Cytomegalovirus Co-infection Research Articles

A rare case of Pneumocystis jirovecii and cytomegalovirus coinfection in the small bowel

Abstract Introduction/Objective Infection with Pneumocystis jirovecii remains a common cause of pneumonia in patients with Acquired Immune Deficiency Syndrome (AIDS). Extrapulmonary manifestations, however, are exceedingly rare. We describe a rare case of coinfection of the small bowel by Pneumocystis jirovecii and cytomegalovirus (CMV). Methods/Case Report A 48-year-old female with a history of HIV/AIDS, remote history of Pneumocystis jirovecii pneumonia, and previous non-compliance with HAART, presented to the emergency department with right lower quadrant abdominal pain, fever, and chills for 1 week. Her recent medical history included a hospital admission 1 month prior for community-acquired pneumonia with CD4 count and viral load of 12 cells/mcl and >680,000 copies/mL, respectively; upon discharge she restarted HAART. When she presented to the emergency department in our case, she demonstrated leukocytosis (14.3 K/mcl), tachycardia (131 bpm), and hypotension (87/58 mmHg). An abdominal CT scan showed free air with concern for perforated viscus and multi-station lymphadenopathy with gastrohepatic and retrocaval nodes >2 cm. A chest x-ray showed nodular and cavitary lesions, stable from prior imaging. The differential diagnoses in an AIDS patient with a gastrointestinal mass includes Kaposi’s sarcoma, lymphoproliferative process, or infection. The surgeons were concerned for tuberculosis as well, due to the hospital’s patient population, her bulky lymphadenopathy, and immune-compromised status. An exploratory laparotomy was performed and found jejunal perforations, mesenteric lymphadenopathy, and 3L of fluid in the abdomen. Pathology received 4 soft lymph nodes and a 57 cm segment of thickened small bowel with purulent perforation but no discrete mass. Microscopic examination showed a perforating pseudotumor and acute serositis extending to the margins of the specimen. Lymph node flow cytometry was negative for clonal populations. GMS stains highlighted innumerable “crushed-ping-pong-ball”-like fungal forms consistent with Pneumocystis in the jejunum and all 4 lymph nodes. A CMV immunohistochemical stain highlighted infected cells with nuclear enlargement and nuclear inclusions in the jejunum. Results (if a Case Study enter NA) NA Conclusion Extrapulmonary Pneumocystis infection is rare but clinicians, pathologists, and microbiologists must keep it in the differential of HIV patients, especially those who are not controlled on antiretroviral therapy.

Cytomegalovirus colitis combined with Clostridium innocuum as a cause of lower GI bleeding in a patient with COVID-19

A 67-year-old woman who presented with fever received a diagnosis of COVID-19 infection and was admitted to the medicine ward. She had a history of hypertension and diabetes. On day 4 of hospitalization, owing to progressive dyspnea and oxygen desaturation, she received intubation and mechanical ventilator support. She received remdesivir, dexamethasone, empiric antibiotics, enoxaparin, and tocilizumab during her hospitalization. On day 24, the patient developed bloody stools, and her hemoglobin level decreased from 11.7 g/dL to 9.2 g/dL. Because of persistent bleeding, she underwent colonoscopy, which revealed colitis and ulcer bleeding at the rectum (A). CT showed wall thickening of the lower part of the rectum (B). A pathologic study of the biopsy specimen showed enlarged nuclei and viral inclusions in both the cytoplasm and the nuclei (C). Immunohistochemical stain was positive for cytomegalovirus (CMV) antigen (D). The result of a blood CMV DNA polymerase chain reaction was positive, and the diagnosis of CMV infection was confirmed. In addition, there was growth of Clostridium innocuum in the stool culture. Her bleeding subsided after ganciclovir and metronidazole treatment, and she was extubated smoothly on day 38. Here we illustrate a COVID-19 patient who presented with lower GI bleeding caused by CMV coinfection and growth of C innocuum simultaneously. Endoscopy plays a crucial role in the treatment of patients with GI bleeding. All authors disclosed no financial relationships. Commentary The healthier you are the healthier you stay; the sicker you are the sicker you get. This case reflects this axiom. This unfortunate patient experienced severe respiratory failure secondary to COVID-19 infection. Colonoscopy revealed a dramatic "punched out" ulcer, highly suggestive of a viral colitis, and indeed the patient was found to have a CMV infection. She was also found to harbor C innocuum, which, despite its name, should not be confused with C difficile. C innocuum is an anaerobic gram-positive rod that is considered to be a variant of normal gut flora. C innocuum usually behaves in a pathogenic manner in patients who are immunocompromised, as was clearly the case with this patient. C innocuum is often seen to cause illness in patients after organ transplantation, most commonly renal transplantation. Fortunately, this patient appears to have done well after aggressive therapy for her COVID-19 infection. Douglas G. Adler, MD, FASGE, GIE Senior Associate Editor, Co-Director, Center for Advanced Therapeutic Endoscopy (CATE), Porter Adventist Hospital, PEAK Gastroenterology, Denver, Colorado Mohamed O. Othman, MD, Associate Editor for Focal Points

