Immunotherapy: RAPID ACCESS TO VIRUS-SPECIFIC T CELLS FOR ADOPTIVE IMMUNOTHERAPY FOR COMPASSIONATE USE IN AUSTRALIA

Background & Aim: Adoptive T cell immunotherapy holds great promise for the treatment of viral complications. Our group has been developing and trialling virus-specific T cell therapies for more than 20 years. Recently, we have generated a repository of multi-virus-specific T cells for our clinical trials. Unfortunately, for many patients with viral complications, there is no suitable trial through which to access these therapies. In Australia, the Therapeutic Goods Administration has a Special Access Scheme (SAS) to enable provision of unapproved therapies for compassionate use. Our research group is now a leading Australian provider of "off-the-shelf" and custom-grown allogeneic virus-specific T cells to hospitals for patients with no other treatment options. Methods, Results & Conclusion(s): We have generated a repository of multi-virus-specific T cells from 20 healthy donors, with up to 150 doses of T cells per donor generated from a single blood sample. Each product batch is thoroughly characterised in terms of viral antigen specificity, HLA restriction and alloreactivity. These T cells target a combination of Epstein-Barr virus, cytomegalovirus, BK polyomavirus, John Cunningham virus and adenovirus epitopes. We have also generated a repository of SARS-CoV-2-specific T cells and occasionally grow custom patient-specific batches of T cells from nominated donors, on request. Since 2008, we have provided virus-specific T cells to 15 hospitals across Australia, and the volume of supply requests has significantly increased in recent years, as clinicians have gained interest in adoptive immunotherapy. In 2022, we provided T cells for 26 patients via the SAS. The majority were experiencing post-transplant complications, including cytomegalovirus disease, BK virus-associated haemorrhagic cystitis and post-transplant lymphoproliferative disorder. Through our clinical trials, we have developed rigorous processes for T cell therapy manufacture and characterisation, in addition to a computer-based selection algorithm, which we apply to SAS cases. As these cases are not part of a clinical trial, concomitant therapy varies, and monitoring is not uniform. However, we have received reports of clinical benefit from adoptive T cell therapy. These include cases of reduction in viral load, improvement in symptoms, and complete resolution of infection. We believe that these promising T cell therapies should be available to hospitals through a nationally funded centre for cellular therapies for critically ill patients.Copyright © 2023 International Society for Cell & Gene Therapy

Transient Decrease in Incidence Rate of Maternal Primary Cytomegalovirus Infection during the COVID-19 Pandemic in Japan.

This study evaluated the impact of the coronavirus disease 2019 (COVID-19) pandemic on the occurrence of maternal primary cytomegalovirus (CMV) infection in Japan. We performed a nested case-control study using data from maternal CMV antibody screening under the Cytomegalovirus in Mother and infant-engaged Virus serology (CMieV) program in Mie, Japan. Pregnant women with negative IgG antibodies at ≤20 weeks of gestation who were retested at ≥28 weeks were enrolled. The study period was divided into 2015-2019 as the pre-pandemic and 2020-2022 as the pandemic period, and the study site included 26 institutions conducting the CMieV program. The incidence rate of maternal IgG seroconversion was compared between the pre-pandemic (7008 women enrolled) and pandemic (2020, 1283 women enrolled; 2021, 1100 women; and 2022, 398 women) periods. Sixty-one women in the pre-pandemic period and five, four, and five women during 2020, 2021, and 2022, respectively, showed IgG seroconversion. The incidence rates in 2020 and 2021 were lower (p < 0.05) than that in the pre-pandemic period. Our data suggest a transient decrease in the incidence of maternal primary CMV infection in Japan during the COVID-19 pandemic, which could be due to prevention and hygiene measures taken at the population level.

