Since May 2022, the mpox outbreak (formerly known as monkeypox) has suddenly and unexpectedly spread in nonendemic countries, suggesting that there may have been some undetected transmissions. Mpox is a viral zoonotic disease endemic in Central and West Africa that is caused by the Mpox virus, which belongs to the Orthopoxvirus genus and Poxviridae family. The clinical manifestations of mpox infection are milder than those of smallpox, and the incubation time of mpox varies from 5 to 21 days.¹ The symptoms of human disease typically begin with fever, chills, lymphadenopathy, headache, backache, muscle aches, and fatigue during the prodrome phase (the time before the appearance of a rash).^{2, 3} The prodrome phase is often followed by maculopapular rash lesion diameters ranging from 0.2 to 1 cm.⁴ The rashes primarily focused on the face, neck, and legs.

Based on molecular analysis, there are two major genetic clades that represent the mpox virus: Clade I (formerly the Congo Basin clade OR the Central African clade) and Clade II (formerly the West African clade).^{2, 5, 6} Clade I has higher mortality rates and more pronounced increased transmissibility, with more human-to-human transmission and more severe clinical manifestations. In contrast, Clade II has lower mortality rates, decreased transmissibility, and milder illness.⁷ The estimated case fatality rate or CFR of Clade II is less than 4%, compared with Clade I, which is up to 10%.^{8, 9} In relation to the geographic origin, Clade II is dichotomized into Clade IIa and Clade IIb. Alarmingly, the clade IIb, responsible for the mpox outbreak in 2022, revealed different lineages in nonendemic countries during the 2022 mpox outbreak based on genetic features, such as A.1. A.1.1, A.2, A.3, and B.1.^9-14 The B.1 lineage is to blame for the present Mpox outbreak.

Yuan et al.¹⁵ reported that the current mpox outbreak in America and Europe is multi-originated, suggesting that the transmission paths might be very complex as well. The Clade II demonstrated human-to-human transmission via different routes of transmission. Previously, human-to-human transmission occurred during the outbreak of mpox in Nigeria in 2017–2018,¹⁶ and in the Democratic Republic of the Congo (DRC),^{17, 18} but in lesser prevalence than the 2022 mopx outbreak. Intriguingly, it was unclear if the mpox virus had been transmitted through the air or without symptoms.¹⁹

Although it may be premature to assume that mpox can travel through the air, it is necessary to take such a possibility amid reported asymptomatic infections, misdiagnosis, inadequate research, limited resources for testing, and surveillance and growing data about the disease^{20, 21}; therefore, the possibility of contracting human mpox through the respiratory system is unknown,²² but cannot be ruled out. Despite the existing epidemiological investigations that haven't found a link between airborne transmission among the human population in the current and previous mpox outbreaks, infection via aerosolized mpox virus has been reported in nonhuman primates (Clade I - Cynomolgus macaques [Macaca fascicularis]) (Table 1).^{19, 24-26} I have reviewed recent evidence regarding the detection of the mpox virus (clade IIb) in air samples collected from the patient's environment during the 2022 mpox outbreak (Table 2). Mpox virus can live in aerosols for up to 90 h and is stable in the environment.²³ In 2003, it was hypothesized that mpox was spread from prairie dogs to people by indirect contact, probably through exposure to fomites or aerosols. In the prairie dog model of infection, it is proved that the mpox virus can spread via the respiratory route more easily for Clade I than Clade II.³³ In addition, patients with mpox admitted to specialized high-consequence infectious disease centers between 2018 and 2021 showed prolonged upper respiratory tract viral DNA shedding after skin lesion resolution.³⁴

