) were significantly higher in acute infection. No biomarker differences were seen post-infection compared with controls. No differences were seen in CSF GFAp, t-tau or p-tau. Conclusion(s): We found no evidence of residual infection (RNA, N-Ag), inflammation (beta2M, IL-6, IFN-gamma, TNF-alpha), astrocyte activity (GFAp) or neuronal injury (NfL, tau) 3-6 months after initial COVID-19, while significantly higher concentrations of several markers were found during acute infection, suggesting that PASC may be a consequence of earlier injury rather than active CNS damage. CSF beta2M, IL-6, IFN-gamma and NfL were significantly lower after 3-6 months than during acute COVID-19 and not different from healthy controls. (Figure Presented).
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INTRODUCTION: In this study, we examined the effect of switching dialysis membranes on the response to influenza virus vaccination in HD patients. METHODS: This study consisted of two phases. In phase 1, antibody titers were measured and compared between HD patients and healthy volunteers (HVs) before and after vaccination against influenza virus. Using antibody titers 4 weeks after vaccination, HD patients and HVs were classified according to seroconversion (i.e., antibody titers against all four strains were >20-fold) or non-seroconversion (i.e., antibody titer against at least one strain was <20-fold). In the phase 2, we examined whether the change in the dialysis membrane from a polysulfone (PS) to a polymethyl methacrylate (PMMA) membrane affected the response to vaccination in HD patients without seroconversion in response to the vaccine the previous year. Patients with seroconversion and non-seroconversion were classified as responders and nonresponders, respectively. Additionally, we compared clinical data. RESULTS: In the phase 1, 110 HD patients and 80 HVs were enrolled, and their seroconversion rates were 58.6% and 72.5%, respectively. In the phase 2, 20 HD patients without seroconversion in response to the vaccine the previous year were enrolled, and the dialyzer membrane was changed to PMMA 5 months before annual vaccination. After annual vaccination, 5 and 15 HD patients were categorized as responders and nonresponders, respectively. In the responders, ß2-microglobulin, white blood cell counts, platelet counts, and serum albumin levels (Alb) were all higher than in the nonresponders. CONCLUSION: The responsiveness to vaccination against influenza virus was lower in HD patients compared with HVs. Changing the dialysis membrane from PS to PMMA appeared to affect the response to vaccination in HD patients.
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Biomarker detection has attracted increasing interest in recent years due to the minimally or non-invasive sampling process. Single entity analysis of biomarkers is expected to provide real-time and accurate biological information for early disease diagnosis and prognosis, which is critical to the effective disease treatment and is also important in personalized medicine. As an innovative single entity analysis method, nanopore sensing is a pioneering single-molecule detection technique that is widely used in analytical bioanalytical fields. In this review, we overview the recent progress of nanopore biomarker detection as new approaches to disease diagnosis. In highlighted studies, nanopore was focusing on detecting biomarkers of different categories of communicable and noncommunicable diseases, such as pandemic COVID-19, AIDS, cancers, neurologic diseases, etc. Various sensitive and selective nanopore detecting strategies for different types of biomarkers are summarized. In addition, the challenges, opportunities, and direction for future development of nanopore-based biomarker sensors are also discussed.Copyright © 2023 Elsevier B.V.
