Common Viral Infections Research Articles

Characteristics of the respiratory season in 2022—23 and 2023—24 according to data from the city children's hospital

The end of the COVID-19 pandemic in the respiratory disease season of 2022—23 was characterized by an increase in the number of cases, a shift in the classic peaks of morbidity for various infections, and a predominance of influenza and respiratory syncytial virus infection (RSVI). Materials and methods. When compared with the last pandemic season, a later start of the 2023—24 respiratory season was noted with a gradual shift to the usual pre-pandemic period timing of viral morbidity increases. Results. The currently prevailing SARS-CoV-2 Omicron variant has acquired the properties of a common respiratory viral infection, currently all-season, with a mild course, without the need for hospitalization. The number of patients with influenza has decreased and there were no patients with a severe course of this infection. A feature of the first post-pandemic season was the outbreak of mycoplasma infection, which was a reason of large number of pneumonia cases.

Emerging and re-emerging viral exanthems among children: what a physician should know.

Viral exanthems can present with diverse morphologies of rash, including macular, maculopapular, papular, urticarial and vesicular, or sometimes a combination of these. There has been an increasing trend towards emerging and re-emerging viral exanthems in recent years, the cause of which is multifactorial, including changing environmental conditions and altered host-vector-agent interaction. The significant temperature variations brought on by climate change and ever-increasing international travel has modified the host-agent interactions, and many re-emerging viral illnesses are now presenting with atypical presentations, including an increased frequency of affliction across broader age groups and heightened manifestations often posing as 'great imitators' mimicking a myriad of other dermatoses. Although final diagnosis often relies on serological and molecular tests, certain cutaneous clues can help arrive at a probable clinical diagnosis and help the clinicians order specific and relevant investigations, especially in resource-poor settings where access to laboratory diagnostic tests is likely to be limited. In this review we explore the changing disease dynamics of common viral infections, especially in resource-poor settings, including coronavirus disease 2019, chikungunya, hand-foot-and-mouth disease and some newly emerging ones like mpox (previously referred to as monkeypox), and highlight recent developments in our understanding of the clinical variations seen in their presentations.

Progress and Challenges in the Management of Congenital Cytomegalovirus Infection

Congenital cytomegalovirus (CMV) infection is the most common intrauterine viral infection with a significant impact on the foetus and newborn. Current diagnostic practice includes serological testing for specific antibodies, but there are no global screening protocols. Maternal CMV screening is often performed in conjunction with antenatal ultrasound. While most infections are asymptomatic, severe cases can lead to long-term disability or death. Antiviral therapies, mainly ganciclovir and valganciclovir, are reserved for symptomatic patients, especially those with central nervous system involvement. Although effective, these treatments are associated with significant side effects such as neutropenia and hepatotoxicity. Foscarnet and cidofovir are used as alternatives, but their efficacy and safety require further study in paediatric patient populations. The effectiveness of passive prophylaxis is still uncertain. The lack of universally accepted guidelines for diagnosis, treatment, and prevention and the risk of serious side effects highlight the need for continued research. This review evaluates current therapeutic strategies, discusses their efficacy and associated risks, and highlights the need for innovative approaches to improve outcomes for affected neonates.

Viral infection and antiviral immunity in the oral cavity.

Individual tissues have distinct antiviral properties garnered through various mechanisms, including physical characteristics, tissue-resident immune cells and commensal organisms. Although the oral mucosa has long been appreciated as a critical barrier tissue that is exposed to a continuous barrage of pathogens, many fundamental aspects of the antiviral immune response in this tissue remain unknown. Several viral pathogens, such as herpesviruses and human papillomaviruses, have been acknowledged both historically and at present for infections in the oral cavity that result in substantial clinical burden. However, recent viral outbreaks, including those with SARS-CoV-2 and mpox, featured oral symptoms even though these viruses are not generally considered oral pathogens. Ensuing studies have shown that the oral cavity is an important locale for viral infection and potential transmission of newly emergent or re-emergent pathogens, highlighting the need for an increased understanding of the mechanisms of antiviral immunity at this site. In this Review, we provide a broad overview of antiviral immune responses in the oral cavity and discuss common viral infections and their manifestations in the oral mucosa. In addition, we present current mouse models for the study of oral viral infections.

Risk Factors for Cytomegalovirus Infection after Haematopoietic Stem Cell Transplantation: A Meta-Analysis.

