Higher Levels of SARS-CoV-2 Genetic Variation in Immunocompromised Patients: A Retrospective Case-Control Study.

BACKGROUND: A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection lasts longer in immunocompromised hosts than in immunocompetent patients. Prolonged infection is associated with a higher probability of selection for novel SARS-CoV-2 mutations, particularly in the spike protein, a critical target for vaccines and therapeutics. METHODS: From December 2020 to September 2022, respiratory samples from 444 immunocompromised patients and 234 health care workers positive for SARS-CoV-2, diagnosed at 2 hospitals in Paris, France, were analyzed using whole-genome sequencing using Nanopore technology. Custom scripts were developed to assess the SARS-CoV-2 genetic diversity between the 2 groups and within the host. RESULTS: Most infections were SARS-CoV-2 Delta or Omicron lineages. Viral genetic diversity was significantly higher in infections of immunocompromised patients than those of controls. Minor mutations were identified in viruses sequenced from immunocompromised individuals, which became signature mutations for newer SARS-CoV-2 variants as the epidemic progressed. Two patients were coinfected with Delta and Omicron variants. The follow-up of immunocompromised patients revealed that the SARS-CoV-2 genome evolution differed in the upper and lower respiratory tracts. CONCLUSIONS: This study found that SARS-CoV-2 infection in immunocompromised patients is associated with higher genetic diversity, which could lead to the emergence of new SARS-CoV-2 variants with possible immune evasion or different virulence characteristics.

Prolonged viral shedding in an immunocompromised Korean patient infected with hMPXV, sub-lineage B.1.3, with acquired drug resistant mutations during tecovirimat treatment.

Following the worldwide surge in mpox (monkeypox) in 2022, cases have persisted in Asia, including South Korea, and sexual contact is presumed as the predominant mode of transmission, with a discernible surge in prevalence among immunocompromised patients. Drugs such as tecovirimat can result in drug-resistant mutations, presenting obstacles to treatment. This study aimed to ascertain the presence of tecovirimat-related resistant mutations through genomic analysis of the monkeypox virus isolated from a reported case involving prolonged viral shedding in South Korea. Here, tecovirimat-resistant mutations, previously identified in the B.1 clade, were observed in the B.1.3 clade, predominant in South Korea. These mutations exhibited diverse patterns across different samples from the same patient and reflected the varied distribution of viral subpopulations in different anatomical regions. The A290V and A288P mutant strains we isolated hold promise for elucidating these mechanisms, enabling a comprehensive analysis of viral pathogenesis, replication strategies, and host interactions. Our findings imply that acquired drug-resistant mutations, may present a challenge to individual patient treatment. Moreover, they have the potential to give rise to transmitted drug-resistant mutations, thereby imposing a burden on the public health system. Consequently, the meticulous genomic surveillance among immunocompromised patients, conducted in this research, assumes paramount importance.

Recombinant mannan-binding lectin magnetic beads increase pathogen detection in immunocompromised patients.

The microbiological diagnosis of infection for hematological malignancy patients receiving chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients relies primarily on standard microbial culture, especially blood culture, which has many shortcomings, such as having low positive rates, being time-consuming and having a limited pathogenic spectrum. In this prospective observational self-controlled test accuracy study, blood, cerebrospinal fluid (CSF), and bronchoalveolar lavage fluid (BALF) samples were collected from chemotherapy or allo-HSCT patients with clinical symptoms of infections who were hospitalized at Peking University First Hospital. Possible pathogens were detected by the method based on recombinant mannan-binding lectin (MBL) magnetic bead enrichment (M1 method) and simultaneously by a standard method. The analytical sensitivity of M1 method was close to that of standard culture method. Besides, the turn-around time of M1-method was significantly shorter than that of standard culture method. Moreover, the M1 method also added diagnostic value through the detection of some clinically relevant microbes missed by the standard method. M1 method could significantly increase the detection efficiency of pathogens (including bacteria and fungi) in immunocompromised patients. KEY POINTS: • The detection results of M1-method had a high coincidence rate with that of standard method • M1 method detected many pathogens which had not been found by standard clinic method.

Pseudomonas otitidis bacteremia in an immunocompromised patient with cellulitis: case report and literature review.