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Introduction: Super high-flux hemodialysis (SHF-HD) provides comparable effectiveness in terms of middle-molecule and protein-bound uremic toxin removal to online hemodiafiltration in prevalent end-stage kidney disease (ESKD). However, dialysate albumin loss is raised awareness of the long-term using SHF-HD. The study aims to monitor the long-term use of SHF-HD in nutritional status change and the sustained effect of uremic toxin removal. Method(s): The present study was prospectively conducted on the 15 prevalent ESKD patients from a run-in period of standard high-flux hemodialysis (HF-HD) with ELISIO-H21 dialyzer for 4 weeks to thereafter 15 months follow-up with SHF-HD. The patients provided high-efficiency (high blood flow and dialysate flow rate) SHF-HD using PES17D alpha dialyzers for the first three months. After the amendment protocol, SHF-HD was run with the same type of dialyzer;ELISIO-17Hx (Nipro Corporation, Osaka, Japan) due to the COVID-19 pandemic. Nutritional parameters, BCM;body composition monitor (FMC, Bad Homburg, Germany), and uremic toxins were measured at baseline and every three months during SHF-HD. Result(s): Fourteen of 15 patients could complete the study. One patient was early terminated due to undergoing kidney transplantation. After 15 months of SHF-HD treatment compared to HF-HD at baseline, there was not a statistically significant change in clinical and laboratory parameters on nutritional status. The mean serum albumin levels were 4.09 (1.36) versus 4.01 (0.3) g/dL, respectively (p=0.52), and the mean difference (SE) of normalized protein catabolic rate (nPCR) was -0.04 (0.08), 95% confidence interval [CI] -0.19, 0.11. On the other hand, lean tissue mass (LTM) was significantly decreased, and fat mass was significantly increased (mean difference (SE) of -3.66 (1.07) gram, 95% CI -5.76, -1.55, and 1.79 (0.80), 95% CI 0.21, 3.36). SHF-HD sustainably and significantly removed medium to large middle-molecule uremic toxins including pre-dialysis beta-2 microglobulin, kappa-free light chain, and lambda-free light chain. In addition, protein-bound uremic toxin;indoxyl sulfate was significantly reduced during long-term follow-up using SHF-HD. SHF-HD with PES17D alpha dialyzer resulted in more dialysate albumin leaks than a newer type of SHF-HD with ELISIO-Hx17. Conclusion(s): Long-term use of SHF-HD in ESKD patients was associated with nutritional safety and effectiveness in middle-molecule and protein-bound uremic toxin removal. Although serum albumin and BMI were not changed. LTM was significantly reduced with lower levels of nPCR than in other studies but trended to increase over time. The LTM absolute levels are not below the 10 percentiles of the healthy reference range. Increasing protein intake to reach the current recommendation and physical activity was advised with long-term use of SHF-HD to avoid further reduce LTM. [Formula presented] [Formula presented] [Formula presented] No conflict of interestCopyright © 2023
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The proceedings contain 15 papers. The topics discussed include: eplet analysis: a tool for risk assessment of de novo donor-specific HLA-DQ-antibodies in patients after lung transplantation;beta-2-microglobulin the neglected edge of HLA class I;temporal loss of HLA heterozygosity in an AML patient prior to stem cell transplantation: does it affect HLA typing strategies?;in-vivo monitoring of CAR-T cell expansion using TaqMan real time PCR;immunogenetic features with SARS-COV-2 breakthrough infections: analyzing 1st/2nd and omicron waves;uterus transplantation from the immunological point of view - experiences from the first center in Germany;follow-up of HLA class I antibodies in neonatal thrombocytopenia;monitoring the in-vivo persistence and expansion of CAR-T cells by TaqMan real-time PCR;and detection of complement-fixing anti-HLA antibodies by a C3D-detecting Luminex technique. is there any additional diagnostic value not available through the use of standard antibody specification at the single antigen level?.
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Background: Since end Dec. 2021, the Omicron SARS-CoV-2 strains have appeared while previous β,g,α or d strains have disappeared. Methods: Analysis of clinical, humoral, cellular and inflammation responses in known patients from the Clinical Immunology Unit [CIU] after Omicron COVID. Recruitment January 1st to June 30th, 2022. Comparison with data of 54 CIU COVID patients from the first wave [1stW]. Measured parameters: β2microglobulin [β2m], C3, C4, ferritin, ECP, anti Spike1 [S1] for Wuhan and Omicron B1.159, ab anti NCP (nucleocapsids) and neutralizing antibodies [NeuAb], Ab phenotyping, leucocyte repartition, lymphocyte phenotyping. Patients: 118 Omicron infected [OmiP]: M 31%, F 69% (Vac 64%, noVac 36%): 24 previously “Naïve COVID” [NaCOV], 18 noVac with a previous β,g,α or d COVID, 64 Vac with no previous COVID and 12 Vac with a previous COVID. Results: No difference between OmiP and 1stW in the kinetics of response to S1 (Omicron or WT) in the first 6 months. It peaks between 45 to 60 d. Anti-NCP ab peaks at 30 to 45 d and is still present ≥ 5 months. Prior infection and/or vaccination is associated with a 2- 3-fold increase of previously detected anti-S1 Wuhan and anti- S1 Omicron. NaCOV develop ab to S1 Wuhan but in much lesser amounts than 1stW. Among OmiP no increased counts of eosinophils and NK as observed in 1stW, neither any increase in β2m and CRP. The majority of OmiP have elevated serum ECP and increased polyclonal ab production for ≥ 4 months. Conclusions: Omicron induces a different immune response than previous strains of SARS-CoV-2.