Cytomegalovirus (CMV) infection is the most common viral infection after haematopoietic stem cell transplantation (HSCT). However, studies on related risk factors give different views without any clear conclusion. Therefore, the purpose of this study was to evaluate the risk variables of CMV infection after HSCT in order to provide recommendations for therapeutic treatment. The National Knowledge Infrastructure [CNKI], Chinese Biomedical Literature database [SinoMed], Wanfang Digital Periodicals [WANFANG] and China Science and Technology Journal [VIP] databases, as well as PubMed, Embase, CENTRAL, Web of Science databases were searched. The search keyword was Cumulative Index of Nursing and Related Health Literature (CINAHL). The search time spanned from the time when the database was created to February 2023. Based on inclusion and exclusion criteria, two researchers independently chose the literature, retrieved data, and assessed the bias risk. The methodological quality of the included studies was assessed by the Newcastle Ottawa scale (NOS). A total of 1,038 literatures were retrieved, of which, 18 studies were finally included. The final results of meta-analysis showed that there were seven risk factors as follows: Acute graft-versus-host disease (aGVHD) grades II-IV (II-IV) [odds ratio = 3.39, 95% CI (2.13, 5.41), p <0.05]; ant-thymocyte globulin (ATG) administration in treatment [odds ratio = 2.53, 95% CI (1.41, 4.53), p <0.05]; cyclosporine level after transplantation (>300 ng/ml) [OR = 3.79, 95% CI (1.24, 11.65), p <0.05]; age [odds ratio = 1.83, 95% CI (1.06, 3.15), p <0.05]; neutrophil deficiency time [odds ratio = 6.58, 95% CI (2.24, 19.30), p <0.05]; CMV infection in recipients before transplantation [odds ratio = 6.32,95% CI (4.03, 9.90), p <0.05]; fungal infection [odds ratio = 2.63, 95% CI (1.09, 6.34), p <0.05]. This study preliminarily revealed that CMV infection after HSCT is related to aGVHD (II-IV), ATG administration in pretreatment, cyclosporine level (>300 ng/ml) after transplantation, age, neutrophil deficiency time, CMV infection in recipients before transplantation and fungal infection. However, the mechanisms behind the risk variables are unclear. Further research is necessary to understand the risk factors and to enhance the care of patients with these risk factors to prevent or control infection. Key Words: Haematopoietic stem cell transplantation, Cytomegalovirus infection, Risk factors, Meta-analysis.

Risk Factors for Cytomegalovirus Infection after Haematopoietic Stem Cell Transplantation: A Meta-Analysis.

Cytomegalovirus (CMV) infection is the most common viral infection after haematopoietic stem cell transplantation (HSCT). However, studies on related risk factors give different views without any clear conclusion. Therefore, the purpose of this study was to evaluate the risk variables of CMV infection after HSCT in order to provide recommendations for therapeutic treatment. The National Knowledge Infrastructure [CNKI], Chinese Biomedical Literature database [SinoMed], Wanfang Digital Periodicals [WANFANG] and China Science and Technology Journal [VIP] databases, as well as PubMed, Embase, CENTRAL, Web of Science databases were searched. The search keyword was Cumulative Index of Nursing and Related Health Literature (CINAHL). The search time spanned from the time when the database was created to February 2023. Based on inclusion and exclusion criteria, two researchers independently chose the literature, retrieved data, and assessed the bias risk. The methodological quality of the included studies was assessed by the Newcastle Ottawa scale (NOS). A total of 1,038 literatures were retrieved, of which, 18 studies were finally included. The final results of meta-analysis showed that there were seven risk factors as follows: Acute graft-versus-host disease (aGVHD) grades II-IV (II-IV) [odds ratio = 3.39, 95% CI (2.13, 5.41), p <0.05]; ant-thymocyte globulin (ATG) administration in treatment [odds ratio = 2.53, 95% CI (1.41, 4.53), p <0.05]; cyclosporine level after transplantation (>300 ng/ml) [OR = 3.79, 95% CI (1.24, 11.65), p <0.05]; age [odds ratio = 1.83, 95% CI (1.06, 3.15), p <0.05]; neutrophil deficiency time [odds ratio = 6.58, 95% CI (2.24, 19.30), p <0.05]; CMV infection in recipients before transplantation [odds ratio = 6.32,95% CI (4.03, 9.90), p <0.05]; fungal infection [odds ratio = 2.63, 95% CI (1.09, 6.34), p <0.05]. This study preliminarily revealed that CMV infection after HSCT is related to aGVHD (II-IV), ATG administration in pretreatment, cyclosporine level (>300 ng/ml) after transplantation, age, neutrophil deficiency time, CMV infection in recipients before transplantation and fungal infection. However, the mechanisms behind the risk variables are unclear. Further research is necessary to understand the risk factors and to enhance the care of patients with these risk factors to prevent or control infection. Key Words: Haematopoietic stem cell transplantation, Cytomegalovirus infection, Risk factors, Meta-analysis.

