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1.
Embase; 28.
Preprint in English | EMBASE | ID: ppcovidwho-346602

ABSTRACT

Chronic infection with human cytomegalovirus (CMV) may contribute to poor vaccine efficacy in older adults. We assessed effects of CMV serostatus on antibody quantity and quality, as well as cellular memory recall responses, after 2 and 3 SARS-CoV-2 mRNA vaccine doses, in older adults in assisted living facilities. CMV serostatus did not affect anti-Spike and anti-RBD IgG antibody levels, nor neutralization capacity against wildtype or beta variants of SARS-CoV-2 several months after vaccination. CMV seropositivity altered T cell expression of senescence-associated markers and increased TEMRA cell numbers, as has been previously reported;however, this did not impact Spike-specific CD4+ T cell memory recall responses. CMV seropositive individuals did not have a higher incidence of COVID-19, though prior infection influenced humoral immunity. Therefore, CMV seropositivity may alter T cell composition but does not impede the durability of humoral protection or cellular memory responses after SARS-CoV-2 mRNA vaccination in older adults. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

2.
Archives of Clinical Infectious Diseases ; 17(3), 2022.
Article in English | EMBASE | ID: covidwho-2067096

ABSTRACT

SARS-CoV-2, the pathogen responsible for COVID-19, has infected hundreds of millions since its emergence in late December 2019. Recently, concern has been raised due to the increased prevalence of co-infections with opportunistic pathogens among these pa-tients. Though not common, co-infections may be associated with adverse outcomes and increased risk of morbidity and mortality among patients suffering from COVID-19. Cytomegalovirus (CMV) infection is a serious problem among immunocompromised and critically ill patients. So far, few cases of co-infection with COVID-19 and CMV have been reported. Here, we report the co-infection with COVID-19 and CMV in a young woman presenting with sudden, progressive fever, delusion, agitation, bizarre behavior, seizure, and loss of consciousness leading to death despite receiving appropriate anti-viral treatment. To the best of our knowledge, this is the first case of coexisting SARS-CoV-2 and CMV infection presenting with severe, progressive meningoencephalitis in the era of COVID-19.

3.
American Journal of Transplantation ; 22(Supplement 3):1069, 2022.
Article in English | EMBASE | ID: covidwho-2063450

ABSTRACT

Purpose: Increasing mismatch between kidneys available for transplant and the number of patients on the transplant wait list has led to research into novel sources of organs. One such source is kidneys from hepatitis C NAT positive deceased donors. This was previously deemed unforbidden territory due to the risk of disease transmission;however, with the development of direct-acting antiviral agents for effective treatment of Hepatitis C, this organ pool is now usable. Method(s): A retrospective analysis of outcomes of Hepatitis C NAT positive kidney transplants into Hepatitis C seronegative recipients was conducted at newly opened Appalachian transplant center. Due to insurance constraints, the criteria to initiate hepatitis C therapy was seroconversion to positive Hepatitis C PCR. Outcomes examined include median creatinine, glomerular filtration rate (GFR), liver function tests, recipient Hepatitis C seroconversion, concomitant Ebstein Barr virus (EBV), Cytomegalovirus (CMV) or polyoma hominis (BK) activation, morbidities and mortality. Result(s): Six transplants (of 15 total kidney transplants) from Hepatitis C NAT positive donors were performed in the first year of establishment. Male to female ratio was 2:1 and median patient age was 55.7 years (Range 42-73 years). Median follow-up was 10 months (Range 2-12 months). Diabetes and hypertensive nephrosclerosis were the most common causes of end stage renal disease at 40%. The average time on dialysis was 2.9 years (Range 1-6 years), the most common type being hemodialysis (67%) followed by peritoneal dialysis (33%). Average time on transplant waitlist was 5.57 months (Range 1.2-13.2 months). All patients seroconverted but with treatment, by 24 weeks all patients maintained undetectable viral loads. Patient survival rate was 83% with a death censored graft survival rate of 100%. One patient died due to respiratory failure from COVID-19 infection. Median creatinine and GFr were 1.96 mg/dL (Range 1.8 - 2.6 mg/dL) and 41.3 (Range 35.3 - 50) respectively. One case each of acute antibody and T cell mediated rejection was seen (6.7%), which were treated successfully. CMV, BK and EBV virus reactivation were seen in one patient each (6.7%). The most common complication was COVID-19 infection (50%) followed by neutropenia (33%). Conclusion(s): With the development of direct-acting antiviral agents offering complete cure of Hepatitis C, kidneys from Hepatitis C positive donors can be used for transplantation with excellent outcomes.

4.
American Journal of Transplantation ; 22(Supplement 3):572, 2022.
Article in English | EMBASE | ID: covidwho-2063393

ABSTRACT

Purpose: To study the clinical application of metagenomic next-generation sequencing (mNGS) in the detection of viral infections in kidney transplant recipients (KTRs) during the COVID-19 pandemic. Method(s): Using mNGS techniques, 50 human fluid samples of KTRs were detected in Henan Province People's Hospital between May 2020 to May 2021, including 20 bronchoalveolar lavage fluid (BALF) samples, 21 urine samples and 9 blood samples. The detected nucleic acid sequences were compared and analyzed with the existing viral nucleic acid sequences in the database, and the virus infection spectrum of KTRs was drawn. Result(s): The viral nucleic acids of 15 types of viruses were detected in 96.00% (48/50) of the samples, of which 11 types of viruses were in BALF (95.00%, 19/20), and the dominant viruses were torque teno virus (TTV) (65.00%;13/20), cytomegalovirus (CMV) (45.00%;9/20) and human alphaherpesvirus 1 (25.00%;5/20). 12 viruses (95.24%, 20/21) were detected in the urine, and the dominant viruses were TTV (52.38%;11/21), JC polyomavirus (52.38%;11/21), BK polyomavirus (42.86%;9/21), CMV (33.33%;7/21) and human betaherpesvirus 6B (28.57%;6/21). 7 viruses were detected in the blood (100.00%, 9/9), and the dominant virus was TTV (100.00%;9/9). Four rare viruses were detected in BALF and urine, including WU polyomavirus, primate bocaparvovirus 1, simian virus 12, and volepox virus. Further analysis showed that TTV infection with high reads indicated a higher risk of acute rejection (P<0.05). Conclusion(s): mNGS detection reveals the rich virus spectrum of infected persons after kidney transplantation, and improves the detection rate of rare viruses. TTV may be a new biomarker for predicting rejection. (Figure Presented).