BACKGROUND: Pseudomonas otitidis belongs to the genus Pseudomonas and causes various infections, including ear, skin, and soft tissue infections. P. otitidis has a unique susceptibility profile, being susceptible to penicillins and cephalosporins but resistant to carbapenems, due to the production of the metallo-ß-lactamase called POM-1. This revealed genetic similarities with Pseudomonas aeruginosa, which can sometimes lead to misidentification. CASE PRESENTATION: We report the case of a 70-year-old Japanese male who developed cellulitis and bacteremia during chemotherapy for multiple myeloma. He was initially treated with meropenem, but blood culture later revealed gram-negative bacilli identified as P. otitidis using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Carbapenem resistance was predicted from previous reports; therefore, we switched to dual therapy with levofloxacin and cefepime, and favorable treatment results were obtained. CONCLUSION: This is the first reported case of P. otitidis cellulitis and bacteremia in an immunocompromised patient. Carbapenems are typically used in immunocompromised patients and P. otitidis is often resistant to it. However, its biochemical properties are similar to those of Pseudomonas aeruginosa; therefore, its accurate identification is critical. In the present study, we rapidly identified P. otitidis using MALDI-TOF MS and switched from carbapenems to an appropriate antimicrobial therapy, resulting in a successful outcome.

Protecting healthcare personnel and patients over 3 years of COVID-19 : Effective protection by masks and hygiene: What else was effective?

Healthcare professionals, particularly those in test centers, laboratories, or specialized COVID-19 wards, are in danger of becoming infected. Patients with special underlying health conditions are at an increased risk of getting very sick, being hospitalized, or dying from COVID-19. Age is a leading risk factor in this context. Currently, FFP2 (Filtering Facepiece 2, European standard), N95 (US standard), and KN95 (Chinese standard) face masks remain the simplest measure of protection. Coronavirus warning apps installed on smartphones have been recommended for anonymous contact tracing and quickly disrupting chains of infection. Preventive testing two to three times per week for healthcare personnel, on the day of hospital admission for patients, and upon facility entry for visitors has been routinely performed or has been requested from external test centers in most medical institutions. However, vaccination is regarded the most effective protective measure against COVID-19. The general recommendation of the World Health Organization is that countries continue to work toward vaccinating at least 70% of their populations, prioritizing the vaccination of 100% of healthcare workers and 100% of the most vulnerable groups, including people who are over 60 years of age and those who are immunocompromised or have underlying health conditions. The most vulnerable individuals among patients and healthcare workers should be identified and then their vaccination status should be checked and, if necessary, optimized by booster administration. In Germany, seasonal and institutional recommendations for individual protection by face masks, for hygiene measures, and for preventive testing must follow the updated coronavirus protection regulations (Coronavirus-Schutzverordnungen).

Reduced Immune Response to Inactivated Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine in a Cohort of Immunocompromised Patients in Chile.

BACKGROUND: Inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been widely implemented in low- and middle-income countries. However, immunogenicity in immunocompromised patients has not been established. Herein, we aimed to evaluate immune response to CoronaVac vaccine in these patients. METHODS: This prospective cohort study included 193 participants with 5 different immunocompromising conditions and 67 controls, receiving 2 doses of CoronaVac 8-12 weeks before enrollment. The study was conducted between May and August 2021, at Red de Salud UC-CHRISTUS, Santiago, Chile. Neutralizing antibody (NAb) positivity, total anti-SARS-CoV-2 immunoglobulin G antibody (TAb) concentrations, and T-cell responses were determined. RESULTS: NAb positivity and median neutralizing activity were 83.1% and 51.2% for the control group versus 20.6% and 5.7% (both P < .001) in the solid organ transplant group, 41.5% and 19.2% (both P < .0001) in the autoimmune rheumatic diseases group, 43.3% (P < .001) and 21.4% (P<.01 or P = .001) in the cancer with solid tumors group, 45.5% and 28.7% (both P < .001) in the human immunodeficiency virus (HIV) infection group, 64.3% and 56.6% (both differences not significant) in the hematopoietic stem cell transplant group, respectively. TAb seropositivity was also lower for the solid organ transplant (20.6%; P < .0001), rheumatic diseases (61%; P < .001), and HIV groups (70.9%; P = .003), compared with the control group (92.3%). On the other hand, the number of interferon γ spot-forming T cells specific for SARS-CoV-2 tended to be lower in all immunocompromising conditions but did not differ significantly between groups. CONCLUSIONS: Diverse immunocompromising conditions markedly reduce the humoral response to CoronaVac vaccine. These findings suggest that a boosting vaccination strategy should be considered in these vulnerable patients. CLINICAL TRIALS REGISTRATION: NCT04888793.