Association of Herpes simplex infection with significantly increased risk of head and neck cancer: real-world evidence of about 500,000 patients.

The role of viral agents in the development of head and neck cancers has remained controversial. While markers of viral origin have been isolated from oral cancer tissues, a causative relationship has yet to be shown. The aim of this study was to evaluate the relationship between head and neck cancers and Herpes simplex virus, one of the most common viral infections of the oral orifice. Here, we conducted a retrospective analysis of two age- and gender-matched cohorts extracted from the real-world database TriNetX on March 10th, 2023, each consisting of 249,272 patients with and without Herpes simplex infections (ICD-10: B00). The diagnoses C00-C14 were analyzed, and risk analysis and Kaplan-Meier survival statics were computed. The strongest association was found for lip cancer (ICD-10: C00) with a hazard ratio [HR (CI 95% low-high)] of 3.08 (1.77-5.35). A significant association with HR of 1.17 (1.02-1.34) was found for the entire group of head and neck cancers. Confounders like smoking and alcohol dependence were considered using propensity score matching. The surprisingly strong correlation with lip, oral cavity, and pharynx neoplasms sheds new light on supposedly harmless herpes simplex infections, suggesting them as a possible new factor for risk stratification.

Hematological Cancer and Viral Infection

Hematological cancer patients are particularly vulnerable to the morbidity and death caused by viral infections. But, it is not well known how common viral infections are or what effects they have on patients undergoing traditional nontransplant treatment. How severe and how long T-cell-mediated immune suppression is determines the variation in viral infection incidence and prognosis between patient groups. Topics covered in this mini-review article include late CMV infection, new viral pathogens (human herpesvirus-6, BK virus, adenovirus, and human metapneumovirus), advancements in molecular diagnostics, and the possibility of novel agents for viral prophylaxis (maribavir) or preemptive therapy (valganciclovir). The infections caused by these viruses have been extensively studied. If we want to understand the range of these viral diseases and come up with effective ways to prevent and cure them, we need well-designed prospective trials. Patients undergoing nontransplant treatment for hematological malignancies are at greater risk for viral infections; this is especially important given the rising use of drugs like alemtuzumab, which cause significant T-cell depletion.

Onychomadesis and Beau’s Lines- Rare Complications of Handfoot- and-mouth Disease

Hand-foot-and-mouth disease (HFMD) is a common self-limiting viral infection in children caused by Coxsackievirus A16 and human enterovirus 71, presenting with fever, erythematous papulovesicular eruptions/ blisters on the palms, soles, knees, buttocks, and oral mucosa. Although rare, complications may arise in nails e. g. onychomadesis (nail separation) and Beau’s lines (transverse lines on the nails). These typically appear within four to eight weeks of HFMD and persist for around 5-6 weeks. No active treatment is required and these nail changes resolve spontaneously within few weeks as the nail bed remain intact. We present here a boy of 4 years who presented with such nail changes after around 5 weeks of HFM disease and diagnosed as onychomadesis and Beau’s lines after ruling out other possible causes of nail changes. BANGLADESH J CHILD HEALTH 2023; VOL 47 (1) : 47-50

Hepatitis B Virus Increases SphK1-S1P Synthesis by Promoting the Availability of the Transcription Factor USF1.

Hepatitis B virus (HBV) is the most common chronic viral infection globally, affecting ∼360 million people and causing about 1 million deaths annually due to end-stage liver disease or hepatocellular carcinoma. Current antiviral treatments rarely achieve a functional cure for chronic hepatitis B, highlighting the need for improved monitoring and intervention strategies. This study explores the role of the sphingosine kinase 1 (SphK1)-sphingosine-1-phosphate (S1P) axis in HBV-related liver injury. We investigated the association between serum S1P concentration and HBV DNA levels in chronic hepatitis B patients, finding a significant positive correlation. Additionally, SphK1 was elevated in liver tissues of HBV-positive hepatocellular carcinoma patients, particularly in HBsAg-positive regions. HBV infection models in HepG2-sodium taurocholate cotransporting polypeptide cells confirmed that HBV enhances SphK1 expression and S1P production. Inhibition of HBV replication through antiviral agents and the CRISPR-Cas9 system reduced SphK1 and S1P levels. Further, we identified the transcription factor USF1 as a key regulator of SphK1 expression during HBV infection. USF1 binds to the SphK1 promoter, increasing its transcriptional activity, and is upregulated in response to HBV infection. In vivo studies in mice demonstrated that HBV exposure promotes the expression of USF1 and SphK1-S1P. These findings suggest that the SphK1-S1P axis, regulated by HBV-induced USF1, could serve as a potential biomarker and therapeutic target for HBV-related liver injury.