5.
American Journal of Transplantation ; 22(Supplement 3):574, 2022.
Article in English | EMBASE | ID: covidwho-2063363

ABSTRACT

Purpose: This study assessed outcomes of hepatitis C virus (HCV) donor positive to recipient negative (D+/R-) kidney transplants (KT) in high immunologic risk patients. Literature reports positive short-term outcomes in low immunologic risk patients, but limited data exists to support HCV D+/R- KT in high immunologic risk patients. Method(s): This retrospective cohort study included HCV antibody negative (-) recipients of a nucleic acid test (NAT) positive (+) KT who received HCV treatment with direct-acting antiviral therapy from 12/1/20 and 11/30/21. NAT+ KT recipients were matched 1:1 with NAT - KT recipients based on age, body mass index, and gender. All serologies were confirmed prior to study inclusion. The primary outcome was a composite of patient and graft survival 3 months post-KT. Secondary outcomes included percent of patients with sustained virologic response (SVR), time to HCV treatment initiation, incidence of cytomegalovirus (CMV) and BK viremia, presence of de novo donor specific antibody (DSA), rejection and HCV treatment related adverse drug reactions (ADRs). Descriptive statistics were used for baseline characteristics and a Log-Rank test was used for the primary outcome. Result(s): Eighteen HCV NAT+ KT recipients were matched with 18 HCV NAT- KT recipients. Study population was similar between groups and had end stage renal disease due to diabetes and/or hypertension, mean class I PRA >14%, pre-transplant DSA in 16% of patients in each cohort, and all received induction with rabbit anti-thymocyte globulin (Table 1). There was no difference in patient (p=0.32) and graft survival (p=0.99) between groups at 3 months post-KT. One death due to COVID-19 occurred in the NAT- group. There was no difference in estimated glomerular filtration rate (eGFR) at 1 (p=0.39) and 3 months (p=0.28), incidence of delayed graft function (DGF) (p= 0.67) or CMV (p=0.1) and BK viremia (p=1) between groups. (Table 2). HCV transmission occurred in all NAT+ KT recipients, and all who completed therapy achieved SVR. Treatment was initiated on average 8.5 weeks post-KT (Table 3). Notably, 33% of patients required financial assistance to obtain HCV treatment. Conclusion(s): Use of HCV D+/R- KT resulted in no difference in patient and graft survival at 3 months in this matched cohort. HCV NAT + KT patients should be connected with financial assistance programs early to promote timely treatment initiation. (Table Presented).

6.
Chest ; 162(4):A895, 2022.
Article in English | EMBASE | ID: covidwho-2060719

ABSTRACT

SESSION TITLE: Pathologies of the Post-COVID-19 World SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: SARS-CoV-2 related autoimmune and thrombotic complications due to vigorous immune system stimulation and induction of hypercoagulable state are not uncommon. Two hypotheses have been proposed for thrombotic microangiopathy associated with low ADAMTS13 levels in patients with COVID-19 disease. First underscores a significant increase in von Willebrand factor (vWF), likely due to endothelial activation, that overwhelms ADAMTS13. It is observed in the absence of thrombocytopenia or ADAMTS13 inhibitor. The second highlights the formation of autoantibodies against ADAMTS13 because of an immunological trigger (SARS-CoV-2), resulting in the diagnosis of TTP. CASE PRESENTATION: This is a case of a 72-year-old Caucasian man with a history of hypertension, diabetes, chronic obstructive lung disease, and asymptomatic SARS-CoV-2 infection three weeks ago who was transferred to our institution to initiate plasmapheresis for suspected TTP due to new-onset confusion, anemia and worsening renal function. Patient had presented with confusion a day before transfer. Vital signs were remarkable for tachycardia (heart rate of 105 beats/min). Labs were significant for anemia (hemoglobin:6.7 g/dL), thrombocytopenia (platelet count:13 K/µL), acute kidney injury (creatinine:1.8 mg/dL), elevated lactate dehydrogenase (1983 IU/L), high bilirubin (2.3 mg/dL), low haptoglobin (<4 mg/dL), and demonstration of schistocytes on peripheral smear. The coagulation profile was normal. On arrival, he required emergent intubation due to multiple seizures. Computed tomography scan of the head was normal. SARS-CoV-2 molecular testing was negative. Given a PLASMIC score of six, urgent plasmapheresis and high-dose methylprednisolone were started. Screening for human immunodeficiency virus, hepatitis viruses, Epstein-Barr virus, and Cytomegalovirus were negative. Subsequently, his ADAMTS13 activity resulted as being ≤5% with an elevated inhibitor Bethesda titer of 0.9 (normal < 0.4). The patient completed six sessions of plasmapheresis. He was discharged on steroid taper and weekly rituximab. DISCUSSION: COVID-19 associated de-novo TTP has been mostly reported with typical COVID-19 symptoms within a few days of a positive test. One report described presentation with only neurological symptoms 19 days after a positive test with low autoantibody titers, favoring the hypothesis of consumption of ADAMTS13. To the best of our knowledge, this is the first case of new, late-onset immune TTP developing three weeks after asymptomatic COVID-19 infection with a robust positive inhibitor screen and infinitesimal ADATMS13 levels. The temporal sequence of events and lack of other plausible causes aided in the diagnosis of COVID-19 induced TTP. CONCLUSIONS: Our report aims to make clinicians aware of ruling out TTP as a cause of thrombocytopenia and/or altered mental status in patients with past COVID-19 infection, aiding in early management. Reference #1: 1. Mancini I, Baronciani L, Artoni A, Colpani P, Biganzoli M, Cozzi G, Novembrino C, Boscolo Anzoletti M, De Zan V, Pagliari MT, Gualtierotti R, Aliberti S, Panigada M, Grasselli G, Blasi F, Peyvandi F. The ADAMTS13-von Willebrand factor axis in COVID-19 patients. J Thromb Haemost. 2021 Feb;19(2):513-521. doi: 10.1111/jth.15191. Epub 2020 Dec 18. PMID: 33230904;PMCID: PMC7753796. Reference #2: 2. Tehrani HA, Darnahal M, Vaezi M, Haghighi S. COVID-19 associated thrombotic thrombocytopenic purpura (TTP);A case series and mini-review. Int Immunopharmacol. 2021;93:107397. doi:10.1016/j.intimp.2021.107397 Reference #3: 3. Beaulieu, M.-C., Mettelus, D.S., Rioux-Massé, B. and Mahone, M. (2021), Thrombotic thrombocytopenic purpura as the initial presentation of COVID-19. J. Thromb. Haemost., 19: 1132-1134. https://doi-org.libproxy.uams.edu/10.1111/jth.15231 DISCLOSURES: No relevant relationships by Harmeen Goraya No relevant relationships by PRACHI SALUJA

