Cytomegalovirus Co-infection Research Articles

Co-infection of cytomegalovirus and Leishmania without splenomegaly resulting in immunosuppression in an HIV-negative patient

Background: Leishmaniasis is caused by the parasite Leishmania donovani and transmitted by the bite of the sand fly vector Phlebotomus. This disease is endemic in the Bihar region of India. There are three common forms of the disease – cutaneous, mucosal and visceral leishmaniasis. The most common presentation of this disease is prolonged unexplained fever with hepatosplenomegaly. Case description: We report an unusual case of pyrexia of unknown origin (PUO) in a patient who was extensively worked up for PUO. She was found to have low CD4 counts even though serial samples were negative for HIV. Workup for PUO revealed a positive result for cytomegalovirus (CMV) IgM and polymerase chain reaction (PCR), fundoscopy suggestive of CMV retinitis and bone marrow biopsy suggestive of visceral leishmaniasis. Interestingly, there was no evidence of hepatosplenomegaly. She was diagnosed as a case of CMV infection and visceral leishmaniasis resulting in immunosuppression and was managed with parenteral ganciclovir followed by oral valganciclovir and amphotericin respectively. She had a dramatic response to the treatment and was discharged after two months of in hospital management. Conclusion: Co-infection of CMV and Leishmania in an immunocompromised patient with HIV-negative status without hepatosplenomegaly posed a diagnostic dilemma and is a rare presentation. This report shows the importance of diagnosis of this co-infectious state, which upon management with ganciclovir and amphotericin lead to resolution of symptoms and pancytopenia. Clinicians should be aware of the unusual presentation to avoid missing the diagnosis of this potentially life-threatening treatable condition.

Clinical impact of metagenomic next-generation sequencing of bronchoalveolar lavage fluids for the diagnosis of pulmonary infections in respiratory intensive care unit

BackgroundThe real-world clinical impact of mNGS on BALF in the respiratory intensive care unit (RICU) is not yet fully understood. MethodsWe investigated the clinical impact of mNGS on BALF samples obtained from 92 patients admitted to the RICU over a 2-year period. We utilized both mNGS and culture methods to evaluate the effectiveness of mNGS in diagnosing pulmonary infections. The clinical impact of mNGS were evaluated by the clinician committees. ResultsAmong the 92 diagnosed patients, 78 cases (84.7 %) were determined to have infectious diseases caused by pathogenic microorganisms, and the bacterial infections constituted the most prevalent diagnostic category. For mixed infection, the most common type was the Pneumocystis jironecii and cytomegalovirus co-infection. The mNGS results had a positive impact on the clinical management of 43 cases (46.7 %). Moreover, 19 cases (44.2 %) of positive clinical impacts were solely based on new diagnoses made possible by mNGS results. These new diagnoses were particularly helpful for identifying rare pathogens, which could not be detected by conventional diagnostic methods. ConclusionsThe BALF mNGS has a positive real-world impact in RICU. Clinician committee play a critical role in ensuring the appropriate use of mNGS.

Coinfection of viruses in children with community-acquired pneumonia

BackgroundVirus, particularly respiratory tract virus infection is likely to co-occur in children with community-acquired pneumonia (CAP). Study focusing on the association between common viruses coinfection and children with CAP is rare. We aimed to study the association between seven common viruses coinfection and clinical/laboratory indexes in children with CAP.MethodsSix hundred and eighty-four CAP cases from our hospital were enrolled retrospectively. Seven common viruses, including influenza A (FluA), influenza B (FluB), human parainfluenza virus (HPIV), Esptein-Barr virus (EBV), coxsackie virus (CoxsV), cytomegalovirus (CMV), and herpes simplex virus (HSV) were investigated for their associations with CAP. We analyzed the differences of hospitalization days, white blood cell (WBC), c-reactive protein (CRP), platelet (PLT), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), urine red blood cell (uRBC), blood urea nitrogen (BUN), serum creatinine (Scr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase isoenzyme (CKMB) among different viruses coinfection groups by using one-way ANOVA analysis. The differences of clinical/laboratory indexes between ordinary and severe pneumonia groups, as well as non-virus vs multi co-infection viruses groups, and single vs multi co-infection viruses groups by using independent samples T test. Receiver operating characteristic (ROC) curve analyses were applied to test the the predictive value of the clinical/laboratory parameters for the risk of viruses coinfections among CAP. Binary logistic analysis was performed to test the association between various indexes and viruses co-infection.ResultsEighty-four multiple viruses coinfections yielded different prognosis compared with that in 220 single virus coinfection. CMV coinfection was associated with longest hospitalization days, highest ALT, AST and CKMB level. HSV coinfection was associated with highest WBC count, CRP, ESR, and BUN. EBV coinfection was associated with highest PLT and PCT level. FluB coinfection was associated with highest Scr level. CoxsV coinfection was associated with highest uRBC, LDH and CK level. ROC curve analyses showed that CK had the largest area under the curve (AUC: 0.672, p < 10–4) for the risk of viruses coinfections risk in CAP. Significant association between PLT, uRBC, BUN, CK, and CKMB and virus coinfection risk in CAP was observed.ConclusionsMultiple viruses coinfections indicated different prognosis. Different viruses coinfection yielded varying degrees of effects on the cardiac, liver, kidney and inflamatory injury in CAP. The alterations of clinical/laboratory parameters, particularly CK may be associated with the risk of viruses coinfections in CAP.

