Alzheimer's disease and herpes viruses: Current events and perspectives.

Alzheimer's disease (AD) is a real and current scientific and societal challenge. Alzheimer's disease is characterised by a neurodegenerative neuroinflammatory process, but the etiopathogenetic mechanisms are still unclear. The possible infectious aetiology and potential involvement of Herpes viruses as triggers for the formation of extracellular deposits of amyloid beta (Aß) peptide (amyloid plaques) and intraneuronal aggregates of hyperphosphorylated and misfold could be a possible explanation. In fact, the possible genetic interference of Herpes viruses with the genome of the host neuronal cell or the stimulation of the infection to a continuous immune response with a consequent chronic inflammation could constitute those mechanisms underlying the development of AD, with possible implications in the understanding and management of the disease. Herpes viruses could be significantly involved in the pathogenesis of AD and in particular, their ability to reactivate in particular conditions such as immunocompromise and immunosenescence, could explain the neurological damage characteristic of AD. Our review aims to evaluate the state of the art of knowledge and perspectives regarding the potential relationship between Herpes viruses and AD, in order to be able to identify the possible etiopathogenetic mechanisms and the possible therapeutic implications.

Serological Response and Clinical Protection of Anti-SARS-CoV-2 Vaccination and the Role of Immunosuppressive Drugs in a Cohort of Kidney Transplant Patients.

Vaccination against SARS-CoV2 represents a key weapon to prevent COVID-19, but lower response rates to vaccination have frequently been reported in solid organ transplant recipients. The aim of our study was to evaluate the rate of seroconversion to SARS-CoV-2 mRNA vaccines in a cohort of kidney transplant recipients and the potential role of the different immunosuppressive regimens. We conducted an observational retrospective cohort study in kidney transplant patients vaccinated for COVID-19. For each patient, we evaluated IgG anti-S-RBD SARS-CoV-2 titers immediately before the administration of first COVID-19 vaccination dose, 20 days after the first dose and 40 days after the second dose. Moreover, we evaluated the type of immunosuppressive treatment and the incidence of vaccine breakthrough SARS-CoV-2 infection. We enrolled 121 kidney transplant patients vaccinated for COVID-19. At the time of administration of the first vaccine dose, all patients had a negative antibody titer; only 4.1% had positive antibody titers 20 days after the first dose. More than half patients 62 (51%) had protective antibody titers 40 days after the second dose. A total of 18 Solid Organ Transplant Recipients (SOTRs) (14.9%) got a SARS-CoV-2 breakthrough infection during the study period. With regard to immunosuppressive regimen, patients on mycophenolate-based regimen (48.7%) showed the lowest antibody response rates (27.5%) compared to other regimens. Our study confirms that kidney transplant patients show a poor response to two doses of COVID-19 vaccination. Moreover, in our study the use of mycophenolate is significantly associated with a non-response to COVID-19 m-RNA vaccines.

A simple non-invasive C reactive protein-based score can predict outcome in patients with COVID-19

BackgroundWe evaluated the role of CRP and other laboratory parameters in predicting the worsening of clinical conditions during hospitalization, ICU admission and fatal outcome among patients with COVID-19. MethodsWe enrolled consecutive adult inpatients with SARS-CoV-2 infection and respiratory symptoms treated in three different COVID centres. We looked for laboratory parameters collected within 48 hours from hospital admission as predictors of clinical condition. ResultsThree-hundred ninety patients were included in the study. At the correlation and regression analysis, age, baseline CRP and LDH were associated with a P/F ratio<200 during hospitalization. At the multivariate analysis, male gender and CRP > 60 mg/l at admission showed to be independently associated with ICU admission. Lymphocytes<1000 cell/L at admission were associated with worst P/F ratio. The only laboratory predictor of fatal outcome was CRP>60 mg/l at admission. Based on these results, we devised an 11-points numeric ordinary score based on age, sex, CRP and LDH at admission (ASCL score). Patients with ASCL score of 0 or 2 showed to be protected against a P/F ratio<200, while patients with ASCL score of 6, 7 and 8 showed to be at risk for P/F ratio<200. Patients with ASCL score[≥]7 had a significant increase to die during the hospitalization. ConclusionsPatients with CRP>60 mg/l or LDH>300 IU/l at hospital admission, as well as patients with an ASCL score>6 at hospital admission, should be prioritized for careful respiratory function monitoring and early treatment to prevent a progression of the disease.

Casirivimab and Imdevimab for Pregnant Women Hospitalized for Severe Coronavirus Disease 2019.