7.
Chest ; 162(4):A865-A866, 2022.
Article in English | EMBASE | ID: covidwho-2060714

ABSTRACT

SESSION TITLE: Studies on COVID-19 Infections Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/18/2022 01:30 pm - 02:30 pm PURPOSE: Latent Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are commonly reactivated in critically ill patients with severe infections. This study aimed to evaluate the proportion of reactivation of EBV and CMV and its impact on length of stay, need for ventilation, and Ichikado CT scores in patients with coronavirus disease 2019 (COVID-19). METHODS: A retrospective study was conducted comprising adult patients admitted to our hospital with COVID-19 infection from June 2021 to September 2021. Patients were divided into groups: virus-free, EBV-only, CMV-only, and EBV and CMV detected. Primary outcomes were length of stay, need for ventilation, and Ichikado CT score. Descriptive statistics, one-way ANOVA, Games-Howell, and Kruskal-Wallis tests were used. RESULTS: 189 patients were included with a median age of 51 years [41 – 66], 80 (42.3%) were female and 109 (57.7%) were male. CD4(+) counts were lower in all viral reactivation groups. EBV-only (157 cell/µl [93 – 279.2] ), CMV-only (82.5 cell/µl [65.5 – 323.7] ), both viruses (62.5 cell/µl [47.5 – 135.5]) and virus-free (221 cell/µl [117 – 318]), (H(3) = 12.029, p = < 0.01). A significant increase in the Ichikado CT score was seen in the viral reactivation groups. EBV 186.5 [43.6], CMV 177.5 [41.6], both-viruses group 204 [50.3] vs. virus-free 161 [45.8],( H(3) = 15.770, p = < 0.01). There was an increase in days of hospitalization when comparing the virus-free and the viral reactivation groups. EBV (9 days [5.5-15.5]), CMV (17 days [3-33]), both viruses (23 days [8-31]) vs. virus-free (5 days [3.5-9]), (H(3) = 15.487, p = < 0.01). Regarding the need for assisted ventilation, there was no difference between groups. 7 (9.1%) patients in the virus-free group, 29 (29.9%) patients in the EBV group, 2 (33.3%) patients in the CMV group, and 2 (22.2%) patients in the both-viruses group needed mechanical ventilation (X2 (3, N=189) = 11.699, p= 0.08). Additionally, a statistically significant decrease in albumin levels on admission was found in the EBV-only patients compared to the virus-free group, (3.4 g/dL [0.44] vs 3.75 g/dL [0.46], F(3,185) = 5.483, p = < 0.01). CONCLUSIONS: Viral reactivation is associated with lower CD4(+) count, an increase in length of stay, and higher Ichikado CT scores. CLINICAL IMPLICATIONS: EVB and CMV reactivation is associated with low CD4(+) counts and longer hospital stay. DISCLOSURES: No relevant relationships by David Akinwale No relevant relationships by Angelica Almaguer No relevant relationships by Sushen Bhalla No relevant relationships by Ailine Canete Cruz No relevant relationships by Ndiya Emeaba Speaker/Speaker's relationship with johnson and johnson Please note: approx year 2000 Added 03/31/2022 by Joseph Gathe, value=Honoraria clinical research relationship with gilead Please note: since 1990 Added 03/31/2022 by Joseph Gathe, value=Grant/Research clinical research relationship with ansun Please note: 2020 Added 03/31/2022 by Joseph Gathe, value=Grant/Research Support clinical research relationship with regeneron Please note: 2020 Added 03/31/2022 by Joseph Gathe, value=Grant/Research Support No relevant relationships by Jesus Salvador Gonzalez Lopez No relevant relationships by Najia Hussaini No relevant relationships by Claudia Ramirez No relevant relationships by Salim Surani No relevant relationships by Daryelle Varon No relevant relationships by Joseph Varon No relevant relationships by Mohamed Ziad

8.
Chest ; 162(4):A755, 2022.
Article in English | EMBASE | ID: covidwho-2060683

ABSTRACT

SESSION TITLE: COVID-19 Co-Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Human cytomegalovirus (CMV) is a herpesvirus with a high prevalence that causes latent disease in immunocompetent hosts. It is an important opportunistic infection with a variety of clinical manifestations, including pneumonia, in immunocompromised patients.[1] CASE PRESENTATION: A 45-year-old man with no past medical history presented with fever and dyspnea and was positive for coronavirus disease 2019 (COVID-19). He developed acute respiratory distress syndrome (ARDS) and was intubated 13 days after presentation, but developed refractory hypoxemia requiring veno-venous extracorporeal membrane oxygenation (ECMO) (cannulated 16 days after presentation). He received a 5-day course of remdesivir and 10 days of dexamethasone 6 mg daily. His course was complicated by acute renal failure requiring continuous renal replacement therapy, septic shock due to a pseudomonal ventilator-associated pneumonia, right ventricular failure, heparin induced thrombocytopenia, and right pneumothorax requiring chest tube thoracostomy. After 4 weeks of ECMO there was lung recovery with ECMO sweep gases <1L/minute, improved radiographic appearance and tidal volumes, and decannulation was anticipated. However, he subsequently developed profound shock of unknown etiology with a rapid worsening of his lung function requiring increased ECMO support. Care was withdrawn at ECMO day 46 due to multiorgan failure. Pathology of his lungs at autopsy showed prominent intranuclear viral inclusions and positive immunohistochemistry in alveolar macrophages consistent with a diagnosis of CMV pneumonia. DISCUSSION: While CMV typically causes latent disease it can reactivate in the setting of immunosuppression and/or critical illness.[1] Patients with severe COVID-19 frequently are treated with immunosuppressive therapies, such as corticosteroids, anti-interluekin-6 therapies, and JAK inhibitors. Due to this immunosuppression, opportunistic infections have been reported in these patients.[2] It can be difficult to differentiate COVID-19 pneumonia from other respiratory infections based on imaging and lab studies alone, especially in patients with prolonged mechanical ventilation and with severe parenchymal disease requiring ECMO support. Little is known about the incidence of CMV and COVID-19 coinfection. There are several cases of biopsy-proven CMV pneumonia in immunocompromised critically ill patients with COVID-19, but this is the first reported case in an immunocompetent patient. CONCLUSIONS: This case highlights the need to maintain a high degree of suspicion for CMV pneumonia in patients with severe COVID-19 pneumonia who receive immunosuppressive therapies. While the diagnosis was made at autopsy in this case, it may be possible to arrive at an earlier diagnosis with CMV polymerase chain reaction (PCR) assays sent from the serum and bronchoalveolar lavage (as lung biopsies are usually impractical in ARDS). Reference #1: de la Hoz RE, Stephens G, Sherlock C. Diagnosis and treatment approaches of CMV infections in adult patients. J Clin Virol. 2002 Aug;25 Suppl 2:S1-12. doi: 10.1016/s1386-6532(02)00091-4. PMID: 12361752. Reference #2: Abdoli A, Falahi S, Kenarkoohi A. COVID-19-associated opportunistic infections: a snapshot on the current reports [published online ahead of print, 2021 Aug 23]. Clin Exp Med. 2021;1-20. doi:10.1007/s10238-021-00751-7 DISCLOSURES: No relevant relationships by Nancy Law No relevant relationships by Mazen Odish No relevant relationships by Robert Owens No relevant relationships by Travis Pollema No relevant relationships by Alyssa Self No relevant relationships by Cassia yi