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Background: Patients with chronic lymphocytic leukemia (CLL) show high infection-related morbidity and mortality due to variable degree of humoral and cellular immune deficiency. High Covid-related mortality and reduced response to the SARS-Cov-2 vaccine have been reported in this patient population. Aims: We carried out a prospective multicenter study to define the rate of CLL patients with an appropriate immune response after the mRNA SARS-CoV2 vaccine (Pfizer-BioNTech;Moderna). Methods: Two-hundred patients with CLL received the first dose of the SARS-CoV-2 vaccine between February and August 2021. Centralized assessment of the anti-SARS-Cov-2 IgG levels (Sero Index, Kantaro Quantitative SARS-CoV-2 IgG Antibody, RUO-R&D System) was performed at the Istituto Superiore di Sanità of Rome, Italy. The median followup of this study is 10.7 months (range 1-12.9). Results: The median age of patients was 70 years, the median IgG level was 635 mg/dl, 61% of patients were IGHV unmutated, and 34% showed TP53 disruption. The majority of patients, 83.5%, were previously treated. Prior treatment included chemoimmunotherapy in 20 (10%) patients, ibrutinib-based therapy in 72 (36%;front-line, 21%;advanced line, 15%), venetoclax-based therapy in 75 (37.5%;front-line, 13.5%;advanced line, 24%). Overall, 135 (77.5%) patients had been previously treated with rituximab, 33 (16.5%) of them within 12 months before vaccination. We assessed the serologic response after the second dose of the SARS-CoV2 vaccine in 195 patients while five were excluded from the analysis (positive test before vaccination, 3 patients;lost to the follow-up, 1;Richter syndrome, 1). Adequate levels of anti-SARS-Cov-2 IgG were detected in 76/195 (39%) patients. Age (<70 vs.≥ 70 years;p <0.0001), CIRS value (<6 vs. ≥6;p=0.005), beta-2 microglobulin (<3.5 vs. ≥ 3.5mg/dl;p=0.04), IgG levels (<550 vs. ≤ 550 mg/dl;p <0.0001), prior treatment (p=0.0001), number of prior treatments (0+1 vs. ≥ 2;p=0.002) and the time between prior rituximab and vaccination (>12 vs. ≤12 month;p=0.001) showed a significant impact on the humoral response. In multivariate analysis only age (OR: 0.92 [95% CI: 0.92-0.97] p=0.0001), IgG levels (OR: 0.28 [95% CI: 0.13-0.58] p<0.001), and the time between prior rituximab and vaccination (OR: 0.10 [95% CI: 0.03-0.37] p=0.001), revealed a significant and independent impact on response. When the analysis was restricted to patients who received targeted therapy, in addition to the younger age (OR: 0.96 [95% CI: 0.92-0.99] p=0.04), higher IgG levels at baseline (OR: 0.31 [95% CI: 0.12-0.79] p=0.014), longer time between the start of ibrutinib or venetoclax-based therapy and vaccination (<18 vs.≥18 months;OR: 0.17 [95% CI: 0.06-0.44], p <0.0001) showed a favorable and independent impact on response. Ninety-three% (182/195) of patients received a third dose of the vaccine. A significant increase in the rate of serologic responses, 51.5% (85/165 evaluated patients, p=0.019), was observed after the booster dose. Moreover, a response was detected in 25% (26/103 evaluated patients) of previously seronegative patients. Summary/Conclusion: In this prospective, multicenter, centralized study, we recorded an effective immune response to the SARS-CoV-2 vaccine in about a third of patients with CLL. Younger age, higher IgG levels, no prior treatment, or stable disease after targeted therapy that suggest preserved immunocompetence were associated with a greater likelihood of achieving an effective immune response. A booster dose of the SARS-CoV-2 vaccine proved beneficial also in previously seronegative patients.
