Varicella-zoster virus meningitis with hypoglycorrhachia: A case report

BACKGROUND Varicella-zoster virus(VZV)is a common viral infection,but meningitis is a rare complication of VZV infection.The cerebrospinal fluid glucose of viral meningitis is usually within the normal range,which is different from bacteria,fungi,and cancerous meningitis.This paper reports a case of VZV meningitis with hypoglycorrhachia and the relevant literature was reviewed.CASE SUMMARY We report a case of an immunocompetent 39-year-old male,presenting with severe headache and fevers,without meningeal signs or exanthem,found to have VZV meningitis by the metagenomic next-generation sequencing of cerebrospinal fluid.The cerebrospinal fluid analysis revealed hypoglycorrhachia(cerebrospinal fluid glucose of 2.16)and he was treated successfully with intravenous acyclovir.Our literature review identified only ten cases diagnosed with VZV meningitis with hypoglycorrhachia previously reported to date in the English literature whose cerebrospinal fluid glucose was from 1.6 to 2.7mmol/L,with a ratio of cerebrospinal fluid to serum glucose from 0.30 to 0.49.CONCLUSION Although rare,the cerebrospinal fluid of patients with VZV meningitis may have hypoglycorrhachia,which broadens the understanding of the disease.

Varicella-zoster virus-associated meningitis,encephalitis,and myelitis with sporadic skin blisters:A case report

BACKGROUND Varicella-zoster virus(VZV)generally causes chickenpox at first infection in childhood and then establishes latent infection in the dorsal root ganglia of the spinal cord or other nerves.Virus reactivation owing to an impaired immune system causes inflammation along spinal nerves from the affected spinal segment,leading to skin manifestations(herpes zoster).Viremia and subsequent hematogenous transmission and nerve axonal transport of the virus may lead to meningitis,encephalitis,and myelitis.One such case is described in this study.CASE SUMMARY A 64-year-old man presented with dysuria,pyrexia,and progressive disturbance in consciousness.He had signs of meningeal irritation,and cerebrospinal fluid(CSF)analysis revealed marked pleocytosis with mononuclear predominance and a CSF/serum glucose ratio of 0.64.Head magnetic resonance imaging revealed hyperintense areas in the frontal lobes.He had four isolated blisters with papules and halos on his right chest,right lumbar region,and left scapular region.Infected giant cells were detected using the Tzanck test.Degenerated epidermal cells with intranuclear inclusion bodies and ballooning degeneration were present on skin biopsy.Serum VZV antibody titers suggested previous infection,and the CSF tested positive for VZV-DNA.He developed paraplegia,decreased temperature perception in the legs,urinary retention,and fecal incontinence.The patient was diagnosed with meningitis,encephalitis,and myelitis and was treated with acyclovir for 23 days and prednisolone for 14 days.Despite gradual improvement,the urinary retention and gait disturbances persisted as sequelae.CONCLUSION VZV reactivation should be considered in differential diagnoses of patients with sporadic blisters and unexplained central nervous system symptoms.

Microbiology laboratory and the management of motherchild varicella-zoster virus infection

Varicella-zoster virus, which is responsible for varicella(chickenpox) and herpes zoster(shingles), is ubiquitous and causes an acute infection among children, especially those aged less than six years. As 90% of adults have had varicella in childhood, it is unusual to encounter an infected pregnant woman but, if the disease does appear, it can lead to complications for both the mother and fetus or newborn. The major maternal complications include pneumonia, which can lead to death if not treated. If the virus passes to the fetus, congenital varicella syndrome, neonatal varicella(particularly serious if maternal rash appears in the days immediately before or after childbirth) or herpes zoster in the early years of life may occur depending on the time of infection. A Microbiology laboratory can help in the diagnosis and management of mother-child infection at four main times:(1) when a pregnant woman has been exposed to varicella or herpes zoster, a prompt search for specific antibodies can determine whether she is susceptible to, or protected against infection;(2) when a pregnant woman develops clinical symptoms consistent with varicella, the diagnosis is usually clinical, but a laboratory can be crucial if the symptoms are doubtful or otherwise unclear(atypical patterns in immunocompromised subjects, patients with post-vaccination varicella, or subjects who have received immunoglobulins), or if there is a need for a differential diagnosis between varicella and other types of dermatoses with vesicle formation;(3) when a prenatal diagnosis of uterine infection is required in order to detect cases of congenital varicella syndrome after the onset of varicella in the mother; and(4) when the baby is born and it is necessary to confirm a diagnosis of varicella(and its complications), make a differential diagnosis between varicella and other diseases with similar symptoms, or confirm a causal relationship between maternal varicella and malformations in a newborn.

