Most cases are usually mild and self-limiting, and most patients will recover within 2 to 4 weeks without treatment.

  • Typically, more than 90% of survivors have no complications, regardless of smallpox vaccination status. In survivors who do develop long-term complications, the most common sequelae are disfiguring scarring of the skin (including pitted scars) and blindness.[1]

  • The acute infectious illness results in immunity following recovery. Relapse of disease is rare, but is possible. One UK patient experienced a mild relapse 6 weeks after hospital discharge in 2019. The relapse was short, and was not associated with detectable viraemia.[214]

  • The occurrence of a second febrile period when the lesions become pustular has been associated with deterioration of the patient’s general condition.[129]

Severe or complicated disease and death occurs more commonly in younger children and immunocompromised people.

  • Most reported deaths, prior to the 2022 global outbreak, occurred in younger children and immunocompromised people (e.g., poorly controlled HIV infection).[1]

  • In the early years of human infection, 100% of deaths were in children <10 years of age. However, between 2000 and 2019, children <10 years of age accounted for only 37.5% of deaths.[4] 

  • Patients with fatal disease had higher viral loads of the virus in their blood, maximum skin lesion count, and elevated transaminases.[1]

  • Severe complications and sequelae were more common among unvaccinated patients (74%) compared with vaccinated patients (40%).[129]

Case fatality rates (CFRs) vary according to virus clade, geographical location, and availability of medical facilities, and are vulnerable to case ascertainment bias during outbreaks.

  • Historically, the CFR of the Clade I virus has been estimated to be 1% to 10%, while the CFR of the Clade IIa virus has been estimated to be 1.4% to 3%.[1]​ The estimated pooled CFR was 8.7% for both clades in one systematic review (10.6% for Clade I and 3.6% for Clade IIa).[4]​ The overall CFR was 0% in an outbreak in the US in 2003.[31]

  • Overall mortality has decreased in the 2022 global outbreak compared with previous outbreaks.[11]​ The overall CFR is 0.09% (as of 20 January 2023).[7] Fatalities due to the Clade IIb virus are rare. Causes of death have included multi-organ failure and encephalitis.[239][240] Whether mortality is associated with any specific factors is currently unknown.

  • An apparent case of reinfection has been reported 4 months after recovery from initial infection. Further research is required on immunity after recovering from infection.[241]

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