Patients with hematologic malignancies (HMs) are at a significantly higher risk of contracting COVID-19 and experiencing severe outcomes compared to individuals without HMs. This heightened risk is influenced by various factors, including the underlying malignancy, immunosuppressive treatments, and patient-related factors. Notably, immunosuppressive regimens commonly used for HM treatment can lead to the depletion of B cells and T cells, which is associated with increased COVID-19-related complications and mortality in these patients. As the pandemic transitions into an endemic state, it remains crucial to acknowledge and address the ongoing risk for individuals with HMs. In this review, we aim to summarize the current evidence to enhance our understanding of the impact of HMs on COVID-19 risks and outcomes, identify particularly vulnerable individuals, and emphasize the need for specialized clinical attention and management. Furthermore, the impaired immune response to COVID-19 vaccination observed in these patients underscores the importance of implementing additional mitigation strategies. This may include targeted prophylaxis and treatment with antivirals and monoclonal antibodies as indicated. To provide practical guidance and considerations, we present two illustrative cases to highlight the real-life challenges faced by physicians caring for patients with HMs, emphasizing the need for individualized management based on disease severity, type, and the unique circumstances of each patient.

BACKGROUND: Effective disease surveillance, including that for COVID-19, is compromised without a standardised method for categorising the immunosuppressed as a clinical risk group.
METHODS: We conducted a systematic review and meta-analysis to evaluate whether excess COVID-associated mortality compared to the immunocompetent could meaningfully subdivide the immunosuppressed. Our study adhered to UK Immunisation against infectious disease (Green Book) criteria for defining and categorising immunosuppression. Using OVID (EMBASE, MEDLINE, Transplant Library, and Global Health), PubMed, and Google Scholar, we examined relevant literature between the entirety of 2020 and 2022. We selected for cohort studies that provided mortality data for immunosuppressed subgroups and immunocompetent comparators. Meta-analyses, grey literature and any original works that failed to provide comparator data or reported all-cause or paediatric outcomes were excluded. Odds Ratios (OR) and 95% confidence intervals (CI) of COVID-19 mortality were meta-analysed by immunosuppressed category and subcategory. Subgroup analyses differentiated estimates by effect measure, country income, study setting, level of adjustment, use of matching and publication year. Study screening, extraction and bias assessment were performed blinded and independently by two researchers; conflicts were resolved with the oversight of a third researcher. PROSPERO registration number is CRD42022360755.
RESULTS: We identified 99 unique studies, incorporating data from 1,542,097 and 56,248,181 unique immunosuppressed and immunocompetent patients with COVID-19 infection, respectively. Compared to immunocompetent people (pooled OR, 95%CI), solid organ transplants (2.12, 1.50-2.99) and malignancy (2.02, 1.69-2.42) patients had a very high risk of COVID-19 mortality. Patients with rheumatological conditions (1.28, 1.13-1.45) and HIV (1.20, 1.05-1.36) had just slightly higher risks than the immunocompetent baseline. Case type, setting income and mortality data matching and adjustment were significant modifiers of excess immunosuppressed mortality for some immunosuppressed subgroups.
CONCLUSIONS: Excess COVID-associated mortality among the immunosuppressed compared to the immunocompetent was seen to vary significantly across subgroups. This novel means of subdivision has prospective benefit for targeting patient triage, shielding and vaccination policies during periods of high disease transmission.