Evolution in Infectious Causes of Death in Liveborn Children in a Major Tertiary Children's Hospital: A Retrospective Autopsy Review of over 1200 Cases

Background: Infections have historically been a leading cause of death, particularly in children. Medical advances, including vaccines and antimicrobials, have significantly decreased infection-related deaths, but infections remain a cause of pediatric mortality, especially in premature infants. The types of infections implicated in childhood deaths have changed with these advances, for example, meningitis and meningococcal infections were leading causes in 1981 but not in the later period. The incidence and etiologies of infection- related deaths may be altered by major events that modify not only medical practices but also societal attitudes and activities. Examples of such events include the HIV/AIDS epidemic that began in the early 1980s and the more recent COVID-19 pandemic. In order to investigate changes in infection-related pediatric deaths over time, we analyzed and compared autopsy cases performed during 5-year span prior to both the HIV/AIDS epidemic and the COVID-19 pandemic in which infections contributed to death. Method(s): Review of all autopsy cases performed at our institution between 1/1/1975-1/1/1980 and between 1/1/2015-1/1/2020 was performed to identify cases in which infection directly contributed to death, comprising 1262 cases. Only liveborn children were considered, and neonatal sepsis from amniotic sac infections was excluded. Comparison of decedent characteristics and infectious etiologies between the two time periods was performed, identifying age, race, sex, gestational age (for decedents less than 3 months of age), and etiologic class of agent (bacterial, viral, fungal or parasitic). TORCH infections and vaccine-preventable illnesses were specifically assessed. Proportions were compared using 1 (assessing TORCH, vaccine-preventable, and prematurity deaths)- or 2-tailed (all others) z-tests, with significance calculated at the < 0.05 level. Result(s): In the 1970s cohort, 300 infectious autopsy cases were identified in liveborn children;73 were identified in the 2010s. Compared to the 2010s cohort, the 1970s decedents were more likely to be white (85% v 53%, p=0.012), comprise children aged 1-5 and 13+ (22% v 6.8% [p=0.003] and 16.4% v 8.3% [p=0.036]), and were less likely to be premature (66.7% v 80.4%, p=0.039). Vaccine-preventable illnesses (for example: measles) accounted for 36 deaths in the 1970s cohort but only 2 in the 2010s cohort (p=0.009). Thirteen children died of TORCH infections (CMV, toxoplasmosis and HSV) versus 5 in the 2010s (CMV and HSV), which did not reach statistical significance. Conclusion(s): Pediatric mortality secondary to infections has decreased significantly compared to fifty years ago, especially in younger children and in relation to vaccine-preventable infections such as meningococcal disease. This drop is largely attributed to medical advances, including vaccines and antimicrobial medications. Additional contributing factors could include practices adopted post-HIV/AIDS, especially in the community. Further exploration of how such changes in medical and social practice impacted mortality and comparing them to changes occurring in the intra/post-COVID-19 era, is helpful. Yet, with the increased survival of premature infants, they remain at risk of devastating consequences from infections.

Rising level of pulmonary dioxin might trigger CMV and HSV-1 reactivation via bHLH/PAS/AhR:ARNT transcription pathway in lungs of immunocompetent COVID-19 patients with ARDS

