Pathology and Monkeypox virus Localization in Tissues From Immunocompromised Patients With Severe or Fatal Mpox.

BACKGROUND: Pathology and Monkeypox virus (MPXV) tissue tropism in severe and fatal human mpox is not thoroughly described but can help elucidate the disease pathogenesis and the role of coinfections in immunocompromised patients. METHODS: We analyzed biopsy and autopsy tissues from 22 patients with severe or fatal outcomes to characterize pathology and viral antigen and DNA distribution in tissues by immunohistochemistry and in situ hybridization. Tissue-based testing for coinfections was also performed. RESULTS: Mucocutaneous lesions showed necrotizing and proliferative epithelial changes. Deceased patients with autopsy tissues evaluated had digestive tract lesions, and half had systemic tissue necrosis with thrombotic vasculopathy in lymphoid tissues, lung, or other solid organs. Half also had bronchopneumonia, and one-third had acute lung injury. All cases had MPXV antigen and DNA detected in tissues. Coinfections were identified in 5 of 16 (31%) biopsy and 4 of 6 (67%) autopsy cases. CONCLUSIONS: Severe mpox in immunocompromised patients is characterized by extensive viral infection of tissues and viremic dissemination that can progress despite available therapeutics. Digestive tract and lung involvement are common and associated with prominent histopathological and clinical manifestations. Coinfections may complicate mpox diagnosis and treatment. Significant viral DNA (likely correlating to infectious virus) in tissues necessitates enhanced biosafety measures in healthcare and autopsy settings.

Immunophenotype of lymphocytes and real-world outcome of COVID-19 infection in children with hematology and oncology.

BACKGROUND: Patients with immunocompromise were suspected to encounter a high risk for severe coronavirus disease 2019 (COVID-19) infection on early period; however, data is lacking nowadays and immune response remain unclear. METHODS: In this retrospective study, internet questionnaire survey and medical records were acquired in pediatric hematology oncology patients. Clinical severity, immunological characteristics, and outcomes were analyzed from December 1, 2022 to January 31, 2023 at the 3rd year of pandemic in China. RESULTS: A total of 306 patients were included, with 21 patients (6.9%) asymptomatic, 262 (85.6%) mild severity, 17 (5.6%) moderate severity, 5 (1.6%) severe severity, and 1 (0.3%) critical severity. Seventy-eight (25.5%) patients were on intensive chemotherapy, and 32.0% children were on maintenance chemotherapy. Delays in cancer therapy occurred in 86.7% patients. Univariable analysis revealed active chemotherapy (P < 0.0001), long duration of symptom (P < 0.0001), low lymphocytes count (P = 0.095), low CD3 + and CD8 + T cell count (P = 0.013, P = 0.022), high percentage of CD4 + TCM (P = 0.016), and low percentage of transitional B cells (P = 0.045) were high risk factors for severe COVID-19 infection. Cox regression model showed that the absolute lymphocytes count (P = 0.027) and long duration of symptom (P = 0.002) were the independent factors for severity. Patients with CD8 + dominant and B cell depletion subtype wasn't related with severity, but had higher percentage of CD8 + effector memory T cells (TEM) and terminally differentiated effector memory T cells (TEMRA) (P < 0.001, P < 0.001), and a longer COVID-19 duration (P = 0.045). CONCLUSION: The severity was relatively mild in children with immunodeficiencies in the third year of COVID-19 pandemic. Low lymphocyte count and long duration of symptom were the independent risk factors with COVID-19 severity. Delays in cancer care remain a major concern and the long outcome is pending.

The Burden of COVID-19 in the Immunocompromised Patient: Implications for Vaccination and Needs for the Future.