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Background: The Bruton's tyrosine kinase (BTK) inhibitor acalabrutinib is approved for treatment of chronic lymphocytic leukemia(CLL). Acalabrutinib induces durable remissions in most CLL patients, which mostly are partial remissions (PR), and therefore treatment typically is given as long-term monotherapy. As a potential alternative we developed a time-limited regimen, combining acalabrutinib with obinutuzumab. Aims: Here, we report early results from 14 treatment-naïve patients with CLL who enrolled in this ongoing phase 2 trial (NCT04505254) since September, 2020 at MD Anderson Cancer Center. Methods: Patients and Study Design: Treatment-naïve CLL patients requiring therapy as per iwCLL criteria receive acalabrutinib 100 mg orally twice a day for 24 cycles, combined with monthly obinotuzumab for 6 doses, starting in cycle 3. The first dose of obinutuzumab is divided into 100 mg on day 1 and 900 mg on day 2 of cycle 3;1000 mg are given during subsequent cycles (cycles 4-8). Patients who do not achieve a complete remission (CR) after cycle 8 can receive an additional 6 monthly doses of obinotuzumab during cycles 9 -14. Treatment is discontinued after 24 cycles, and patients will be monitored. The primary objective is to determine the durability of remissions after treatment discontinuation, secondary objectives are to determine clinical and laboratory characteristics that predict for early versus late relapse after time-limited therapy. Results: The median age of the patients is 70 yrs (range, 40 -83 yrs), 14% had del17p or TP53 mutation, 43% had an unmutated IgHV and 71% advance stage disease (RAI stage III and IV). The median baseline absolute lymphocyte count (ALC) and b2 microglobulin at start of therapy were 39.2x109/L (range: 7.1 - 188.4 x 109/L) and 4.2 mg/L (range: 2.2 - 7.9 mg/L), respectively. After a median follow-up of 7 months (2 - 16 months), 13 (93%) of patients remain on study;one patient died (7%) due from complications from a presumed bacterial (COVID19-negative) pneumonia after 2 months on therapy. The estimated one-year PFS and OS for the cohort is 92.8 %. Seven patients were evaluable for response assessment after 8 months of therapy. No patient has yet discontinued therapy. All patients achieved a PR (one patient with undetectable minimal residual disease/U-MRD in the bone marrow), accounting for an overall responsonse rate of 100%. The median levels of bone marrow infiltration by CLL cells, quantified by flow cytometry, declined from 83.6% (range: 54.3 - 94.0 %) at baseline to 4.1% (range, 0.0 - 63.3%, n=7, p<0.05, see figure) after 6 cycles of combination treatment. Sixty-four percent of patients completed all doses of obinotuzumab, 50% requiered a dose reduction of acalabrutinib to 100 mg per day due to adverse events (AE). Grade 33 AE were observed in 4 patients (29%), which included decreased neutrophil counts (n=2), syncope (n=1), and grade 5 lung infection (COVID19 not detected, n=1). The most frequently reported non-serious related AE (3 2 patients) were anemia (n=5 [36%]), decreased platelets counts (n=3 [21%]), bruising (n=3 [21%]), limbs edema (n=2 [15%]) and headache (n=2 [15%]). All these events were grade 1. Importantly, no bleeding or atrial fibrillation events were observed. 3285 (Figure Presented ) Summary/Conclusion: Our preliminary data indicate that combination therapy of acalabrutinib plus obinotuzumab induces remissions with a major reduction in bone marrow disease after 6 months of combination therapy. Longer treatment and follow-up is warranted to determine the durability of responses after therapy discontinuation.
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Drug repositioning may be a promising way to find potential therapies against coronavirus disease 2019. Although chloroquine and hydroxychloroquine showed controversial results against the coronavirus disease 2019 disease, the potential common and diverging mechanisms of action are not reported and need to be dissected for better understanding them. An integrated strategy was proposed to systematically decipher the common and diverging aspects of mechanism of chloroquine and hydroxychloroquine against coronavirus disease 2019-disease network based on network pharmacology and in silico molecular docking. Potential targets of the two drugs and coronavirus disease 2019 related genes were collected from online public databases. Target function enrichment analysis, tissue enrichment maps and molecular docking analysis were carried out to facilitate the systematic understanding of common and diverging mechanisms of the two drugs. Our results showed that 51 chloroquine targets and 47 hydroxychloroquine targets were associated with coronavirus disease 2019. The core targets include tumor necrosis factor, glyceraldehyde 3-phosphate dehydrogenase, lymphocyte-specific protein-tyrosine kinase, beta-2 microglobulin, nuclear receptor coactivator 1, peroxisome proliferator-activated receptor gamma and glutathione disulfide reductase. Both chloroquine and hydroxychloroquine had good binding affinity towards tumor necrosis factor (affinity=-8.6 and -8.4 kcal/mol, respectively) and glyceraldehyde 3-phosphate dehydrogenase (-7.5 and -7.5 kcal/mol). Chloroquine and hydroxychloroquine both had good affinity with angiotensin-converting enzyme 2, 3-chymotrypsin-like protease and transmembrane serine protease 2. However, hydroxychloroquine manifested better binding affinity with the three proteins comparing with that of chloroquine. Chloroquine and hydroxychloroquine could have potential to inhibit over-activated immunity and inflammation. The potential tissue-specific regulation of the two drugs against severe acute respiratory syndrome coronavirus 2 infection may related with the lung, liver, brain, placenta, kidney, blood, eye, etc. In conclusion, our data systematically demonstrated chloroquine and hydroxychloroquine may have potential regulatory effects on coronavirus disease 2019 disease network, which may affect multiple organs, protein targets and pathways. Routine measurements of the chloroquine and hydroxychloroquine blood concentrations and tailored therapy regimen may be essential. But, further rigorous and high quality randomized controlled clinical trials are warranted to validate the antiviral effects of chloroquine and hydroxychloroquine against severe acute respiratory syndrome coronavirus 2. Our proposed strategy could facilitate the drug repurposing efforts for coronavirus disease 2019 treatment.