Review of varicella-zoster virus infections in pregnant women and neonates

Even though varicella is rare in pregnancy, the disease can lead occasionally to disastrous illnesses for both the mother and her neonate. By contrast, normal zoster is not associated with special problems during pregnancy and peri- natal period. Pregnant women, who contract varicella, are at risk of varicella pneumonia which must be regarded as medical emergency. At any stage during pregnancy, chickenpox may cause intrauterine infection. The consequences for the fetus depend on the time of maternal disease. During the first two trimesters, maternal varicella may result in congenital varicella syndrome which may occur in nearly 2%. Typical symptoms are skin lesions in dermatomal distribution, neurological defects, eye diseases, and skeletal anomalies. Maternal infection near term is associated with a substantial risk of intrauterine acquired neonatal chickenpox in the neonate. If the mother develops varicella rash between day 4 (5) ante partum and day 2 post partum, generalized neonatal varicella leading to death in about 20% of the cases has to be expected. The present paper reviews the clinical consequences and the currently available concepts of prevention, diagnosis, and therapy of varicella-zoster virus infections during pregnancy.

Varicella-zoster virus meningitis after spinal anesthesia:A case report

BACKGROUND Headache is a common complication of regional anesthesia.The treatment of post spinal anesthesia headache varies depending on the cause.Although meningitis is rare,it can cause significant harm to the patient.Post dural puncture headache and septic meningitis are the most commonly suspected causes of post spinal anesthesia headache;however,other causes should also be considered.CASE SUMMARY A 69-year-old woman was scheduled for varicose vein stripping surgery under spinal anesthesia.The procedure was performed aseptically,and surgery was completed without any complications.After 4 d,the patient visited the emergency room with complaints of headache,nausea,and anorexia.Clinical examination revealed that the patient was afebrile.Considering the history of spinal anesthesia,post dural puncture headache and septic meningitis was initially suspected,and the patient was treated with empirical antibiotics.Subsequently,varicella-zoster virus PCR test result was positive,and all other test results were negative.The patient was diagnosed with meningitis caused by varicella-zoster virus and was treated with acyclovir for 5 d.The headache improved,and the patient was discharged without any problems.CONCLUSION Viral meningitis due to virus reactivation may cause headache after regional anesthesia.Therefore,clinicians should consider multiple etiologies of headache.

Dynamical study of varicella-zoster virus model in sense of Mittag-Leffler kernel

The primary varicella-zoster virus(VzV)infection that causes chickenpox(also known as varicella),spreads quickly among people and,in severe circumstances,can cause to fever and encephalitis.In this paper,the Mittag-Leffler fractional operator is used to examine the mathematical representation of the vzV.Five fractional-order differential equations are created in terms of the disease's dynamical analysis such as S:Susceptible,V:Vaccinated,E:Exposed,I:Infectious and R:Recovered.We derive the existence criterion,positive solution,Hyers-Ulam stability,and boundedness of results in order to examine the suggested fractional-order model's wellposedness.Finally,some numerical examples for the VzV model of various fractional orders are shown with the aid of the generalized Adams-Bashforth-Moulton approach to show the viability of the obtained results.

