Host Immune Responses to SARS Coronavirus in Humans

The severe acute respiratory syndrome (SARS) is a newly identified infectious disease caused by a novel zoonotic coronavirus (SARS-CoV) with unknown animal reservoirs. The risk of SARS reemergence in humans remains high due to the large animal reservoirs of SARS-CoV-like coronavirus and the genome instability of RNA coronaviruses. An epidemic in 2003 affected more than 8,000 patients in 29 countries, with 10% mortality. SARS infection is transmitted by air droplets. Clinical and laboratory manifestations include fever, chills, rigor, myalgia, malaise, diarrhea, cough, dyspnoea, pneumonia, lymphopenia, neutrophilia, thrombocytopenia, and elevated serum lactate dehydrogenase, alanine aminotransferase, and creatine kinase activities. Health care workers are a high-risk group, and advanced age is strongly associated with disease severity. Treatment has been empirical, and there is no licensed SARS vaccine for humans so far. However, presence of long-lived neutralizing antibodies and memory T- and B-lymphocytes in convalescent SARS patients raises hope for active immunization. Furthermore, results from preclinical SARS vaccines expressing spike protein to elicit neutralizing antibodies and cellular responses that are protective in mouse and nonhuman primate models are encouraging. Very little is known of the early events in viral clearance and the onset of innate and inflammatory responses during the SARS infection. Regulation of the innate immune response is associated with the development of adaptive immunity and disease severity in SARS infection. Notably, SARS-CoV has evolved evasive strategies to suppress antiviral type I interferon responses in infected cells. In addition, inflammatory responses are characterized by upregulation of proinflammatory cytokines/chemokines such as IL-6, IP-10, and MCP-1 in tissues and serum, and massive infiltrations of inflammatory cells such as macrophages in infected tissues. Due to the lack of animal models that mimic the clinical manifestations of human SARS infection for mechanistic study and vaccine evaluation, development of a safe prophylactic SARS vaccine for human use remains a huge challenge. This chapter is written to summarize and highlight the latest clinical, serological, and immunological parameters relevant to the pathogenesis and protective immunity of SARS infection in humans.