Host Immune Responses to SARS Coronavirus in Humans

Abstract

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.

Primary Severe Acute Respiratory Syndrome Coronavirus Infection Limits Replication but Not Lung Inflammation upon Homologous Rechallenge

“…Lymphopenia in patients was a common hematological feature in acute SARS-CoV infection, with several studies documenting reduced numbers of both CD4 and CD8 T lymphocytes (25). Although the AGMs in our studies showed no significant changes in peripheral blood populations following experimental SARS-CoV infection, there was a significant reduction in the proportion of T lymphocytes of total lung leukocytes at 14 dpi.…”

An overview of COVID-19

“…In severe forms of COVID-19, the ensuing inflammatory cascade may lead to a cytokine storm, as observed in a recent study that documented elevated serum cytokine levels, including IL-2, IL-7, IL-10, granulocyte colony-stimulating factor (G-CSF), monocyte chemotactic protein (MCP), and TNF-α . The cytokine storm is believed to be a key factor driving both ARDS and extra-pulmonary organ failure (Li and Xu, 2010).…”

Perspectives on therapeutic neutralizing antibodies against the Novel Coronavirus SARS-CoV-2

“…Resistance to SARS-CoV infections is associated with both innate and adaptive immune responses [16]. The innate immune response to SARS-CoV has not been completely defined [17].…”