9.
Chest ; 162(4):A625, 2022.
Article in English | EMBASE | ID: covidwho-2060650

ABSTRACT

SESSION TITLE: Unusual Pneumonias SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Cytomegalovirus (CMV) is an important infectious organism in the morbidity and mortality of immunocompromised patients. CMV is a known cause of pneumoina in transplant patients, such as lung transplant recepients. Pneumocytis Jiroveci Pneumonia (PCP) is also a known risk factor for potentially life-threatening infections in immunocompromised patients. In this , we are presenting a rare case of an immunocompromised patient who had penumonia caused by a concurrent CMV and PCP infections. CASE PRESENTATION: A 53 year-old female patient with history of Rheumatoid Arthritis treated with immunomodulating medications admitted for Shortness of breath, fatigue and tiredness but no fever. COVID-19 and influenza infections (PCR) tests were both negative. At presentation, her WBC was 9900. CT with contrast of her chest showed no embolism, but multi-focal widespread groundglass opacities. Blood culture was negative, MRSA screen was negativetoo, but Fungitell test was positive (with a value of more than 500) and serum LDH test was elevated to 382. CMV quantitaive PCR was elevated to 10,000 copies. A bronchoscopy was done and CMV PCR Bronchoalveolar lavage (BAL) is detected at 650 copies/ ml. A BAL EBV PCR tests was negative. Pneumocystis Jiroveci pneumonia was detected on BAL Direct fluorescent antibody test (DFA). CMV retinitis has been ruled out by an ophthalmology exam. Patient was diagnosed with concurrent CMV and PCP pneumonia infection and her respiratory status worsened mandating a brief ICU stay. Treatment was started with Bactrim, Valganciclovir and Ganciclovir with progressive improvement. In a follow up appointment at the infectious diease clinic two months later, the patient condition improved but was still in need for supplemental oxygen through nasal canula. DISCUSSION: A concurrent CMV and PCP microorganisms lung infection is rare, but patient with underlying immunocompromise constitue a major risk factor for that. CONCLUSIONS: Patients with underlying immuncompromise conditions are at risk of many infections with grave morbidity and mortality risks. Though it is a rare to have a concurrent CMV and PCP lung infection, a patient treated with immunomodulating medications including methotrexate, prednisone and rituximab was a culprit for severe infection. Reference #1: Peghin, M., Hirsch, H. H., Len, Ó., Codina, G., Berastegui, C., Sáez, B., Solé, J., Cabral, E., Solé, A., Zurbano, F., López-Medrano, F., Román, A., & Gavaldá, J. (2016). Epidemiology and immediate indirect effects of respiratory viruses in lung transplant recipients: A 5-year prospective study. American Journal of Transplantation, 17(5), 1304–1312. https://doi.org/10.1111/ajt.14042 DISCLOSURES: No relevant relationships by MohD Ibrahim

10.
Chest ; 162(4):A419-A420, 2022.
Article in English | EMBASE | ID: covidwho-2060591

ABSTRACT

SESSION TITLE: COVID-19 Co-Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Herpes simplex type 1 (HSV-1) related respiratory tract infections have been described in critically ill or immunocompromised patients. We present a case of HSV-1 pneumonia in a mechanically ventilated and immunocompromised patient in the setting of SARS CoV-2 infection. CASE PRESENTATION: A 54-year-old female on Rituximab for Rheumatoid arthritis presented with shortness of breath and cough. She was afebrile, tachypneic and hypoxic. She was discharged 1 week prior after a 3 weeklong treatment for COVID-19 pneumonia. CT Angiogram showed extensive bilateral patchy consolidations with ground-glass infiltrates and subsegmental pulmonary emboli. Patient was initiated on heparin and broad-spectrum IV antibiotics with steroids for presumed ARDS with superimposed bacterial pneumonia. Her respiratory failure worsened requiring invasive mechanical ventilation. Failing oxygenation despite aggressive therapy prompted further workup that showed a normal echo and negative blood cultures. Sputum was negative for Pneumocystis pneumonia and Tuberculosis. Cytology from tracheal aspirate showed bronchial cells with inclusions and multinucleations consistent with HSV-associated cytopathic changes. A positive serum HSV-1 IgG and serum quantitative PCR of HSV-1 DNA solidified the diagnosis. Ganciclovir therapy was initiated to cover for HSV and Cytomegalovirus (CMV), however, a serum CMV PCR was negative. Within a day, her clinical course took a downward spiral. CT chest was repeated which showed worsening airspace disease. Despite ganciclovir therapy, the severity of lung disease led to eventual failure of oxygenation and patient demise. DISCUSSION: Prolonged mechanical ventilation due to ARDS is a risk factor for HSV bronchopneumonia in patients with COVID-19 and has shown an increased mortality 1,2. Diagnosis can be achieved by viral culture or observing cytopathic effects of HSV on cells in tracheobronchial aspirates, bronchoalveolar lavage, or biopsy3. In critically ill patients early treatment has been shown to prolong the ICU time to death and improved oxygenation4. It is important to test for co-infections as about 65% of HSV pneumonia cases are associated with pathogens like CMV and Pneumocystis5. CONCLUSIONS: Worsening respiratory disease in mechanically ventilated COVID-19 patients despite antibiotic therapy for suspected superimposed bacterial infection warrants a workup for secondary viral infections like HSV. Increased mortality is seen if not promptly treated. Reference #1: 1. Meyer A, Buetti N, Houhou-Fidouh N, et al. HSV-1 reactivation is associated with an increased risk of mortality and pneumonia in critically ill COVID-19 patients. Critical Care. 2021/12/06 2021;25(1):417. doi:10.1186/s13054-021-03843-8 Reference #2: Le Balc'h P, Pinceaux K, Pronier C, Seguin P, Tadié J-M, Reizine F. Herpes simplex virus and cytomegalovirus reactivations among severe COVID-19 patients. Critical Care. 2020/08/28 2020;24(1):530. doi:10.1186/s13054-020-03252-3 Reference #3: Shah JN, Chemaly RF. Herpes Simplex Virus Pneumonia in Patients with Hematologic Malignancies. Pulmonary Involvement in Patients with Hematological Malignancies. 2010:301-311. doi:10.1007/978-3-642-15742-4_24 DISCLOSURES: No relevant relationships by Andrew Cox No relevant relationships by Syeda Hassan No relevant relationships by Maria Khan No relevant relationships by Malik Muhammad Uzair Khan No relevant relationships by Rameesha Mehreen No relevant relationships by Rahat Ahmed Memon No relevant relationships by Ifrah Naeem No relevant relationships by Laura Walters