Severe cases of strongyloidiasis are most often associated with multiple causes of immune suppression, such as corticoid treatment and HTLV (human T-lymphotropic virus) coinfection. Diabetes is not traditionally considered a risk factor for the development of severe strongyloidiasis. We report a rare case of autochthonous severe strongyloidiasis in Romania, a European country with a temperate climate. A 71-year-old patient with no prior travel history was admitted with multiple gastrointestinal complaints and recent weight loss. CT (computed tomography) scans indicated duodenal wall thickening, and duodenal endoscopy evidenced mucosal inflammation, ulcerations and partial duodenal obstruction at D4. Microscopic examination of stool samples and biopsy specimens from the gastric and duodenal mucosa revealed an increased larval burden characteristic of Strongyloides stercoralis hyperinfection. Sequential treatment with albendazole and ivermectin achieved parasitological cure and complete recovery. The novelty of our case stems from the scarcity of severe strongyloidiasis cases reported in Europe and especially in Romania, the absence of other risk factors in our patient aside from diabetes, the involvement of the gastric mucosa and the rare presentation as partial duodenal obstruction. This case highlights the importance of considering strongyloidiasis as a differential diagnosis, even in temperate climates where cases are sporadic, in cases in which immune suppression is not evident and in the absence of eosinophilia. The case is presented in the context of the first literature review examining the relationship between severe strongyloidiasis and diabetes, emphasizing diabetes as a possible risk factor for severe strongyloidiasis.

Gastrointestinal histoplasmosis (GIH) is infrequently described in people without underlying HIV infection. We aimed to compare the clinical presentation of GIH in people with and without HIV infection. We conducted a literature search of published cases of GIH from 2001-2021 and found 212 cases. Of these, 142 (67.0%) were male, and 124 (58.5%) had HIV infection. Most cases were from North America (n = 88, 41.5%) and South America (n = 79, 37.3%). Of the 212 cases, 123 (58.0%) were included in both clinical and pathological analyses. The remainder were excluded as details about clinical and pathological findings were not available. Of the 123 cases, 41 had HIV infection while 82 were without HIV infection. The diagnosis was predominantly by histopathology (n = 109, 88.6%). A significant proportion of people with HIV infection had abdominal pain as the most predominant symptom of GIH compared to those without HIV infection (65.9% versus 41.9%, p < 0.05). The colon was the most affected site with a slightly higher proportion in those with HIV infection compared with cases without HIV infection (46.3% versus 42.7%). The commonest pathologic findings were caecal and ileal ulcers. Caecal ulcers were significantly more frequent in cases with HIV infection compared to those without HIV (32.1% versus 7.1%, p < 0.05). Despite being more common in people with HIV infection, GIH also affects people without HIV infection with similar clinical presentations.

The characterization of cutaneous squamous cell carcinoma (cSCC) at the molecular level is lacking in the current literature due to the high mutational burden of this disease. Immunosuppressed patients afflicted with cSCC experience considerable morbidity and mortality. In this article, we review the molecular profile of cSCC among the immunosuppressed and immunocompetent populations at the genetic, epigenetic, transcriptomic, and proteometabolomic levels, as well as describing key differences in the tumor immune microenvironment between these two populations. We feature novel biomarkers from the recent literature which may serve as potential targets for therapy.

UNASSIGNED: Coinfection with Pneumocystis jirovecii and Mycobacterium tuberculosis is rare in HIV-seronegative patients. Because it is associated with unknown morbidity and a high mortality rate especially in patients with immunosuppression, health care practitioners should have a high index of suspicion when dealing with such patients.
UNASSIGNED: A 66-year-old man with glucocorticoid therapy for 9 years had a fever after getting a cold and developed respiratory failure rapidly within 3 days. He was given trimethoprim-sulfamethoxazole empirically before Pneumocystis pneumonia (PCP) was confirmed with the presence of cysts in the sputum. Although there was a partial improvement of symptoms, an area of consolidation on the left upper lung lobe gradually enlarged. Bronchoscopy was performed 3 times and Mycobacterium tuberculosis infection was finally diagnosed. For 1 years, he was treated with standard antituberculosis agents, and his psychological well-being was managed using traditional Chinese medicine techniques. After 3 years of follow-up, his outcome was very good.
UNASSIGNED: HIV-seronegative patients on long-term glucocorticoid therapy in areas with a high incidence of Mycobacterium tuberculosis may be co-infected with Pneumocystis jirovecii. When opportunistic infections are suspected, diagnostic procedures including invasive ones should be performed as soon as possible and appropriate interventions need to be carried out promptly.

