Table 2.
Clinical signs and laboratory findings associated with mortality in human CCHF cases and their presence in animal models for CCHFV infection
| Humans | Animals | |||||||
|---|---|---|---|---|---|---|---|---|
| Ergonul, Celikbas et al. (2006); Ergonul, Tuncbilek et al. (2006) | Cevik et al. (2008) | Ozturk et al. (2012) | Kaya et al. (2014) | Ergönül et al. (2017) | IFNAR−/− mice | STAT‐1 KO mice | Humanized mice | |
| Clinical signs | ||||||||
| Hematemesis | Yes (.009) | Yes (.030) | Yes (<.001) | – | – | N | N | N |
| Epistaxis | ns | ns | Yes (.002) | – | – | N | N | N |
| Gingival bleeding | – | Yes (.044) | Yes (<.001) | – | – | N | N | N |
| Melena | Yes (.001) | Yes (<.001) | Yes (<.001) | – | Yes (.001) | N | N | N |
| Skin bleeding | – | – | Yes (<.001) | – | – | N | N | N |
| Somnolence | Yes (.022) | Yes (.004) | – | Yes (.003) | – | N | N | N |
| Anorexia | – | ns | – | – | – | Weight loss | Weight loss | Weight loss |
| Petechiae | – | ns | – | ns | Yes (.03) | N | N | N |
| Maculopapular rash | ns | ns | – | ns | – | N | N | N |
| Ecchymosis | ns | Yes (.007) | ns | ns | Yes (.04) | N | N | N |
| Hepatomegaly | – | No | – | ns | – | Virus + | Virus + | Virus + |
| Jaundice | – | – | – | Yes (.01) | – | N | N | N |
| Splenomegaly | – | ns | – | – | – | Virus + | Virus + | Virus + |
| Fever > 38°C | ns | ns | ns | – | – | – | – | – |
| Laboratory findings | ||||||||
| Increased viremia | – | – | – | p < .0001 | – | Y | Y | Y |
| Elevated AST | Yes (.004) | Yes (<.001) | Yes p = .009 | – | Yes (<.05) | Y | – | – |
| Elevated ALT | Yes (<.001) | Yes (<.001) |
No p = .107 |
– | Yes (<.05) | Y | Y | – |
| Elevated CPK | ns | Yes (.004) | No p = .061 | – | – | – | – | – |
| Elevated LDH | ns | Yes (<.001) | Yes (<.006) | – | Yes (<.05) | – | ‐ | – |
| Decreased fibrinogen | Yes (.012) | ns | Yes (.027) | – | Yes (<.001) | Increased | – | – |
| PT elongation | Yes (.002) | Yes (<.001) | Yes (.003) | <.001 | Yes (<.001) | N | – | – |
| aPTT elongation | Yes (<.001) | Yes (.002) | Yes (<.001) | .001 | Yes (<.001) | Y | – | – |
| Elevated INR | – | Yes (<.001) | Yes (.005) | <.001 | – | – | – | – |
| Thrombocytopenia | Yes (.038) | Yes (.036) | Yes (<.001) | – | – | Y | Y | Y |
| Leukopenia | – | ns | – | – | ns | – | Y | N |
| Leukocytosis | ns | ns | – | – | – | – | N | Y |
| Elevated C3 | – | – | Yes (.048) | – | – | – | – | – |
| Elevated C4 | – | – | Yes (.025) | – | – | – | – | – |
| Decreased IgM | – | – | Yes (.003) | – | – | – | Not detected | – |
| Decreased IgG | – | – | Yes (.040) | – | – | – | – | – |
| Decreased IgA | – | – | ns | – | – | – | – | – |
| Increased IL‐6 | – | – | – | Yes (<.001) | .037 | Y | Y | – |
| Decreased IL‐10 | – | – | – | ns | ns | Increased | Increased | – |
| Increased TNF‐α | – | – | – | Yes (<.001) | ns | Y | Y | – |
| Increased IFN‐γ | – | – | – | ns | ns | Y | Y | – |
| Increased IL‐8 | – | – | – | – | Yes (.037) | – | – | – |
Y, sign exhibited in animal model; N, sign not exhibited in animal model; Yes, finding associated with mortality in human CCHF cases; ns, finding not significantly associated with mortality in human CCHF cases; p‐values indicated in brackets where available. Expressions in IFNAR−/− and STAT‐1 KO mice were compared with respective WT mice infected with CCHFV.
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