Acute Lupus Pneumonitis with Cytomegalovirus Co-infection in Patients with Lupus Nephritis

Introduction: Most patients with systemic lupus erythematosus (SLE) show signs of pulmonary involvement. The clinical manifestations of Lupus Pneumonitis are the similar to those of acute interstitial pneumonia. The use of cyclophosphamide in lupus nephritis (LN) is associated with high CMV titers. Ganciclovir is the main choice of therapy for CMV pneumonia infection. Case presentation: A 19-year-old female with previous history of lupus nephritis presented with worsening dyspnea, productive cough with yellowish sputum and hemoptysis. Following physical, laboratory and radiological examinations, the patient was diagnosed with acute lupus pneumonitis, with a differential diagnosis of pneumonia infection. During treatment in the intensive care unit (ICU), she was put on ventilator and received routine hemodialysis due to pulmonary edema. She was given intravenous antibiotics before the culture results came out, but there was no clinical improvement. Once the culture results returned negative, the antibiotics were discontinued and IV pulse methylprednisolone was started. There was significant clinical, radiological, and laboratory improvements. After discharge, the patient experienced hemoptysis again due to CMV pneumonia infection and was given ganciclovir therapy with satisfactory results. Conclusion: In patients with advanced LN and pulmonary involvement, distinguishing between infection and SLE flares may be challenging, which can cause dilemma in diagnosis and treatment decisions. Adequate oxygenation with ventilator, hemodialysis, and administration of ganciclovir and mycophenolic acid provides significant improvements in patient care.

Challenges of managing HIV cytomegalovirus co-infection in the presence of pancytopenia

A 60-year-old male patient who presented with generalized weakness and low-grade fever was diagnosed to be human immunodeficiency virus (HIV) positive with a CD4 count of 17. Routine laboratory investigations revealed pancytopenia. Serum cytomegalovirus (CMV) DNA polymerase chain reaction (PCR) was positive and fundoscopy showed CMV retinitis in the right eye. The patient was started on tablet valganciclovir. After 2 weeks, the patient was brought back in an altered sensorium. He was found to have hyponatremia which was corrected. He was started on antiretroviral therapy and tablet valganciclovir was continued. The patient came back again after one and a half months with a urinary tract infection and fissure-in-ano. He was found to have severe neutropenia. Valganciclovir was stopped. He was started on injection granulocyte colony-stimulating factor. The patient clinically improved and his hematological parameters became normal. Patients having HIV and CMV co-infection with pre-existing pancytopenia have to be closely monitored as the medicines used for treatment can exacerbate the existing conditions.