Vaccine-Associated Measles Encephalitis in Immunocompromised Child, California, USA.

We report a fatal case of vaccine-associated measles encephalitis in an immunocompromised child in California, USA. The infection was confirmed by whole-genome RNA sequencing of measles virus from brain tissue. We observed biased matrix-gene hypermutation consistent with persistent measles virus central nervous system infection.

Babesia crassa-Like Human Infection Indicating Need for Adapted PCR Diagnosis of Babesiosis, France.

Human babesiosis in Europe is caused by multiple zoonotic species. We describe a case in a splenectomized patient, in which a routine Babesia divergens PCR result was negative. A universal Babesia spp. PCR yielded a positive result and enabled classification of the parasite into the less-described Babesia crassa-like complex.

Targeted Screening for Chronic Q Fever, the Netherlands.

Early detection of and treatment for chronic Q fever might prevent potentially life-threatening complications. We performed a chronic Q fever screening program in general practitioner practices in the Netherlands 10 years after a large Q fever outbreak. Thirteen general practitioner practices located in outbreak areas selected 3,419 patients who had specific underlying medical conditions, of whom 1,642 (48%) participated. Immunofluorescence assay of serum showed that 289 (18%) of 1,642 participants had a previous Coxiella burnetii infection (IgG II titer >1:64), and 9 patients were suspected of having chronic Q fever (IgG I y titer >1:512). After medical evaluation, 4 of those patients received a chronic Q fever diagnosis. The cost of screening was higher than estimated earlier, but the program was still cost-effective in certain high risk groups. Years after a large Q fever outbreak, targeted screening still detected patients with chronic Q fever and is estimated to be cost-effective.

Seroconversion following the first, second, and third dose of SARS-CoV-2 vaccines in immunocompromised population: a systematic review and meta-analysis.

BACKGROUND: Immunocompromised (IC) patients are at higher risk of more severe COVID-19 infections than the general population. Special considerations should be dedicated to such patients. We aimed to investigate the efficacy of COVID-19 vaccines based on the vaccine type and etiology as well as the necessity of booster dose in this high-risk population. MATERIALS AND METHODS: We searched PubMed, Web of Science, and Scopus databases for observational studies published between June 1st, 2020, and September 1st, 2021, which investigated the seroconversion after COVID-19 vaccine administration in adult patients with IC conditions. For investigation of sources of heterogeneity, subgroup analysis and sensitivity analysis were conducted. Statistical analysis was performed using R software. RESULTS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we included 81 articles in the meta-analysis. The overall crude prevalence of seroconversion after the first (n: 7460), second (n: 13,181), and third (n: 909, all population were transplant patients with mRNA vaccine administration) dose administration was 26.17% (95% CI 19.01%, 33.99%, I2 = 97.1%), 57.11% (95% CI: 49.22%, 64.83%, I2 = 98.4%), and 48.65% (95% CI: 34.63%, 62.79%, I2 = 94.4%). Despite the relatively same immunogenicity of mRNA and vector-based vaccines after the first dose, the mRNA vaccines induced higher immunity after the second dose. Regarding the etiologic factor, transplant patients were less likely to develop immunity after both first and second dose rather than patients with malignancy (17.0% vs 37.0% after first dose, P = 0.02; 38.3% vs 72.1% after second dose, P < 0.001) or autoimmune disease (17.0% vs 36.4%, P = 0.04; 38.3% vs 80.2%, P < 0.001). To evaluate the efficacy of the third dose, we observed an increasing trend in transplant patients after the first (17.0%), second (38.3%), and third (48.6%) dose. CONCLUSION: The rising pattern of seroconversion after boosting tends to be promising. In this case, more attention should be devoted to transplant patients who possess the lowest response rate.

Antimicrobials and resistance part II: Antifungals, antivirals, and antiparasitics.