Approximately 3% of US adults are immunocompromised and less capable of fighting infections such as SARS-CoV-2 (the causative agent of COVID-19). Individuals may be immunocompromised for reasons related to an underlying medical condition or to immunomodulatory therapies that alter the immune response. In general, vaccination with mRNA-based vaccines is effective at reducing COVID-19-associated hospitalization and death among immunocompromised populations, particularly after 3 or more doses. However, the immunocompromised population is heterogeneous, with COVID-19 vaccine-elicited immune responses and risk for severe COVID-19 existing on a continuum. Therefore, understanding the impact of vaccination and the complexity of immune responses across heterogeneous immunocompromised individuals is essential for guiding effective vaccination regimens including additional (booster) doses. In this article, we provide an overview of the immunocompromised population and the burden of disease attributable to COVID-19, while discussing key opportunities and challenges of vaccinating immunocompromised individuals.

Immune Status and SARS-CoV-2 Viral Dynamics.

Immunocompromised individuals are disproportionately affected by severe coronavirus disease 2019, but immune compromise is heterogenous, and viral dynamics may vary by the degree of immunosuppression. In this study, we categorized ACTIV-2/A5401 participants based on the extent of immunocompromise into none, mild, moderate, and severe immunocompromise. Moderate/severe immunocompromise was associated with higher nasal viral load at enrollment (adjusted difference in means: 0.47 95% confidence interval, .12-.83 log10 copies/mL) and showed a trend toward higher cumulative nasal RNA levels and plasma viremia compared to nonimmunocompromised individuals. Immunosuppression leads to greater viral shedding and altered severe acute respiratory syndrome coronavirus 2 viral decay kinetics. Clinical Trials Registration. NCT04518410.

Dual Antiviral Therapy for Persistent Coronavirus Disease 2019 and Associated Organizing Pneumonia in an Immunocompromised Host.

The management of patients with prolonged viral shedding and coronavirus disease 2019 symptoms remains unclear. Combining antivirals, as practiced in other infections, is theoretically advantageous. We present a case of persistent, symptomatic severe acute respiratory syndrome coronavirus 2 infection and associated organizing pneumonia that was successfully treated with an extended course of combination antiviral therapy.

Remdesivir Resistance in Transplant Recipients With Persistent Coronavirus Disease 2019.

New mutations conferring resistance to SARS-CoV-2 therapeutics have important clinical implications. We describe the first cases of an independently acquired V792I RNA-dependent RNA polymerase mutation developing in renal transplant recipients after remdesivir exposure. Our work underscores the need for augmented efforts to identify concerning mutations and address their clinical implications.

Successful Treatment of Prolonged, Severe Coronavirus Disease 2019 Lower Respiratory Tract Disease in a B cell Acute Lymphoblastic Leukemia Patient With an Extended Course of Remdesivir and Nirmatrelvir/Ritonavir.

A patient with B-cell acute lymphoblastic leukemia (ALL) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had persistent, progressive pneumonia with viremia after 5 months of infection despite monoclonal antibodies, intravenous (IV) remdesivir and prolonged oral steroids. Twenty days of nirmatrelvir/ritonavir and 10 days of IV remdesivir led to full recovery.

Coronavirus disease 2019 (Covid-19) vaccination recommendations in special populations and patients with existing comorbidities.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a crucial step in ending the current worldwide pandemic. However, several particularly vulnerable groups in the population were not included in sufficient numbers in coronavirus disease 2019 (Covid-19) vaccine trials. Therefore, as science advances, the advice for vaccinating these special populations against Covid-19 will continue to evolve. This focused review provides the latest recommendations and considerations for these special populations (i.e., patients with rheumatologic and autoimmune disorders, cancer, transplant recipients, chronic liver diseases, end-stage renal disease, neurologic disorders, psychiatric disorders, diabetes mellitus, obesity, cardiovascular diseases, chronic obstructive pulmonary disease, human immunodeficiency virus, current smokers, pregnant and breastfeeding women, the elderly, children, and patients with allergic reactions) using the currently available research evidence.

Post-acute sequelae of COVID-19 in solid organ transplant recipients.

