Since the outbreak of coronavirus disease 2019 (Covid‐19) in December 2019, caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the number of confirmed infections has risen to more than 242 million worldwide, with nearly 5 million deaths. Currently, nine Covid‐19 vaccine candidates based on the original Wuhan‐Hu‐1 strain are at the forefront of vaccine research. All nine had an efficacy over 50% against symptomatic Covid‐19 disease: NVX‐CoV2373 (∼96%), BNT162b2 (∼95%), mRNA‐1273 (∼94%), Sputnik V (∼92%), AZD1222 (∼81%), BBIBP‐CorV (∼79%), Covaxin (∼78%), Ad26.CoV.S (∼66%) and CoronaVac (∼51%). However, vaccine efficacy (VE) can be jeopardised by the rapid emergence and spread of SARS‐CoV‐2 variants of concern (VOCs) that could escape from neutralising antibodies and/or cell‐mediated immunity. Rare adverse events have also been reported soon after administration of viral vector and mRNA vaccines. Although many Covid‐19 vaccines have been developed, additional effective vaccines are still needed to meet the global demand. Promising Covid‐19 vaccines such as WIBP‐CorV, AD5‐nCOV, ZyCoV‐D, CVnCoV, EpiVacCorona and ZF2001 have advanced to clinical studies. This review describes the most relevant mutations in the SARS‐CoV‐2 spike protein, discusses VE against VOCs, presents rare adverse events after Covid‐19 vaccination and introduces some promising Covid‐19 vaccine candidates.

In RNA viruses, a small increase in their mutation rates can be sufficient to exceed their threshold of viability. Lethal mutagenesis is a therapeutic strategy based on the use of mutagens, driving viral populations to extinction. Extinction catastrophe can be experimentally induced by promutagenic nucleosides in cell culture models. The loss of HIV infectivity has been observed after passage in 5-hydroxydeoxycytidine or 5,6-dihydro-5-aza-2′-deoxycytidine while producing a two-fold increase in the viral mutation frequency. Among approved nucleoside analogs, experiments with polioviruses and other RNA viruses suggested that ribavirin can be mutagenic, although its mechanism of action is not clear. Favipiravir and molnupiravir exert an antiviral effect through lethal mutagenesis. Both drugs are broad-spectrum antiviral agents active against RNA viruses. Favipiravir incorporates into viral RNA, affecting the G→A and C→U transition rates. Molnupiravir (a prodrug of β-d-N⁴-hydroxycytidine) has been recently approved for the treatment of SARS-CoV-2 infection. Its triphosphate derivative can be incorporated into viral RNA and extended by the coronavirus RNA polymerase. Incorrect base pairing and inefficient extension by the polymerase promote mutagenesis by increasing the G→A and C→U transition frequencies. Despite having remarkable antiviral action and resilience to drug resistance, carcinogenic risks and genotoxicity are important concerns limiting their extended use in antiviral therapy.

Several epidemiological studies demonstrated that coxsackievirus B4 (CVB4) causes viral pancreatitis and can ultimately result in type 1 diabetes mellitus (T1D). Prevention of CVB4 infection is therefore highly desirable. There is currently no vaccine or antiviral therapeutic reagent in clinical use. VLP are structurally similar to native virus particles and therefore are far better immunogens than any other subunit vaccines. Many studies have shown the potential of capsid protein VP1 on providing protective effects from different viral strains. In this study, we contributed towards the development of a CVB4 VLP-based vaccine from the total protein VP1 of the diabetogenic CVB4E2 strain and assessed whether it could induce a protective immunity against both the wild-type CVB4JBV and the diabetogenic CVB4E2 strains in mice model. Serum samples, taken from mice immunized with VLP, were assayed in vitro for their anti-CVB4 neutralizing activity and in vivo for protective activity. We show that VLP vaccine generates robust immune responses that protect mice from lethal challenges. Results demonstrate that CVB4 VP1 capsid proteins expressed in insect cells have the intrinsic capacity to assemble into non-infectious VLP, which afforded protection from CVB4 infection to mice when used as a vaccine.

Objective: Disorders of sexual development (DSD) are a heterogeneous group of genital defects affecting chromosomal, gonadal and anatomical sex. 46,XY DSD is a subset of DSD which covers a wide range of phenotypes in which 46,XY gonadal dysgenesis (GD) is the most severe form. In this study, we report on the clinical and molecular cytogenetic findings of a study on a Tunisian girl with the syndromic form of 46,XY DSD. Methods: This case was a phenotypic female patient having several congenital anomalies including growth retardation. Karyotype, fluorescence in situ hybridization and array Comparative Genome Hybridization (array CGH) were performed. Results: The proband exhibited a de-novo 46,X,der(Y) karyotype. Array CGH revealed a pathogenic 27.5Mb gain of an Xp21.2 chromosome segment leading to Xp functional disomy. No deletion was observed in the Y-chromosome. The duplicated region encompassed the NR0B1 (DAX1) and MAGEB genes, located within the dosage sensitive sex (DSS) reversal locus, known as promote genes responsible for human sex reversal and testis repression. The extra-dosage and interactions of these genes with different specific genes could result in the impairment of the male sex pathway. Over-dosage of KAL1 and IL1RAPL1 genes fall within the somatic features observed in the patient. Conclusion: To the best of our knowledge, we report on the fourth case of Xp21.2-pter duplication within Xp;Yp translocation associated with XY GD. Our findings suggest that when duplicated, the NR0B1 and MAGEB genes could be a major cause of XY GD. Therefore, we emphasize the usefulness of a combined cytogenetic approach in order to provide an accurate genetic diagnosis for those patients having syndromic XY DSD in a clinical setting.

The IFNAR2 gene encodes an essential component of the type I interferon receptor, which is essential for antiviral defense. It has been proven that the severity of COVID-19 may be influenced by the genetic variants in IFNAR2; however, the results are inconclusive in the African cohorts. Thus, in this study, we investigate the association between three IFNAR2 SNPs and the critical form of COVID-19 in the Tunisian population. A total of 413 COVID-19 patients classified as hospitalized with critical illness (ICU) (n = 46) and non-hospitalized (n = 367) are included. Genotyping of three IFNAR2 polymorphisms (rs1051393, rs2236757, rs9984273) was performed using Taq Man RT-PCR assays. rs2236757 (OR = 0.31, 95% CI: 0.16–0.60), p = 4 × 10⁻⁴) and rs9984273 (OR = 0.41, 95% CI: 0.22–0.76, p = 0.0055) were associated with COVID-19 severity with a potential protective effect. However, rs1051393 did not show a significant association with disease severity. Additionally, exploratory haplotype analysis suggested a possible protective association for the TAC haplotype (OR = 0.11, 95% CI: 0.02–0.86, p = 0.036), based on a very small number of carriers and not significant after correction for multiple testing. The GAC haplotype, absent from ICU patients, yielded a continuity-corrected OR of 0.03 (95% CI [0.002–0.53]); this estimate rests on a zero cell and is hypothesis-generating only. These preliminary findings, obtained from a single-center cohort with a limited number of critically ill patients, warrant replication in larger, independent, and multicentric populations.