The available antifungal armamentarium consists of only a few drug classes, many limited in their use by significant toxicities and dangerous drug interactions. Rising opportunistic multidrug-resistant pathogens in the last few decades are further limiting available treatment options in life-threatening invasive fungal diseases. Similarly, antiviral resistance, although uncommon in healthy hosts, remains a challenge in immunocompromised patients with a risk for dissemination and severe disease. As evidenced by a dry pipeline, the gravity of antifungal, antiviral, and antiparasitic resistance has yet to draw the same attention as antibacterial resistance. Resistance disproportionately affects immunocompromised and vulnerable hosts, underscoring the urgent need to develop novel therapeutics. Antifungals, antiparasitics, and antivirals of main significance will be reviewed here, along with resistance concerns and some therapeutic agents under investigation.

[Cycloferon in local immunotherapy in patients with virus-associated rhinitis]. / Tsikloferon v lokal'noi immunoterapii u patsientov s virus-assotsiirovannym rinitom.

Evaluation of the effectiveness of various schemes of local immunotherapy in immunocompromised patients with allergic rhinitis was carried out. MATERIALS AND METHODS: A comparative analysis of the treatment of 72 patients with allergic rhinitis, divided into groups: I (main, n=21), which included immunocompromised patients who received sublingual allergen-specific immunotherapy with antipollin and inhaled immunotherapy with cycloferon (every other day, a course of 10 procedures, the total dose of Cycloferon per course is 1250 mg); II (comparison, n=22) - immunocompromised patients who received monotherapy with antipollinum and III (control, n=29) - patients with allergic rhinitis without signs of immunocompromise, who also received antipollinum. The effectiveness of therapy was assessed by the quality of life (RQLQ questionnaire), the severity of nasal symptoms (the patient's self-observation diary) and the need for drugs after a course of intranasal immunotherapy. RESULTS: The inclusion of cycloferon in the treatment of immunocompromised patients with allergic rhinitis increased its effectiveness - the severity of nasal symptoms decreased: in terms of sneezing, a decrease of 53.5 times versus 1.82 - in the control, «nasal congestion¼ - 6.3 times versus 2.6 - in the control, «itching in the nose¼ - 4.9 and 4.2 times, respectively (p<0.05). The changes had a positive effect on the total indicator of the quality of life of patients - an increase of 6.2 times (by 83.7%) (p>0.05) and significantly reduced the need for cromones (18 times, versus 10.3 - in the group comparison), inhaled corticosteroids (10.4 times versus 8 times in the comparison group, and in decongestans - 8.1 times versus 6.1 - in the comparison group (p>0.05)). CONCLUSIONS: The combined use of local immunotherapy with cycloferon and sublingual allergen-specific immunotherapy with antipollinum in immunocompromised patients with allergic rhinitis is the first-line method of choice that statistically significantly changes the quality of life of patients.

Endovascular Infection with Kingella kingae Complicated by Septic Arthritis in Immunocompromised Adult Patient.

We report a case of Kingella kingae endovascular infection in an immunocompromised elderly patient in Israel who had culture-negative septic arthritis. This case highlights potential sources of metastatic infection other than infective endocarditis, and emphasizes the need for molecular diagnostic methods in detection of pathogens in culture-negative septic arthritis in immunocompromised patients.

Efficacy and safety of ribavirin therapy for chronic hepatitis E after kidney transplantation.

Hepatitis E virus (HEV) infection has been recognized as an acute condition. However, recent reports have shown that immunocompromised patients, such as those receiving solid-organ transplantation, can develop chronic hepatitis with HEV infection. We report two cases of chronic hepatitis E after kidney transplantation (KT) who were successfully treated with ribavirin monotherapy. Several years after KT, both patients had sustained elevations in the levels of liver enzymes for a period of more than 6 months. Both patients had HEV infection, genotype 3a. Histological studies showed infiltration of inflammatory cells without fibrosis. Treatment included ribavirin monotherapy at a dosage of 600 mg daily for 3 months. One month after therapy initiation, HEV-RNA turned to negative, and remained negative at 24 weeks after ribavirin therapy without severe complications. Although the treatment of chronic hepatitis E is not fully established, ribavirin therapy can be a safe and effective treatment for chronic hepatitis E.

Onychomycosis Associated with Superficial Skin Infection Due to Aspergillus sydowii in an Immunocompromised Patient.

Opportunistic fungal infections of the skin and nail are frequently encountered in human. Recent years have shown increased incidence of fungal infections especially in immunocompromised patients. Onychomycosis in HIV-infected patients is reported to occur in 15-40%, four times more than in the general population. Here, we report a case of fingernail proximal subungual onychomycosis with associated skin infection caused by an opportunistic mold, Aspergillus sydowii, in a HIV positive individual. Isolation of A. sydowii from nail and skin of an immunocompromised person needs accurate identification for successful treatment.