11.
Chest ; 162(4):A281-A282, 2022.
Article in English | EMBASE | ID: covidwho-2060548

ABSTRACT

SESSION TITLE: Extraordinary Cardiovascular Reports SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: Acute myocarditis from COVID-19 has been well documented, but there are few cases of COVID -19 patients developing dilated cardiomyopathy (3). We present a case of COVID-19 induced dilated cardiomyopathy leading to cardiogenic shock. CASE PRESENTATION: A 49-year-old African-American female presented to the emergency department (ED) with shortness of breath. She was diagnosed with COVID-19 infection four weeks prior to presentation, and since that time she experienced continuously worsening dyspnea, congestion, and weakness. In the ED, the patient was found to have pulmonary edema and bilateral pleural effusions on chest x-ray, as well as acute kidney injury with a creatinine level of 2.85 mg/dL. An echocardiogram revealed a new diagnosis of dilated cardiomyopathy with reduced ejection fraction of 10-15% with a large left ventricular thrombus. Heparin infusion was initiated and intravenous furosemide was administered for diuresis. Her renal function continued to worsen, which was attributed to cardiorenal syndrome. She became hypotensive and was found to be in cardiogenic shock, which required intensive care unit admission with the initiation of continuous renal replacement therapy (CRRT). The patient improved with CRRT, however her renal function did not recover and she continued to require hemodialysis. She was able to be transferred out of the intensive care unit, and the heparin was bridged to warfarin. Goal-directed medical therapy was initiated for her heart failure. She was eventually discharged home with an external cardioverter-defibrillator vest. A follow-up echocardiogram three months later revealed the left ventricular thrombus had resolved, however, her ejection fraction had improved to only 15-20% despite medication compliance. An implantable cardioverter-defibrillator (ICD) was placed and the patient continues to be followed closely by cardiology. DISCUSSION: Viral infection is a well-documented cause of myocarditis with some patients developing dilated cardiomyopathy (1). Inflammatory dilated cardiomyopathy occurs most commonly in patients infected with Coxsackie B virus, Human Parvovirus B19, Adenovirus, Human Immunodeficiency Virus, Hepatitis C Virus, Cytomegalovirus, Epstein-Barr Virus, and Human Herpes Virus 6 (1). The proposed mechanism of inflammatory cardiomyopathy includes infection of the myocytes, incomplete viral elimination, and persistent retained viral components in the myocytes(2). This may cause direct viral injury or chronic myocardial inflammation leading to remodeling (2). It is documented in the literature that COVID-19 can lead to myocarditis and various types of acute cardiomyopathy (3). However, there have been only a few reported cases of COVID - 19 induced dilated cardiomyopathy (3). CONCLUSIONS: While rarely reported thus far, it should be established that COVID-19 alone can cause dilated cardiomyopathy and lead to heart failure (3). Reference #1: Schultheiss H-P, Baumeier C, Pietsch H, Bock C-T, Poller W, Escher F. Cardiovascular consequences of viral infections: from COVID to other viral diseases. Cardiovascular Research. Published online October 5, 2021. doi:10.1093/cvr/cvab315 Reference #2: Kühl U, Pauschinger M, Seeberg B, et al. Viral Persistence in the Myocardium Is Associated With Progressive Cardiac Dysfunction. Circulation. 2005;(13):1965-1970. doi:10.1161/circulationaha.105.548156 Reference #3: Komiyama M, Hasegawa K, Matsumori A. Dilated Cardiomyopathy Risk in Patients with Coronavirus Disease 2019: How to Identify and Characterise it Early? European Cardiology Review. Published online May 27, 2020. doi:10.15420/ecr.2020.17 DISCLOSURES: No relevant relationships by Amanda Cecchini No relevant relationships by Austin Richardson No relevant relationships by Krupa Solanki

12.
ProQuest Central; 2022.
Preprint in English | ProQuest Central | ID: ppcovidwho-345507

ABSTRACT

Background: Leptomeningeal metastasis is an infrequent form of cancer expression, and it has a poor prognosis due to its torpid evolution and its challenging diagnosis. Case report: We report the case of a 68-year-old woman with rapidly progressing cognitive decline and focal epilepsy. Brain magnetic resonance imaging showed extensive gyriform hypersignal in the right precentral sulcus region, without mass effect, tenuous contrast uptake, and hydrocephalus with transependymal edema. The body tomographic study was negative for solid cancer and the 18F-FDG PET-CT revealed a severe hypermetabolism in the right lung upper lobe. These findings were suggestive of lung cancer with leptomeningeal metastasis. We performed a brain biopsy, finding atypical cells in the leptomeningeal region with positive immunohistochemical staining for CK7 and negative for CK20 corresponding to lung adenocarcinoma. The patient was evaluated in the oncology service and scheduled for radiotherapy and chemotherapy. Conclusions: Focal leptomeningeal disease is an entity that should be considered as a differential diagnosis in all cases of focal leptomeningitis. Timely diagnosis and adequate cancer management can increase patient survival.