Epidemiology and Clinical Impact of Respiratory Coinfections at Diagnosis of Pneumocystis jirovecii Pneumonia.

The role of respiratory coinfections at diagnosis of Pneumocystis jirovecii pneumonia (PcP) on clinical impact has been underestimated. A retrospective observational study was conducted January 2011 to April 2019 to evaluate respiratory coinfections at diagnosis of PcP patients in 2 tertiary care hospitals. Coinfection was defined by identification of pathogens from P. jirovecii-positive samples. Of 7882 respiratory samples tested for P. jirovecii during the 8-year study, 328 patients with diagnosis of PcP were included. Mean age was 56.7 (SD 14.9) years, 193 (58.8%) were male, 74 (22.6%) had positive HIV serology, 125 (38.1%) had viral coinfection, 76 (23.2%) bacterial coinfection, and 90-day mortality was 25.3%. In the overall population, 90-day mortality was independently associated with solid tumor underlying disease (odds ratio [OR], 11.8; 95% confidence interval [CI], 1.90-78.0; P = .008), sepsis-related organ failure assessment score (SOFA) at admission (OR, 1.62; 95% CI, 1.34-2.05; P< .001), and cytomegalovirus (CMV) respiratory coinfection (OR, 3.44; 95% CI, 1.24-2.90; P = .02). Among HIV-negative patients, respiratory CMV coinfection was associated with worse prognosis, especially when treated with adjunctive corticosteroid therapy. Respiratory CMV coinfection at PcP diagnosis was independently associated with increased 90-day mortality, specifically in HIV-negative patients.

The TLR9 2848C/T Polymorphism Is Associated with the CMV DNAemia among HIV/CMV Co-Infected Patients.

Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and are essential components of the host’s innate immune response. The aim of this study was to determine the TLR9 genotype frequency and investigate the association between TLR9 polymorphisms and cytomegalovirus (CMV) DNAemia in human immunodeficiency virus (HIV)/CMV co-infected patients. A total of 205 HIV/CMV co-infected adults were screened for the presence of the four TLR9 polymorphisms (−1237T/C, −1486T/C, 1174G/A, and 2848C/T) by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Mutation presented in at least one allele of the TLR9 2848C/T single nucleotide polymorphism (SNP) was associated with the occurrence of CMV DNAemia among HIV-infected patients with CMV co-infection (p = 0.004). The level of CMV DNA was higher in patients who were homozygous recessive or heterozygous for the 2848C/T polymorphism compared with those who had a wild-type genotype for this polymorphism (p = 0.005). Mutation detected in at least one allele of this SNP was also associated with a lower interferon type β (IFN-β) concentration (p = 0.048), while no relationships between TLR9 −1237T/C, −1486T/C, and 1174G/A SNPs and CMV DNAemia were observed. Our findings suggest that the mutation present in at least one allele of the TLR9 2848C/T SNP may be associated with the active CMV infection in HIV/CMV co-infected subjects.