Study objective. It has been shown that human common viruses are new target genes for host cell dioxin receptor transcriptional (AhR-ARNT) complex initially proven to up-regulate mammalian genes containing dioxin-response elements (DRE) in the promoters [doi:10.1016/j.ijid.2012.05.265]. Initially, transactivation of HIV-1 and HBV by 2,3,7,8-tetrachlodibenzop- dioxin (TCDD) at low nanomolar range was demonstrated [doi:10.3109/00498259309057034]. Noteworthy, transactivation of human cytomegalovirus (CMV) was shown with 0.3 ppt dioxin, i.e. lower than its current background level in the general population (~3.0 ppt). Recently, reactivation of CMV infection was found to influence worse clinical outcome following SARS-CoV-2 infection (doi: 10.1186/s12979-020- 00185-x). Other findings showed that CMV and herpes simplex virus 1 (HSV-1) reactivation were observed in immunocompetent patients with COVID-19 acute respiratory distress syndrome (ARDS) (doi.org/10.1186/s13054-020-03252-3). Addressing occurrence of Herpesviridae reactivation in severe COVID-19 patients, and still unspecified real triggers of CMV and HSV-1 reactivations, we tested TCDD, which current body burden (DBB) ranges from 20 pg/g (TEQ in fat) in general population to 100 pg/g in older people. Methods. In Silico quantitation of active DRE in promoters of viral genes. Virus DNA hybridization assay. Clinical and epidemiological analyses. Results and Discussion. In this study, a computational search for DRE in CMV and HSV-1 genes was performed by SITECON, a tool recognizing potentially active transcriptional factor binding sites. In silico analysis revealed in regulatory region of CMV IE genes from 5 to 10 DRE, and from 6 to 8 DRE in regulatory region of HSV-1 IE genes.We established that a low picomolar TCDD can trigger up-regulation of CMV and HSV-1 genes via AhR:Arnt transcription factor in macrophage(doi.org/10.1016/ j.ijid.2012.05.265) and glial human cell lines (doi.org/10.1016/j. jalz.2016.06.1268), respectively. In fact, viral reactivation may be triggered in COVID-19 ARDS patients by higher pulmonary TCDD concentrations, because "lipid storm" within lungs of severe COVID-19 patients has been recently reported (doi.org/ 10.1101/2020.12.04.20242115). TCDD is known as the most potent xenobiotic, which bioaccumulates and has estimation half-life in humans of up to 10 yr. Due to hydrophobic character (Log P octanol/water: 7.05), TCDD partitions into inflammatory lipids in lung tissue thus augmenting its local concentration. Population-based epidemiological data on SARS-CoV-2 first wave of pandemic revealed high level of CMV seropositivity and cumulative mortality rate 4.5 times in Lombardi region of Italy, where after Seveso industrial accident TCDD plasma level in pre-exposed subjects is 15 times the level in rest of Italy (doi. org/10.3389/fpubh.2020.620416). Also, Arctic Native (AN) peoples consume dioxin-contaminated fat in seafood and have TCDD DBB, i.e. 7 times that in general population. To the point of this paper, their COVID-19 mortality is 2.2 times of that among non-AN Alaskans (doi: 10.15585/mmwr.mm6949a3). Conclusion(s): TCDD in the picomolar range may trigger CMV expression in lung cells and commit virus to the lytic cycle, which can be applied to reactivation of Herpesviridae infection in immunocompetent patients with COVID-19 ARDS syndrome.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Early infection risk in patients with systemic lupus erythematosus treated with rituximab or belimumab from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR): a prospective longitudinal study

Background: Patients with systemic lupus erythematosus (SLE) are at an increased risk of infection relative to the general population. We aimed to describe the frequency and risk factors for serious infections in patients with moderate-to-severe SLE treated with rituximab, belimumab, and standard of care therapies in a large national observational cohort. Method(s): The British Isles Lupus Assessment Group Biologics Register (BILAG-BR) is a UK-based prospective register of patients with SLE. Patients were recruited by their treating physician as part of their scheduled care from 64 centres across the UK by use of a standardised case report form. Inclusion criteria for the BILAG-BR included age older than 5 years, ability to provide informed consent, a diagnosis of SLE, and starting a new biological therapy within the last 12 months or a new standard of care drug within the last month. The primary outcome for this study was the rate of serious infections within the first 12 months of therapy. Serious infections were defined as those requiring intravenous antibiotic treatment, hospital admission, or resulting in morbidity or death. Infection and mortality data were collected from study centres and further mortality data were collected from the UK Office for National Statistics. The relationship between serious infection and drug type was analysed using a multiple-failure Cox proportional hazards model. Finding(s): Between July 1, 2010, and Feb 23, 2021, 1383 individuals were recruited to the BILAG-BR. 335 patients were excluded from this analysis. The remaining 1048 participants contributed 1002.7 person-years of follow-up and included 746 (71%) participants on rituximab, 119 (11%) participants on belimumab, and 183 (17%) participants on standard of care. The median age of the cohort was 39 years (IQR 30-50), 942 (90%) of 1048 patients were women and 106 (10%) were men. Of the patients with available ethnicity data, 514 (56%) of 911 were White, 169 (19%) were Asian, 161 (18%) were Black, and 67 (7%) were of multiple-mixed or other ethnic backgrounds. 118 serious infections occurred in 76 individuals during the 12-month study period, which included 92 serious infections in 58 individuals on rituximab, eight serious infections in five individuals receiving belimumab, and 18 serious infections in 13 individuals on standard of care. The overall crude incidence rate of serious infection was 117.7 (95% CI 98.3-141.0) per 1000 person-years. Compared with standard of care, the serious infection risk was similar in the rituximab (adjusted hazard ratio [HR] 1.68 [0.60-4.68]) and belimumab groups (1.01 [0.21-4.80]). Across the whole cohort in multivariate analysis, serious infection risk was associated with prednisolone dose (>10 mg;2.38 [95%CI 1.47-3.84]), hypogammaglobulinaemia (<6 g/L;2.16 [1.38-3.37]), and multimorbidity (1.45 [1.17-1.80]). Additional concomitant immunosuppressive use appeared to be associated with a reduced risk (0.60 [0.41-0.90]). We found no significant safety signals regarding atypical infections. Six infection-related deaths occurred at a median of 121 days (IQR 60-151) days from cohort entry. Interpretation(s): In patients with moderate-to-severe SLE, rituximab, belimumab, and standard immunosuppressive therapy have similar serious infection risks. Key risk factors for serious infections included multimorbidity, hypogammaglobulinaemia, and increased glucocorticoid doses. When considering the risk of serious infection, we propose that immunosupppressives, rituximab, and belimumab should be prioritised as mainstay therapies to optimise SLE management and support proactive minimisation of glucocorticoid use. Funding(s): None.Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