Children and adolescents form a large proportion of societies and play an important role in the transmission of COVID-19. On the other hand, their education, mental and physical wellness, and safety are compromised which makes vaccination a crucial step to return to normal life. In the current systematic review, the COVID-19 vaccination was evaluated in a total of 50,148 children and adolescents in 22 published studies and 5,279 participants in two ongoing clinical trials. The study was registered in the PROSPERO with the ID# CRD42022303615. Data were collected about multiple vaccines including BNT162b2 (Pfizer), mRNA-1273 (Moderna), JNJ-78436735 (Johnson and Johnson), CoronaVac (Sinovac), BBIBP-CorV (Sinopharm), adenovirus type-5-vectored vaccine, ZyCov-D, and BBV152 (COVAXIN). The immune response and efficacy of such vaccines were 96% - 100% in healthy children and adolescents and were also acceptable in those with underlying diseases and suppressed immune systems. The current systematic review revealed favorable safety profiles of employed vaccines in children and adolescents; however, adverse reactions such as myocarditis and myopericarditis were reported which were transient and resolved entirely. Consequently, vaccinating children and adolescents aged 2 - 21 years old is beneficial to abort the COVID-19 pandemic. Moreover, the risk-benefit assessments revealed favorable results for vaccinating children and adolescents, especially those with underlying diseases and immunosuppressed conditions, alongside adults to prevent transmission, severe infection, negative outcomes, and new variants formation. Also, according to the meta-analysis, the efficacy and immune response of vaccines after the first and second doses were 91% and 92%, respectively. Meanwhile, overall immune response for all vaccines was 95% and 91% for Pfizer vaccine.

Therapeutic management of solid organ transplant (SOT) recipients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), may challenge healthcare providers given a paucity of clinical data specific to this cohort. Herein, we summarize and review the studies that have formed the framework for current COVID-19 consensus management guidelines. Our review focuses on COVID-19 treatment options including monoclonal antibody products, antiviral agents such as remdesivir, and immunomodulatory agents such as corticosteroids, interleukin inhibitors, and kinase inhibitors. We highlight the presence or absence of clinical data of these therapeutics related to the SOT recipient with COVID-19. We also describe data surrounding COVID-19 vaccination of the SOT recipient. Understanding the extent and limitations of observational and clinical trial data for the prevention and treatment of COVID-19 specific to the SOT population is crucial for optimal management. Although minimal data exist on clinical outcomes among SOT recipients treated with varying COVID-19 therapeutics, reviewing these agents and the studies that have led to their inclusion or exclusion in clinical management of COVID-19 highlights the need for further studies of these therapeutics in SOT patients with COVID-19.

Children with autoimmune disorders are especially at risk of vaccine-preventable diseases due to their underlying disease and the immunosuppressive treatment often required for a long period. In addition, vaccine coverage remains too low in this vulnerable population. This can be explained by a fear of possible adverse effects of vaccines under immunosuppression, but also a lack of data and clear recommendations, particularly with regard to vaccination with live vaccines. In this review, the latest literature and recommendations on vaccination in immunosuppressed children are discussed in detail, with the aim to provide a set of practical guidelines on vaccination for specialists caring for children suffering from different autoimmune disorders and treated with various immunosuppressive regimens.

Despite major advances in antimicrobial prophylaxis and therapy, opportunistic infections remain a major cause of morbidity and mortality after pediatric hematopoietic cell transplant (HCT). Risk factors associated with the development of opportunistic infections include the patient\'s underlying disease, previous infection history, co-morbidities, source of the donor graft, preparative therapy prior to the graft infusion, immunosuppressive agents, early and late toxicities after transplant, and graft-vs.-host disease (GVHD). Additionally, the risk for and type of infection changes throughout the HCT course and is greatly influenced by the degree and duration of immunosuppression of the HCT recipient. Hematopoietic cell transplant recipients are at high risk for rapid clinical decompensation from infections. The pediatric intensivist must remain abreast of the status of the timeline from HCT to understand the risk for different infections. This review will serve to highlight the infection risks over the year-long course of the HCT process and to provide key clinical considerations for the pediatric intensivist by presenting a series of hypothetical HCT cases.