Crimean Congo Hemorrhagic Fever Virus for Clinicians—Virology, Pathogenesis, and Pathology

C rimean-Congo hemorrhagic fever (CCHF) was clinically categorized as a disease during World War II when, after being exposed to ticks, ≈200 soldiers from the Soviet Union stationed in the Crimean Peninsula during 1944-1945 developed hemorrhagic fever symptoms, as part of an illness initially termed Crimean hemorrhagic fever.Similar clinical features had been described in present-day Tajikistan and Uzbekistan as early as the 12th Century (1,2).An enveloped, single-stranded RNA virus isolated from an infected patient in 1967 was named Crimean hemorrhagic fever virus.Another virus (Congo virus) was identified following a hemorrhagic fever outbreak in the current Democratic Republic of the Congo (formerly Zaire) in 1956 (2).In the early 1970s, the name was changed to Crimean-Congo hemorrhagic fever virus (CCHFV), after Crimean hemorrhagic fever virus and Congo viruses were found to be serologically indistinguishable in 1967.Human CCHFV infection mainly occurs through the bite of an infected tick or exposure to blood or tissue from infected animals; human-to-human transmission, particularly in healthcare settings, has been reported (3-5).Approximately 10,000-15,000 CCHF cases are estimated to occur worldwide each year, but more definitive numbers are difficult to ascertain.Uncertainty arises because up to 88% of cases are thought to be subclinical (6-8), unrecognized, or occur in locations with limited disease surveillance or laboratory testing capability; also, the case definition for CCHF is not standardized across endemic regions (9,10).A recent worldwide systematic review and meta-analysis, using data collected during 1974-2020, reported an overall case-fatality rate of 11.7% for humans with acute CCHFV infection (defined as presence of live virus, viral antigen, or RNA), a prevalence of 22.5% (n = 35,198), recent infection (defined as presence of IgM) seroprevalence of 11.6% (n = 27,173), and an overall past infection (defined as presence of IgG) seroprevalence of 4.3% (n = 74,900) in humans (11).CCHFV is an enveloped, multisegmented, singlestranded, negative-sense RNA virus (genus Orthonairovirus, order Bunyavirales, family Nairoviridae).The viral genome exists as 3 single-stranded, negativesense RNA molecules, leading to a complex replication program.Replication of the trisegmented CCH-FV genome is error prone, leading to antigenic drift Crimean Congo-Hemorrhagic Fever Virus for Clinicians-Virology, Pathogenesis, and Pathology