Sequential or Combination Treatments as Rescue Therapies in Immunocompromised Patients with Persistent SARS-CoV-2 Infection in the Omicron Era: A Case Series.

Prolonged SARS-CoV-2 infections are widely described in immunosuppressed patients, but safe and effective treatment strategies are lacking. We aimed to outline our approach to treating persistent COVID-19 in patients with immunosuppression from different causes. In this case series, we retrospectively enrolled all immunosuppressed patients with persistent SARS-CoV-2 infections treated at our centers between March 2022 and February 2023. Patients received different sequential or combination regimens, including antivirals (remdesivir, nirmatrelvir/ritonavir, or molnupiravir) and/or monoclonal antibodies (mAbs) (tixagevimab/cilgavimab or sotrovimab). The main outcome was a complete virological response (negative SARS-CoV-2 RT-PCR on nasopharyngeal swabs) at the end of treatment. Fifteen patients were included as follows: eleven (11/15; 73%) with hematological disease and four (4/15; 27%) with recently diagnosed HIV/AIDS infection. Six patients (6/15; 40%) received a single antiviral course, four patients (4/15; 27%) received an antiviral and mAbs sequentially, and two patients (13%) received three lines of treatment (a sequence of three antivirals or two antivirals and mAbs). A combination of two antivirals or one antiviral plus mAbs was administered in three cases (3/15, 20%). One patient died while still positive for SARS-CoV-2, while fourteen (14/15; 93%) tested negative within 16 days after the end of treatment. The median time to negativization since the last treatment was 2.5 days. Both sequential and combination regimens used in this study demonstrated high efficacy and safety in the high-risk group of immunosuppressed patients.

Urgent need of rapid tests for SARS CoV-2 antigen detection: Evaluation of the SD-Biosensor antigen test for SARS-CoV-2.

At the time of writing, FIND has listed four CE-marked SARSCoV-2 antigen tests. We evaluated the recently CE-approved rapid POCT SD-Biosensor for SARS-CoV-2 nucleoprotein detection in nasopharyngeal secretions from 330 patients admitted to the Emergency Room for a suspect of COVID-19 and travelers returning home from high risk countries. Sensitivity, specificity, accuracy, negative and predictive values were consistent with the use of the test to mass-screening for SARS-CoV-2 surveillance.

HHV8-positive, HIV-negative multicentric Castleman's disease: early and sustained complete remission with rituximab therapy without reactivation of Kaposi sarcoma.

Multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder with systemic symptoms and poor prognosis and is characterized by an abnormal proliferation of polyclonal plasmablasts in the mantle zone of B-cell follicles. The disease is found primarily in chronic HIV carriers and is usually strictly associated with human herpes virus type 8 (HHV-8) coinfection, which is believed to play a key role in the pathogenesis of MCD. The disease is also diagnosed in HIV-negative patients, who are usually elderly or immunosuppressed; however, in about half of these cases, no evidence of HHV8 infection is found. The anti-CD20 monoclonal antibody rituximab is now the preferred treatment for HIV-positive MCD. However, it is not clear whether rituximab is effective in HIV-negative patients with MCD, particularly in the HHV8-positive subset. We report here the clinical and biologic courses of two HIV-negative, HHV8-positive patients with MCD who were treated with rituximab. In both cases, a significant clinical improvement was observed after the first two infusions, which was shortly followed by a drop in HHV8 viremia to undetectable levels. Both patients underwent complete clinical remission, which persisted without relapse at 30 and 9 months of follow-up, respectively. No reactivation of the Kaposi sarcoma found in a lymph node of one of the patients was observed. Our report, along with additional data present in the literature, suggests that rituximab may be an appropriate and safe first-line therapy for HIV-negative, HHV8-positive MCD.

Valganciclovir as pre-emptive therapy for cytomegalovirus infection post-allogenic stem cell transplantation: implications for the emergence of drug-resistant cytomegalovirus.

