Transmission of monkeypox virus through the saliva and air that need careful management.

Dear Editor, The ongoing outbreak of monkeypox is believed to be predominantly transmitted through direct contact with lesions or infected bodily fluids, with possible involvement of fomites and large respiratory droplets1–5. We read with great interest three letters to the editor entitled “Salivary transmission of monkeypox virus – a potential possibility that needs careful management?,” “Can monkeypox virus be transmitted through the air?,” and “Should not airborne transmission be ignored in the 2022 monkeypox outbreak?” recently published in the International Journal of Surgery6–8. Due to the lack of direct evidence in the letters, the authors only put forward the hypothesis that the monkeypox virus (MPXV) can be transmitted through oral saliva and air, respectively6–8. In fact, the detection of MPXV DNA in the saliva was reported a little earlier in the previous studies9–11, before the time (6 September 2022) of the letter submitted by Ganapathy et al.6 Furthermore, the evidence on transmission of MPXV through the saliva and air are newly reported in the literature12,13. The current correspondence attempts to conduct a compact review of PubMed and Web of Science online databases of studies reporting the evidence on the detection of MPXV in saliva and air, so as to improve knowledge on the transmission and management of the virus. As for salivary transmission of MPXV, there are 32 cases studied in four existing studies (Table 1). Of these, the virus DNA in saliva samples of 30 cases was positively detected. The high concordance (93.75%) of MPXV infection between saliva and skin lesion, indicating that saliva-based tests may be a viable method for MPXV DNA detection. Ganapathy et al.6 stated that medical literature demonstrating monkeypox in saliva is unclear. Nowadays, MPXV in the saliva is demonstrated and salivary transmission should be substantial. Compared with MPXV detection sampling from anatomical sites, salivary diagnostics has some advantages, such as noninvasive, easy collection, even self-collection, less exposure of healthcare workers and risk of cross-infection, no need of specific instruments. More importantly, the positive prevalence (93.75%) and viral load (median Ct, 27) of MPXV DNA test in saliva (Table 1) was reported to be higher than those in other bodily fluids, such as semen, blood, urine 14. In addition to the diagnosis itself, the research on molecular feature of the saliva containing cytokines, chemokines, immunoglobulins, proteomic, and metabolomics at different times of disease course in cases of monkeypox will help understanding molecular changes of transmissible viral form. Highlights Monkeypox virus (MPXV) in saliva is demonstrated and salivary transmission is substantial. MPXV in air samples is demonstrated and the evidence on airborne transmission is substantial. Saliva is a promising sampling material for diagnosis and for public health goals for MPXV testing. Airborne transmission of MPXV is of public health importance that inform policy to protect health-care workers. Table 1 - Current evidence on the detection of monkeypox virus DNA in saliva or air specimens in literature References Country Number of specimens tested Specimen type Detection method No. positive tests Positive (%) Mean C t values Antinori et al. 9 Italy 1 Saliva RealStar Orthopoxvirus PCR Kit (Altona Diagnostics GmbH); Monkeypox-specific Generic Real-Time PCR Assay within TNF Alpha Gene 1 100 27.1 Peiró-Mestres et al. 10 Spain 12 Saliva Commercial Orthopox generic real-time PCR assay (Lightmix Roche Diagnostics); Monkeypox-specific Generic Real-Time PCR Assay within TNF Alpha Gene 12 100 29.1 Tan et al. 11 Canada 1 Saliva Monkeypox infection was confirmed by real-time PCR 1 100 – Allan-Blitz et al. 12 USA 18 Saliva Acrometrix Monkeypox Thermo Control+Human DNA Control (ThermoFisher Scientific Inc. Waltham, MA, USA) Genomic DNA from a prior case of monkeypox (Monkeypox Virus; USA-2003-BEI-NR-4928) 16 88.90 26.6 Gould et al. 13 UK 20 Air Air sampling using the MD8 Airport (with gelatine filters, flow rate 50 l/min for 10 min; Sartorius, Goettingen, Germany); Monkeypox-specific Real-Time PCR Assay 5 25 35.5 Ct, quantitative PCR crossing threshold value of moneypox DNA detected. As for airborne transmission of MPXV, there was theoretical risk of airborne transmission but lack of direct evidence on positive air samples or viable MPXV detected in environmental air where patients with monkeypox have been managed, before the time of the letter submitted by Wang et al.7 and Saied 8. Engrossingly, MPXV in air samples is demonstrated and the substantial evidence on airborne transmission is contributed by Gould et al.13. The authors report for the first time the detection of MPXV DNA and viable virus in air samples collected at distances of greater than 1.5 m from the patient’s bed and at a height of about 2 m supports the theory that MPXV can be present in either aerosols or suspended skin particles or dust containing virus, and not only in large respiratory droplets that fall to the ground within 1–1.5 m of an infected individual. MPXV DNA is also detected on the personal protective equipment (PPE) of healthcare workers and in areas used for the removal of PPE 13. These evidence supports the use of PPE, including respiratory protection equipment, regular surface cleaning, and appropriate doffing, and the disposal of materials that are likely to be contaminated. Further investigation should consider the effectiveness of cleaning protocols and doffing procedures in decontaminating environments, and explore further the risk of respiratory transmission. Understanding the mode of transmission could allow for the development of proper interventional approaches to reduce the intensity of the current outbreak 15. Taken together, the current evidence supports MPXV transmission through the saliva and air that need careful management, especially in the current 2022 outbreak of disease. Saliva is a promising sampling material for diagnosis of monkeypox infection and may emerge as a viable sample for public health goals for MPXV testing. Notably, it is of public health importance that airborne transmission of MPXV is demonstrated in hospital settings, which should inform policy to protect healthcare workers and reduce the risk of nosocomial transmission of monkeypox. Ethical approval Not applicable. Sources of funding The authors are supported by Science and Technology Commission of Shanghai Municipality (21XD1432900), Hainan Province Clinical Medical Center for Stomatology, Hainan Natural Science Foundation (822MS191), and Innovative Research Team of High-Level Local Universities in Shanghai (SSMU-ZLCX20212300). Authors’ contribution X.Y. and Q.L.: screening and data extraction; writing – original draft. F.X. and W.L.: conceptualization and writing – review and editing. Conflicts of interest disclosure The authors declare that they have no financial conflict of interest with regard to the content of this report. Research registration unique identifying number (UIN) Not applicable. Guarantor Wei Liu.