Evaluation and control strategy analysis of influenza cases in Jiujiang City, Jiangxi Province, China from 2018 to 2022.

According to World Trade Organization (WTO) statistics, the incidence of seasonal influenza in China has been on the rise since 2018. The aim of this study was to identify and investigate the influence of factors related to the incidence of four common types of influenza viruses. Data of patients with common cold and associated virus infections are described, and a logistic regression model based on gender, age and season was established. The relationship between virus type and the above three factors was analyzed in depth and significant (p<0.05) associations noted. We noted a fluctuation trend, with the infection rate of influenza virus showing an upward trend from 2018 to 2019 and from 2021 to 2022 and a downward trend from 2019 to 2021. The total number of cases in adolescents aged 18-30 years was higher than that in the elderly. The impact of different types of influenza virus on the population ranked from large to small, with special roles played by Influenza B/Victoria, H3N2, Influenza A/H1N1 pdm and Influenza B/Yamagata.

Common viral respiratory infections in children with cancer during the COVID-19 pandemic: a multicenter study from Türkiye.

Microbiologic confirmation of respiratory tract infections gained importance during the coronavirus disease 2019 (COVID-19) pandemic. This study retrospectively evaluated seasonal distribution, clinical presentation, and complications of respiratory viral infections (RVIs) other than COVID-19 in children with cancer during and after the pandemic lockdown. Two hundred and sixty-five inpatient and outpatient RVI episodes in 219 pediatric cancer patients confirmed by multiplex reverse transcriptase polymerase chain reaction (RT-PCR) panels from 13 centers were enrolled. Eighty-six (32.5%) of the total 265 episodes occurred in 16 months corresponding to the lockdowns in Türkiye, and the remaining 67.5% in 10 months thereafter. Human rhinovirus/enterovirus (hRE) (48.3%) was the most common agent detected during and after lockdown. Parainfluenza virus (PIV) (23.0%), influenza virus (9.8%), and respiratory syncytial virus (RSV) (9.1%) were the other common agents. The 28.7% of episodes were lower respiratory tract infections (LRTIs), and complications and mortality were higher than upper respiratory tract infections (URTIs) (25.0% vs 5.3%). Bacteremia was identified in 11.5% of culture-drawn episodes. Treatment delay in one-third and death within four weeks after RVI in 4.9% of episodes were observed. During the pandemic, fewer episodes of RVIs occurred during the lockdown period. Respiratory viruses may cause complications, delays in treatment, and even death in children with cancer. Therefore, increased awareness of RVIs and rapid detection of respiratory viruses will benefit the prevention and, in some cases, abrupt supportive and some antiviral treatment of RVI in children with cancer.

A rare case of respiratory syncytial virus bronchiolitis with spontaneous L pneumothorax in an infant

Abstract: The most common self-limiting viral infection of the lower respiratory tract in the pediatric population is bronchiolitis, which most commonly affects infants. In most cases, respiratory syncytial virus (RSV) is the causative agent. In general, the recovery occurs within 5–7 days without any complications. Spontaneous pneumothorax is one of the rare and less-reported complications of bronchiolitis. We report a case of a male child aged 5 months with bilateral spontaneous pneumothorax (PNO) with subcutaneous emphysema following bronchiolitis. The nasopharyngeal swab was positive for RSV, and all other investigations ruled out any underlying illness causing spontaneous PNO. Although it is a rare complication of bronchiolitis, it may occur late during the disease course. Pediatricians must be aware of this life-threatening complication, which may develop during the disease course despite an early clinical improvement.

