A recent study published in Lancet microbe Evidence for respiratory transmission of smallpox is summarized.

Rapid transmission of clade II mpox virus (MPXV) in humans occurred in 2022, resulting in thousands of cases globally. Routes of acquisition of MPXV include percutaneous exposure (direct skin exposure), mucosal exposure (oral, vaginal, and rectal mucous membranes), and inhalation of infectious virus particles.
Sources of infection include humans, animals, and contaminated tools. In the current outbreak of smallpox, the prevalence of anogenital lesions in the cases indicates that sexual contact is the primary route of infection. In this study, the authors describe evidence of respiratory transmission of MPXV from studies conducted between 1961 and 2022.
MPXV respiratory transmission in animal models
Studies of nonhuman primates and prairie dogs have shaped understanding of smallpox transmission. These dogs are useful in studies because they are susceptible to infection, display longer incubation periods, and can transmit the virus. Furthermore, prairie dogs are the only small animals to develop the characteristic rash observed in cases of human smallpox infection. Non-human primates are also of value, given the disease’s genetic proximity and similar presentation to humans.
A study showed that experimental inoculation through the upper respiratory tract of prairie dogs could establish the infection model. In 2013, respiratory transmission with clade I MPXV was demonstrated in prairie dogs. Transmission to naive dogs was not detected with clade II MPXV. In the 1970s, studies in non-human primates also suggested respiratory transmission of MPXV.
Manifestations of the human respiratory system
Severe respiratory distress is observed in the late disease course with MPXV clade I infection. Oral lesions and oropharyngeal signs/symptoms were reported both historically and during the 2022 outbreak. Sore throat was commonly observed in up to 37% of cases in 2022. Cough was reported in approximately 50% of patients prior to 2022, but In 2022, it was less common, along with shortness of breath and nasal congestion.
Historical and recent studies have described viral isolations from oral/respiratory anatomic sites. In a case series in the United Kingdom (UK), clade II MPXV DNA was isolated from the upper respiratory tract when respiratory symptoms were absent and even after resolution of skin lesions. in some patients, virus secretion It persists from the upper respiratory tract for more than three weeks.
Outbreak of smallpox in humans
Most of the research on smallpox in humans before 2022 was done in Africans. Close contact within homes is involved in long chains of transmission spanning several generations. In the 2003 outbreak in the United States (USA), all people with symptoms of smallpox had contact with prairie dogs or contaminated tools.
Being in close proximity to the infected animal was not associated with MPXV infection. Moreover, healthcare professionals did not become infected, even when most reported infrequent use of an N95 respirator or surgical mask. Human-to-human transmission was documented during a re-emergence of smallpox in Nigeria in 2017 in five individuals, including one healthcare worker and four incarcerated individuals.
During 2018-21, eight travelers from Nigeria to the US, UK, Israel and Singapore were diagnosed with smallpox. Four were asymptomatic during the flight, and Contact tracing You have identified any additional cases. Notably, the use of face masks during flights in 2021 as part of public health measures against coronavirus disease 2019 (COVID-19) could have prevented respiratory transmission.
In endemic areas, healthcare workers are at greater risk than the general population. However, one study conducted in Colorado, United States in 2022 noted that healthcare workers who were exposed to cases of smallpox did not become infected. Outbreak and clinical data have shown that transmission of smallpox occurs during prolonged close contact, and human-to-human transmission has not been reported in residential/congregate settings.
Concluding remarks
Together, the authors summarized the different types of evidence to understand the contribution of respiratory transmission to the spread of smallpox. Respiratory symptoms and isolation of viral DNA from the respiratory tract suggest respiratory transmission but do not definitively reflect respiratory transmission.
In addition, environmental monitoring studies have observed MPXV competent to replicate on surfaces and in the air, but the presence of the virus does not imply infection or transmission. Furthermore, outbreak analyzes with improved documentation of exposure history can help determine the final mode of transmission. So far, the odds of respiratory transmission seem low based on the available evidence, but studies should continue to evaluate this possibility.