Similarities of immune reactions between hepatitis C and severe acute respiratory syndrome-associated coronavirus infections.

To the Editor,

Severe acute respiratory syndrome (SARS) is an emerging disease caused by a novel coronavirus (SARS–CoV). It has caused worldwide outbreaks, resulting in 8102 cases in 29 countries, with 744 fatalities in 2003. SARS–CoV belongs to the Coronaviridae genus, and hepatitis C virus (HCV) belongs to the Flaviviridae genus. These are two different viruses, but both are positive single strain RNA viruses (+ssRNA), which have some similar characteristics in immune responses that might offer some insight into the treatment of SARS.

Cinatl et al. first reported that interferon beta could inhibit SARS–CoV replication in in vitro culture. A similar result was confirmed by Hensley et al. Furthermore, other forms of interferon (interferon‐alpha and ‐gamma) have also had an anti‐SARS effect in in vitro studies. , Loutfy et al. reported a potential benefit from the interferon alfacon‐1 plus corticosteroids in SARS treatment, and found that the treatment group seemed to have reduced disease‐associated impaired oxygen saturation, more rapid resolution of radiographic lung abnormalities and lower levels of creatine kinase. Zhao et al. also reported that SARS patients randomly receiving interferon alpha tended to have the shortest admission days, time needed for improvement of dyspnea and time for improvement of chest X‐ray films than other treatment regimens. Ribavirin alone was not efficacious in in vitro anti‐SARS–CoV test, or in the Zhao's randomized trial, although some have suggested its clinical value. Cinatl and colleagues tested certain potential anti‐SARS–CoV drugs including ribavirin, 6‐azauridine, pyrazofurin, mycophenolic acid and glycyrrhizin, and showed that glycyrrhizin has the best potency in inhibiting the replication of SARS–CoV. These results suggest that interferon alpha and glycyrrhizin could be beneficial in SARS treatment. Similarly, interferon alpha and glycyrrhizin are also effective in treating HCV infections. , Glycyrrhizin lowers serum ALT during treatment, reduces the inflammation of HCV infection, and prevents the development of hepatoma. , Glycyrrhizin has fewer side‐effects and seems more effective than ribavirin in treating HCV infections. Taken together, these results suggest that SARS–CoV and HCV might have similar immunopathogenesis.

Patients with chronic HCV infection tend to have Th2 dominance. In a previous study, we also found, as did Wang et al., that a Th2 predominant cytokine profile with increases of TGFβ and IL‐13 in the early stages of SARS infection (within 7 days after symptoms), followed by a Th1 predominant cytokine profile with elevation of IL‐2 and IL‐18 in the late stage (≥2 weeks after symptoms). This suggests that the host immune response in early SARS infection might favor viral replication, but 2–3 weeks after SARS–CoV infection, the host immune response can induce specific immunity for virus clearance or immune‐mediated damage. Based on the skewed immune responses, we therefore postulate to use interferon alpha in the early stage of SARS infection to deviate Th2 predominant reaction to Th1 reaction, and hold back corticosteroids until appearance of late exacerbation showing augmented Th1 response.

Another similarity between HCV and SARS–CoV infections is related to elevation of blood IL‐8 levels. Polyak et al. have reported that chronic HCV infection with elevated IL‐8 levels is associated with the resistance to interferon therapy. , One possible mechanism might be related to activation of p38 MAP kinase that is associated with elevated IL‐8 levels and resistant interferon therapy. We have recently shown that SARS infections were associated with mild elevation of IL‐8 in conjunction with p38 activation in CD14+ cells. How to prove the relationships between p38 activation–related interferon resistance and SARS–CoV‐ or HCV‐related immune response deserves further investigation.