COVID-19 pandemic: A multidisciplinary perspective on the pathogenesis of a novel coronavirus from infection, immunity and pathological responses

Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus2 (SARS-CoV-2), has spread to more than 200 countries and regions, having a huge impact on human health, hygiene, and economic activities. The epidemiological and clinical phenotypes of COVID-19 have increased since the onset of the epidemic era, and studies into its pathogenic mechanisms have played an essential role in clinical treatment, drug development, and prognosis prevention. This paper reviews the research progress on the pathogenesis of the novel coronavirus (SARS-CoV-2), focusing on the pathogenic characteristics, loci of action, and pathogenic mechanisms leading to immune response malfunction of SARS-CoV-2, as well as summarizing the pathological damage and pathological manifestations it causes. This will update researchers on the latest SARS-CoV-2 research and provide directions for future therapeutic drug development.

Keywords: COVID-19; SARS-CoV-2; immune pathogenesis; pathogenic mechanism; virus infected.

Figure 1

Schematic diagram showing SARS-CoV-2 injecting RNA into the host cell by binding to the ACE2 receptor on normal cells via the S protein. The injected RNA uses the nutrients in the host cell to replicate itself and make the structural proteins it needs. The structural proteins combine with the RNA to form a new virus.

Figure 2

Schematic diagram showing the process by which the new coronavirus enters the human body and triggers an inflammatory response. ACE2 and TMPRSS2 play a decisive role in neo-coronavirus invasion. The major PRRs against viruses are present on the cytoplasmic and endosomal membranes of immune cells and recognize foreign viruses. After a series of processes, they finally produce transcription factors NF-κB and IFRs on the cell membrane. Next, they migrate to the nucleus and induce the expression of encoded cytokines and IFN-I and IFN-III, pro-inflammatory cytokines, and chemokines, which in turn accumulate large numbers of neutrophils. The secretion of neutrophils, cytokines, and chemokines promotes further accumulation of immune cells, producing an excessive inflammatory response or further triggering the cytokine storm mentioned below.

Figure 3

Schematic diagram showing the pathogenic mechanism of diffuse lung injury caused by 2019-nCoV. SARS-CoV-2 binds to ACE2 receptors on human alveolar epithelial cells via S proteins and enters the cells. NK cells, natural killer cells, macrophages, dendritic cells, monocytes, etc., release cytokines (e.g., IL-6, IL-7, IL-8, IL-17, etc.) and chemokines (e.g., CCL-2, CCL-3, CCL-5, etc.). CD8⁺ T cells secrete substances such as Perforin, CD107a, and Granzyme B. CD4⁺ T cells are activated and differentiate into Th1, Th2 effector cells, and other subpopulations (including Tfh cells, etc.), and also secrete cytokines (e.g., INFγ) and chemokines to recruit Immune cells are also secreted (e.g., INFγ) and chemokines are recruited, resulting in a cytokine storm that causes diffuse lung injury.