Rational Use of Monoclonal Antibodies as Therapeutic Treatment in an Oncologic Patient with Long COVID

We present the case of a 76-year-old male patient persistently infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the setting of a stage IIIC cutaneous melanoma and non-Hodgkin’s lymphoma (NHL). Due to the persistent coronavirus disease 19 (COVID-19), all cancer treatments were discontinued. Because of the worsening of his clinical state and the persistence of SARS-CoV-2 positivity for more than six months, the patient was treated with sotrovimab, which was ineffective due to resistance mutations acquired during that time. In order to resume cancer treatment and make the patient free from SARS-CoV-2, an in vitro screening of Evusheld monoclonal antibodies (tixagevumab–cilgavimab) against the viral strains isolated from the subject was performed. The promising results obtained during in vitro testing led to the authorization of the off-label use of Evusheld, which made the patient negative for SARS-CoV-2, thus, allowing him to resume his cancer treatment. This study highlights the Evusheld monoclonal antibodies’ efficacy, not only in prevention but also in successful therapy against prolonged COVID-19. Therefore, testing neutralizing monoclonal antibodies in vitro against SARS-CoV-2 mutants directly isolated from patients could provide useful information for the treatment of people affected by long COVID

Epidemiologic Relationship between Toscana Virus Infection and Leishmania infantum Due to Common Exposure to Phlebotomus perniciosus Sandfly Vector

Sand flies are recognised vectors of parasites in the genus Leishmania and a number of arthropod-borne viruses, in particular viruses within the genus Phlebovirus, family Bunyaviridae. In southern France, Toscana phlebovirus (TOSV) is recognized as a prominent cause of summer meningitis. Since Leishmania and TOSV have a common vector (Phlebotomus perniciosus), an epidemiologic link has been assumed for a long time. However, there is no scientific evidence of such a link between human leishmaniosis and phleboviral infections. To identify a possible link, we investigated the presence and distribution of antibodies against these two microorganisms (i) in individuals and (ii) at a spatial level in the city of Marseille (south-eastern France). Five hundred sera were selected randomly in the biobank of the Department of Parasitology of the Public Hospitals of Marseille. All sera were previously tested for IgG against Leishmania by Western Blotting, and TOSV IgG were detected by indirect immunofluorescence. The seropositivity rates were 21.4% for TOSV and 28% for Leishmania. Statistical analysis demonstrated that seropositivity for one pathogen was significantly associated with seropositivity to the other pathogen. This result provided the first robust evidence for the existence of an epidemiological relationship between Leishmania infantum and TOSV. Addresses of tested patients were geolocalized and integrated into Geographical Information System software, in order to test spatial relationship between the two pathogens. Spatial analysis did not allow to identify (i) specific patterns for the spatial distribution of positive serological results for TOSV or Leishmania, and (ii) a spatial relationship between Leishmania and TOSV positive serological results. This may reflect the fact that the sample studied was not powerful enough to demonstrate either a spatial clustering or co-location, i.e. that the actual risk exposure area is smaller than the mean of distance between patients in our study (245 m)

Immunoprotectivity of HLA-A2 CTL Peptides Derived from Respiratory Syncytial Virus Fusion Protein in HLA-A2 Transgenic Mouse

Identification of HLA-restricted CD8+ T cell epitopes is important to study RSV-induced immunity and illness. We algorithmically analyzed the sequence of the fusion protein (F) of respiratory syncytial virus (RSV) and generated synthetic peptides that can potentially bind to HLA-A*0201. Four out of the twenty-five 9-mer peptides tested: peptides 3 (F33–41), 13 (F214–222), 14 (F273–281), and 23 (F559–567), were found to bind to HLA-A*0201 with moderate to high affinity and were capable of inducing IFN-γ and IL-2 secretion in lymphocytes from HLA-A*0201 transgenic (HLA-Tg) mice pre-immunized with RSV or recombinant adenovirus expressing RSV F. HLA-Tg mice were immunized with these four peptides and were found to induce both Th1 and CD8+ T cell responses in in vitro secondary recall. Effector responses induced by these peptides were observed to confer differential protection against live RSV challenge. These peptides also caused better recovery of body weight loss induced by RSV. A significant reduction of lung viral load was observed in mice immunized with peptide 23, which appeared to enhance the levels of inflammatory chemokines (CCL17, CCL22, and IL-18) but did not increase eosinophil infiltration in the lungs. Whereas, significant reduction of infiltrated eosinophils induced by RSV infection was found in mice pre-immunized with peptide 13. Our results suggest that HLA-A2-restricted epitopes of RSV F protein could be useful for the development of epitope-based RSV vaccine

Age-Dependent Seroprevalence of Toscana Virus in Central Italy and Correlation with the Clinical Profile▿