IDWeek 2022

IDWeek is the joint annual meeting of the Infectious Diseases Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), the Pediatric Infectious Diseases Society (PIDS) and the Society of Infectious Diseases Pharmacists (SIDP). For the first time since the COVID-19 public health emergency began, IDWeek 2022 returned to in-person attendance. It was held in Washington, D.C., and the meeting comprised 5 days of live sessions and on-demand content that included posters and oral presentations.Copyright © 2023 Clarivate.

Immunoserologic and hemotherapy considerations in patients undergoing hematopoietic progenitor cell transplantation

With increasing evidence of the success of hematopoietic progenitor cell (HPC) transplantation in the cure of many benign and malignant diseases, such interventions have been performed at increasing rates for the past several years. Due to myelosuppression caused by the conditioning and graft-versus-host disease (GVHD) prophylaxis regimens, blood component transfusions are almost inevitably needed. During transplantation, patient's hematopoietic lineages reconstitute to the HPC donor's progenitor cell types. Therefore, specific immunoserologic and hemotherapeutic aspects need to be considered for the selection of blood components during different phases of transplantation for successful outcomes. Those considerations include but are not limited to ABO and human leucocyte antigen (HLA) compatibility of the transfused blood components with either or both the patient and the HPC donor according to the particular phase of transplantation, and the special blood component processing to reduce the risk of transfusion associated graft-versus-host disease (TA-GVHD), cytomegalovirus (CMV) transmission in CMV seronegative patients and immune mediated platelets refractoriness. Complications may still arise, particularly in major, minor, or bidirectional ABO mismatched transplantations and/or due to the HLA mismatch and alloimmunization. Here we discuss the indications, immunoserologic considerations and the special component processing of red blood cells (RBCs), platelets, granulocytes, and plasma transfusions, based upon the current evidence and describe the prevention and management of salient, pertinent complications.Copyright © 2022 The authors.

Aspects of cytomegalovirus reactivation in critically ill patients.

Cytomegalovirus plays an essential role in human pathology. Primary infection usually occurs in childhood and subsequently, a lifelong latency is formed which the virus replicates by evading the immune response. In recent years, more and more researchers have concluded that cytomegalovirus reactivation may occur in critically ill patients. Despite the available evidence, data on reactivation in this group of patients are limited by the relatively small sample size, the variety of patient groups studied, the differences in study methodology, and the variability in reported results, which excludes the possibility of summarizing the results. This study aimed to determine the frequency of reactivation of cytomegalovirus infection in critically ill patients and to identify its main clinical features. Materials and methods. The study included 118 critically ill patients with severe bacterial and viral-bacterial infections accompanied by multiple organ dysfunction. Cytomegalovirus reactivation was determined by the detection of DNA in combination with the presence of IgG. Results. Reactivation was detected in 36.4% of cases. Frequency and terms of reactivation in blood and sputum as well as trends of viral load changes in dynamics were shown. The main clinical features of reactivation in different pathologies (sepsis of bacterial etiology, COVID-19, non-septic critical patients) were noted. HCMV DNA was more frequently detected in the blood of septic patients (44.8%) compared with COVID-19 (13.0%, p<0.05) and non-septic critically ill patients (19.2%, p<0.05). COVID-19 was characterized not only by lower detection of HCMV DNA in the blood but also by the lowest viral loads (p<0.05). HCMV DNA in sputum was detected comparably frequently in sepsis (38.1%) and COVID-19 (33.3%), but the highest viral loads were characteristic of patients with sepsis (p<0.05).Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.