Disseminated Spiroplasma apis Infection in Patient with Agammaglobulinemia, France.

We report a disseminated infection caused by Spiroplasma apis, a honeybee pathogen, in a patient in France who had X-linked agammaglobulinemia. Identification was challenging because initial bacterial cultures and direct examination by Gram staining were negative. Unexplained sepsis in patients with agammaglobulinemia warrants specific investigation to identify fastidious bacteria such as Spiroplasma spp.

Multiple Spitz nevi after allogeneic hematopoietic stem cell transplantation.

Spitz nevus commonly appears as a solitary lesion. A 12-year-old male patient presented with a 6-month history of several pigmented lesions on his trunk and lower extremities. He had undergone chemoradiotherapy and unrelated umbilical cord blood transplantation against recurring acute lymphoblastic leukemia for 6 years. After that, several pigmented lesions abruptly developed on his trunk and lower extremities, and the number of those increased significantly. Pathologically, the diagnosis of multiple Spitz nevi was made. In a clinical correlation, we diagnosed multiple Spitz nevi resulting from such an immunocompromised condition. This is the first description of clinical, dermoscopic, and histopathologic features of multiple Spitz nevi in the hematopoietic cell transplantation (HSCT) recipient child.

Human Sparganosis in Korea.

BACKGROUND: Sparganosis is a larval cestodiasis caused by the plerocercoid of Spirometra spp. Since the first description of human sparganosis in 1924, several hundred cases have been reported in Korea. However, systematic approaches for literature surveys of Korean sparganosis have seldom appeared. METHODS: We searched publicly available databases such as PubMed, Research Information Sharing Service, and Korea Medical Citation Index with relevant Medical Subject Headings. RESULTS: At least 438 Korean sparganosis cases have been described from 1924 to 2015. Preoperative diagnosis has been significantly increased since the 1980s due to popularization of serological and imaging diagnostics. Cases were largely detected from fifth decades in general, but cerebral sparganosis was detected in relatively young age groups (third and fourth decades). Sparganosis was prevalent in men (75.9%). Consumption of frog/snake and drinking unfiltered water were found in 63.4% and 16.9% of patients, respectively. Most frequently affected sites were subcutaneous tissues (49.9%), followed by the central nervous system (36.2%). Involvements of visceral organs (7.6%), ocular regions (3.6%), and muscles (2.7%) were noticed. In women, breast sparganosis constituted a large proportion (34.2%). Sparganosis associated with immunocompromised patients has recently been reported. CONCLUSION: Sparganosis has been continuously reported in Korea during the past 90 years, although its incidence has decreased during the last 20 years. The disease is mostly characterized by subcutaneous nodule, but infection of the worm in vital organs often results in serious illness. Continuous awareness is warranted to monitor sparganosis occurrence and associated clinical consequences.

A Case of Cutaneous Mycosis Caused by Scedosporium dehoogii on an Immunocompromised Patient.

This report describes a 77-year-old man with cutaneous mycosis caused by Scedosporium dehoogii while taking oral betamethasone and tacrolimus for the treatment of rheumatoid arthritis. At examination in our clinic, the patient had multiple cystic lesions and nodules with slight tenderness, varying in size up to 4 cm, on his left knee and shin. He had not noticed any traumatic injury at the site of the lesions. Fungal cultures of samples taken from the abscesses, scales, and crusts of the lesions yielded white, later grayish brown, fluffy surfaced colonies. Partial sequencing of the ß-tubulin gene confirmed the species of the isolate. The patient was initially treated with oral voriconazole and local hyperthermia, but experienced hepatic injury 2 weeks later. His treatment was changed to itraconazole (ITC) and local hyperthermia, followed by a combination of ITC and terbinafine. The patient recovered completely during the 12-month course of treatment.

Enterovirus D68-Associated Acute Flaccid Myelitis in Immunocompromised Woman, Italy.

In Italy in 2016, acute flaccid myelitis developed in a woman who had received a hematopoietic stem cell transplant. Enterovirus D68 viral genome was detected in respiratory and cerebrospinal fluid samples, and the viral protein 1 sequence clustered with lineage B3. Immunocompromised adults may be at risk for enterovirus D68-associated neurologic complications.