Coinfection of Cytomegalovirus (Immunoglobulin G) Antibody in Anti-hepatitis C Virus Seropositive Cases at a Tertiary Care Hospital

Coinfection of Cytomegalovirus (Immunoglobulin G) Antibody in Anti-hepatitis C Virus Seropositive Cases at a Tertiary Care Hospital

BK Virus and Cytomegalovirus Coinfections in Kidney Transplantation and Their Impact on Allograft Loss.

We aimed to ascertain the interaction and effects of combined reactivations of BK virus and cytomegalovirus on kidney graft function. All consecutive kidney transplant recipients (KTR) between 2003 and 2016 were included. Of 1976 patients who received a kidney transplant, 23 (1.2%) presented BKV-associated nephropathy (BKVAN). Factors independently associated with BKVAN were diabetes mellitus (odds ratios (OR) 3.895%, confidence intervals (CI) (1.4–10.5)), acute allograft rejection (OR 2.8 95%, CI (1.1–7.6)) and nephrostomy requirement (OR 4.195%, CI (1.3–13)). Cytomegalovirus infection was diagnosed in 19% of KTR patients. Recipients with BKVAN presented more frequently with cytomegalovirus (CMV) infection compared to patients without BKVAN (39% vs. 19%, p = 0.02). Acute allograft rejection (OR 2.95%, CI (1.4–2.4)) and nephrostomy requirement (OR 2.95%, CI (1.2–3)) were independently associated with CMV infection. Sixteen patients (69%) with BKVAN had graft dysfunction at one-year post-transplant and eight of them (35%) lost their graft. Patients presenting with BKVAN and graft loss presented more frequently a cytomegalovirus infection (OR 2.295%, CI (1.3–4.3)). In conclusion, we found a relation between CMV infection and graft loss in patients presenting BKVAN, suggesting that patients with CMV reactivation should be actively screened for BKV.

Human Immunodeficiency Virus (HIV) and Human Cytomegalovirus (HCMV) Coinfection of Infant Tonsil Epithelium May Synergistically Promote both HIV-1 and HCMV Spread and Infection.

Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) and human cytomegalovirus (HCMV) may occur during pregnancy, labor, or breastfeeding. These viruses from amniotic fluid, cervicovaginal secretions, and breast milk may simultaneously interact with oropharyngeal and tonsil epithelia; however, the molecular mechanism of HIV-1 and HCMV cotransmission through the oral mucosa and its role in MTCT are poorly understood. To study the molecular mechanism of HIV-1 and HCMV MTCT via oral epithelium, we established polarized infant tonsil epithelial cells and polarized-oriented ex vivo tonsil tissue explants. Using these models, we showed that cell-free HIV-1 and its proteins gp120 and tat induce the disruption of tonsil epithelial tight junctions and increase paracellular permeability, which facilitates HCMV spread within the tonsil mucosa. Inhibition of HIV-1 gp120-induced upregulation of mitogen-activated protein kinase (MAPK) and NF-κB signaling in tonsil epithelial cells, reduces HCMV infection, indicating that HIV-1-activated MAPK and NF-κB signaling may play a critical role in HCMV infection of tonsil epithelium. HCMV infection of tonsil epithelial cells also leads to the disruption of tight junctions and increases paracellular permeability, facilitating HIV-1 paracellular spread into tonsil mucosa. HCMV-promoted paracellular spread of HIV-1 increases its accessibility to tonsil CD4 T lymphocytes, macrophages, and dendritic cells. HIV-1-enhanced HCMV paracellular spread and infection of epithelial cells subsequently leads to the spread of HCMV to tonsil macrophages and dendritic cells. Our findings revealed that HIV-1- and HCMV-induced disruption of infant tonsil epithelial tight junctions promotes MTCT of these viruses through tonsil mucosal epithelium, and therapeutic intervention for both HIV-1 and HCMV infection may substantially reduce their MTCT. IMPORTANCE Most HIV-1 and HCMV MTCT occurs in infancy, and the cotransmission of these viruses may occur via infant oropharyngeal and tonsil epithelia, which are the first biological barriers for viral pathogens. We have shown that HIV-1 and HCMV disrupt epithelial junctions, reducing the barrier functions of epithelia and thus allowing paracellular penetration of both viruses via mucosal epithelia. Subsequently, HCMV infects epithelial cells, macrophages, and dendritic cells, and HIV-1 infects CD4+ lymphocytes, macrophages, and dendritic cells. Infection of these cells in HCMV- and HIV-1-coinfected tonsil tissues is much higher than that by HCMV or HIV-1 infection alone, promoting their MTCT at its initial stages via infant oropharyngeal and tonsil epithelia.