Insights into varicella-zoster virus assembly from the B-and C-capsid at near-atomic resolution structures

Varicella-zoster is a highly communicable virus that can be transmitted through the airborne route.About one quarter of people are infected with this virus.Previous studies have described the structure of A-capsid and a blurred reconstruction of the C-capsid with icosahedral symmetry.In this study,we have determined the more precise detailed structures of the varicella-zoster virus(VZV)B-and C-capsid in icosahedral symmetry using a combination of block-based reconstruction and symmetry relaxation strategies.In addition,we are reporting structural details of the portal vertex reconstructions in five-fold symmetry and portal reconstructions in twelve-fold symmetry.The structures unveil the basis for the high thermal stability of the VZV capsid.The conformational flexibility of structural elements of the capsid plays a role in the assembly of the capsid and drives processes critical for the viral life cycle.The results of the study open up new avenues for the development of drugs against a highly prevalent and contagious pathogen.

Ambispective epidemiological observational study of varicella-zoster virus infection: An 18 year-single-center Bulgarian experience

BACKGROUND Varicella(chickenpox)and herpes zoster(shingles)are outcomes of varicella-zoster virus(VZV)infection,and understanding their incidence trends is vital for public health planning.AIM To conduct an ambispective epidemiological study by analyzing the main epidemiological characteristics of VZV infection during an 18 year-period(2000-2018).METHODS We used descriptive and epidemiological methods to characterize chickenpox in Bulgaria,the city of Plovdiv and the region for a period of 18 years(2000-2018).RESULTS The average incidence of varicella-zoster infection for the period 2000–2018 in the Plovdiv region was estimated at 449.58‰.The highest relative share of the infection was assessed in the month of January at 13.6%,and the lowest in the months of August and September at 2.9%(both months).The age group most affected by the infection was 1-4 years,followed by 5-9 years.This corresponds to the so-called"pro-epidemic population"-a phenomenon typical for airborne infections,confirming their mass impact on the perpetuation of VZV infection.CONCLUSION Our findings reveal significant insights into VZV epidemiology,including age-specific incidence rates,clinical manifestations,and vaccination impact.This comprehensive analysis contributes to the broader understanding of VZV infec-tion dynamics and may inform evidence-based preventive measures.

Truncated glycoprotein E of varicella-zoster virus is an ideal immunogen for Escherichia coli-based vaccine design

Varicella-zoster virus(VZV)is a highly infectious agent responsible for both varicella and herpes zoster disease.Despite high efficacy,there remain safety and accessibility concerns with the licensed vaccines.Here,we sought to produce a VZV g E immunogen using an E.coli expression system.We found that the soluble expression and yield of g E protein could be enhanced via C-terminal truncations to the protein,thereby facilitating a robust and scalable purification process for the purpose of vaccine manufacturing.The lead truncated g E(aa 31–358),hereafter referred to as tg E,was a homogenous monomer in solution and showed excellent antigenicity.Finally,we assessed and compared the immunogenicity of tg E with commercial v Oka LAV and Shingrix vaccine.We found that aluminum-adjuvanted tg E was immunogenic as compared with v Oka LAV.When adjuvanted with AS01B,a two-dose immunization of tg E showed comparable or better potency in antibody responses and cell-mediated immunity with those of the Shingrix vaccine at the same dosage,especially in terms of the proportion of IFN-γ-expressing CD4^(+)T cells.In conclusion,this method of E.coli-mediate tg E expression offers a cost-effective and scalable strategy to generate an ideal VZV g E immunogen for the development of both varicella and zoster vaccines.

Immune Responses to Varicella-Zoster Virus Glycoprotein E Formulated with Poly(Lactic-co-Glycolic Acid) Nanoparticles and Nucleic Acid Adjuvants in Mice