Predictable correlation between ACTH and Cortisol in Women with Aborted Pregnancies and its Association with Cytomegalovirus (CMV) Infection

Background: Abortion is a spontaneous termination of pregnancy with various causes, including infections like cytomegalovirus (CMV). Cytomegalovirus is a common viral infection that can affect various organs and systems in the body. Aim of study: This research aims to investigate the concertation level of Cortisol and ACTH hormones that may play a role in crucial processes during pregnancy. Materials and methods: This study conducted at Maternity and Children's Hospital in Hilla from November 2023 to March 2024 focused on 250 women who had undergone abortions. Participants were divided into two groups: 200 women with abortions (Positive Group) and 50 healthy married women (Control Group). Results: we found 60 Cytomegalovirus were positively obtained from women with abortion, The serological diagnosis for CMV-positive samples found that 6 samples were seropositive to CMV IgM, 14 samples were seropositive for both IgM &amp; IgG, and 40 (samples were seropositive for CMV IgG only. The study investigated the concertation hormone levels of Cortisol and ACTH in women who had experienced abortions with cytomegalovirus (CMV) infection compared to a Control group of healthy married women. The results showed that the patient group had significantly lower cortisol levels, at a mean value of 42.1158. On the other hand,(ACTH) of (78.1468).conclusion: High levels are present in the blood of women with CMV. There is a decreased level of Cortisol in women miscarriage with CMV infection which is statically significant.

Maternal Cytomegalovirus (CMV) Serology: The Diagnostic Limitations of CMV IgM and IgG Avidity in Detecting Congenital CMV Infection.

Congenital cytomegalovirus (cCMV) is a common congenital viral infection. Testing for cCMV usually begins with assessing maternal CMV serology, specifically IgM and IgG antibodies. A negative maternal CMV IgM suggests a low risk of recent maternal CMV infection, thereby suggesting a low risk of cCMV in the fetus. Consequently, cCMV is often ruled out when maternal CMV IgM is negative. In our perinatal autopsy and placental pathology database, we identified 5 cases of cCMV despite negative maternal CMV IgM results in the second trimester. In all 5 cases, fetal abnormalities were first detected by ultrasound in the second trimester, prompting maternal CMV testing. Since second trimester maternal CMV IgM was negative in all cases, cCMV was considered unlikely, thus precluding further prenatal CMV testing in 4 of these cases. The diagnosis of cCMV was subsequently made through placental and/or autopsy examinations. Following this diagnosis, retrospective CMV serology and IgG avidity testing was performed on stored frozen first-trimester maternal blood samples in 3 cases. Among these, the first-trimester samples in 2 cases were IgG+, IgM+, and exhibited low IgG avidity, suggesting a primary maternal CMV infection around the time of conception. In the third case, both first and second-trimester maternal blood samples were IgG+, IgM-, and showed high IgG avidity, suggesting a non-primary maternal CMV infection (i.e., reactivation or reinfection of CMV). A negative maternal CMV IgM in the second trimester cannot exclude cCMV infection. While CMV IgG avidity testing and analysis of stored frozen first-trimester maternal blood samples provide valuable insights, they have limitations. CMV PCR performed on amniotic fluid is a useful prenatal diagnostic tool. For cases of unexplained fetal abnormalities or death, autopsy and placental examination are recommended.

A prospective longitudinal study assessing the impact of rhinovirus and bacterial infections in acute exacerbations of chronic rhinosinusitis.

Acute exacerbations of chronic rhinosinusitis (AECRS) are thought to arise from common viral infections progressing to secondary bacterial infections. However, the pathophysiology of AECRS remains poorly understood due to a lack of prospective longitudinal studies. We conducted a one-year prospective longitudinal study involving chronic rhinosinusitis (CRS) adults. At baseline, we assessed subjective symptom scores using a validated upper respiratory infection questionnaire (WURSS), sinonasal outcome testing scores (SNOT-22), and endoscopic scores (modified Lund-Kennedy score). Every 2weeks, we contacted subjects to collect WURSS and SNOT-22 scores. If WURSS scores were ≥1 and SNOT-22 scores were ≥ 8.9 compared with baseline, subjects underwent an AECRS assessment. We identified rhinovirus (RV) incidence through viral nasal brushings at each visit and bacterial infection through bacterial swabs if mucus scores were ≥1. Thiry-five of 80 CRS subjects reported at least one AECRS episode during the year, predominantly occurring in the fall and winter seasons. RV infections were detected in 8 of 35 cases, bacterial infections in 17 of 35, and co-occurring infections in 7 of 35. All subjects with AECRS visits exhibited significantly higher endoscopic scores compared with baseline. Subjects with co-occurring RV and bacterial infections demonstrated higher disease severity compared with those with either RV or bacterial infection, or no infection. In a one-year prospective longitudinal study involving CRS adults, we identified significant risk factors for AECRS including seasonality and the presence of RV and bacterial infections. These data suggest a standard definition of AECRS and the need to target RV and bacterial infections if we are to help reduce disease severity.