A case report of Nocardia asiatica in a renal transplant recipient

Nocardiosis is a life-threatening disease in solid organ transplant recipients. It is an uncommon but important infection in these patients. Nocardiosis is caused by a Gram-positive, weakly acid fast, branching filamentous aerobic bacteria belonging to the order Actinomycetales. It causes pulmonary and systemic infections in immunocompromised patients. The common species of Nocardia causing infections are Nocardia asteroids, Nocardia brasiliensis, Nocardia farscinica, and Nocardia nova. Here, we report a case of a 32-year-old female postrenal transplant recipient developing pulmonary nocardiosis by a rare species of Nocardia called Nocardia asiatica. A modified Ziehl–Neelsen stain using 1% H2SO4 in the endotracheal (ET) secretion revealed numerous acid fast branching filamentous organisms morphologically resembling Nocardia spp., and the culture grew Nocardia and it was confirmed as N. asiatica by MALDI TOF. Our patient had cytomegalovirus co-infection. The patient was started on trimethoprim-sulfamethoxazole. This case shows the importance of keeping nocardiosis as a differential diagnosis in immunocompromised patients.

THE OROPHARYNX MICROBIOME PROFILE OF CHILDREN WITH INFECTIOUS MONONUCLEOSIS EPSTEIN-BARR VIRAL ETIOLOGY

Relevance. The microbiota of the oral cavity is individual and the consistency of its composition provides a protective function that is regulated by the immune system. Dysbiotic changes in the oral microbiota composition lead to a devastation of local immunity and provide to the disease's development. Herpes virus infection аctivation suppresses the immune response which increases the level of oral mucosa bacteria colonization in particular during the acute course of infectious mononucleosis (IM).&#x0D; Objective: to study the features of the oral microbiome composition and its sensitivity to antibacterial drugs in patients with infectious mononucleosis and acute tonsillitis.&#x0D; Materials and methods. We examined 306 children aged 7 to 236 months. The main group (n = 280) – children with IM. Comparison group (n = 26) – children diagnosed with acute tonsillitis. The main group was divided into two subgroups: subgroup I – 234 children with MI caused by the Epstein-Barr virus (EBV), and subgroup II – 46 children with co-infection with the EBV virus and cytomegalovirus (CMV). The examination was performed according to the treatment protocol: general and biochemical analysis of blood, determination of IgM antibodies to Epstein-Barr virus and cytomegalovirus, bacteriological examination of oropharyngeal mucus, followed by determination of the sensitivity of the identified pathogens to antibacterial drugs.&#x0D; The results. In oral microbiome of children with IM caused by EBV and CMV co-infection pneumococcus dominant. In children with acute tonsillitis, Staphylococcus aureus, S. pyogenes infection, and yeast-like fungi were predominant. S. pyogenes, in children with co-infection, has a high level of resistance to β-lactam antibiotics. Higher levels of antibiotic-resistant strains were found among Enterococcus spp. Isolates, especially in children with EBV-induced MI and co-infection of EBV and CMV.&#x0D; Conclusions. The development of MI is accompanied by microecological dysbiosis of the mucous membranes of the oropharynx and tonsils, which do not provide enough level of colonization resistance, contributing to the spread of antibiotic resistance among resident and transient microbiota.