13.
Ann Intensive Care ; 12(1): 87, 2022 Sep 24.
Article in English | MEDLINE | ID: covidwho-2043139

ABSTRACT

BACKGROUND: Lung reactivations of Herpesviridae, herpes simplex virus (HSV) and cytomegalovirus (CMV) have been reported in COVID-19 patients. Whether or not those viral reactivations are more frequent than in other patients is not known. METHODS: Retrospective monocentric cohort study of 145 patients with severe COVID-19 pneumonia requiring invasive mechanical ventilation and who were tested for HSV and CMV in bronchoalveolar lavage performed during fiberoptic bronchoscopy for ventilator-associated pneumonia suspicion. Rates of HSV and CMV lung reactivations, and HSV bronchopneumonitis were assessed and compared with an historical cohort of 89 patients with severe influenza pneumonia requiring invasive mechanical ventilation. RESULTS: Among the 145 COVID-19 patients included, 50% and 42% had HSV and CMV lung reactivations, respectively, whereas among the 89 influenza patients, 63% and 28% had HSV and CMV lung reactivations, respectively. Cumulative incidence of HSV lung reactivation (taking into account extubation and death as competing events) was higher in influenza than in COVID-19 patients (p = 0.03), whereas the rate of HSV bronchopneumonitis was similar in both groups (31% and 25%, respectively). Cumulative incidence of CMV lung reactivation (taking into account extubation and death as competing events) was similar in COVID-19 and influenza patients (p = 0.07). Outcomes of patients with HSV or CMV lung reactivations were similar to that of patients without, whatever the underlying conditions, i.e., in COVID-19 patients, in influenza patients, or when all patients were grouped. CONCLUSIONS: HSV and CMV lung reactivations are frequent in COVID-19 patients, but not more frequent than in patients with influenza-associated severe pneumonia, despite a higher severity of illness at intensive care unit admission of the latter and a longer duration of mechanical ventilation of the former. Although no impact on outcome of HSV and CMV lung reactivations was detected, the effect of antiviral treatment against these Herpesviridae remains to be determined in these patients.

14.
Kidney International Reports ; 7(9):S514, 2022.
Article in English | EMBASE | ID: covidwho-2041722

ABSTRACT

Introduction: Kidney transplant recipients (KTRs) have to receive lifelong immunosuppressive therapy. Consequently they are predisposed to life threatening infections. Even though the data on infectious pathologies have been described in KTRs, the data on long term sequalae of such diseases is lacking. Methods: In this single high volume centre we followed up 100 KTRs, who presented to us with signs of infections. Patients presenting with acute drug reaction or toxicity, malignancy, and auto-immune disorders were excluded. Results: Majority of the patients were male (80%) with a median age of 47years and the median duration of follow up is 34 months. Comorbidites were present in majority of patients in the form of hypertension (83%), Diabetes (11%), heart disease (7%). Amongst infections prior to kidney transplant, TB (28%), HCV (11%) and HBV (1%) were the predominant. 33% patients had acute graft dysfunction, which on biopsy showed mostly ATN and was managed conservatively. However one patient had features of CMV viremia, which was managed with iv Valganciclovir. During follow up 57% of patients presented to us with at least one episode of infection, while 24% patients had 3 more episodes of infection during the follow up period. First episode of infection occurred after a median duration of 10 months. The most common infections were UTI (40%), acute gastroenteritis (35%), CMV infections (10%),pyelonephritis (5%), bacterial pneumonia (5%) protozoal infections (2%), COVID (2%). Most of the infections were managed successfully however 10% patients had graft dysfunction and are on maintenance hemodialysis. Conclusions: Infections in KTRs are a serious debilitating condition which affect graft function. Prompt and aggressive treatment is warranted for graft survival. No conflict of interest

15.
Kidney International Reports ; 7(9):S508-S509, 2022.
Article in English | EMBASE | ID: covidwho-2041721

ABSTRACT

Introduction: Because of the limited donor pool, transplants are being done across the blood group and even HLA incompatibility barriers. But this comes at the cost of increased immunosuppression and the side effects. Effect of this intensified immunosuppression on the incidence of post transplant infections and the type of infection has not been studied extensively. Methods: We retrospectively analysed the incidence of infection in ABO incompatible transplants (ABOi) and compared it with propensity matched cohort of ABO compatible transplants(ABOc) over the same timeframe i.e. 2011 to April 2019. using hospital eHIS record system. Patients were matched with 1:2 ratio (ABOi: ABOc) for age (<60yr, >60yrs),sex, number of previous transplants, pretransplant infections, history of prior immunosuppression, diabetic status, NODAT, and induction agent used. Desensitization protocol for ABO incompatible transplant includes rituximab with double filtration plasmapheresis, plasmapharesis or immunoadsorption to target anti blood group titre of 8. Patient with high immunological risk (e.g.second transplant, HLA incompatible) receive ATG induction while others receive basiliximab induction. Valganciclovir prophylaxis was given only in patients with ATG induction. Results: [Formula presented] [Formula presented] During the study period 89 patients underwent ABOi transplants which were compared with 178 ABOc transplants. (Table1)Mean follow up duration was 50.45months (SD 26.8) in ABOi group and 49.47months (SD28.7) in ABOc group. 17% patients lost to follow up with their last follow up being more than 2 years before. Incidence of overall infections was similar in both the groups (59% (43/89) Vs 44.3% (79/178);p=0.6). (Table2) Incidence of urinary tract infections(UTI)was significantly more in ABOi group vs ABOc group.(23.5% (21/89) vs 11.79% (21/178);p=0.019). Cytomegalovirus infections (CMV) were significantly more in ABOi group 12.3% (11/89) as compared to ABOc group 5% (9/187) (p=0.04). All the patients with CMV infection were CMV IgG positive pretransplant except 2, one from ABOc group who was CMV IgG negative and another from ABOi group who’s pretransplant CMV serology was unavailable. There was no significant difference in incidence of fungal infection, pneumocystis infection, diarrheal infections (other than CMV),pneumonia (other than CMV, PCP, fungal), Herpes, BKV infection. Incidence of post-transplant tuberculosis (3.3% (3/89) Vs 2.8% (5/178);p=1.0) and SARS COV2 infections (12.3% (11/89) vs 9% (16/178);p=0.39 was similar in both the groups. Patient survival was similar in both the groups i.e.95.5% but death censored graft loss was significantly more in ABOi group 0.9% (8/89) as compared ABOc group 0.3% (5/178) p=0.03. Reason of graft loss in all the patients was immunological and not infection. Infection was cause for death in three ABOi patients and four ABOc patients. Conclusions: Overall incidence of infections in ABOi transplants was similar to Abo compatible transplant. Incidence of UTIs and CMV infections were significantly higher in ABOi group. No conflict of interest