Seasonal Patterns of Common Respiratory Viral Infections in Immunocompetent and Immunosuppressed Patients.

Several respiratory viruses have been shown to have seasonal patterns. The aim of our study was to evaluate and compare these patterns in immunocompetent and immunosuppressed patients for five different respiratory viruses. We performed a retrospective analysis of results for 13,591 respiratory tract samples for human metapneumovirus (HMPV), influenza virus, parainfluenza virus (PIV) and respiratory syncytial virus (RSV) in immunocompetent and immunosuppressed patients. A seasonal pattern was aligned to the data of immunocompetent patients through a logistic regression model of positive and negative test results. A narrow seasonal pattern (January to March) was documented for HMPV. Most RSV infections were detected in the winter and early spring months, from December to March, but occasional cases of RSV could be found throughout the year. The peak season for PIV-3 was during the summer months, and that for PIV-4 was mostly in autumn. A narrow seasonal pattern emerged for influenza virus as most infections were detected in the winter, in January and February. The seasonal patterns of HMPV, RSV, PIV, and influenza virus were similar for both immunocompetent and immunocompromised patients. We found no difference in the seasonality of HMPV, RSV, PIV, and influenza virus infections between immunosuppressed and immunocompetent hosts.

Expert recommendations for the prevention of common respiratory viral infections in neonates

Neonates, particularly preterm infants, are a susceptible population to respiratory viral infections. Currently, aside from influenza, there are no antiviral medications specifically approved for the treatment of respiratory viral infections in neonates; therefore, prevention of these viral infections is particularly crucial for neonates. The Neonatal HealthCare Committee of Chinese Maternal and Child Health Association, based on domestic and international clinical evidence and combined with clinical practice experience, and after thorough discussion by relevant experts, has developed eight expert recommendations. These include preventive strategies against influenza virus, respiratory syncytial virus, and severe acute respiratory syndrome coronavirus 2 infections, intended for reference in clinical practice.

Cutting Edge: Retinoic Acid Promotes Brain-homing of CD8+ T Cells during Congenital Cytomegalovirus Infection.

The most common congenital viral infection is CMV, which leads to numerous neurologic disabilities. Using a mouse model of congenital CMV, we previously determined that Ag-specific CD8+ T cells traffic to the brain in a CCR9-dependent manner. The mechanism by which these CD8+ T cells acquire a CCR9-dependent "brain-tropic" phenotype remains unclear. In this study, we identify the key factor that imprints brain homing specificity on CD8+ T cells, the source of production, and the location where CCR9 expression is induced. Specifically, we discovered that CCR9 is induced on CD8+ T cells by retinoic acid-producing CD8α+ dendritic cells in the cervical lymph node postinfection. We found that retinoic acid is important for CD8+ T cells to establish tissue residency in the brain. Collectively, our data expand the role of retinoic acid during infection and mechanistically demonstrate how CD8+ T cells are primed to protect the brain during congenital viral infection.

Changing Epidemiology of Hand, Foot, and Mouth Disease Causative Agents and Contributing Factors.

Hand, foot, and mouth disease (HFMD) is a common viral infection primarily affecting children. It causes vesicles on the skin and inside the mouth. Although most cases get better on their own, severe cases can lead to complications such as brain stem encephalitis, meningoencephalitis, acute flaccid paralysis, and pulmonary edema. Hand, foot, and mouth disease is caused by various enteroviruses, with enterovirus A71 (EV-A71) and coxsackievirus A16 being the most common. However, recent studies have shown a shift in the molecular epidemiology of HFMD-causing pathogens, with coxsackievirus A6 and coxsackievirus A10 causing more infections. In addition, extensive recombination events have been identified among enterovirus strains, which may have a role in faster evolution and extinction of dominant enterovirus serotypes. Other strains of enterovirus can also cause severe complications, and there has been an increase in mortality associated with brain stem encephalitis in children under 3 years of age and teenagers. Currently, there are no effective antiviral therapies available to treat enterovirus infections. Vaccines against EV-A71 have been approved and are now used in mainland China. Studying the changing epidemiology of HFMD pathogens and the evolution patterns of its causative agents is crucial in developing effective prevention and control strategies. Increased interest in the molecular epidemiology of HFMD causative agents has led to a better understanding of the critical drivers of HFMD outbreaks, which can inform efforts to prevent and control the disease.