BACKGROUND: Post-acute sequelae of coronavirus disease 2019 (COVID-19) (PASC), defined as prolonged symptoms following an episode of COVID-19, is not well-characterized in solid organ transplant recipients (SOTR). In this study, we aimed to assess the prevalence of PASC in SOTR, its descriptive characteristics, and associated risk factors. METHODS: We retrospectively identified SOTRs with acute COVID-19 between June 1, 2020 and April 15, 2022, and abstracted demographic and medical history, characteristics of acute COVID-19 illness, and COVID-19 vaccination status. We defined PASC as ongoing/new symptoms present at 6 weeks or longer following acute COVID-19 diagnosis. RESULTS: Among 208 SOTRs with acute COVID-19, 72 (35%) developed PASC. Common symptoms were respiratory symptoms (67%), headache (40%), and difficulty concentrating (10%). Severe acute COVID-19 disease and presence of respiratory symptoms were associated with higher odds of PASC in multivariable analyses, while receipt of at least one COVID-19 vaccination prior to transplantation was protective. CONCLUSION: We found that PASC occurs in about a third of SOTRs with acute COVID-19 and has similar symptoms as described previously in immunocompetent hosts. Pre-transplant vaccination may be protective. Further prospective multicenter studies are needed.

Wound Restorative Power of Halimeda macroloba/ Mesenchymal Stem Cells in Immunocompromised Rats via Downregulating Inflammatory/Immune Cross Talk.

Impaired skin wound healing is still a major challenge, especially with immunocompromised patients who express delayed healing and are susceptible to infections. Injection of rat-derived bone marrow mesenchymal stem cells (BMMSCs) via the tail vein accelerates cutaneous wound healing via their paracrine activity. The present work aimed to investigate the combined wound-healing potential of BMMSCs and Halimeda macroloba algae extract in immunocompromised rats. High-resolution liquid chromatography-mass spectrometry (HR-LC-MS) investigation of the extract revealed the presence of variant phytochemicals, mostly phenolics, and terpenoids, known for their angiogenic, collagen-stimulating, anti-inflammatory, and antioxidant properties. The BMMSCs were isolated and characterized for CD markers, where they showed a positive expression of CD90 by 98.21% and CD105 by 97.1%. Twelve days after inducing immunocompromise (40 mg/kg hydrocortisone daily), a circular excision was created in the dorsal skin of rats and the treatments were continued for 16 days. The studied groups were sampled on days 4, 8, 12, and 16 after wounding. The gross/histopathological results revealed that the wound closure (99%), thickness, density of new epidermis and dermis, and skin elasticity in the healed wounds were considerably higher in the BMMSCs/Halimeda group than the control group (p < 0.05). RT-PCR gene expression analysis revealed that the BMMSCs/Halimeda extract combination had perfectly attenuated oxidative stress, proinflammatory cytokines, and NF-KB activation at day 16 of wounding. The combination holds promise for regenerative medicine, representing a revolutionary step in the wound healing of immunocompromised patients, with still a need for safety assessments and further clinical trials.

The immune landscape in BCR-ABL negative myeloproliferative neoplasms: inflammation, infections and opportunities for immunotherapy.

Breakpoint cluster region-Abelson (BCR-ABL) negative myeloproliferative neoplasms (MPNs) are chronic myeloid neoplasms initiated by the acquisition of gene mutation(s) in a haematopoietic stem cell, leading to clonal expansion and over-production of blood cells and their progenitors. MPNs encompass a spectrum of disorders with overlapping but distinct molecular, laboratory and clinical features. This includes polycythaemia vera, essential thrombocythaemia and myelofibrosis. Dysregulation of the immune system is key to the pathology of MPNs, supporting clonal evolution, mediating symptoms and resulting in varying degrees of immunocompromise. Targeting immune dysfunction is an important treatment strategy. In the present review, we focus on the immune landscape in patients with MPNs - the role of inflammation in disease pathogenesis, susceptibility to infection and emerging strategies for therapeutic immune modulation. Further detailed work is required to delineate immune perturbation more precisely in MPNs to determine how and why vulnerability to infection differs between clinical subtypes and to better understand how inflammation results in a competitive advantage for the MPN clone. These studies may help shed light on new designs for disease-modifying therapies.