Aspects of cytomegalovirus reactivation in critically ill patients.

Cytomegalovirus plays an essential role in human pathology. Primary infection usually occurs in childhood and subsequently, a lifelong latency is formed which the virus replicates by evading the immune response. In recent years, more and more researchers have concluded that cytomegalovirus reactivation may occur in critically ill patients. Despite the available evidence, data on reactivation in this group of patients are limited by the relatively small sample size, the variety of patient groups studied, the differences in study methodology, and the variability in reported results, which excludes the possibility of summarizing the results. This study aimed to determine the frequency of reactivation of cytomegalovirus infection in critically ill patients and to identify its main clinical features. Materials and methods. The study included 118 critically ill patients with severe bacterial and viral-bacterial infections accompanied by multiple organ dysfunction. Cytomegalovirus reactivation was determined by the detection of DNA in combination with the presence of IgG. Results. Reactivation was detected in 36.4% of cases. Frequency and terms of reactivation in blood and sputum as well as trends of viral load changes in dynamics were shown. The main clinical features of reactivation in different pathologies (sepsis of bacterial etiology, COVID-19, non-septic critical patients) were noted. HCMV DNA was more frequently detected in the blood of septic patients (44.8%) compared with COVID-19 (13.0%, p<0.05) and non-septic critically ill patients (19.2%, p<0.05). COVID-19 was characterized not only by lower detection of HCMV DNA in the blood but also by the lowest viral loads (p<0.05). HCMV DNA in sputum was detected comparably frequently in sepsis (38.1%) and COVID-19 (33.3%), but the highest viral loads were characteristic of patients with sepsis (p<0.05).Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.

Single Center Comparative Analysis of Abo Compatible Versus Abo Incompatible Kidney Transplant with Short Term 1 Year Follow Up

Introduction: Kidney transplantation is the best treatment option for patients with end-stage kidney diseases. Quality and longevity of life are better with kidney transplant than chronic dialysis. Kidney paired donation and ABO incompatible kidney transplant (ABOiKT) are among the strategies to expand the living donor pool to overcome shortage of organs. Although first ABOiKT done in 1951 by Hume et al. was an unsuccessful attempt;Alexander et al. in 1987, proposed desensitization protocol with successful ABOiKT. Advancements in desensitization protocols have resulted in increasing success with ABOiKT. In developing countries like India, numbers of ABOiKT are steadily increasing. Aim of this study was to assess short term outcome of ABOiKT and their comparison with ABO compatible kidney transplant (ABOcKT). Method(s): This was a single center prospective observational study done over a period of 2 years. All the living donor kidney transplants including both ABOcKT and ABOiKT done between September 2020 to August 2021 at Jaslok Hospital and Research Center, Mumbai were included in this study. All ABOiKT recipients underwent pre-transplantation desensitization with injection rituximab and plasmapheresis. Pretransplant isoagglutinin titer of <= 1 : 8 was considered acceptable. Inj. Antithymocyte globulin (ATG) (1mg/kg), Inj. Anti-T lymphocyte globulin (ATLG) (3 to 5 mg/kg) or Inj. Basiliximab (20mg 2 doses 4 days apart) was used as induction agent. Triple immunosuppression regimen of prednisolone, tacrolimus and mycofenolate mofetil was started 7 days prior to transplant in ABOiKT and 2 days prior to transplant in ABOcKT and continued in post-transplant period. Valganciclovir was given to all patients for Cytomegalovirus (CMV) infection prophylaxis for 6 months. All the transplant recipients were followed up at 0, 3, 6, 9 and 12 months after transplant and in between when clinically indicated. Data collected was analyzed at the end of 1 year for outcomes of rejection episodes, graft dysfunction, graft loss, infections and death. Result(s): Total 95 patients were included in study, 29 (30.5%) out of them were ABOiKT recipients. Mean (SD) age of study population was 37.8 (+/- 10.5) years. Blood group B to B was the most common ABOcKT and B to O was the most common ABOiKT. Highest baseline isoagglutinin titer was 1:1024.There was no significant difference for rejection episodes, graft dysfunction, graft loss and death in ABOiKT and ABOcKT groups. Urinary tract infection was the most common infection in post-transplant period. COVID-19 was most common viral infection followed by CMV infection. Bacterial infections and overall infections were significantly higher in ABOiKT recipients (p value 0.001 and 0.006 respectively) but severe infections requiring hospitalizations and ICU care were not significantly higher. Two deaths occurred during our study, one in each group. One death was related to COVID-19 infection and second was because of pulmonary mucormycosis. Conclusion(s): Contrary to belief, ABOiKT has non inferior short term outcomes when compared with ABOcKT. Though in our study, bacterial infections were significantly higher in ABOiKT recipients, severe infections requiring hospitalization and ICU care were not increased. ABO incompatible kidney transplantation is an effective modality to increase donor pool and can be applied more widely. No conflict of interestCopyright © 2023