16.
Kidney International Reports ; 7(9):S508, 2022.
Article in English | EMBASE | ID: covidwho-2041720

ABSTRACT

Introduction: Infections occurring in the post transplant period are the major cause of morbidity and mortality in renal transplant recipients. Early infections (within the first month) are more likely to be due to nosocomially acquired pathogens, surgical issues, and donor-derived infections. Opportunistic pathogens occur after 6 months, reflects the greater impact of immunosuppressive therapies. Late infections may be secondary to opportunistic pathogens or conventional ones. Methods: It is a retrospective observational study.All hospitalised patients with infections were included between November 2019 to march 2022 excluding covid 19 infections.Infections were categorised based on time line of infection into less than one month, 1-6 months and more than 6 months and sub categorised based on type of organisms and source of infection.All baseline characteristics, labs, microbiological including serology, PCR and cultures, radiological findings and histopathological findings were noted.Complications including graft dysfunction and need for various supports such as O2, ionotropes, ventilator and dialysis and treatment details and in hospital patient outcomes were analysed using descriptive statistics. Results: 53 patients admitted with infection in the given period were included in the study.Among them 88.67% were males and 11.33% females. In the study population 66.03 % underwent live related renal transplant and 33.97% underwent deceased donor transplantation. Mean age of the study population was 35.2 years. There were 118 events of infection identified during the study period.UTI was the most common post-transplant infection and occurred in 36.44 % of total events. There were 13 events of post-transplant infection in the first month. Most common infection in early post-transplant period was UTI, 53.84 % of events of UTI occurred followed by pneumonia in 23.07% of total events. E coli was isolated in 57.14 % of events There were 48 events of infections in the period of 1- 6 months.UTI was the most common infection (37.5 % of total events ) and E coli was the most common organism isolated(44.44 %). Pneumonia was the second commonly occurred event in 18.75 % of total events and Klebsiella was the most common isolated ( 55.56 % ).CMV disease was identified in 10.41% events, 40 % had tissue invasive CMV, 60% presented with cytopenia. There were 57 events of infections after 6 months, UTI was the most common infection(31.57% events) and E coli was the most common organism (44.00%).Pneumonia occurred in 19.29% followed by skin and soft tissue infection (13.94 %)herpes zoster ( 8.75% ) gastroenteritis(7.01%), BKVN (5.26%),oral candidiasis (3.50%)CMV disease (3.50%), tuberculosis(3.5%), meningitis (1.75%) and dengue(1.75%). 95.76% of infectious event was associated allograft dysfunction and 22.64 % of the study population had PTDM. In 15.25 % of events, patients had septic shock at presentation.Amongst them 44.44% had urosepsis, 33.33% had pneumonia, 22.22% had acute gastroenteritis. 18.86 % expired during hospital stay,amongst them 60 % had pneumonia and 30% had urosepsis and 10% had acute gastroenteritis. [Formula presented] [Formula presented] [Formula presented] [Formula presented] Conclusions: Patients who undergo renal transplantation are subjected to immunosuppression which increase the burden of infections in the post-transplant period.Early and accurate diagnosis is the key to prevent morbidity and mortality of renal transplant recipients No conflict of interest

17.
Chinese Traditional and Herbal Drugs ; 53(15):4781-4794, 2022.
Article in Chinese | EMBASE | ID: covidwho-2033401

ABSTRACT

Objective To explore the application pattern and mechanism of medicine and food homologous traditional Chinese medicine (TCM) against modern viral diseases. Methods The method of literature mining was applied based on the characteristics of modern viral diseases, combining with ancient books and modern prescriptions for the prevention and treatment of viral diseases to build a relevant prescription database. Then SPSS and R language were used to analyze the high-frequency medicine and food homologous TCM and high confidence medicine and food homologous prescriptions in these prescriptions, and cluster analysis was carried out. The antiviral characteristic active ingredients of high-frequency medicinal and food homologous TCN were identified and analyzed, and the action mechanism of active ingredients against modern viral diseases was evaluate by network pharmacology. Results In the prevention and treatment of modern viral diseases, Gancao (Glycyrrhizae Radix et Rhizoma)-Chenpi (Citri Reticulatae Pericarpium)-Fuling (Poria) had the highest confidence, Glycyrrhizae Radix et Rhizoma-Jiegeng (Platycodonis Radix) had the highest support. At the same time, the prescriptions were clustered and analyzed to obtain Jinyinhua (Lonicerae Japonicae Flos)-Huangqi (Astragali Radix)-Huoxiang (Agastache rugosa), Glycyrrhizae Radix et Rhizoma-Xingren (Armeniacae Semen Amarum)-Poria-Platycodonis Radix-Citri Reticulatae Pericarpium, Ganjiang (Zingiberis Rhizoma)-Renshen (Ginseng Radix et Rhizoma), Zisu (Perilla frutescens)-Gegen (Puerariae Lobatae Radix), Lugen (Phragmitis Rhizoma)-Sangye (Mori Folium), Shengjiang (Zingiberis Rhizoma Recens)-Dazao (Jujubae Fructus) clustering new prescription. The core action targets of EGFR, CASP3, VEGFA, STAT3, MMP9, HSP90AA1, mTOR, PTGS2, MMP2, TLR4, MAPK14, etc were identified. The action mechanism involved human cytomegalovirus infection, coronavirus disease-coronavirus disease 2019 (COVID-19), etc. The core action pathway were phosphatidylinositol-3/kinase protein kinase B (PI3K/Akt) signal pathway, mitogen activated protein kinase (MAPK) signal pathway, interleukin-17 (IL-17) signal pathway, Janus kinase/signal transducer and activator of transcription (JAK/STAT) signal pathway, etc. Conclusion Through data mining, six new prescriptions for preventing and controlling modern viral diseases were obtained, and the mechanism of action was preliminarily discussed, which provided some reference for the research and development of medicine and food homologous TCM prescriptions for the prevention and treatment of viral epidemics and related health products.