Pulmonary co-infections by Pneumocystis jirovecii and Herpesviridae: a seven-year retrospective study

BackgroundPneumocystis jirovecii (P. jirovecii) is an opportunistic fungus responsible for Pneumocystis pneumonia (PCP) in deeply immunocompromised patients and for pulmonary colonization in individuals with mild immunosuppression or impaired respiratory function. PCP and Cytomegalovirus (CMV) co-infections have been widely described whereas those involving other Herpesviruses (HVs) such as Epstein-Barr virus (EBV), Herpes simplex virus type 1 and type 2 (HSV-1 and -2), and Varicella zoster virus (VZV) remain scarce. To date, no data are available concerning HVs co-infections in P. jirovecii colonization.MethodsOur main objective was to evaluate the frequency of HVs in bronchoalveolar lavage fluid (BALF) samples from patients with PCP or with pulmonary colonization. The secondary objective was to assess the relationship between HVs and the mortality rate in PCP patients. A retrospective single-center study over a seven-year period was conducted. All patients with P. jirovecii detected using PCR in a BALF sample and for whom a PCR assay for HVs detection was performed were included in the study.ResultsOne hundred and twenty-five patients were included, corresponding to 77 patients with PCP and 48 colonized patients. At least one HV was detected in 54/77 (70.1%) PCP patients and in 28/48 (58.3%) colonized patients. EBV was the most frequent in both groups. Furthermore, the 30-day survival rate in PCP patients was significantly lower with [EBV + CMV] co-infection than that with EBV co-infection, [EBV + HSV-1] co-infection and without HV co-infection.ConclusionOur results show that the frequency of HV, alone or in combination is similar in PCP and colonization. They also suggest that [EBV + CMV] detection in BALF samples from PCP patients is associated with an increased mortality rate, underlying the significance to detect HVs in the course of PCP.

Life-threatening Pneumocystis jiroveci Pneumonia with Cytomegalovirus Coinfection in a Follicular Lymphoma Patient During Rituximab-based Chemotherapy

Abstract In the era of target therapy, we face the challenge of the risk of opportunistic infection in patients with B-cell lymphoma who receiving rituximab-based chemotherapy. Opportunistic infections such as Pneumocystis jiroveci pneumonia (PJP) and Cytomegalovirus (CMV) pneumonia are life-threatening diseases. However, PJP with CMV coinfection is rare. Here, we report a follicular lymphoma patient who suffered from PJP with CMV coinfection after receiving three cycles of rituximab, cyclophosphamide, vincristine, and prednisone regimen and was successfully rescured after timely identification and treatment. We emphasize that physicians should be alert for the coinfection of PJP and CMV in lymphoma patients receiving rituximab-based chemotherapy and the timely recognition, and treatment that may avoid a deadly outcome.

CMV and HIV Coinfection in Women from a Region in Eastern Europe.

(1) Background: Human cytomegalovirus (CMV) infection is one of the most frequent opportunistic infections in immunosuppressed patients. Romania has one of the highest incidences of patients living with human immunodeficiency virus (HIV) which determines an immunosuppressive state. The aim of this study was to establish the prevalence of CMV infection among women living with HIV in Southeastern Romania and also to evaluate and correlate antiretroviral therapy (ART) with CD4 level and CMV disease evolution. (2) Methods: Seventy women living with HIV from Southeastern Romania were screened for CMV infection using antigen quantification. Of these, 50 were included in the study. First, the patients filled out a questionnaire regarding social conditions and other associated diseases. Then, we explored the statistical correlations between the data and HIV status, CD4+ cell counts, viral load, and antiretroviral therapy (ART). (3) Results: Median age of the patients was 33 years. Twenty-nine cases were diagnosed with HIV after sexual life beginning and 21 before. Most of the patients had a CD4 level over 200 cells/µL. ART duration in the CD4 under 200 cells/µL group was a bit longer than that in the CD4 over 200 cells/µL group. Forty-one patients had undetectable viremia. CD4 average value in the lot of patients with undetectable viremia was 704.71 cells/µL and in the lot with detectable viremia was 452.44 cells/µL. Viremia values correlated negatively with CD4 level. A positive correlation between IgG CMV values and ART therapy length was identified. A negative significant correlation between values of IgG CMV and values of CD4 was identified. CD4 value correlated negatively with IgG CMV values and with CMV avidity. (4) Conclusions: IgG CMV values had a weak positive correlation with ART therapy length, and a negative statistically significant correlation with values of CD4. CMV avidity has a negative correlation with CD4 value.