OBJECTIVE: Our objective was to evaluate the safety and efficacy of casirivimab/imdevimab therapy in pregnant women with severe coronavirus disease 2019 (COVID-19) requiring oxygen therapy. STUDY DESIGN: This was a prospective case series study aimed to evaluate the safety and efficacy of casirivimab/imdevimab therapy in unvaccinated pregnant women with severe COVID-19. Inclusion criteria were severe acute respiratory syndrome coronavirus 2 infection documented with polymerase chain reaction, pregnancy, severe COVID-19 requiring oxygen therapy, duration of symptoms of 10 days or less, and able to provide informed consent. Vaccinated women and those with mild-to-moderate disease were excluded from the study. Included patients received casirivimab and imdevimab as a single intravenous dose of 4,000/4,000 mg. Women were also treated with low molecular weight heparin, steroids, and antibiotics, if necessary. The primary outcome was maternal death. Secondary outcomes were the rate of adverse events during infusion or within 72 hours and the rate of abortion. RESULTS: Thirteen hospitalized unvaccinated pregnant women with severe COVID-19 requiring oxygen and treated with casirivimab/imdevimab were included in the study. We observed no maternal death, and no patients required intubation or admission to the intensive care unit. No abortion or fetal loss was recorded. Nine pregnancies were still ongoing, and there were three cesarean deliveries and one vaginal delivery. Two were preterm deliveries (at 31 and 34 weeks), and two were term deliveries. CONCLUSION: Casirivimab/imdevimab therapy may be considered as a therapy in unvaccinated pregnant women with severe COVID-19.

Nirmatrelvir/ritonavir and molnuipiravir in the treatment of mild/moderate COVID-19: results of a real-life study

Molnupiravir and Nirmatrelvir are the first available oral antivirals (OA) active against SARS-CoV-2. However, the trials evaluating the efficacy of OAs involved patients unvaccinated and infected with variants different from those currently circulating. The purpose of this study is to provide real-life data on the efficacy and safety of OAs during the omicron surge of COVID-19 pandemic in a cohort of mostly vaccinated patients. We conducted a retrospective study on patients with confirmed SARS-CoV-2 infection treated with OAs during the omicron surge in Italy. We enrolled 257 patients. Of these, 146 (56.8%) were treated with molnupiravir and 111 (43.2%) with nirmatrelvir/ritonavir. Patients in molnupiravir group were older, had a lower body mass index, and a higher rate of chronic heart disease than those treated with nirmatrelvir/ritonavir. During the 14-day follow-up, four hospitalizations were recorded (1.6%), three in molnupiravir (2.1%) and 1 in nirmatrelvir/ritonavir (0.9%) group. Only one patient (who had received molnupiravir) died. Median time-to-negativity of nasal swab was 8 days (8 days in nirmatrelvir/ritonavir vs. 10 days in molnupiravir group, p<0.01). Globally, we recorded 37 adverse drug reactions (mainly dysgeusia, diarrhea, and nausea) in 31 of 257 individuals (12.1%). Only two patients (0.8%), both receiving molnupiravir, terminated treatment due to the development of adverse drug reactions. In conclusion, during the omicron surge, in a population of mostly vaccinated patients treated with molnupiravir or nirmatrelvir/ritonavir, we observed a low rate of hospitalization, death, and adverse drug reactions. These rates were even lower than those reported in pivotal trials.

Monoclonal antibodies against SARS-CoV-2: potential game-changer still underused

Even several months after the start of a massive vaccination campaign against COVID-19, mortality and hospital admission are still in considerable numbers in many nations. Monoclonal antibodies are the ideal complement to vaccination in high-risk subjects who have been infected by SARS-CoV-2 and are at high risk of developing severe disease. Combining data provided by clinal trials and demographics of SARS-CoV-2 infections, this analysis tries to predict the benefits of an extensive use of monoclonal antibodies to reduce hospital admissions, deaths, and costs.

Common variants at 21q22.3 locus influence MX1 gene expression and susceptibility to severe COVID-19

The COVID-19 disease, caused by the SARS-Cov-2, presents a heterogeneous clinical spectrum. The risk factors do not fully explain the wide spectrum of disease manifestations, so it is possible that genetic factors could account for novel insights into its pathogenesis. In our previous study, we hypothesized that common variants on chromosome 21, near TMPRSS2 and MX1 genes, may be genetic risk factors associated to the different clinical manifestations of COVID-19. Here, we performed an in-depth genetic analysis of chromosome 21 exploiting the genome-wide association study data including 6,406 individuals hospitalized for COVID-19 and 902,088 controls with European genetic ancestry from COVID-19 Host Genetics Initiative. We found that five single nucleotide polymorphisms (SNPs) within TMPRSS2 and near MX1 gene show suggestive associations (P[≤]1x10-5) with severe COVID-19. All five SNPs replicated the association in two independent cohorts of Asian subjects while two and one out of the 5 SNPs replicated in African and Italian populations, respectively (P[≤]0.05). The minor alleles of these five SNPs correlated with a reduced risk of developing severe COVID-19 and increased level of MX1 expression in blood. Our findings provide further evidence that host genetic factors can contribute to determine the different clinical presentations of COVID-19 and that MX1, an antiviral effector of type I and III interferon pathway, may be a potential therapeutic target.