Geotrichum spp: An overlooked and fatal etiologic agent in immunocompromised patients. A case series from a referral center in Mexico.

Geotrichum spp. is an emergent pathogen. We aimed to describe Geotrichum spp. invasive fungal infections (IFI) in patients from Mexico. We reviewed cases with Geotrichum spp. isolated in clinical samples, from 2001 to 2019. Descriptive analysis was used for clinical data. Twenty patients with proven/probable Geotrichum spp. IFI were analyzed. The median age was 43; 55% were males. Hematologic malignancy was found in 60% (12/20); 75% (15/20) received systemic immunosuppressors. The most common presentation was lower respiratory tract infection. In-hospital mortality was 45% (9/20). Geotrichum spp. should be acknowledged as a pathogen causing atypical pneumonia in immunocompromised Latin American patients. LAY SUMMARY: Geotrichum spp. causes invasive infection in immunocompromised hosts. We describe a case series of 20 patients from Mexico City. Hematologic malignancy was the most common comorbidity. Clinical presentation was mainly lower respiratory tract infection. Mortality was high despite antifungal therapy.

Prolonged Severe Acute Respiratory Syndrome Coronavirus 2 Replication in an Immunocompromised Patient.

We describe a case of chronic coronavirus disease 2019 (COVID-19) in a patient with lymphoma and associated B-cell immunodeficiency. Viral cultures and sequence analysis demonstrate ongoing replication of infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for at least 119 days. The patient had 3 admissions related to COVID-19 over a 4-month period and was treated twice with remdesivir and convalescent plasma with resolution of symptoms. The patient's lack of seroconversion and prolonged course illustrate the importance of humoral immunity in resolving SARS-CoV-2 infection. This case highlights challenges in managing immunocompromised hosts, who may act as persistent shedders and sources of transmission.

Clinical Manifestations and Outcomes in Immunocompetent and Immunocompromised Patients With Blastomycosis.

BACKGROUND: Blastomyces is a dimorphic fungus that infects persons with or without underlying immunocompromise. To date, no study has compared the clinical features and outcomes of blastomycosis between immunocompromised and immunocompetent persons. METHODS: A retrospective study of adult patients with proven blastomycosis from 2004-2016 was conducted at the University of Wisconsin. Epidemiology, clinical features, and outcomes were analyzed among solid-organ transplantation (SOT) recipients, persons with non-SOT immunocompromise (non-SOT IC), and persons with no immunocompromise (NIC). RESULTS: A total of 106 cases met the inclusion criteria including 74 NIC, 19 SOT, and 13 non-SOT IC (malignancy, HIV/AIDS, idiopathic CD4+ lymphopenia). The majority of patients (61.3%) had at least 1 epidemiologic risk factor for acquisition of Blastomyces. Pneumonia was the most common manifestation in all groups; however, immunocompromised patients had higher rates of acute pulmonary disease (P = .03), more severe infection (P = .007), respiratory failure (P = .010), and increased mortality (P = .02). Receipt of SOT primarily accounted for increased severity, respiratory failure, and mortality in immunosuppressed patients. SOT recipients had an 18-fold higher annual incidence of blastomycosis than the general population. The rate of disseminated blastomycosis was similar among NIC, SOT, and non-SOT IC. Relapse rates were low (5.3-7.7%). CONCLUSIONS: Immunosuppression had implications regarding the acuity, severity, and respiratory failure. The rate of dissemination was similar across the immunologic spectrum, which is in sharp contrast to other endemic fungi. This suggests that pathogen-related factors have a greater influence on dissemination for blastomycosis than immune defense.

Invasive fungal pharyngitis in a pediatric bone marrow transplant patient.