In order to estimate the antibody prevalence rates for Toscana virus (TOSV) among children and adults, we evaluated the seroprevalence of TOSV in a population (n = 2,737) living in Tuscany during the period of 1999 to 2006. The seroprevalence rate was 19.8% in adults and 5.8% in children, showing an age-dependent increase in TOSV-specific immunity. Meningitis due to TOSV infection was more frequent in adults than in children

In vitro neuraminidase inhibitory effect and activity against influenza virus A H1N1 of herbal drugs used for common cold

Influenza viruses are causative agents of common respiratory infections, often underestimated and badly managed. Monomolecular anti-inflammatory and anti-pyretic drugs are extensively used in infection related symptoms, but they do not trigger virus replication. Also herbal drugs are traditionally used [1], although specific anti influenza activities are rarely recorded and little investigated. By means of validated in vitro tests, in this study we investigated the effect of ten herbal extracts and poplar propolis commonly used for respiratory infections. We tested their effectiveness against an influenza A H1N1 strain in pre- and post cell infection and neuraminidase activity inhibition. Camellia sinensis Kuntze leaves dried extract 60% catechins (CSE), Pelargonium sidoides DC. roots standardized d.e. (PS) and Cistus creticus L. subsp. eriocephalus (Viv.) Greuter & Burdet (formerly Cistus incanus L.) aerial parts commercial d.e. 20% polyphenols (CIS) showed a strong anti-neuraminidase effect (IC50<25 μg/ml). Only these extracts were efficacious in in vitro inhibiting influenza virus entry and (in a weaker manner) virus replication in MDCK cells; toxic/effective concentration ratio was >4 only for CIS. Chemical analyses showed that galloil derivatives and flavan-3-ols oligomers mainly occur in CIS and, similarly to PS and CSE, these constituents are likely to contribute more to the antiviral efficacy [2], [3]. Our findings suggest that C. creticus subsp. eriocephalus is worth to be better investigated for its anti-influenza efficacy and ongoing researches are aiming to investigate molecular mechanisms of CIS constituents on viral targets such as the influenza virus glycoproteins, emoagglutinin and neuraminidase

Overview of Anti-SARS-CoV-2 Immune Response Six Months after BNT162b2 mRNA Vaccine

Background: We have designed a prospective study aiming to monitor the immune response in 178 health care workers six months after BNT162b2 mRNA vaccination. Methods: The humoral immune response of all subjects was evaluated by chemiluminescence (CMIA); in 60 serum samples, a live virus-based neutralization assay was also tested. Moreover, 6 months after vaccination, B-and T-cell subsets from 20 subjects were observed by FACS analysis after restimulation with the trimeric SARS-CoV-2 Spike protein as an antigen, thus mimicking reinfection in vitro. Results: A significant decrease of circulating IgG levels and neutralizing antibodies over time were observed. Moreover, six months after vaccination, a variable T-cell immune response after in vitro antigen stimulation of PBMC was observed. On the contrary, the analysis of B-cell response showed a shift from unswitched to switched memory B-cells and an increase of Th17 cells. Conclusions: Although the variability of the CD4+ and CD8+ immune response and an antibody decline was observed among vaccinated subjects, the increase of switched memory B-cells and Th17 cells, correlating with the presence of neutralizing antibodies, opened the debate on the correct timing of vaccination

Retrospective diagnosis of West Nile virus infection in a patient with meningoencephalitis in Tuscany, Italy

We report a case of West Nile virus (WNV) infection in a symptomatic woman living in Tuscany in 2007. A retrospective analysis on cerebrospinal fluids drawn from people affected by neurological diseases with unknown etiology allowed the identification of a case of WNV infection before the WNV outbreak in the Northeast Italy in 2008. This emphasizes the importance of maintaining a high level of epidemiological surveillance all over the Italian territory

Humoral immunity to Respiratory Syncytial Virus in young and elderly adults.

SUMMARYRespiratory syncytial virus (RSV) has been demonstrated to cause substantial disease in elderly and immunocompromised subjects. The relationship of serum antibody to RSV infection and the risk of infection in elderly subjects is controversial, thus we evaluated the presence of neutralizing antibodies to RSV in healthy people of different age groups and the correlation with viral protection. Baseline blood samples from 197 subjects aged 20–80 years were analysed for the presence of anti-RSV antibodies either by indirect immunofluorescence and microneutralization test. The percentage of people who had neutralizing antibodies to RSV was significantly higher (P=0·001) in the youngest group (92·51%) compared to the frail group (36·21%). The RSV antibody level tends to wane in some older people; this factor could determine proneness to RSV re-infections in the elderly who are at a greater risk of developing severe respiratory disease