Etrasimod for the treatment of ulcerative colitis: analysis of infection rates from the phase 3 ELEVATE UC 52 and ELEVATE UC 12 clinical trials

Background: Infections are an important safety concern in patients with IBD and may be due to its therapies, such as corticosteroids. Etrasimod is an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 (S1P1,4,5) modulator in development for the treatment of moderately to severely active ulcerative colitis (UC). The biologic effect of etrasimod leads to selective and reversible lymphocyte retention in lymph nodes with a decrease in peripheral lymphocyte count. We report the infection events from the phase 3 ELEVATE programme. Method(s): Infection events were evaluated in the pivotal UC pooled safety analyses set comprising two phase 3 studies: ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369). Subjects (16- 80 years) with moderately to severely active UC were randomised 2:1 to once-daily etrasimod 2 mg or placebo (PBO). We report the n (%) and exposure-adjusted incidence rate (EAIR) of infections including serious infections, severe infections, opportunistic infections (including tuberculosis), and herpes infections. Infections were considered adverse events of special interest (AESI) if they were severe (>= CTCAE Grade 3), were opportunistic infections, or were herpes zoster or herpes simplex infections. Result(s): From the pooled ELEVATE UC 12 and ELEVATE UC 52 trials, 527 subjects received >=1 dose of etrasimod 2 mg (265.6 subject-years of exposure) and 260 subjects were randomised to PBO (103.0 subjectyears of exposure). Infections were similar between treatment groups (etrasimod: 99 [18.8%], EAIR=0.41;PBO: 46 [17.7%], EAIR=0.52). The most frequent infections in both groups were COVID-19, urinary tract infections, and nasopharyngitis (Table 1). Serious infections occurred in 3 (0.6%) subjects in the etrasimod arm (EAIR=0.01) and 5 (1.9%) in PBO arm (EAIR=0.05). Two cases of herpes zoster were reported in each treatment group (etrasimod: 0.4%, EAIR<0.01;PBO: 0.8%, EAIR=0.02);these were localised and nonserious. One opportunistic infection was reported in each arm (etrasimod: Subject withdrew from the study on day 20, the AE of Cytomegalovirus infection [Grade 2] was reported on day 36;PBO: Tuberculosis [Grade 2]). Overall, 3 cases of infection led to discontinuation: 2 in the etrasimod arm (both mild) and 1 in the PBO arm (Table 2). No subject with an absolute lymphocyte count <0.2x109/L subsequently reported a serious/ severe or opportunistic infection. There were no deaths. Downloaded from https://academic.oup.com/ecco-jcc/article/17/Supplement-1/i689/7010119 by guest on 04 February 2023 Sample output to test PDF Combine only i690 Poster presentations In these trials, etrasimod-treated subjects reported no in-crease in infections relative to PBO. Serious infections and herpes zoster were more commonly reported in the PBO-treated group. Longer-term follow-up data from the ongoing 5-year open-label extension will fur-ther characterize the etrasimod safety profile.

