The MBL2 genotype relates to COVID-19 severity and may help to select the optimal therapy.

OBJECTIVES: Sars-CoV-2 acute infection is clinically heterogeneous, ranging from asymptomatic cases to patients with a severe, systemic clinical course. Among the involved factors age and preexisting morbidities play a major role; genetic host susceptibility contributes to modulating the clinical expression and outcome of the disease. Mannose-binding lectin is an acute-phase protein that activates the lectin-complement pathway, promotes opsonophagocytosis and modulates inflammation, and is involved in several bacterial and viral infections in humans. Understanding its role in Sars-CoV-2 infection could help select a better therapy. METHODS: We studied MBL2 haplotypes in 419 patients with acute COVID-19 in comparison to the general population and related the haplotypes to clinical and laboratory markers of severity. RESULTS: We recorded an enhanced frequency of MBL2 null alleles in patients with severe acute COVID-19. The homozygous null genotypes were significantly more frequent in patients with advanced WHO score 4-7 (OR of about 4) and related to more severe inflammation, neutrophilia, and lymphopenia. CONCLUSIONS: Subjects with a defective MBL2 genotype (i.e., 0/0) are predisposed to a more severe acute Sars-CoV-2 infection; they may benefit from early replacement therapy with recombinant MBL. Furthermore, a subset of subjects with the A/A MBL genotype develop a relevant increase of serum MBL during the early phases of the disease and develop a more severe pulmonary disease; in these patients, the targeting of the complement may help. Therefore, COVID-19 patients should be tested at hospitalization with serum MBL analysis and MBL2 genotype, to define the optimal therapy.

The Immune Response to SARS-CoV-2 Vaccine in a Cohort of Family Pediatricians from Southern Italy.

In Italy, from January 2021, the Ministry of Health indicated a vaccination plan against COVID for frail patients and physicians based on a three-dose scheme. However, conflicting results have been reported on which biomarkers permit immunization assessment. We used several laboratory approaches (i.e., antibodies serum levels, flow cytometry analysis, and cytokines release by stimulated cells) to investigate the immune response in a cohort of 53 family pediatricians (FPs) at different times after the vaccine. We observed that the BNT162b2-mRNA vaccine induced a significant increase of specific antibodies after the third (booster) dose; however, the antibody titer was not predictive of the risk of developing the infection in the six months following the booster dose. The antigen stimulation of PBMC cells from subjects vaccinated with the third booster jab induced the increase of the activated T cells (i.e., CD4+ CD154+); the frequency of CD4+ CD154+ TNF-α+ cells, as well as the TNF-α secretion, was not modified, while we observed a trend of increase of IFN-γ secretion. Interestingly, the level of CD8+ IFN-γ+ (independently from antibody titer) was significantly increased after the third dose and predicts the risk of developing the infection in the six months following the booster jab. Such results may impact also other virus vaccinations.

Pandemic COVID-19, an update of current status and new therapeutic strategies.

The global COVID-19 pandemic is underway. In recent weeks, several countries throughout the globe, and particularly in Europe, have experienced an exponential increase in the number of individuals infected with COVID-19, probably induced by a new variant of SARS-CoV-2, called the "Omicron variant." Mass vaccination against COVID-19 continues worldwide. Are authorized mRNA vaccines effective against the new Omicron variant? Recently, several pharmaceutical companies have developed oral antiviral pills against SARS-CoV-2, i.e., molnupiravir and paxlovid, that inhibit SARS-CoV-2 viral replication by acting on the RNA polymerase of SARS-CoV. In pre-registration clinical trials, molnupiravir and paxlovid have shown excellent clinical efficacy results, but what impact will these new oral antiviral agents have against pandemic COVID-19? In what specific clinical situations are they preferred over other antivirals such as remdesivir? In this brief review, we explore these important aspects.

Advances in the Omicron variant development.