Risk Factors of Mortality From Pneumocystis Pneumonia in Non-HIV Patients: A Meta-Analysis.

Background: We performed a meta-analysis to systematically review the risk factors of mortality from non-HIV-related Pneumocystis pneumonia (PcP) and provide the theoretical basis for managing non-HIV-related PcP.Methods: PubMed, Embase, Web of Science, the Cochrane Library and CNKI databases were searched. A meta-analysis of the risk factors of mortality from non-HIV-related PcP was conducted.Results: A total of 19 studies and 1,310 subjects were retrieved and included in the meta-analysis, including 485 and 825 patients in the non-survivor and survivor groups, respectively. In the primary analysis, age, concomitant with other pulmonary diseases at diagnosis of PcP, solid tumors, cytomegalovirus(CMV) co-infection, lactate dehydrogenase (LDH), lymphocyte count, invasive ventilation during hospitalization, and pneumothorax were associated with mortality from non-HIV-related PcP, whereas sex, albumin, PcP prophylaxis, use of corticosteroids after admission, and time from onset of symptoms to treatment were not associated with mortality from non-HIV-related PcP.Conclusions: The mortality rate of non-HIV-infected patients with PcP was still high. Age, concomitant with other pulmonary diseases at diagnosis of PcP, solid tumors, CMV co-infection, LDH, lymphocyte count, invasive ventilation during hospitalization, and pneumothorax were risk factors of mortality from non-HIV-related PcP. Improved knowledge of prognostic factors is crucial to guide early treatment.

Clinical consequences of asymptomatic cytomegalovirus in treated human immunodeficency virus infection.

Despite antiretroviral therapy (ART)-mediated viral suppression, people with human immunodeficiency virus (HIV) (PWH) have increased morbidity and mortality. Immune activation and inflammation persist on ART and predict these complications. Over 90% of PWH have cytomegalovirus (CMV) co-infection, and CMV is considered a plausible contributor to this persistent immune activation. A detailed understanding of the link between CMV and multimorbidity is needed, particularly as research moves toward identifying potential targeted therapeutics to attenuate inflammation-mediated morbidity and mortality in treated HIV. We review the literature on the association between CMV and immune activation as well as multiple end-organ complications including cardiovascular disease, venous thromboembolic disease, metabolic complications, gastrointestinal dysfunction, central nervous system involvement, birth sex-related differences, and the relation to the HIV reservoir. We conclude with a discussion of ongoing therapeutic efforts to target CMV. As CMV is a plausible driver of multiple comorbidities through persistent immune activation in treated HIV, future research is needed and planned to address its causal role as well as to test novel therapeutics in this setting.

Role of Interleukin-28 B Gene Polymorphism and Cytomegalovirus Coinfection in Hepatocellular Carcinoma Patients with Chronic Hepatitis C Virus

Background: Liver diseases including HCC are life-threatening morbidities. Mechanisms of HCC are still unclear. Cytomegalovirus (CMV) is DNA virus characterized by latency and cellular transformation. Genetic polymorphisms especially SNPs are the most common genetic variation. It plays a critical role in regulation of cellular interaction and cytokine production. CMV infection and its role in HCC is under investigation. Objectives: to profile IL28B single-nucleotide polymorphism in development of HCC in chronic HCV, and identify the relationship between human cytomegalovirus infection, IL28B SNPs and HCC. Methodology: 120 blood samples were obtained from HCV patients; divided according to clinical, radiological and laboratory data into three equal groups, forty patients each: HCV, HCC, LC groups, and 40 normal persons as controls. SNPs of interleukin-28 (IL28B rs12979860) by RFLP and CMV viral DNA by real-time polymerase chain reaction were investigated. Results: IL28B /CC genotype was increased significantly in controls and TT genotype in HCC group. A positive correlation among HCV viral load, CMV with the genotype IL28B rs12979860/TT especially in HCC group. Conclusions: IL28B rs12979860/TT is expressed in HCC patients making its role in development of HCC in CMV positive HCV patients cannot be denied.