The subunit herpes zoster vaccine Shingrix is superior to attenuated vaccine Zostavax in both safety and efficacy,yet its unlyophilizable liposome delivery system and the limited supply of naturally sourced immunological adjuvant QS-21 still need to be improved.Based on poly(lactic-co-glycolic acid)(PLGA)delivery systems that are stable during the lyophilization and rehydration process and using a double-emulsion(w/o/w)solvent evaporation method,we designed a series of nanoparticles with varicella-zoster virus antigen glycoprotein E(VZV-g E)as an antigen and nucleic acids including polyinosinic-polycytidylic acid(Poly I:C)and phosphodiester Cp G oligodeoxynucleotide(Cp G ODN),encapsulated as immune stimulators.While cationic lipids(DOTAP)have more potential than neutral lipids(DOPC)for activating g E-specific cell-mediated immunity(CMI)in immunized mice,especially when g E is encapsulated in and presented on the surface of nanoparticles,PLGA particles without lipids have the greatest potential to induce not only the highest g Especific Ig G titers but also the strongest g E-specific CMI responses,including the highest proportions of interferon-c(IFNc)-and interleukin-2(IL-2)-producing CD4?/CD8?T cells according to a flow cytometry assay and the greatest numbers of IFN-c-and IL-2-producing splenocytes according to an enzyme-linked immunospot(ELISPOT)assay.These results showed that immune-stimulating nucleic acids together with the PLGA delivery system showed promise as a safe and economical varicella and zoster vaccine candidate.

IFN-a production by human mononuclear cells infected with varicella-zoster virus through TLR9-dependent and-independent pathways

Understanding the defense mechanisms of the host of an organism is important for infection control.In previous studies,we demonstrated that interferon-a(IFN-a),but not IL-12,was produced by human peripheral blood mononuclear cells infected with varicella-zoster virus(VZV).Here,we investigated what kind of cell(s)and which signal molecule(s)are involved in IFN-a production.Using cell isolation and ELISA,we found that plasmacytoid dendritic cells(pDCs)were responsible for IFN-a production during VZV infection.We also found that Toll-like receptor 9(TLR9)was involved in VZV-induced IFN-a production because inhibitory CpG oligodeoxynucleotide inhibited IFN-a production.UV-inactivated VZV-induced IFN-a production was lower than that of active VZV,indicating another TLR9-independent pathway.Further studies demonstrated that double-stranded RNA-dependent protein kinase,but not DNA-dependent protein kinase was involved in VZV-induced IFN-a production.Together,these results suggest that pDCs play an important role in IFN-a production during VZV infection through TLR9-dependent and-independent pathways.

Varicella-zoster virus ORF7 interacts with ORF53 and plays a role in its trans-Golgi network localization

Varicella-zoster virus(VZV) is a neurotropic alphaherpesvirus that causes chickenpox and shingles. ORF7 is an important virulence determinant of VZV in both human skin and nerve tissues,however, its specific function and involved molecular mechanism in VZV pathogenesis remain largely elusive. Previous yeast two-hybrid studies on intraviral protein-protein interaction network in herpesviruses have revealed that VZV ORF7 may interact with ORF53, which is a virtually unstudied but essential viral protein. The aim of this study is to identify and characterize VZV ORF53, and to investigate its relationship with ORF7. For this purpose, we prepared monoclonal antibodies against ORF53 and, for the first time, characterized it as a ~40 k Da viral protein predominantly localizing to the trans-Golgi network of the infected host cell. Next, we further confirmed the interaction between ORF7 and ORF53 by co-immunoprecipitation and co-localization studies in both plasmid-transfected and VZV-infected cells. Moreover, interestingly, we found that ORF53 lost its trans-Golgi network localization and became dispersed in the cytoplasm of host cells infected with an ORF7-deleted recombinant VZV, and thus ORF7 seems to play a role in normal subcellular localization of ORF53. Collectively, these results suggested that ORF7 and ORF53 may function as a complex during infection, which may be implicated in VZV pathogenesis.