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Methods of wastewater concentration (electro-negative filtration (ENF) versus magnetic bead-based concen-tration (MBC)) were compared for the analysis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), beta-2 micro-globulin, and human coronavirus OC43. Using ENF as the concentration method, two quantitative polymerase chain reaction (qPCR) analytical methods were also compared: volcano second generation (V2G)-qPCR and reverse transcriptase (RT)-qPCR measuring three different targets of the virus responsible for the COVID-19 illness (N1, modified N3, and ORF1ab). Correlations between concentration methods were strong and statistically significant for SARS-CoV-2 (r = 0.77, p < 0.001) and B2M (r = 0.77, p < 0.001). Comparison of qPCR analytical methods indicate that, on average, each method provided equivalent results with average ratios of 0.96, 0.96, and 1.02 for N3 to N1, N3 to ORF1ab, and N1 to ORF1ab and were supported by significant (p < 0.001) correlation coefficients (r = 0.67 for V2G (N3) to RT (N1), r = 0.74 for V2G (N3) to RT (ORF1ab), r = 0.81 for RT (N1) to RT (ORF1ab)). Overall results suggest that the two concentration methods and qPCR methods provide equivalent results, although variability is observed for individual measurements. Given the equivalency of results, additional advantages and disadvantages, as described in the discussion, are to be considered when choosing an method.
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Background: The underlying CNS pathogenesis in COVID-19 is not clear and viral RNA is rarely detected in cerebrospinal fluid (CSF). We measured viral antigen and biomarker profiles in CSF in relation to neurological symptoms and disease severity. Methods: We included 44 (32% female) hospitalized patients (26 moderate, 18 severe COVID-19) and 10 healthy controls (HC). 21 patients were neuroasymptomatic (NA), 23 neurosymptomatic (NS;encephalopathy=21, encephalitis=1, GBS=1). For antigen and cytokine analyses, a patient control (PC;n=41) group (COVID-negative with no sign of CNS infection in clinical CSF samples) was used. CSF nucleocapsid antigen (N-Ag) was analyzed using an ultrasensitive antigen capture immunoassay platform, S-PLEX direct detection assay, S-PLEX SARS-CoV-2 N Kit (MesoScale Diagnostics, LLC. Rockville, MD). Additional analyses included CSF neopterin, β2-microglobulin, cytokines and neurofilament light (NfL). Results: CSF N-Ag was detected in 31/35 patients (0/41 controls) while viral RNA was negative in all. CSF N-Ag was significantly correlated with CSF neopterin (r=0.38;p=0.03) and IFN-γ (r=0.42;p=0.01) adjusted for sampling day. No differences in CSF N-Ag concentrations were found between patient groups. All patient groups had markedly increased CSF neopterin, β2M, IL-6, IL-10 and TNF-α compared to controls, while IL-2, IL-1β and IFN-γ were significantly increased only in the NS group. CSF biomarkers were associated with time from symptom onset to CSF sampling. After adjusting for time of sampling, the NS group had significantly higher CSF IFN-γ (p=0.03), and showed a statistical trend towards significantly higher CSF neopterin, IL-6 and TNF-α (p=0.056-0.06) than the NA group. Additionally, age-adjusted CSF NfL was higher in the NS compared to the HC (p=0.01) group. No differences were seen in any CSF biomarkers in moderate compared to severe disease. Conclusion: Viral antigen is detectable in CSF in a majority of patients with COVID-19 despite the absence of detectable viral RNA, and is correlated to CNS immune activation markers. Patients with neurological symptoms had a more marked immune activation profile compared to NA patients, as well as signs of neuroaxonal injury compared to controls. These observations could not be attributed to a difference in COVID-19 severity. Our results highlight the importance of neurological symptoms and indicate that the CNS immune response and CNS pathogenesis can be initiated by viral components without direct viral invasion of the CNS.