POS-092 CYTOMEGALOVIRUS AND SARS-COV-2 COINFECTION IN KIDNEY TRANSPLANT RECIPIENT: A CASE REPORT

Cytomegalovirus (CMV) is one of the most common causative agents of infections that affect renal transplant recipients. Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has rapidly spread worldwide. The clinical presentation of this infection can vary from an asymptomatic course to acute respiratory distress syndrome (ARDS) requiring invasive mechanical ventilation and extracorporeal membrane oxygenation. Little of studies reported the Coinfection with SARS-COV-2 and Cytomegalovirus. We describe the first case of COVID-19 and cytomegalovirus (CMV) co-infection in kidney transplant recipient. A 36 years old woman, with a clinical history of severe lupus erythematosus received a renal transplant from cadaveric donor on October 02, 2019. Her immunosuppressant regime included prednisone 5mg daily,tacrolimus0.15mg/kg/day and Sirolimus 1mg daily.Of note, the hydroxychloroquine was interrupted since six years ago due to toxic maculopathy.On july 23, 2020 , she was hospitalized for recurrent CMV disease treated by intra veinous gancilovir 10 mg/kg/day for 60 days. On day 35 of hospitalization, she presented an isolated cough. Physical examination was otherwise unremarkable, including breath sounds on chest auscultation. Her oxygen saturation was 98%. A routine blood test showed worsening lymphopenia, initially improved with the gancilovir therapy.She elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH). The liver enzymes were slightly increased and her serum creatinine was still within the normal range.However,cough disappeared after72 hours. In the meantime, a COVID-19 was diagnosed in the nurse who taked care of our patient .As part of contact tracing ,a nasopharyngeal swab was performed for she and it was positive for SARS CoV-2.However, she had no complaints.Her physical examination and her laboratory testing were otherwise unremarkable. we report the first case of COVID-19 in kidney transplant patient in our country with excellent outcome despite the coinfection with SARS-COV-2 and Cytomegalovirus (CMV). So, it can be supposed that she might be protected by the antiviral therapy, ganciclovir or by the immunomodulatory effects of CMV.

Immune activation during Paenibacillus brain infection in African infants with frequent cytomegalovirus co-infection

SummaryInflammation during neonatal brain infections leads to significant secondary sequelae such as hydrocephalus, which often follows neonatal sepsis in the developing world. In 100 African hydrocephalic infants we identified the biological pathways that account for this response. The dominant bacterial pathogen was a Paenibacillus species, with frequent cytomegalovirus co-infection. A proteogenomic strategy was employed to confirm host immune response to Paenibacillus and to define the interplay within the host immune response network. Immune activation emphasized neuroinflammation, oxidative stress reaction, and extracellular matrix organization. The innate immune system response included neutrophil activity, signaling via IL-4, IL-12, IL-13, interferon, and Jak/STAT pathways. Platelet-activating factors and factors involved with microbe recognition such as Class I MHC antigen-presenting complex were also increased. Evidence suggests that dysregulated neuroinflammation propagates inflammatory hydrocephalus, and these pathways are potential targets for adjunctive treatments to reduce the hazards of neuroinflammation and risk of hydrocephalus following neonatal sepsis.