Invasive fungal disease of the head and neck is a potentially fatal infection most commonly seen in immunocompromised patients. Even in the setting of combined surgical and medical treatment, prognosis is generally poor. We report the first pediatric case of invasive fungal pharyngitis and summarize a review of the literature. A 10-year-old female patientwith aplastic anemia status post-bone marrow transplant and accompanying immunosuppression initially presented with a diagnosis of a peritonsillar abscess. Incision and drainage did not show purulence, but culture grew out Rhizopus species. Immediately after diagnosis, the patient was treated successfully with aggressive staged surgical debridement and antifungal medications and had an excellent functional outcome 2 years after initial presentation. Invasive fungal disease is most common in the sinonasal region, but alternative sites of disease must be considered in immunocompromised patients who present with atypical symptoms.

Changing demographics and risk factors for cryptococcosis: A 12-year review at a tertiary care centre.

BACKGROUND: Cryptococcosis is classically associated with the immunocompromised patients but there is a rising appreciation for its impact on the immunocompetent hosts. We sought to analyse the trends, diagnosis, treatment of different hosts and the effect of immunodeficiency and chronic liver disease on relapse and in-house mortality. METHODS: This is a retrospective study of 12 years of patients with cryptococcosis, divided into three different groups: HIV-infected, transplant and non-HIV non-transplant (NHNT). Data were analysed with Chi-square, unpaired parametric t test, simple and multivariate logistic regression analysis. RESULTS: Of 114 identified patients, 23 (20.2%) had HIV infection, 11 (9.6%) had transplant, 80 (70.2%) were NHNT patients. Overall, mortality was 28.1% (32/114) and relapse occurred in 10.5% (12/114) of patients. The mortality trend was higher (OR = 2.346, p = .287) in the transplant group (45.5%, 5/11) than in HIV (26.1%, 6/23) and NHNT groups (26.3%, 21/80). HIV was associated with relapse; 30.4% (7/23) for HIV-positive patients and 5.5% (5/91) for HIV-negative patients (OR = 7.525, p = .002). Chronic liver disease had a large and statistically significant association with mortality on multivariate analysis (OR = 3.583, p = .013) which was more pronounced than the HIV or transplant groups. It was independently associated with mortality by chi-square analysis (OR 3.137, p = .012). CONCLUSION: Chronic liver disease represented 30.7% (35/114) of all studied patients. It was a risk factor for in-hospital mortality. HIV infection and transplant were not statistically significant for mortality. Relapse was highest in the HIV-infected patients at 30.4% (7/23). These data highlight the effect of type and degree of immunocompromise on cryptococcosis.

Patterns of cytomegalovirus retinitis at a tertiary referral center in Turkey.

PURPOSE: To analyze predisposing conditions in Turkish patients with CMV retinitis and to compare HIV-positive and HIV-negative patients. METHODS: We reviewed medical charts and ocular images of 41 patients with CMV retinitis diagnosed between 1996 and 2019. RESULTS: Eleven patients (27%) had HIV infection and 30 were immunocompromised from diverse causes. Initial visual acuity, type, zone, and extent of CMV retinitis, and response to anti-CMV treatment were not significantly different between the two groups. Vitreous haze and panretinal occlusive vasculopathy were the presenting features only in non-HIV patients, seen in 34% and 16% of eyes, respectively. Although not statistically significant, recurrent CMV retinitis was more common in non-HIV patients (17.4% vs. 4.3%/eye-year) and immune recovery uveitis was more common in HIV patients (43% vs. 26%/eye-year). Visual outcomes were similar. Final visual acuity of 1 logMAR or worse was significantly associated with the recurrence of CMV retinitis (odds ratio 9.67; p = 0.01) and also with the occurrence of immune recovery uveitis (odds ratio 4.31; p = 0.058). CONCLUSIONS: Diverse immunocompromising conditions are more commonly associated with CMV retinitis than HIV infection in Turkish patients. Intraocular inflammation was more commonly associated with active retinitis in non-HIV patients and immune recovery uveitis was more common in HIV patients.