Advances in Zika virus vaccines and therapeutics:A systematic review

Zika virus(ZIKV)is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide.Its wide transmission route and alarming spread rates are of great concern to the scientific community.Numerous trials have been conducted to develop treatment options for ZIKV infection.This review highlights the latest developments in the fields of vaccinology and pharmaceuticals developments for ZIKV infection.A systematic and comprehensive approach was used to gather relevant and up-to-date data so that inferences could be made about the gaps in therapeutic development.The results indicate that several therapeutic interventions are being tested against ZIKV infection,such as DNA vaccines,subunit vaccines,live-attenuated vaccines,virus-vector-based vaccines,inactivated vaccines,virus-like particles,and mRNA-based vaccines.In addition,approved anti-ZIKV drugs that can reduce the global burden are discussed.Although many vaccine candidates for ZIKV are at different stages of development,none of them have received Food and Drug Authority approval for use up to now.The issue of side effects associated with these drugs in vulnerable newborns and pregnant women is a major obstacle in the therapeutic pathway.

Overview of the immunological mechanisms in hepatitis B virus reactivation:Implications for disease progression and management strategies

Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

Autoimmune hepatitis and primary sclerosing cholangitis after direct-acting antiviral treatment for hepatitis C virus:A case report

BACKGROUND Chronic hepatitis C virus(HCV)infection is a major global health concern that leads to liver fibrosis,cirrhosis,and cancer.Regimens containing direct-acting antivirals(DAAs)have become the mainstay of HCV treatment,achieving a high sustained virological response(SVR)with minimal adverse events.CASE SUMMARY A 74-year-old woman with chronic HCV infection was treated with the DAAs ledipasvir,and sofosbuvir for 12 wk and achieved SVR.Twenty-four weeks after treatment completion,the liver enzyme and serum IgG levels increased,and antinuclear antibody became positive without HCV viremia,suggesting the development of autoimmune hepatitis(AIH).After liver biopsy indicated AIH,a definite AIH diagnosis was made and prednisolone was initiated.The treatment was effective,and the liver enzyme and serum IgG levels normalized.However,multiple strictures of the intrahepatic and extrahepatic bile ducts with dilatation of the peripheral bile ducts appeared on magnetic resonance cholangiopancreatography after 3 years of achieving SVR,which were consistent with primary sclerosing cholangitis.CONCLUSION The potential risk of developing autoimmune liver diseases after DAA treatment should be considered.

Complicated multiple organ infection of Purpureocillium lilacinum and varicella-zoster virus infection in a patient with Evans’ syndrome

Purpureocillium lilacinum(P lilacinum)is a rare pathogenic fungus,which mainly involves immunocompromised individuals.Here,we report a case of complicated multiple-organ infections involving skin,lungs,and spleen in a 63-year-old female with Evans’syndrome after 9 months of glucocorticoid treatment.Microbial examinations of skin biopsy and blood samples revealed Plilacinum infections.Posaconazole was effectivein this patient.During anti-fungitreatment,she developedvaricella-zoster virus infection and was diagnosed through next-generation sequencing examination.In conclusion,Plilacinum may affect different organ systems and is susceptible to posaconazole treatment.The molecular-based methods like microbial cell-free DNA sequencing could provide accurate and timely identification of a wide range of infections.

Current status of liver transplantation for human immunodeficiency virus-infected patients in China's Mainland

According to the report from the Chinese Center for Disease Control and Prevention,the prevalence of human immunodeficiency virus(HIV)infection exceeded 1.2 million individuals by the year 2022,with an annual increase of about 80000 cases.The overall prevalence of hepatitis B surface antigen among individuals co-infected with HIV reached 13.7%,almost twice the rate of the general population in China.In addition to the well-documented susceptibility to opportunistic infections and new malignancies,HIV infected patients frequently experience liver-related organ damage,with the liver and kidneys being the most commonly affected.This often leads to the development of end-stage liver and kidney diseases.Therefore,organ transplantation has emerged as an important part of active treatment for HIV infected patients.However,the curative effect is not satisfactory.HIV infection has been considered a contraindication for organ transplantation.Until the emergence of highly active anti-retroviral therapy in 1996,the once intractable replication of retrovirus was effectively inhibited.With prolonged survival,the failure of important organs has become the main cause of death among HIV patients.Therefore,transplant centers worldwide have resu-med exploration of organ transplantation for HIV-infected individuals and reached a positive conclusion.This study provides an overview of the current landscape of HIV-positive patients receiving liver transplantation(LT)in main-land China.To date,our transplant center has conducted LT for eight end-stage liver disease patients co-infected with HIV,and all but one,who died two months postoperatively due to sepsis and progressive multi-organ failure,have survived.Comparative analysis with hepatitis B virus-infected patients during the same period revealed no statistically significant differences in acute rejection reactions,cytomegalovirus infection,bacteremia,pulmonary infections,acute kidney injury,new-onset cancers,or vascular and biliary complications.