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has spread worldwide, leading the World Health Organization (WHO) to declare a pandemic, on 11 March 2020. Variants of concern have appeared at regular intervals-Alpha, Beta, Gamma, Delta, and now Omicron. Omicron variant, first identified in Botswana in November 2021, is rapidly becoming the dominant circulating variant. In this review, we provide an overview regarding the molecular profile of the Omicron variant, epidemiology, transmissibility, the impact on vaccines, as well as vaccine escape, and finally, we report the pharmacological agents able to block the endocellular entry of SARS-CoV-2 or to inhibit its viral replication. The Omicron has more than 50 mutations, of which the spike protein has 26-35 amino acids different from the original SARS-CoV-2 virus or the Delta, some of which are associated with humoral immune escape potential and greater transmissibility. Omicron has a significant growth advantage over Delta, leading to rapid spread with higher incidence levels. The disease so far has been mild compared to the Delta. The two vaccination doses offer little or no protection against Omicron infection while the booster doses provide significant protection against mild illness and likely offer even greater levels of protection against serious illness. Recently, new oral antiviral agents such as molnupiravir and paxlovid have been approved and represent important therapeutic alternatives to antiviral remdesivir. In addition, monoclonal antibodies such as casirivimab/imdevimab bind different epitopes of the spike protein receptor; is this class of drugs effective against the Omicron variant? However, more research is needed to define whether Omicron is indeed more infectious and whether the vaccines, monoclonal antibodies, and antivirals currently available are effective.

COVID-19 Infection in Children, Infants and Pregnant Subjects: An Overview of Recent Insights and Therapies.

BACKGROUND: The SARS-CoV-2 pandemic has involved a severe increase of cases worldwide in a wide range of populations. The aim of the present investigation was to evaluate recent insights about COVID-19 infection in children, infants and pregnant subjects. METHODS: a literature overview was performed including clinical trials, in vitro studies, reviews and published guidelines regarding the present paper topic. A descriptive synthesis was performed to evaluate recent insights and the effectiveness of therapies for SARS-CoV-2 infection in children, infants and pregnant subjects. RESULTS: Insufficient data are available regarding the relationship between COVID-19 and the clinical risk of spontaneous abortion and premature foetus death. A decrease in the incidence of COVID-19 could be correlated to a minor expression of ACE2 in childrens' lungs. At present, a modulation of the dose-effect posology for children and infants is necessary. CONCLUSIONS: Pregnant vertical transmission has been hypothesised for SARS-CoV-2 infection. Vaccines are necessary to achieve mass immunity for children and also pregnant subjects.

Diagnostic Accuracy of a New Antigen Test for SARS-CoV-2 Detection.

BACKGROUND AND AIMS: Quick and reliable diagnostic tools play an important role in controlling the spread of the SARS-Cov-2 pandemic. The aim of this study was to evaluate the diagnostic accuracy of a new cyto-salivary antigen test aimed at detecting the presence of antigens for SARS-CoV-2, as compared by the gold standard RT-PCR and a lateral flow test. METHODS: A total of 433 healthy volunteers were enrolled in the study and the sensitivity and specificity of the new cyto-salivary antigen test were calculated, as compared to the RT-PCR nasopharyngeal swab and to the lateral flow test. RESULTS: A total of 433 samples were collected and tested at the Mediterranean Fair in Palermo from February 2021 until April 2021. The new cyto-salivary antigen had a sensitivity of 100% and a specificity of 94.2%. The sensitivity and the specificity of the lateral flow test were 55% and 100%, respectively. CONCLUSIONS: The new cyto-salivary antigen test detected more positive cases than the RT-PCR in a sample of asymptomatic subjects, demonstrating to be a promising tool for a more sensitive diagnosis of COVID-19. Further studies are warranted to better characterize its diagnostic accuracy.

Detection of SARS-COV-2 Proteins Using an ELISA Test.

The coronavirus disease 2019 (COVID-19) global pandemic created an unprecedented public health emergency. Early recognition of an infected person and disruption of the transmission pathway are the keys to controlling this major public health threat around the world. The scientifically reliable screening method is an RT-PCR test that is performed on an ororhinopharyngeal swab in the laboratory. In the current severe SARS-CoV-2 pandemic, it is necessary to identify devices for rapid diagnosis to reduce the spread of the disease. The aim of this study was to provide a qualitative, rapid, sensitive, and specific method for a diagnosis of SARS-CoV-2 infection based on the recognition of specific antigens of the SARS-CoV-2 virus. The device was built by assembling commercially available and custom-made semi-finished products. The method was performed in environments outside the laboratory, i.e., "patient side," with an immediate chemocolorimetric response or with a digital reader using an ELISA method.