Acute hepatitis as an independent form of mixed (herpetic and new coronavirus) infections in a child

To date, the association of SARS-CoV-2 infection with the reactivation of herpes viruses has been determined. This has been proven not only by the results of laboratory studies, but also by a clinically confirmed subsequent manifestation of the herpetic process. The article describes a clinical case of Epstein-Barr viral and cytomegalovirus infections reactivation after COVID-19. The child was diagnosed with anicteric form of hepatitis of herpetic etiology. Hepatitis, moderate anicteric form. During treatment, the patient's condition improved. Complete clinical recovery with normalization of the activity of alanine and aspartate aminotransaminases occurred 1 month after the onset of the disease, but the level of lymphocytes and gamma-glutamyl transpeptidase still remained moderately elevated. According to the ultrasound of the abdominal organs, the size of the liver returned to normal. The presented case illustrates that mixed infections are a quite possible situation during the COVID-19 pandemic, which must be taken into account when working with such patients. Copyright © 2022 National Academy of Pediatric Science and Innovation. All rights reserved.

New Onset Cmv Disease in Post Renal Transplant Patients in Association with Covid19 Infection - 2 Cases and Brief Review of Literature

BACKGROUND: Several cases of CMV syndrome and invasive CMV infection have been reported following COVID19 infection worldwide during COVID19 pandemic in both immunocompetent and immunosuppressed patients. AIM OF THE STUDY: We intend to discuss more about the interrelationship of COVID19 and CMV infection in renal transplant patients. METHOD(S): We discuss two clinical cases, and we present a brief review of literature. 30-year-old man with end-stage primary lupus nephritis underwent mother-to-son kidney transplantation. Post-transplant surgery the patient was discharged with 1.8 mg/ml baseline creatinine. After 3 months, he was admitted with complaints of fever for 4 days with no derangement of renal function. He tested positive for COVID 19 infection and was managed conservatively. Subsequently within 10 days, he was readmitted with chief complaints of loose stools abdominal pain and back pain with mildly raised creatinine and leukopenia. CMV PCR detected 128500 copies per ml. This patient was treated with injection ganciclovir and GM-CSF injection. Mycophenolate mofetil was withheld in view of CMV infection. However, the patient complained of persistent back pain with gradual decline in graft and renal function. With decreasing urine output, dialysis was initiated. Subsequently, the patient developed altered sensorium and had cardiac arrest. 34-year-old male with end-stage chronic nephritis had undergone cadaveric kidney transplantation. Post-transplant the patient had delayed onset graft function with baseline creatinine of 2 mgdl on the 10th post-operative day. Subsequently, the patient suffered from active antibody-mediated rejection, and the patient was managed with six cycles of plasmapheresis. One month later, the patient was admitted with fever and cough. The patient tested positive for COVID19 infection and was managed conservatively. Simultaneously, the patient developed multiple episodes of hematochezia pain in abdomen and diarrhea. Urine output was maintained with stable creatinine. Stool routine and microscopic examination revealed multiple RBCs few pus cells - however no parasite was detected. CMV PCR was positive with 3000 copies per ml. The patient was initially treated with injection ganciclovir and was switched to oral valganciclovir. The patient remained afebrile general condition improved with no further episodes of hematochezia and gradual decline of creatinine to baseline level. RESULT(S): In both our cases, COVID19 infection were managed conservatively, and CMV infection was treated with stoppage of mycophenolate mofetil and addition of ganciclovir injection and resulted into one positive and one negative clinical outcome. CONCLUSION(S): CMV reactivation after COVID 19 infection in renal transplant patient may be a common phenomenon. Further studies are immediately needed to know whether CMV viremia should be routinely tested in all renal transplant patients in India who get COVID19 infection. Studies are also required to determine if clinical outcomes of CMV disease after COVID19 infection in renal transplant patients are different from CMV disease outcomes in other renal transplant patients who have no history of immediately preceding COVID 19 infection.