18.
HemaSphere ; 6:1395-1396, 2022.
Article in English | EMBASE | ID: covidwho-2032168

ABSTRACT

Background: Persistent cytopenia due to poor graft function (PGF) is a life-threatening complication in patients undergoing allogeneic HSCT (allo-HSCT). Several therapeutic approaches have been tested in this subset of patients with poor clinical results. Aims: The objective of this multicenter open-label interventional prospective phase II Novartis study (ELTION, ClinicalTrials.gov id: NCT03718533), was to analyze efficacy and safety of EPAG in patients with post-allo-HSCT poor graft function. Methods: Adult patients diagnosed with PGF (defined as severe cytopenia after day +30 post-transplant, with two or more of the following: platelets <20000/μL-mandatory-, ANC <1000/μL, hemoglobin< 10 g/dL), and full donor chimerism, were eligible to enter the trial. Study treatment consisted of EPAG. at 150 mg/day administered up to 36 weeks;dose adjustments were contemplated as per protocol on an individual basis. The primary efficacy endpoint was the overall hematologic response (partial and complete), as determined by platelet, hemoglobin and neutrophil counts by 16 weeks after the initiation of EPAG. Results: Although the aim of the study was to include 33 patients, recruitment stopped prematurely due to the difficulties for hospital visits posed during COVID-19 pandemic, and eventually only 10 patients were included. The decision for this premature termination is not related to any safety concern related to the drug. Patient characteristics are shown in the table 1 attached below. At EPAG. initiation, all 10 patients showed thrombocytopenia (<20000/μcL), 5 presented with anemia (Hgb <10 g/dL), and 4 had neutropenia (ANC <1000/μcL). Four patients discontinued EPAG before week 12 due to: disease progression/relapse (2 patients), protocol deviation (1 patient), and CMV infection (1 patient). In none of the cases, the event was related to study drug. At week 16, 4 patients (4/10, 40%) and at week 24, 5 patients, showed improvement in at least one of the 3 hematologic cell lines (partial response), respectively. Counts pre-and post-EPAG and global response in patients who stayed on treatment > 12 weeks are displayed below: Image: Summary/Conclusion: In our experience, EPAG worked well in subjects with PGF, an otherwise life-threatening condition for patients, and its use at 150 mg/day is safe and well tolerated in this setting. Our data suggest that eltrombopag might improve hematologic cell counts in patients with PGF, especially in those patients who remained on treatment at week 24, however further research is warranted to extend its applicability for larger cohorts.

19.
HemaSphere ; 6:3634-3635, 2022.
Article in English | EMBASE | ID: covidwho-2032113

ABSTRACT

Background: Prognosis of r/r B-NHL is detrimental. Potentially curative therapeutic approaches, such as autologous stem cell transplantation and innovative CAR-T cell therapy, require maximum disease control to achieve optimal results. Glofitamab is a new bispecific antibody, with a unique 2:1 molecular configuration resulting in superior potency compared with other CD20xCD3 bispecific antibodies with a 1:1 format. Aims: Based on these encouraging results, we included 5 heavily pretreated patients in the early access program of Glofitamab, available in our country. Methods: We collected the data of 5 consecutive patients with r/r B-NHL, who were treated with Glofitamab in our department during the last 15 months. Results: Three men and 2 women, median age of 57 years (38-62), were resistant to 4 (n = 3) and 5 (n = 2) previous lines of treatment. The underlying lymphoma was Richter's transformation of CLL after allogeneic transplantation (alloHSCT), transformed follicular lymphoma (tFL), primary mediastinal B-cell lymphoma (PMBCL), r/r diffuse large B-cell lymphoma (DLBCL) after CAR-T therapy and gray zone lymphoma (GZL) transformed to DLBCL. The median number of Glofitamab cycles administered was 3 (2-7). All 5 patients responded early to treatment, which became apparent immediately after the first dose of 2.5 mg. The patient with Richter's syndrome achieved metabolic remission after the 4th cycle and underwent second alloHSCT after the 7th cycle. Unfortunately, he passed away 8 months after alloHSCT due to disseminated atypical mycobacterial infection, remaining however disease free. The patient with tFL also achieved metabolic remission, but the drug was discontinued after the 7th cycle due to COVID-19 infection. He died two months after Glofitamab interruption due to disease progression and CMV encephalitis. The patient with PMBCL, responded partially after Glofitamab and had mediastinal radiotherapy as bridging therapy to CAR-T therapy. As the latter was delayed due to CMV reactivation and CMV enteritis, our patient deceased due to progressive disease. The patient with DLBCL after CAR-T therapy had initial clinical response after two Glofitamab cycles. Due to severe COVID-19, we decided to hold Glofitamab. COVID-19 and disease progression led to his death, a few weeks after COVID-19 diagnosis. Finally, the patient with transformed GZL had Glofitamab administered as bridging therapy prior to CAR-T treatment. After 3 cycles, while she was prepared to proceed to CAR-T therapy, she was diagnosed with invasive aspergillosis. She is currently been treated with antifungal agents, whereas disease is still active. Cytokine release syndrome (CRS) occurred in 3 out of 5 patients. In all cases it was grade 1-2 and manifested at the first administration of the drug, after 4, 32 and 10 hours respectively, from infusion initiation. CRS was managed with antipyretics and steroids, whereas none patient required Intensive Care Unit support. Only one patient required tocilizumab. No Immune effector cell-Associated Neurotoxicity Syndrome (ICANS) was observed. Summary/Conclusion: Glofitamab is effective in treating patients with r/r aggressive B-cell NHL. Efficacy makes it an appropriate bridging tool to autologous, alloHSCT or CAR-T therapy. Nevertheless, relapse remains a challenge for r/r disease. Adverse events, such as CRS, were generally manageable. Given the fact that it was administered to heavily pretreated patients, caution to opportunistic pathogens should be paid. Indeed, toxicity profile may be proven to be more favorable if the agent is being administered earlier in therapeutic algorithms.

20.
Vaccines (Basel) ; 10(8)2022 Aug 12.
Article in English | MEDLINE | ID: covidwho-2024370

ABSTRACT

Dense bodies (DB) are complex, noninfectious particles produced during CMVinfection containing envelope and tegument proteins that may be ideal candidates as vaccines. Although DB were previously described in fibroblasts, no evidence of DB formation has been shown after propagating CMV in epithelial cells. In the present study, both fibroblast MRC-5 and epithelial ARPE-19 cells were used to study DB production during CMV infection. We demonstrate the formation of epithelial cell-derived DB, mostly located as cytoplasmic inclusions in the perinuclear area of the infected cell. DB were gradient-purified, and the nature of the viral particles was confirmed using CMV-specific immunelabeling. Epithelial cell-derived DB had higher density and more homogeneous size (200-300 nm) compared to fibroblast-derived DB (100-600 nm).In agreement with previous results characterizing DB from CMV-infected fibroblasts, the pp65 tegument protein was predominant in the epithelial cell-derived DB. Our results also suggest that epithelial cells had more CMV capsids in the cytoplasm and had spherical bodies compatible with nucleus condensation (pyknosis) in cells undergoing apoptosis that were not detected in MRC-5 infected cells at the tested time post-infection. Our results demonstrate the formation of DB in CMV-infected ARPE-19 epithelial cells that may be suitable candidate to develop a multiprotein vaccine with antigenic properties similar to that of the virions while not including the viral genome.

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