Serum ferritin at admission in hospitalized COVID-19 patients as a predictor of mortality

IntroductionSome COVID-19 patients have higher mortality and the responsible factors for this unfavorable outcome is still not well understood. ObjectiveTo study the association between ferritin levels at admission, representing an inflammatory state, and hospital mortality in COVID-19 patients. MethodsFrom May through July 2020, SARS-CoV-2 positive patients with moderate to severe clinical symptoms were evaluated at admission, regarding clinical and laboratory data on renal and hepatic function, hematologic parameters, cytomegalovirus co-infection, and acute phase proteins. ResultsA total of 97 patients were included; mean age=59.9±16.3 years, 58.8% male, 57.7% non-white, in-hospital mortality=45.4%. Age, ferritin, C-reactive protein, serum albumin and creatinine were significantly associated with mortality. Ferritin showed area under the curve (AUC) of 0.79 (p<0.001) for the cut-off of 1873.0ng/mL, sensitivity of 68.4% and specificity of 79.3% in predicting in-hospital mortality. Age ≥60 years had an odds ratio (OR) of 10.5 (95% CI=1.8–59.5; p=0.008) and ferritin ≥1873.0ng/mL had an OR of 6.0 (95% CI=1.4–26.2; p=0.016), both independently associated with mortality based on logistic regression analysis. ConclusionThe magnitude of inflammation present at admission of COVID-19 patients, represented by high ferritin levels, is independently predictive of in-hospital mortality.

Anticytomegalovirus CD4+ T Cells Are Associated With Subclinical Atherosclerosis in Persons With HIV.

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Cutaneous Coinfection of Cytomegalovirus and Mycobacterium chelonae Accelerated by Immunosuppression

A mildly diabetic 58-year-old male had traumatic ulceration on the left popliteal fossa, and the lesion progressed to a painful 6 cm deep ulcer. After surgical debridement and skin grafting, ulceration recurred. Pyoderma gangrenosum was clinically diagnosed after the first biopsy, indicating a noninfective ulcer. Immunosuppressive therapy (prednisolone and cyclosporine A) induced complete epithelialization in three months. Four months later, subcutaneous nonulcerated nodules appeared on the anterior area of the left lower leg. Subcutaneous induration progressed and ulceration recurred, so that immunosuppressive therapy continued for one year. Cytomegalovirus (CMV) viremia was detected, and the second biopsy demonstrated CMV inclusions of endothelial and perivascular cells in fibrosing septolobular panniculitis. Cyclosporine A was cancelled, prednisolone was tapered, and ganciclovir started. Viremia soon disappeared, but the lesion progressed to large induration with multiple ulcers measuring up to 3 cm. The third biopsy disclosed infection of Gram-positive mycobacteria, accompanying fat droplet-centered suppurative granulomas without CMV infection. Microbial culture identified Mycobacterium chelonae. Clarithromycin with thermotherapy was effective. A review of the second biopsy confirmed coinfection of CMV and Gram-positive mycobacteria. Immunostaining using a panel of anti-bacterial antibodies visualized the mycobacteria in the lesion. Positive findings were obtained with antibodies to Bacillus Calmette-Guérin, Bacillus cereus, MPT64 (Mycobacterium tuberculosis-specific 24 kDa secretory antigen), LAM (Mycobacterium tuberculosis-related lipoarabinomannan), and PAB (Propionibacterium acnes-specific lipoteichoic acid).

A Clinically Diagnosed Congenital Rubella Syndrome and Congenital Cytomegalovirus Co-infection

This is a case of a four-month-old female infant who presented with clinical manifestations of congenital rubella syndrome (CRS) — bilateral cataracts, poorly-dilating pupils, microcorneas, salt and pepper retinopathies seen after cataract extractions, bilateral sensorineural hearing loss, patent ductus arteriosus, microcephaly, history of blueberry spots and low birth weight, and positive serum IgM and IgG tests for rubella. The patient’s mother also had prenatal rubella infection. However, the patient also presented with additional set of clinical findings not seen in recent patients with CRS and not commonly reported in literature: visual acuities of poor to no dazzle, bilateral choroidal thickening on ocular ultrasound that spontaneously resolved, optic nerve inflammation that became atrophic, vessel tortuosities seen after cataract extractions, bilateral subependymal cysts with lenticulostriate vasculopathy in basal ganglia, basal ganglia hyperintensity suggestive of calcification, and jaundice. These findings plus the overlapping clinical manifestations with CRS and the positive IgM and IgG for cytomegalovirus (CMV) made us consider a congenital CMV co-infection. CRS already causes significant childhood morbidity. Getting co-infected with CMV in utero worsens morbidity and makes management more difficult. This case presented a congenital co-infection of rubella and CMV and discussed the added challenges in their diagnosis and management.