Viable (infectious) and nonviable viruses cannot be distinguished by PCR testing; therefore, it is unknown whether asymptomatic or subclinical infections are fueling the present global outbreak.³⁵ To validate the existence of an infectious virus in chosen positive samples, a virus culture should be carried out.³⁶ The infection-competent virus was detected in the air in an air sample collected during bedding change in the UK-based study,³⁰ and nonviable mpox DNA virus was detected in the Spain-based study.³¹ While aerosols taken from a hospital isolation room holding a mpox patient contained high concentrations of mpox virus DNA mpox (using nanofiber filters).³¹ Air samples did not reveal any infectious mpox virus, which might be because the low viral loads captured from the air weren't sufficient to recover the virus in cell cultures.³¹ In addition, the detection of viable viruses depends on the filters used to capture airborne viruses. Viable mpox virus DNA was found in the exhaled droplet from infected patients (6.25% in Spain-based study³¹). In outpatient settings, the two previous studies (France and Spain) focused on air sampling and found positive qPCR results, but neither study found an infectious virus.^{31, 32} The replication-competent mpox virus in the air collected during bed linen changes leads some researchers to hypothesize that the viruses found in the air sample may actually correspond to viruses that have been re-aerosolized from fomites rather than those produced by the patient's breathing.³⁰ Noteworthy, environments of mpox cases' household and patient care facilities have reportedly been contaminated with mpox virus DNA³⁷ as well as in places where they spent less time, like high-touchpoint regions like door handles and light switches.³⁸ Widespread surface contamination (56 [93%] of 60 samples were positive) was found in occupied patient rooms, on healthcare worker PPE after use, and in PPE donning areas.³⁰ As a result, combining surface and air sampling in future research may be able to yield more information.²²

De Baetselier and colleagues³⁹ found that mpox virus can transmit from asymptomatic patients to close contacts, indicating silent spread. In France, the intra-familial transmission of mpox virus was reported.⁴⁰ In Belgium, the primary symptom of mpox virus infection was urethritis without skin lesions.⁴¹ Multiple PCR-positive samples have been reported in asymptomatic individuals.⁴² It is believed that people who are asymptomatic or paucisymptomatic may spread the mpox virus.⁴³ In addition, Maruotti et al., found that undetected mpox cases are reported in many countries, suggesting an increase in the number of infections than the observed number.⁴⁴ So, asymptomatic infections can contribute to viral spread in the community. Recently, it was found that mpox virus can survive on surfaces for weeks, while it is unknown if the virus remains infectious for this duration.^45-47 Strikingly, the USA and the Democratic Republic of the Congo both reported asymptomatic mpox infections.¹⁹ Mpox infection in smallpox-vaccinated people was observed to cause little or no cutaneous lesions.⁴⁸ Additionally, serological surveys revealed asymptomatic human mpox infections in people who had received smallpox vaccinations and in some people who had not^49-51; however, it is not known how often the asymptomatic infection may occur.

It is currently thought that certain activities could cause the mpox virus to be suspended in the air.³⁰ Practices that could aerosolize virus particles, such as shaking bed linens or an aerosol-generating procedure (such as intubation)⁵² or such as opening of doors,²⁹ vacuum cleaning and transport of contaminated items for washing,³⁸ should be avoided; therefore, the need for healthcare professionals to wear the proper respiratory protection when conducting tasks that could cause infectious material to be suspended in polluted surroundings is essential.³⁰ Further studies are needed to evaluate the extent to which the presence of mpox virus DNA in the air could affect immunocompromised patients in healthcare facilities, and further epidemiological studies are crucial, especially in Africa. Currently, Africa is still experiencing outbreaks of clade I and clade II infections, and both have different routes of transmission; therefore, study designs and research goals must take into account these priorities.⁵³

In conclusion, further longitudinal studies are required to reveal the infectiousness of mpox virus DNA in air samples via cultures of mpox virus from air samples with high viral loads is crucial amid current evidence, especially among vulnerable individuals and in Africa. Taking account of the discovered Clade IIb lineages, such as B1, A1, and A3; therefore, gained data about clade IIb detection in the air should lead us to open the brackets regarding respiratory transmission and also identify the risk factors related to mpox clades and even lineages.

CONFLICT OF INTEREST STATEMENT

The author declares no conflict of interest.