Cytomegalovirus reactivation in a SARS-CoV-2 infected woman experiencing fetal demise in the first trimester with fetal trisomy 21: A case report.

Cytomegalovirus (CMV) is the most common cause of congenital viral infections. Women seropositive for CMV prior to pregnancy can develop a non-primary CMV infection. Here, we present a case of first trimester pregnancy loss during active SARS-CoV-2 infection. There was no evidence of SARS-CoV-2 RNA in placenta and fetal tissue, but there was presence of congenital cytomegalovirus infection by nested PCR. To the best of our knowledge, this is the first report demonstrating association of early congenital CMV infection due to reactivation and fetal demise in a SARS-CoV-2 positive woman with fetal trisomy 21.

Expert Group Opinion for Respiratory Infections in Solid Organ Transplant Recipients in South Asia

Respiratory infections are among the most common and serious infections after solid organ transplantation (SOT). Infections within a month after transplant are usually donor-derived or bacterial infections related to surgical infections or ventilator associated. Infections between 1-6 months after SOT are mostly opportunistic due to various viruses, or fungal infections. After 6 months of transplantation usually community acquired infections predominate, however it is not uncommon to find opportunistic fungal and viral infections in this period. The signs and symptoms of these infections are often mitigated in SOT recipients, so a high index of suspicion is required along with microbiological or tissue diagnosis early in the course to timely treat these infections. Thorough screening for common infections and endemic infections is required in donor and recipients before transplantation to reduce the risk of infections in posttransplant period. Finally, a longer duration of treatment and prophylaxis is required for adequately treat these infections and prevent the relapse. Copyright © 2022 Indian Journal of Transplantation Published by Wolters Kluwer - Medknow.

Two Case Reports of Cytomegalovirus Induced Collapsing Focal Segmental Glomerulosclerosis in Immunocompetent Hosts

Introduction: Collapsing focal segmental glomerulosclerosis (cFSGS) refers to a distinct pattern of glomerulopathy characterized by a glomerular capillary collapse in a segmental global manner, podocyte proliferation, and tubulointerstitial injury. Viral infections like HIV, Parvovirus B19, and CMV seem to be prominent triggers for the development of a conventional histological pattern of FSGS. CMV-associated renal disease has been described only in transplant and immunocompromised patients. Case Description: Case 1 18-year-old female with history of asthma and HbSS disease presented with fever, nausea, vomiting, and neck pain Physical examination revealed a temperature of 102 F, icterus, negative meningeal signs, no rales, rhonchi or wheezing. Initial creatinine 0.2 mg/dL. COVID-19 PCR was negative but IgG antibodies positive. Patient developed non-oliguric AKI with fluid overload requiring hemodialysis. CMV IgM and CMV PCR were positive. She recieved antibiotic therapy and also ganciclovir. Biopsy revealed collapsing FSGS with acute tubular injury. A week after completion of ganciclovir therapy creatinine returned to baseline of 1.7 mg/dL. Case 2 40-year-old African American male with history of diabetes and asthma presented with fever, fatigue, epigastric pain and chest pain. Initial creatinine 1.2 mg/dl, hepatic function (AST 333 U/L, ALT 265 U/L, ALK 207 U/L), ferritin (13682 ng/ml), triglycerides (276 mg/dl) and proteinuria (urine protein /creatinine ratio: 2, urine albumin/creatinine:1016 mg/gm). Patient developed anuric renal failure which required hemodialysis. Biopsy revealed collapsing FSGS with diffuse podocyte effacement, moderate tubular atrophy, and interstitial fibrosis. CMV DNA antibodies were positive. Methylprednisolone and valganciclovir were started with patient creatinine trending down to 3.7 mg/dL. Three weeks following discharge, creatinine levels were 1.5 mg/dL with decreased proteinuria. Discussion(s): Collapsing FSGS in immunocompetent patients is uncommon. Reports mention benefits of ganciclovir and steroid therapy for CMV infection in immunocompromised patients. CMV infection should be considered in patients with systemic inflammatory disease and severe renal failure, as early treatment with steroids and antivirals helps preserve renal function.