Cytomegalovirus Reactivation in Postrenal Transplant Patients Immediately in Association with Coronavirus Disease 2019 (COVID-19) Infection: A Case Report of 2 Patients and a Brief Review of the Literature

Introduction: The coronavirus disease 2019 (COVID-19) infection has been associated with multiple opportunistic infections, including secondary cytomegalovirus (CMV) reactivation. Several cases of CMV syndrome and invasive CMV infection have been reported following severe COVID-19 infection worldwide during the COVID-19 pandemic in both immunocompetent and immunosuppressed patients. A case-control study conducted in India showed that during the first and second waves, CMV was the most common co-infection among fatal cases of severe COVID-19 lung infection in Indian renal transplant recipients. Case Presentation: We present 2 cases of CMV disease in postrenal transplant patients who developed clinical manifestations of CMV co-infection after mild COVID-19 infection during the fourth wave of COVID-19 infection in India. In both cases, CMV infection was treated by discontinuing mycophenolate mofetil and administering ganciclovir injections. However, the treatment resulted in 2 contrasting clinical outcomes: Cure and death. Conclusions: We reviewed the recent literature on the increased incidence of CMV reactivation after both COVID-19 infection and vaccination in immunocompetent and immunocompromised populations. Subsequently, we discussed some clinical questions relevant to the population of postrenal transplant recipients after the detection of mild COVID-19 infection.

Baseline Cytomegalovirus Viremia at Cryptococcal Meningitis Diagnosis Is Associated With Long-term Increased Incident TB Disease and Mortality in a Prospective Cohort of Ugandan Adults With HIV.

Adults with HIV-associated cryptococcal meningitis have overlapping burdens of cytomegalovirus (CMV) and tuberculosis (TB) coinfections. CMV infection/reactivation is strongly associated with CMV-specific memory T-cell activation and upregulation of type 1 interferons, which may lead to increased risk of TB disease and poor outcomes. We conducted a cohort study of 2-week survivors of cryptococcal meningitis during 2010-2021 to determine TB incidence and all-cause mortality over time stratified by baseline CMV status. We followed 497 Ugandans with HIV-associated cryptococcal meningitis for a median (interquartile range) of 4.6 (2.6-53.9) months. Overall, 42% (210/497) developed incident TB disease or died. One-fifth (98/497, 19.7%) developed incident TB disease, and 29% (142/497) of participants died during follow-up. Of 259 participants with CMV viral load measured at baseline, 37% (96/259) had concurrent CMV viremia (defined as anyone with detectable CMV DNA in plasma/serum by qualitative polymerase chain reaction [PCR] detection). Of 59 with measured CMV immunoglobulin G (IgG), 100% had positive CMV IgG antibody serology (≥10 enzyme-linked immunosorbent assay units/mL). CMV viremia was positively associated with higher HIV viral load (196 667 vs 73 295 copies/mL; P = .002) and higher cerebrospinal fluid fungal burden (68 500 vs 14 000 cfu/mL; P = .002) compared with those without. Participants with high-level CMV viremia (defined as CMV viral load ≥1000 IU/mL) had twice the risk of incident TB (subdistribution adjusted hazard ratio [aHR], 2.18; 95% CI, 1.11-4.27) and death (aHR, 1.99; 95% CI, 1.14-3.49) compared with participants with no or low-level CMV viremia. There was no association between the CMV IgG index and the incidence of TB/death (P = .75). CMV viremia >1000 IU/mL at meningitis diagnosis was associated with increased incident TB disease and mortality during long-term follow-up. Future studies to determine the causal relationship and potential for therapeutic intervention are warranted.

Measles virus and cytomegalovirus co-infection, in a child with recent SARS-CoV-2 infection, during COVID-19 pandemic: a case report

Measles virus (MV) and cytomegalovirus (CMV) may cause pediatric infection. We report the first described case of MV and CMV co-infection in an unvaccinated 13-mo-old girl, with a recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, occurred during coronavirus disease 2019 (COVID-19) pandemic. The COVID-19 pandemic context, combined with patient’s complex clinical scenario, presenting symptoms as persistent fever, diarrhea, vomiting, maculopapular rash and edema, in addition to high level of inflammatory markers, led to a suspicion of multisystemic inflammatory syndrome in children (MIS-C). The final diagnosis and the successfully management of the case, discharged after resolution of symptoms, was achieved by a proper virological diagnosis and a close two-way cooperation between pediatricians and clinical microbiologists. The report mainly highlights that awareness about measles should be raised in unvaccinated patients with consistent symptoms, even in the COVID-19 era.