Addressing the Impact of the Coronavirus Disease 2019 (COVID-19) Pandemic on Hematopoietic Cell Transplantation: Learning Networks as a Means for Sharing Best Practices.

The full impact of the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), on the field of hematopoietic cell transplantation (HCT) is unknown. This perspective paper reviews the following: current COVID-19 epidemiology, diagnosis, and potential therapies; care considerations unique to HCT recipients; and the concept of a learning network to assimilate emerging guidelines and best practices and to optimize patient outcomes through facilitating shared learning and experience across transplantation centers.

Diagnosis and treatment of mycoplasmal septic arthritis: a systematic review.

PURPOSE: Septic arthritis caused by Mycoplasma is rare. The diagnosis and effective treatment of mycoplasmal septic arthritis remains a serious problem for clinicians. The aim of this systematic review was to document the available evidence on the diagnosis and treatment methods for mycoplasmal septic arthritis and to provide guidance for clinicians. METHODS: The PubMed, EMBASE, and Cochrane Library databases were searched in December 2018.The searches were limited to the English language. Article screening and data extraction and compilation were conducted by two independent reviewers. All the included studies were assessed using the Methodological Index for Non-randomized Studies (MINORS) tool. RESULTS: There was a total of 33 articles including 34 cases of mycoplasmal septic arthritis and eight of them were periprosthetic joint infection (PJI). Twenty-four patients (70.6%) were immunocompromised, and the synovial fluid white blood cell (WBC) count was significantly lower in the immunocompromised group than in the immunocompetent group (48,527 × 106/L vs. 100,640 × 106/L; P = 0.009). The traditional culture method took longer, and the positivity rate was lower than that of nucleic acid testing (50% vs. 100%; P = 0.016). Only 19.2% (5/26) of patients treated with empiric antibiotics were relieved of symptoms, while 82.4% (28/34) of patients achieved satisfactory results after being treated with antibiotics against Mycoplasma. CONCLUSION: The possibility of mycoplasmal septic arthritis should be considered if patients with joint infections have a history of immunocompromised, repeated negative cultures, and poor empiric antibiotic treatment results. The rational use of nucleic acid testing technologies can help in the clinical diagnosis and treatment of mycoplasmal septic arthritis.

Prevalence and Etiology of Community-acquired Pneumonia in Immunocompromised Patients.

BACKGROUND: The correct management of immunocompromised patients with pneumonia is debated. We evaluated the prevalence, risk factors, and characteristics of immunocompromised patients coming from the community with pneumonia. METHODS: We conducted a secondary analysis of an international, multicenter study enrolling adult patients coming from the community with pneumonia and hospitalized in 222 hospitals in 54 countries worldwide. Risk factors for immunocompromise included AIDS, aplastic anemia, asplenia, hematological cancer, chemotherapy, neutropenia, biological drug use, lung transplantation, chronic steroid use, and solid tumor. RESULTS: At least 1 risk factor for immunocompromise was recorded in 18% of the 3702 patients enrolled. The prevalences of risk factors significantly differed across continents and countries, with chronic steroid use (45%), hematological cancer (25%), and chemotherapy (22%) the most common. Among immunocompromised patients, community-acquired pneumonia (CAP) pathogens were the most frequently identified, and prevalences did not differ from those in immunocompetent patients. Risk factors for immunocompromise were independently associated with neither Pseudomonas aeruginosa nor non-community-acquired bacteria. Specific risk factors were independently associated with fungal infections (odds ratio for AIDS and hematological cancer, 15.10 and 4.65, respectively; both P = .001), mycobacterial infections (AIDS; P = .006), and viral infections other than influenza (hematological cancer, 5.49; P < .001). CONCLUSIONS: Our findings could be considered by clinicians in prescribing empiric antibiotic therapy for CAP in immunocompromised patients. Patients with AIDS and hematological cancer admitted with CAP may have higher prevalences of fungi, mycobacteria, and noninfluenza viruses.