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.