Overlapping Infection by Strongyloides spp. and Cytomegalovirus in the Immunocompromised Host: A Comprehensive Review of the Literature.

Strongyloides and cytomegalovirus co-infections are rarely reported, even though they are distinguished by high morbidity and mortality, especially in immunocompromised hosts. We narratively reviewed the literature on reported cases of Strongyloides and CMV co-infections in immunosuppressed patients. Most cases occurred in males with a median age of 47 (IQR, 37-59). Strongyloides/CMV co-infections occurred among immunocompromised hosts, especially in solid organ transplants and hematological or rheumatological diseases. Most of the patients underwent a course of steroid treatment before the diagnosis of co-infections. Other common immunomodulatory agents were tacrolimus and mycophenolate. The first clinical manifestations of co-infections were mainly gastrointestinal, followed by respiratory symptoms. CMV was, in most patients, co-infected with an isolated reactivation, although Strongyloides manifested especially as hyperinfection syndrome. Ganciclovir and ivermectin are the mainstays of CMV and Strongyloides treatment. However, the treatment mortality reported in this narrative review is around 52.4%. Interestingly secondary bacterial infections are common in CMV/Strongyloides-infected patients.

Cytomegalovirus and Epstein–Barr virus co-infected young and middle-aged adults can have an aging-related T-cell phenotype

Cytomegalovirus (CMV) is known to alter circulating effector memory or re-expressing CD45RA+ (TemRA) T-cell numbers, but whether Epstein–Barr virus (EBV) does the same or this is amplified during a CMV and EBV co-infection is unclear. Immune cell numbers in blood of children and young, middle-aged, and senior adults (n = 336) were determined with flow cytometry, and additional multivariate linear regression, intra-group correlation, and cluster analyses were performed. Compared to non-infected controls, CMV-seropositive individuals from all age groups had more immune cell variance, and CMV+ EBV− senior adults had more late-differentiated CD4+ and CD8+ TemRA and CD4+ effector memory T-cells. EBV-seropositive children and young adults had a more equal immune cell composition than non-infected controls, and CMV− EBV+ senior adults had more intermediate/late-differentiated CD4+ TemRA and effector memory T-cells than non-infected controls. CMV and EBV co-infected young and middle-aged adults with an elevated BMI and anti-CMV antibody levels had a similar immune cell composition as senior adults, and CMV+ EBV+ middle-aged adults had more late-differentiated CD8+ TemRA, effector memory, and HLA-DR+ CD38− T-cells than CMV+ EBV− controls. This study identified changes in T-cell numbers in CMV- or EBV-seropositive individuals and that some CMV and EBV co-infected young and middle-aged adults had an aging-related T-cell phenotype.

SARS-CoV-2 and Cytomegalovirus Coinfection in a Patient With Myocarditis and Severe COVID-19 Infection.

SARS-CoV-2 and Cytomegalovirus Coinfection in a Patient With Myocarditis and Severe COVID-19 Infection.

Epstein–Barr virus and cytomegalovirus coinfection in Egyptian COVID-19 patients

BackgroundReactivation of herpesviruses such as Epstein–Barr virus (EBV) and cytomegalovirus (CMV) in COVID-19 patients reported in many studies in different countries during the pandemic. We aimed to measure prevalence of this coinfection in Egyptian COVID-19 patients with elevated liver enzymes and its relation to the severity and the outcome of COVID-19 infection in those patients.MethodsA cross-sectional study was carried out on 110 COVID-19 patients with elevated liver enzymes regardless the severity of COVID-19 disease. All patients were subjected to medical history, clinical examination, laboratory investigations, high-resolution computed tomography chest (HRCT chest). Epstein–Barr virus (EBV) and Human cytomegalovirus (HCMV) were determined by VCA IgM and CMV IgM respectively by enzyme-linked immunosorbent assay (ELISA).ResultsOf the included 110 patients with COVID-19 illness, 5 (4.5%) were Epstein–Barr virus seropositive and 5 (4.5%) were human cytomegalovirus seropositive. Regarding the symptoms, the incidence of fever in the EBV and CMV seropositive group was apparently higher than that in the EBV and CMV seronegative group. In lab tests, the platelets and albumin of EBV and CMV seropositive group decreased more significantly than EBV and HCMV seronegative group, and serum ferritin, D-dimer, and C-reactive protein show higher values in seropositive group than in seronegative group but not statistically significant. Seropositive group had received higher doses of steroids than seronegative group. The median of hospital stay in seropositive group was (15 days) nearly double that of seronegative group with statistically significant difference between both groups.ConclusionCoinfection of EBV and CMV in COVID-19 Egyptian has no effect on the disease severity or the clinical outcome of the disease. But those patients had higher hospital stay duration.

