Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is responsible for the global epidemic of Coronavirus Disease 2019 (COVID-19), with a significant impact on the global economy and human safety. Reverse transcription-quantitative polymerase chain reaction (RT-PCR) is the gold standard for detecting SARS-CoV-2, but because the virus’s genome is prone to mutations, the effectiveness of vaccines and the sensitivity of detection methods are declining. Variants of concern (VOCs) include Alpha, Beta, Gamma, Delta, and Omicron, which are able to evade recognition by host immune mechanisms leading to increased transmissibility, morbidity, and mortality of COVID-19. A range of research has been reported on detection techniques for VOCs, which is beneficial to prevent the rapid spread of the epidemic, improve the effectiveness of public health and social measures, and reduce the harm to human health and safety. However, a meaningful translation of this that reduces the burden of disease, and delivers a clear and cohesive message to guide daily clinical practice, remains preliminary. Herein, we summarize the capabilities of various nucleic acid and protein-based detection methods developed for VOCs in identifying and differentiating current VOCs and compare the advantages and disadvantages of each method, providing a basis for the rapid detection of VOCs strains and their future variants and the adoption of corresponding preventive and control measures.

Hand, foot, and mouth disease (HFMD) is a mild exanthematous, febrile disease, but it also remains a threat to global public health. HFMD is characterized by a brief febrile illness in children and with a typical skin rash of the hand and foot, with or without mouth ulcers. However, the morphology and distribution of vesicles, as well as accompanying symptoms, are varied among atypical HFMD. An upsurge in atypical presentations of HFMD caused by Coxsackievirus A6 (CVA6), including Gianotti–Crosti-like eruptions, eczema coxsackium, petechial/purpuric eruption, and vesiculobullous exanthema, can be difficult to diagnose clinically as it may mimic other severe skin diseases, such as eczema herpeticum, varicella, disseminated zoster, and erythema multiforme major. The recognition of the distinguishing features of atypical HFMD is vital for an accurate and timely diagnosis, as is initiating appropriate laboratory evaluation and supportive care. Clinicians must identify the wide range of cutaneous and mucosal alterations caused by atypical HFMD. A systemic, high-quality overview of atypical HFMD is needed for advances in better strategies for clinical diagnosis and treatment. Hence, this review is aimed at summarizing the available data on clinical investigations and differential diagnostics to provide a scientific guide for the timely diagnosis of HFMD for preventing serious complications.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the Coronaviridae family, which is responsible for the COVID-19 pandemic followed by unprecedented global societal and economic disruptive impact. The innate immune system is the body’s first line of defense against invading pathogens and is induced by a variety of cellular receptors that sense viral components. However, various strategies are exploited by SARS-CoV-2 to disrupt the antiviral innate immune responses. Innate immune dysfunction is characterized by the weak generation of type I interferons (IFNs) and the hypersecretion of pro-inflammatory cytokines, leading to mortality and organ injury in patients with COVID-19. This review summarizes the existing understanding of the mutual effects between SARS-CoV-2 and the type I IFN (IFN-α/β) responses, emphasizing the relationship between host innate immune signaling and viral proteases with an insight on tackling potential therapeutic targets.

Sporadic occurrences and outbreaks of hand, foot, and mouth disease (HFMD) caused by Coxsackievirus A2 (CVA2) have frequently reported worldwide recently, which pose a great challenge to public health. Epidemiological studies have suggested that the main cause of death in critical patients is pulmonary edema. However, the pathogenesis of this underlying comorbidity remains unclear. In this study, we utilized the 5-day-old BALB/c mouse model of lethal CVA2 infection to evaluate lung damage. We found that the permeability of lung microvascular was significantly increased after CVA2 infection. We also observed the direct infection and apoptosis of lung endothelial cells as well as the destruction of tight junctions between endothelial cells. CVA2 infection led to the degradation of tight junction proteins (e.g., ZO-1, claudin-5, and occludin). The gene transcription levels of von Willebrand factor (vWF), endothelin (ET), thrombomodulin (THBD), granular membrane protein 140 (GMP140), and intercellular cell adhesion molecule-1 (ICAM-1) related to endothelial dysfunction were all significantly increased. Additionally, CVA2 infection induced the increased expression of inflammatory cytokines (IL-6, IL-1β, and MCP-1) and the activation of p38 mitogen-activated protein kinase (MAPK). In conclusion, the disruption of the endothelial barrier contributes to acute lung injury induced by CVA2 infection; targeting p38-MAPK signaling may provide a therapeutic approach for pulmonary edema in critical infections of HFMD.

Coxsackievirus A2 (CVA2) has emerged as an active pathogen that has been implicated in hand, foot, and mouth disease (HFMD) and herpangina outbreaks worldwide. It has been reported that severe cases with CVA2 infection develop into heart injury, which may be one of the causes of death. However, the mechanisms of CVA2-induced heart injury have not been well understood. In this study, we used a neonatal mouse model of CVA2 to investigate the possible mechanisms of heart injury. We detected CVA2 replication and apoptosis in heart tissues from infected mice. The activity of total aspartate transaminase (AST) and lactate dehydrogenase (LDH) was notably increased in heart tissues from infected mice. CVA2 infection also led to the disruption of cell-matrix interactions in heart tissues, including the increases of matrix metalloproteinase (MMP)3, MMP8, MMP9, connective tissue growth factor (CTGF) and tissue inhibitors of metalloproteinases (TIMP)4. Infiltrating leukocytes (CD45⁺ and CD11b⁺ cells) were observed in heart tissues of infected mice. Correspondingly, the expression levels of inflammatory cytokines in tissue lysates of hearts, including tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), IL6 and monocyte chemoattractant protein-1 (MCP-1) were significantly elevated in CVA2 infected mice. Inflammatory signal pathways in heart tissues, including phosphatidylinositol 3-kinase (PI3K)-AKT, mitogen-activated protein kinases (MAPK) and nuclear factor kappa B (NF-κB), were also activated after infection. In summary, CVA2 infection leads to heart injury in a neonatal mouse model, which might be related to viral replication, increased expression levels of MMP-related enzymes and excessive inflammatory responses.

Hand, Foot, and Mouth Disease (HFMD) is an infectious disease caused by enteroviruses (EVs) and is extremely contagious and prevalent among infants and children under 5 years old