Discussion
Crimean-Congo hemorrhagic fever (CCHF) is a life-threatening zoonosis resulting from infection with Crimean-Congo hemorrhagic fever virus (CCHFV), belonging to the Nairovirus genus of the Bunyaviridae family. Hyalomma ticks and livestock transmit this zoonotic infection through exposure to infected body fluids. Iran is ranked second after Turkey for CCHF cases in the Eastern Mediterranean Region of the World Health Organisation (WHO)(3). The western areas of Iran are endemic for the CCHF, with summertime being the most active season due to increased tick bites. On the other hand, the COVID pandemic has led to an increased rate of SARS-CoV-2 coinfections with any other pathogen, including nairoviruses like CCHFV(4, 5). In the current era of SARS-CoV-2 dominance, outbreaks of CCHF can be an essential health threat in endemic countries like Iran, leading to worsened outcomes and increased mortality.
These coinfections can cause many challenges in diagnosis and management as clinical manifestations sometimes overlap. The similarities between CCHF and SARS-CoV-2 infection presentations make early diagnosis difficult, mainly if the clinical findings are inconclusive. However, understanding the similarities and differences between these two infections can help clinicians differentiate them in a timelier manner(6).
From an epidemiological view, SARS-CoV-2 is a pandemic worldwide, while CCHF is distributed from the Black Sea to southern Africa, most heavily concentrated in Turkey, Iran, and other Mediterranean countries(7). CCHF is usually demonstrated in farmers, veterinarians, and slaughterhouse employees, while SARS-CoV-2 is specified to have no occupation.
The transmission mode is airborne in COVID-19, while CCHFV is mainly spread through bloodborne and sometimes aerogenic transmission(8). The diagnosis of CCHF can be troublesome without a history of tick bites. Our patient also did not recall a tick bite. However, his occupation and epidemiological and geographical characteristics led us to suspect CCHF.
The incubation period for both infections ranges from 2-14 days. Moreover, some of the manifestations of the prehemorrhagic phase of CCHF are similar to prodromal features of SARS-CoV-2 infection, including fever, chills, myalgia, arthralgia, and malaise. However, with disease progression after about one week, clinical findings may become more apparent and different from each other, as SARS-CoV-2 infection may lead to respiratory symptoms such as coryza, cough, and shortness of breath. At the same time, CCHF may enter the hemorrhagic phase, manifesting as petechiae, ecchymoses, hematemesis, melena, hematuria, epistaxis, and hemoptysis. However, bleeding diatheses occur if disseminated intravascular coagulation (DIC) complicates COVID and only in severe and critical cases. Both conditions can end in DIC and multiorgan failure if not treated effectively(9, 10).
Typical laboratory abnormalities in SARS-CoV-2 infection include elevated D-dimer, ferritin, and CRP levels and lymphopenia, while CCHF predominantly manifests as thrombocytopenia and impaired liver function and coagulation tests(11, 12).
Diagnosis of CCHF is suspected based on clinical and epidemiologic findings and confirmed by identifying viral RNA by RT-PCR or the presence of serologic evidence of recent exposure to the virus, including IgM and IgG detection by sensitive and specific methods like enzyme-linked immunosorbent assay (ELISA) (13). In contrast, COVID-19 is suspected by clinical findings and confirmed by PCR or chest imaging. It should be noted that high-resolution computed tomography (HRCT) has a special place in diagnosing PCR-negative cases of SARS-CoV-2 infection(14). SARS-CoV-2 and CCHFV infections may or may not lead to pulmonary involvement. Nonetheless, various lung radiographic features might be demonstrated if this occurs. Ground-glass opacities and multiple pulmonary infiltrates are the characteristic features of chest CT in COVID-19, while a mild case of CCHF spares the lungs, and ground-glass opacity is only demonstrated in the settings of CCHF if alveolar hemorrhage intervenes(15-19). Pulmonary embolism is a common finding in COVID-19, while this complication only rarely occurs in the settings of CCHF(20, 21). Acute respiratory distress syndrome (ARDS) may occur in the late stages of both infections, indicative of a poor prognosis(22).
Supportive care is the cornerstone of treatment for both SARS-CoV-2 and CCHFV infections. However, antiviral therapy may be effective in some conditions, especially in the early or viremic phase of these two conditions. The efficacy of ribavirin in the management of CCHF is controversial even in the early stages, while antiviral agents like favipiravir and remdesivir have been successfully applied to control SARS-CoV-2 infection in the early days of diagnosis(23, 24). Nevertheless, favipiravir has been utilized to manage CCHFV infection in animals(5). Therefore, the administration of favipiravir in our patient could have done a favor to both infections and accelerated the improvement course of both SARS-CoV-2 and CCHFV. If not contraindicated, anticoagulation is recommended for severe to critical cases of COVID-19, while this therapeutic option is usually avoided in CCHF, primarily if severe thrombocytopenia or DIC occurs. Moreover, thromboconcentrate replacement therapy, cryoprecipitate, and albumin are frequently administered to manage CCHF(25). The fatality rate of CCHF is much higher than COVID-19, approximately 30%, vs. up to 10% in severe cases(26, 27).
Our patient’s primary clinical findings were consistent with COVID-19, while later manifestations and laboratory test results suggested CCHF. The ultimate diagnosis was based on medical tests proving SARS-CoV-2 and CCHFV coinfection. To our knowledge, this was among a few cases of SARS-CoV-2 and CCHFV coinfection reported so far.