Gastric ulcer and duodenitis associated with coinfection of human herpesvirus-8 and cytomegalovirus in a renal transplant recipient: a case report

BackgroundThe coinfection between cytomegalovirus (CMV) and either human herpesvirus‐6 (HHV‐6) or HHV-7 in renal transplant recipients is well known; however, there have been few reports of coinfection of CMV associated with HHV-8. This paper presents a first case of acute gastric ulcer and duodenitis associated with CMV and HHV‐8 coinfection after renal transplantation.Case presentationA 33-year-old male with a history of kidney transplantation was admitted to hospital because of postural epigastric pain. The recipient was CMV seropositive prior to transplantation and received trimethoprim-sulfamethoxazole without universal prophylaxis. Approximately 5 months after renal transplant, the recipient complained postural epigastric pain. An endoscopy revealed diffuse ulcerative lesions in the lower body and in the antrum of the stomach, as well as several erythematous mucosal lesions in the duodenum. Histopathologic examination identified CMV inclusions consistent with invasive CMV disease and immunohistochemical staining showed positive results for HHV-8 and CMV. No tumorous diseases such as Kaposi’s sarcoma were detected. After 3 weeks of intravenous ganciclovir treatment, we observed that serum CMV PCR remained within the normal range and clinical symptoms improved. A follow-up endoscopy performed 3 weeks later showed that the severity of the above mentioned lesions had improved.ConclusionsWe report the first case of a renal transplant recipient diagnosed with acute gastric ulcer and duodenitis associated with coinfection of CMV and HHV-8. Ganciclovir appears to be effective in diseases associated with coinfection of CMV and HHV-8.

Cytomegalovirus and Herpes Simplex Virus Co-Infection: Recurrence in a Kidney Transplant Recipient.

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Severe acute respiratory syndrome coronavirus-2 Alpha variant (B.1.1.7), original wild-type severe acute respiratory syndrome coronavirus 2, and cytomegalovirus co-infection in a young adult with acute lymphoblastic leukemia, case report, and review of the possible cytomegalovirus reactivation mechanisms

BackgroundLike other viral infections, severe acute respiratory syndrome coronavirus-2 infection could affect different human body systems, including host immune responses. Three years after its pandemic, we learn more about this novel coronavirus. As we expected, different co-infections with various organisms, such as viruses, bacteria, and even fungi, have been reported. However, concurrent infection with two severe acute respiratory syndrome coronavirus-2 strains and cytomegalovirus is extremely unusual. We have only a rudimentary understanding of such co-infections and their long-term consequences for patients with cancer.Case presentationAn 18-year-old young Iranian adult with acute lymphoblastic leukemia presented with abdominal pain, diarrhea, nausea, and vomiting following a recent history of severe acute respiratory syndrome coronavirus-2 infection. The patient never experienced respiratory symptoms, and the chest imaging study was normal on admission. His primary laboratory investigation revealed prerenal azotemia and severe abnormal liver function tests (blood urea nitrogen 32 mg/dL, creatinine 1.75 mg/dL, prothrombin time 66 s, partial thromboplastin time 44.5 s, international normalized ratio 5.14, total bilirubin 2.9 mg/dL, and direct bilirubin 2.59 mg/dL). Cytomegalovirus disease was diagnosed by polymerase chain reaction in his blood and stool samples. The patient’s gastrointestinal signs and symptoms improved shortly after receiving intravenous ganciclovir treatment. His gastrointestinal symptoms continued intermittently for weeks despite maintenance valganciclovir prescription, necessitating frequent hospitalizations. The patient was complicated by the recurrence of gastrointestinal symptoms during the sixth hospitalization, even though he had no respiratory symptoms, and the nasopharyngeal test revealed severe acute respiratory syndrome coronavirus-2 Wuhan strain for the first time. Remdesivir and valganciclovir were administrated due to persistent enteritis and evidence of intestinal tissue invasion by severe acute respiratory syndrome coronavirus 2 and cytomegalovirus on multiple intestinal biopsies, which led to partial clinical responses. Cytomegalovirus and severe acute respiratory syndrome coronavirus-2 fecal shedding continued for more than 6 months despite repeated antiviral therapy, and the Wuhan and Alpha strains were also detected in his nasopharyngeal samples through repeated sampling (confirmed by four nasopharyngeal sampling and multiple stool specimens and several intestinal biopsies). Finally, during the Delta-variant (B.1.617.2) outbreak in Iran, the patient was admitted again with febrile neutropenia and decreased level of consciousness, necessitating respiratory support and mechanical ventilation. During the Delta-variant peak, the patient’s nasopharyngeal sample once more tested positive for severe acute respiratory syndrome coronavirus 2. The patient died a few days later from cardiopulmonary arrest.ConclusionThe coronavirus disease 2019 pandemic has encountered patients with cancer with critical diagnostic and treatment challenges. Patients who are immunocompromised may co-infect with multiple severe acute respiratory syndrome coronavirus-2 strains and cytomegalovirus, and even with timely diagnosis and treatment, the prognosis may be poor.