OBJECTIVES: Valganciclovir is a well established drug for the management of cytomegalovirus (CMV) infection in haematopoietic stem cell transplantation (HSCT). Data concerning its safety regarding the development of drug resistance are required. The aim of the present study was to retrospectively investigate CMV drug resistance in a group of HSCT patients experiencing relapses of CMV infection after a first-line pre-emptive antiviral therapy. METHODS: Thirteen adult HSCT patients out of 26 with asymptomatic CMV infection, experiencing relapsing infections 45-155 days after either intravenous (iv) ganciclovir (2 patients) or valganciclovir (11 patients), were studied. Genotypic assays for mutations in the viral phosphotransferase (UL97) and DNA-polymerase (UL54) genes were directly applied on patient specimens. Baseline CMV sequences were compared with those at the time of relapses to identify drug-resistant strains. RESULTS: UL97 mutations A594V and M460V known to confer drug resistance developed in one relapsing patient who received iv ganciclovir as first-line therapy, corresponding to a rate of 7.7% of relapses due to drug-resistant strains and an overall 3.8% rate of infections due to CMV drug-resistant strains. UL54 drug resistance mutations were absent. No evidence of drug resistance was found in patients on valganciclovir either as first-line therapy or as treatment for relapses. CONCLUSIONS: The safety profile of valganciclovir as anti-CMV pre-emptive therapy was confirmed, as well as that monitoring CMV drug resistance with genotypic tests on sequential isolates over the time-course of therapy offers guidance to tailor antiviral treatment in a clinically relevant time frame.

COBAS AmpliPrep-COBAS TaqMan hepatitis B virus (HBV) test: a novel automated real-time PCR assay for quantification of HBV DNA in plasma.

Success in antiviral therapy for chronic hepatitis B is supported by highly sensitive PCR-based assays for hepatitis B virus (HBV) DNA. Nucleic acid extraction from biologic specimens is technically demanding, and reliable PCR results depend on it. The performances of the fully automatic system COBAS AmpliPrep-COBAS TaqMan 48 (CAP-CTM; Roche, Branchburg, NJ) for HBV DNA extraction and real-time PCR quantification were assessed and compared to the endpoint PCR COBAS AMPLICOR HBV monitor (CAHBM; Roche). Analytical evaluation with a proficiency panel showed that CAP-CTM quantitated HBV DNA levels in one single run over a wide dynamic range (7 logs) with a close correlation between expected and observed values (r = 0.976, interassay variability below 5%). Clinical evaluation, as tested with samples from 92 HBsAg-positive patients, demonstrated excellent correlation with CAHBM (r = 0.966, mean difference in quantitation = 0.36 log(10) IU/ml). CAP-CTM detected 10% more viremic patients and longer periods of residual viremia in those on therapy. In lamivudine (LAM)-resistant patients, the reduction of HBV DNA after 12 months of Adefovir (ADF) was higher in the combination (LAM+ADF) schedule than in ADF monotherapy (5.1 logs versus 3.5 logs), suggesting a benefit in continuing LAM. CAP-CTM detected HBV DNA in liver biopsy samples from 15% of HBsAg-negative, anti-HBcAg-positive graft donors with no HBV DNA in plasma. The amount of intrahepatic HBV DNA was significantly lower in occult HBV infection than in overt disease. CAP-CTM can improve the management of HBV infection and the assessment of antiviral therapy and drug resistance, supporting further insights in the emerging area of occult HBV infection.

Antimicrobial activity of euplotin C, the sesquiterpene taxonomic marker from the marine ciliate Euplotes crassus.

Strains of the marine ciliate protist Euplotes crassus produce exclusive terpenoids called euplotins that play an ecological role. Among these derivatives, euplotin C is the main of four secondary metabolites isolated from cultures of this protozoon and represents the sesquiterpene taxonomic marker from E. crassus. Because different terpenoid metabolites of plant origin showed a certain antimicrobial activity, we assessed the compound euplotin C, purified by high-pressure liquid chromatography and solubilized in two solubility enhancers, against the protozoa Leishmania major and Leishmani infantum, the fungus Candida albicans, and nine strains of gram-positive and gram-negative microorganisms. An activity of euplotin C against Leishmania promastigotes was demonstrated (50% lethal doses were 4.6 or 8.1 microg/ml depending on the agent used to solubilize the compound), while the effect was less evident on Candida and nearly absent on bacteria. A nonsignificant cytotoxicity (50% lethal dose, >200 microg/ml) against the J774 cell line was observed. A leishmanicidal activity was also shown by the living, euplotin-producing cells of E. crassus cultured together with promastigotes; this activity increased with time from 10 min to 6 h of incubation. This study provides an initial rationale for the evaluation of euplotin C and other similar natural products as alternative or possibly synergistic compounds for current antiprotozoon chemotherapeutics.