Pushing the frontiers of military medical excellence:updates,progress and future needs

Since its establishment in 2014,Military Medical Research has come a long way in becoming a premier journal for scientific articles from various different specialties,with a special emphasis on topics with military relevance.The field of military medicine may be obscure,and may not be readily encountered by the typical clinician on a day-today basis.This journal aims not only to pursue excellence in military research,but also to keep current with the latest advancements on general medical topics from each and every specialty.This editorial serves to recap and synthesize the existing progress,updates and future needs of military medical excellence,discussing foremostly the unique traits of literature published in this journal,and subsequently presenting the discourse regarding wartime and peacetime medicine,the role of the military in a public health emergency,as well as wound healing and organ regeneration.Special attention has been devoted to military topics to shed light on the effects of Chemical,Biological,Radiological and Explosive warfare,environmental medicine and military psychiatry,topics which rarely have a chance to be discussed elsewhere.The interconnectedness between military combat and soldier physical and mental well-being is intricate,and has been distorted by pandemics such as coronavirus disease 2019(COVID-19).This journal has come a long way since its first article was published,steadily contributing to the existing knowledge pool on general medical topics with a military slant.Only with continuous research and sharing,can we build upon the work of the scientific community,with hopes for the betterment of patient care.

Understanding neutralising antibodies against SARS-CoV-2 and theirimplications in clinical practice

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is a newly identified member of the coronavirus family that has caused the coronavirus disease 2019 (COVID-19) pandemic. This rapidly evolving and unrelenting SARS-CoV-2has disrupted the lives and livelihoods of millions worldwide. As of 23 August 2021, a total of 211,373,303 COVID-19cases have been confirmed globally with a death toll of 4,424,341. A strong understanding of the infection pathway of SARS-CoV-2, and how our immune system responds to the virus is highly pertinent for guiding the development and improvement of effective treatments. In this review, we discuss the current understanding of neutralising antibodies(NAbs) and their implications in clinical practice. The aspects include the pathophysiology of the immune response,particularly humoral adaptive immunity and the roles of NAbs from B cells in infection clearance. We summarise the onset and persistence of IgA, IgM and IgG antibodies, and we explore their roles in neutralising SARS-CoV-2, their persistence in convalescent individuals, and in reinfection. Furthermore, we also review the applications of neutralising antibodies in the clinical setting—from predictors of disease severity to serological testing to vaccinations, and finally in therapeutics such as convalescent plasma infusion.

Distinctive serotypes of SARS-related coronaviruses defined by convalescent sera from unvaccinated individuals

Multiple Omicron sub-lineages have emerged,with Omicron XBB and XBB.1.5 subvariants becoming the dominant variants globally at the time of this study.The key feature of new variants is their ability to escape humoral immunity despite the fact that there are limited genetic changes from their preceding variants.This raises the question of whether Omicron should be regarded as a separate serotype from viruses serologically clustered with the ancestral severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus.Here,we present cross-neutralization data based on a pseudovirus neutralization test using convalescent sera from naïve individuals who had recovered from primary infection by SARS-CoV-1 and SARS-CoV-2 strains/variants including the ancestral virus and variants Beta,Delta,Omicron BA.1,Omicron BA.2 and Omicron BA.5.The results revealed no significant cross-neutralization in any of the three-way testing for SARS-CoV-1,ancestral SARS-CoV-2 and SARS-CoV-2 Omicron subvariants.The data argue for the assignment of three distinct serotypes for the currently known human-infecting SARS-related coronaviruses.

Diagnostic performance of different specimens in detecting enterovirus A71 in children with hand,foot and mouth disease

Hand,foot and mouth disease(HFMD)is a major public health problem among children in the Asia-Pacific region.The optimal specimen for HFMD virological diagnosis remains unclear.Enterovirus A71(EV-A71)neutralizing antibody titres detected in paired sera were considered the reference standard for calculating the sensitivity,specificity,positive and negative predictive value of throat swabs,rectal swabs,stool,blood samples and cerebrospinal fluid(CSF)by RT-PCR or ELISA assay.In this study,clinical samples from 276 HFMD patients were collected for analysing the sensitivity of different kind of specimens.Our results showed that stool had the highest sensitivity(88%,95%CI:74%–96%)and agreement with the reference standard(91%).The order of diagnostic yield for EV-A71 infection was stool samplerectal swab>throat swab>blood sample>CSF sample,and using a combination of clinical samples improved sensitivity for enterovirus detection.The sensitivity of ELISA for IgM antibody detection in sterile-site specimens was significantly higher than that of RT-PCR(serum/plasma:62%vs.2%,CSF:47%vs.0%)(P<0.002).In conclusion,our results suggest that stool has the highest diagnostic yield for EV-A71-infected HFMD.If stool is unavailable,rectal swabs can be collected to achieve a similar diagnostic yield.Otherwise,throat swabs may be useful in detecting positive samples.Although IgM in blood or CSF is diagnostically accurate,it lacks sensitivity,missing 40%–50%of cases.The higher proportion of severe cases and shorter interval between onset and sampling contributed to the increase in congruency between clinical testing and the serological reference standard.

Dicoumarol is an effective post-exposure prophylactic for SARS-CoV-2 Omicron infection in human airway epithelium

Repurposing existing drugs to inhibit SARS-CoV-2 infection in airway epithelial cells(AECs)is a quick way to find novel treatments for COVID-19.Computational screening has found dicoumarol(DCM),a natural anticoagulant,to be a potential SARS-CoV-2 inhibitor,but its inhibitory effects and possible working mechanisms remain unknown.Using air-liquid interface culture of primary human AECs.

Modular micro-PCR system for the onsite rapid diagnosis of COVID-19

Effective containment of the COVID-19 pandemic requires rapid and accurate detection of the pathogen.Polymerase chain reaction(PCR)remains the gold standard for COVID-19 confirmation.In this article,we report the performance of a cost-effective modular microfluidic reverse transcription(RT)-PCR and RT-loop mediated isothermal amplification(RTLAMP)platform,Epidax®,for the point-of-care testing and confirmation of SARS-CoV-2.This platform is versatile and can be reconfigured either for screening using endpoint RT-PCR or RT-LAMP tests or for confirmatory tests using realtime RT-PCR.Epidax®is highly sensitive and detects as little as 1 RNA copy perµL for real-time and endpoint RT-PCR,while using only half of the reagents.We achieved comparable results with those of a commercial platform when detecting SARS-CoV-2 viruses from 81 clinical RNA extracts.Epidax®can also detect SARS-CoV-2 from 44 nasopharyngeal samples without RNA extraction by using a direct RT-PCR assay,which shortens the sample-to-answer time to an hour with minimal user steps.Furthermore,we validated the technology using an RT-LAMP assay on 54 clinical RNA extracts.Overall,our platform provides a sensitive,cost-effective,and accurate diagnostic solution for lowresource settings.