TIGIT blockade enhances NK cell activity against autologous HIV-1-infected CD4+ T cells.

ObjectivesDuring chronic human immunodeficiency virus (HIV)‐1 infection, inhibitory molecules upregulated on lymphocytes contribute to effector cell dysfunction and immune exhaustion. People living with HIV (PLWH) are at greater risk for age‐related morbidities, an issue magnified by human cytomegalovirus (CMV) coinfection. As CMV infection modifies natural killer (NK) cell properties and NK cells contribute to protection against HIV‐1 infection, we considered the role of T‐cell immunoreceptor with immunoglobulin and intracellular tyrosine inhibitory motif domains (TIGIT) in NK cell‐based HIV‐1 immunotherapy and elimination strategies.MethodsWe measured TIGIT expression on immune cell subsets of 95 PLWH and assessed its impact on NK cell function, including elimination of autologous CD4+ T cells infected through reactivation of endogenous HIV‐1.ResultsTIGIT was expressed on CD4+ T cells, CD8+ T cells and NK cells from PLWH. Although TIGIT levels on T cells correlated with HIV‐1 disease progression, the extent of TIGIT expression on NK cells more closely paralleled adaptation to CMV. TIGIT interacts with its predominant ligand, poliovirus receptor (PVR), to inhibit effector cell functions. Circulating CD4+ T cells from PLWH more frequently expressed PVR than HIV‐seronegative controls, and PVR expression was enriched in CD4+ T cells replicating HIV‐1 ex vivo. Treatment with anti‐TIGIT monoclonal antibodies increased NK cell HIV‐1‐specific antibody‐dependent cytotoxicity in vitro and ex vivo.ConclusionBlocking TIGIT may be an effective strategy to invigorate antibody‐dependent NK cell activity against HIV‐1 activated in cellular reservoirs for cure or treatment strategies.

Cytomegalovirus and Severe Acute Respiratory Syndrome Coronavirus 2 Co-infection in Renal Transplants: A Retrospective Study from a Single Center.

There is a scarcity of data regarding the impact of cytomegalovirus (CMV) infection complicating the coronavirus disease-2019 (COVID-19) course. The objective of the study was to explore the clinical profile and outcome of CMV co-infection with COVID-19. This is a single-center retrospective study of COVID-19 cases with concomitant CMV infection. A total of 18 cases were diagnosed with CMV infection during the study period May 2020 to December 2020. The median age (Interquartile range) of the study was 45 (53-38) years with predominant male sex (n = 14, 77%). The baseline donor-recipient status for CMV included D+/R+ (10, 55%), D-/R+(6, 33%), and D+/R- (2, 12%). COVID-19 severity in the study included mild (1, 7%), moderate (5, 28%), severe (8, 44%), and critical (4, 22%) cases. Criteria for hyperinflammatory state was met by 77% (n = 14) of cases. The most common therapeutic modality for COVID-19 given was remdesivir (n = 13), tocilizumab (n = 4), and convalescent plasma (n = 4). The median CMV titer at diagnosis was 1200 (1800-1000) copies/mL. The median duration of hospital stay was 12.5 (14-11). Mortality observed in the study was four (22%). The management of CMV co-infection with COVID-19 is associated with high morbidity and mortality, and we suggest screening for CMV infection in all posttransplant COVID-19 cases.