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Background: Often the onset symptoms of a disease don't easily direct towards the correct diagnosis. Furthermore, the CoViD-19 pandemic has often been an obstacle to obtaining a quick diagnosis. Description of the case: Male 49-year-old patient admitted to emergency room for persistent back pain, asthenia and weight loss. Physical examination revealed a palpable mass in the right gluteal region, chest X ray an enlargement of mediastinum. Nasopharingeal swab for CoViD-19 was positive (even if negative for CoViD-related symptoms);he was so hospitalized in our Internal Medicine CoViD Ward. Blood samples found microcytic anemia (thalassemic trait carrier);high ferritin (1072 ng/ml), aptoglobin (297 mg/dl, nv <200) and B2 microglobulin (3.25 mg/l, nv <2.53);K and L chains normal with K/L serum ratio reduction, increase in urine sample. Lymphocyte subpopulations were indicative of lymphopenia. Suspecting a lymphoproliferative disease, he performed a chest and abdomen CT scan that found: multiple bilateral pulmonary nodules, the largest one 10x9 cm in the left lung;a left renal lesion11x10 cm;a mass 9.5 cm of the sacroiliac left wing and splenomegaly (145 mm). We thus performed a US-assisted biopsy of the mass in the gluteal region. The histological examination allowed to identify metastasis from clear cell renal carcinoma. Conclusions: We report this case to highlight the peculiarity of onset of this renal carcinoma, in absence of genitourinary symptoms. Diagnostic autonomy can be a winning weapon in accelerating the diagnostic process, even more so in times of CoViD-19 pandemic.
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Case report-IntroductionCOVID-19 infection caused by a novel coronavirus SARS-coV-2 has made the diagnosis and the treatment of inflammatory diseases incredibly challenging. On the one hand, because of its pro-inflammatory state, that may aggravate or trigger flares in autoimmune diseases such as systemic lupus erythematosus (SLE). On the other hand, the risk of an immunosuppressive therapy during the active phase SARS-coV-2 infection that may lead to catastrophic outcomes. We report a case of a 24-year-old female newly diagnosed with SLE during COVID-19 pandemic who developed COVID-19 infection during her induction treatment for lupus nephritis.Case report-Case descriptionA 24-year-old Nepali female, with no past medical history of note, presented to her regional hospital with a history of flu-like symptoms few days ago, peripheral oedema, acute kidney injury with proteinuria and hypertension. Further investigations showed a high titre of double-stranded DNA antibodies, anti-cardiolipin IgM and B2 microglobulin positive and low C3. She also developed a haemolytic anaemia and thrombocytopenia during her admission. She received pulsed steroid therapy and was started on mycophenolate mofetil (MMF) for a probable lupus nephritis awaiting the results of biopsy, which showed later a lupus nephritis Class IV-G with active lesions. She then developed symptoms of COVID-19 infection and had a positive PCR leading to an interruption of her induction therapy. She was recruited to the RECOVERY trial on the lopinavir-ritonavir arm and made a good recovery.Case report-DiscussionIt is well known that viruses can trigger or aggravate auto-immune response in patients predisposed genetically. However, the role of SARS-coV-2 is not elucidated yet. The EULAR COVID-19 registry showed that rheumatoid arthritis and SLE were the most prevalent rheumatic diseases, and there was an increased risk in those who are on moderate to high dose corticosteroids. In patients with SLE and COVID-19 infection, it is agreed by all the national and international rheumatology societies to interrupt their immunosuppressive therapy until the symptoms resolve, especially those with renal involvement or an active disease. Which is the case in our patient. Luckily, she resumed her MMF a month later after a negative PCR and her renal function has continued to improve.Case report-Key learning pointsLupus nephritis is a major risk factor for overall morbidity and mortality in SLE. It requires an early immunosuppressive treatment to induce remission.Randomized clinical trials showed that MMF is at least equally effective as cyclophosphamide in inducing remission and that it has been associated with a reduced risk of infection and amenorrhea. It seems to be a suitable alternative in women of childbearing age. In patients with concomitant COVID-19 disease, immunosuppressive therapy should be paused until the symptoms improve.