Impaired Cellular and Antibody immunity after COVID-19 in Chronically Immunosuppressed Transplant Recipients.

Assessment of cellular immunity to the SARS-CoV-2 coronavirus is of great interest in chronically immunosuppressed transplant recipients (Tr), who are predisposed to infections and vaccination failures. We evaluated CD154-expressing T-cells induced by spike (S) antigenic peptides in 204 subjects-103 COVID-19 patients and 101 healthy unexposed subjects. S-reactive CD154+T-cell frequencies were a) higher in 42 healthy unexposed Tr who were sampled pre-pandemic, compared with healthy NT (p=0.02), b) lower in Tr COVID-19 patients compared with healthy Tr (p<0.0001) and were accompanied by lower S-reactive B-cell frequencies (p<0.05), c) lower in Tr with severe COVID-19 (p<0.0001), or COVID-19 requiring hospitalization (p<0.05), compared with healthy Tr. Among Tr with COVID-19, cytomegalovirus co-infection occurred in 34%; further, incidence of anti-receptor-binding-domain IgG (p=0.011) was lower compared with NT COVID-19 patients. Healthy unexposed Tr exhibit pre-existing T-cell immunity to SARS-CoV-2. COVID-19 impairs anti-S T-cell and antibody and predisposes to CMV co-infection in transplant recipients.

REDUCED LEVELS OF NAD IN SKELETAL MUSCLE IN PEOPLE AGING WITH HIV INFECTION ON TREATMENT

Abstract People living with HIV (PLWH) are disproportionately burdened with multimorbidity and decline in physiologic function compared to their uninfected counterparts, but biological mechanisms that differentially contribute to the decline in muscle function in PLWH compared to uninfected people remains understudied. The study site was Brigham and Women’s Hospital, Harvard Medical School, Boston MA. We evaluated skeletal muscle tissue for levels of total NAD, NAD+ and NADH in middle-aged asymptomatic PLWH, coinfected with hepatitis C virus (HCV) and/or cytomegalovirus (CMV) and compared them to uninfected control participants. Of the 54 persons with muscle biopsy data, the mean age 57 years with 33% women. Total NAD levels declined in skeletal muscle in association with HIV infection, and was exacerbated by HCV and CMV coinfection, with lowest levels of total NAD, NAD+ and NADH among persons that were coinfected with all three viruses (P=0.015, P=0.014, P=0.076; respectively). Levels of total NAD, NAD+ and NADH in skeletal muscle were inversely associated with inflammation (P=0.014, P=0.013, P=0.055; respectively). Coinfections were also associated with measures of inflammation (CD4/CD8 ratio: P&amp;lt; 0.001 and sCD163: P&amp;lt; 0.001), immune activation (CD38 and HLA-DR expression on CD8 T cells: P&amp;lt; 0.001). Additionally, coinfection was associated with increased physiologic frailty, based on the VACS Index 1.0 assessment (P=0.001). Further research is warranted to determine the clinical relevance of preclinical deficits in NAD metabolites in skeletal muscle in association with viral coinfection and inflammation, as well as the observed association between viral coinfection and physiologic frailty.