Nipah Virus Unveiled: A Review Article

Nipah virus (NiV) is a highly infectious zoonotic pathogen that poses a significant threat to human and animal health. First identified in Malaysia in 1998, NiV has since caused several outbreaks in Southeast Asia, with sporadic cases reported in Bangladesh and India. The virus is primarily transmitted to humans through direct contact with infected animals, primarily fruit bats, or through the consumption of contaminated fruits and their juices. NiV infection presents a wide spectrum of clinical features, ranging from mild respiratory illness to severe encephalitis, with a high case fatality rate. The incubation period typically ranges from 4 to 14 days, during which patients develop fever, headache, myalgia, and respiratory symptoms such as cough and sore throat. As the disease progresses, neurological signs become prominent, including altered consciousness, seizures, and focal deficits. Severe cases may exhibit acute respiratory distress syndrome and multi organ failure. Laboratory findings often include lymphocytopenia, thrombocytopenia, and elevated liver enzymes. Diagnosis of NiV infection requires specialized laboratory testing, including reverse transcription-polymerase chain reaction (RT-PCR) and serological assays. Currently, no specific antiviral treatment exists for NiV infection, and management primarily focuses on supportive care. Prevention and control strategies encompass public health interventions, surveillance, and raising awareness among healthcare providers and the general population. The emergence and re-emergence of NiV highlight the urgent need for continued research, improved diagnostic capabilities, and the development of effective vaccines and therapeutics to mitigate the impact of this deadly virus.

Epidemiological and Paraclinical Aspects of Helicobacter pylori Infection among Hepatitis B Virus Carriers in the Republic of Congo

Objective: Describe the epidemiological and paraclinical aspects of HP infection in hepatitis B virus carriers. Population and Method: This was a descriptive cross-sectional study running from January 1 to August 30, 2019, a period of 8 months. It took place in the Hospital Centers of the two major cities of Congo (Brazzaville and Pointe-Noire). The target population of our study consists of patients carrying HBV under antiviral treatment or not. Patients aged at least 18 years and consenting with a biological and morphological assessment were included. We did not include in our study patients taking or having taken antibiotics and/or PPIs less than 4 weeks ago. We excluded all patients who did not deposit fresh stools and those in whom stool extraction could not be done manually. The variables studied covered sociodemographic, clinical and paraclinical aspects. Data entry was done using Excel 8.0 software. Statistical analysis was carried out with SPSS 20.0 software. Results: During our study, we included 169 patients. The frequency of HPAG in the stools of HBV carriers in our study population was 63.9% (n = 109). Male patients represented 69% (n = 75) and female patients represented 31% (n = 34). The average age of the patients is 43.92 ± 13.51 years with extremes of 18 years and 80 years. Concerning profession, unemployed patients and those working in the private sector were the most represented in respectively 28.4% (n = 31) and 22.9% (n = 25) without statistical link. Households comprising between 4 - 10 people and the use of public latrines were the risk factors most represented in respectively 69% (n = 75) and 88% (n = 96) without statistical link. Clinically, hepatomegaly and signs of portal hypertension were most represented in 53% (n = 58) and 47% (n = 51). Biologically, HBV DNA was detectable in 60.5% of cases (n = 66).

Emerging role of liquid biopsy in rat sarcoma virus mutated metastatic colorectal cancer:A case report

BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT alone.On the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR antibodies.CASE SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May 2022.At the time of cell-free DNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and cetuximab.In neo-RAS wt patients treated with anti-EGFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EGFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EGFR(ongoing).CONCLUSION Our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.