Pathogenic infection is a leading cause of disease and remains a severe problem for public health, which is involved in more than 20% of deaths per year globally. To accurately identify pathogens and precisely treat the disease, mNGS was initiated at the right moment. The utility of mNGS in providing clinically actionable information was first approved in a 14-year-old boy with neuroleptospirosis in 2014. At present, an increasing number of clinical cohort studies and case reports have confirmed the value of mNGS in pathogen diagnosis. However, the studies on mNGS are mostly comprised of case reports and cohort studies. To the best of our knowledge, this is the first bibliometric analysis focused on mNGS in pathogen detection.
The number of publications significantly increased since 2014. After the first clinical use, a large number of cases have been diagnosed using the new tool, and as a result, more studies were published. In addition to pathogen diagnosis, the use of mNGS in other fields also contributed to the increasing number of publications, such as the surveillance of antimicrobial resistance in the food supply, prediction of the cause of infection, and evaluation of risk. The total citations had a similar trend to the publications. However, there are some fluctuations that may be caused by some extremely highly cited studies in certain years. The classification of the study types revealed that researchers mainly focus on the utility of mNGS in some notable cases and assess the diagnostic performance in some infectious diseases via cohort studies, such as TB and meningitis. With the large number of original articles, some reviews and meta-analysis will be published to summarize the development or efficacy of mNGS in the future.
The studies were mostly published in journals related to general and integrative medicine (Frontiers in Medicine, Annals of Translational Medicine) and infectious diseases (Frontiers in Cellular and Infection Microbiology, Infection and Drug Resistance, BMC Infectious Diseases). This illustrates that the application of mNGS is currently limited in infectious diseases now. Frontiers in Cellular and Infection Microbiology was the most popular cited journal, and also ranked 6th in the co-cited journals, which means it is vital in this field. Clinical Infectious Diseases ranked first in co-cited journals with high IF (20.999). The average IF of the top 10 popular journals was 5.948 and that of the top 10 co-cited journals was 31.165. More articles can be published in more fields in the future based on these high-quality references.
Our study showed that the publications are from many countries. However, People R China and the USA showed such a powerful influence that publications from People R China accounted for approximately 70% of the total. This may be related to the epidemiology in China. Although China has achieved great economic, public health, and healthcare development after the Severe Acute Respiratory Syndrome outbreak in 2003, there are still various infectious diseases. Second, owing to the complex ecological environment, the spectrum of pathogens is broad and includes many rare pathogens. Since mNGS is effective for pathogen identification and can aid doctors in rapid and accurate diagnosis, it has attracted a great deal of attention with plenty of literature published in China. The USA is the birthplace of mNGS for pathogen detection and has lead to extensive cohort studies to examine the efficacy. Furthermore, the USA and People R China have a strong relationship in cooperation with other countries. It can be speculated that mNGS is widely clinically applied in China, and the basic molecular mechanism has been studied extensively in the USA. Additionally, according to the average citations, England ranked the top. The study published in 2009 by Adams et al. from England was the first study to detect pathogens using mNGS in the world with 244 citations, which lead to the highest average citations of England. With the effort of many countries, mNGS can be improved for better application.
Considering the research institutions, Zhejiang University, Fudan University, and BGI in China contributed significantly to this field, while the University of California San Francisco in the USA also played a key role. It can be concluded that collaboration among authors is relatively fixed and independent. This is possibly because mNGS is used for detecting rare pathogens, which are distributed regionally, such as leishmaniasis in the central and western regions of China, hepatic echinococcosis in cattle-producing areas, and Dengue fever in tropical areas. Furthermore, mNGS is still in the development stage and there is currently no deep cross-team collaboration at the moment, and different teams have different research focuses. However, the lack of communication and cooperation among institutions certainly limited the development in this field. Therefore, the exchanges of research findings and more cooperation are essential and the academic barriers should be reduced to promote the development of mNGS.
Based on the results of author analysis, authors from China occupy the vast majority, which is similar to the distribution of countries and institutions. Xia Han from Hugobiotech is the most productive with 14 publications, followed by Feng Jing from Beijing Chaoyang Hospital with 9. Chiu Charles from the University of California San Francisco is one the most influential researches in this field. He is the corresponding author of the first case report of mNGS by Wilson et al. which was published in New England Journal of Medicine as a milestone. Then, a clinical trial investigating the detection efficacy of mNGS in body fluids was published in Nature Medicine with a high IF (87.241) and citation.
Keywords can reflect the core contents and topics of the studies. Through the keyword analysis, the results showed that pneumonia, tuberculosis, central nervous system (CNS) infection, and children had a high frequency or upwards trend.
Pneumonia is one of the most common disease manifestations in respiratory infection and the leading cause of death, especially community acquired pneumonia. Since a variety of pathogens can cause pneumonia and some of the symptoms are nonspecific, the detection rate of traditional culture combined with clinical experience is still low and ineffective. mNGS has shown better diagnostic efficiency for pneumonia and other respiratory system infections. Chen et al. demonstrated that mNGS had high diagnostic accuracy in bronchoalveolar lavage fluid (BALF) with 78% sensitivity and 77% specificity. In a retrospective study focused on mixed respiratory infection cases, compared with the conventional method, the sensitivity was significantly higher (97.2% vs 13.9%, p < 0.001). However, the specificity was the opposite (63.2% vs 94.7%; p = 0.07). Besides, the prevalence of coronavirus disease 2019 (COVID-19) has also contributed to making pneumonia a hotspot in recent years. This novel coronavirus was identified by RNA-based mNGS and the genome was revealed to provide insights for future research. Additionally, acute respiratory distress syndrome (ARDS) in severe pneumonia, such as COVID-19, is critical and rapidly progresses, resulting in high morality and poor prognosis for survivors. mNGS is confirmed to be a valuable tool to improve the management of ARDS and provide better quality of life for survivors. In summary, mNGS is a promising technique to detect pathogens in pneumonia and other respiratory infections.
Similar to pneumonia, TB caused by MTB is another hot topic in mNGS. MTB diagnosis has been a challenge for decades. Because of the specific biological properties of MTB, the positive rate of culture is low and takes a long time. Thus, the diagnosis of TB is a problem that usually leads to TB-related death. mNGS was tested in pulmonary TB and showed outstanding performance in diagnosis with high sensitivity and specificity. In addition, the multiorgan lesions also contribute to diagnosis difficulty, especially extrapulmonary TB (EPTB). Pang et al. revealed that the positive rate for EPTB by traditional tests was only 12.8%. A retrospective study in China assessed the clinical efficacy of mNGS in EPTB diagnosis and found that the positive rate was significantly higher than other routine methods (p < 0.001). Another meta-analysis also proved that mNGS is more effective than traditional tests in TB meningitis. However, the detection threshold and the efficacy in TB-related coinfection are still controversial and deserve further research. All of the evidence indicated that mNGS is a potential resolution for TB diagnosis and more research is necessary in the future.
CNS infections are life-threatening, usually resulting in poor prognosis. Because of the lack of specificity in clinical presentation and cerebrospinal fluid (CSF) parameters, as well as the low pathogen content in CSF, diagnosis remains a challenge. Although the utility of mNGS matures in some samples such as blood and BALF, it remains unclear whether mNGS has better diagnostic efficiency in CSF. A meta-analysis focused on mNGS for bacterial meningoencephalitis elucidated that the diagnostic efficacy is satisfactory with an estimated AUC (area under curve) of the summary receiver operating characteristic curve of 0.91. However, since available evidence is divided and limited, more cohort studies or meta-analysis are expected to eliminate the discrepancy and present more comprehensive and reliable conclusions.