Contributed equally
Recently, severe acute respiratory syndrome (SARS) coronavirus (CoV) 2 (SARS-CoV-2)-causing CoV disease 2019 (COVID-19) emerged in China and has become a global pandemic. SARS-CoV-2 is a novel CoV originating from β-CoVs. Major distinctions in the gene sequences between SARS-CoV and SARS-CoV-2 include the spike gene, open reading frame (ORF) 3b and ORF 8. SARS-CoV-2 infection is initiated when the virus interacts with angiotensin-converting enzyme 2 (ACE2) receptors on host cells. Through this mechanism, the virus infects the alveolar, esophageal epithelial, ileum, colon and other cells on which ACE2 is highly expressed, causing damage to target organs. To date, host innate immunity may be the only identified direct factor associated with viral replication. However, increased ACE2 expression may upregulate the viral load indirectly by increasing the baseline level of infectious virus particles. The peak viral load of SARS-CoV-2 is estimated to occur ~10 days following fever onset, causing patients in the acute stage to be the primary infection source. However, patients in the recovery stage or with occult infections can also be contagious. The host immune response in patients with COVID-19 remains to be elucidated. By studying other SARS and Middle East respiratory syndrome coronaviruses, it is hypothesized that patients with COVID-19 may lack sufficient antiviral T-cell responses, which consequently present with innate immune response disorders. This may to a certain degree explain why this type of CoV triggers severe inflammatory responses and immune damage and its associated complications.
During the Middle of December 2019, a virus-induced pneumonia emerged in Wuhan, China, which ultimately resulted in the current global pandemic (
The databases of Pubmed (date of access, 20/08/2020;
Coronaviruses are RNA viruses that are distributed broadly worldwide. This family of viruses has a large genetic diversity and high prevalence of genome recombination (
Over the previous decades, six coronavirus species that are able to cause human diseases have been identified: 229E, OC43, NL63, HKU1, SARS-CoV and MERS-CoV (
The first reported clinical case of the novel virus can be traced back to the middle of December 2019 (
SARS-CoV-2 belongs to the β-coronavirus (β-CoV) subfamily. Similar to its family members, the diameter of SARS-CoV-2 is 60–140 nm. The viral particles exhibit distinctive spikes, which are generally spherical and exhibit certain pleomorphisms (
SARS-CoV-2 and SARS-CoV share a similar genomic structure with other members of the β-CoV family (
The S protein functions as an epitope of host immune recognition (
A novel short putative protein within ORF 3b has been detected in SARS-CoV-2 (
Although SARS-CoV-2 has a distinct genome sequence, detection of SARS-CoV-2 is not challenging. Reverse transcription-quantitative PCR is effective in identifying SARS-CoV-2 infection (
SARS-CoV, MERS-CoV and SARS-CoV-2 are the three most notable coronaviruses known to infect humans (
Coronaviruses primarily infect the respiratory and digestive systems (
The initial step of viral infection is entry into host cells (
A previous article indicated that ACE2 was highly expressed in alveolar, esophageal epithelial, ileum and colon cells (
The lungs are the primary target of SARS-CoV-2 and other SARS-CoV-like coronaviruses, and they exhibit more severe clinical symptoms compared with other organs (
Aside from pulmonary manifestations, a previous study reported that the levels of liver enzymes in 43 patients were higher compared with those in the normal range, where one patient presented with liver function impairment (
Patients with coronavirus infection may also present with diarrhea and gastrointestinal-associated symptoms (
Although certain patients presented with heart and kidney ailments, there were insufficient studies that have confirmed the presence of the virus in these organs. A previous study indicated that SARS-CoV-2 may bind the ACE2 receptors of tubular cells, causing cytotoxicity and abnormal renal function (
The first pathological report on patients who succumbed to COVID-19 only obtained specimens of the lungs, liver and heart by puncture, rather than performing a complete autopsy (
Since the viral load is proportional to the transmission capacity of the virus, clarifying the viral dynamic patterns of SARS-CoV-2 is crucial (
Apart from the febrile period, the virus replicates from initial infection up until elimination (
These aforementioned publications indicate that, in addition to patients in the acute stage, those at different clinical stages or those with asymptomatic infection also require proper evaluation of their contagious capacities and potentially isolation for disease management.
The natural course of viral infection is intricate and variable, making it challenging to identify the influential factors underlying viral replication. Currently, the full-length genome sequencing results of different virus samples obtained from patients with COVID-19 were almost identical with a few site mutations (
In the host, the innate immune response determines the level of the coronavirus replication (
To date, host innate immunity may be the only direct factor identified to be associated with viral replication (
As mentioned previously, the replication of human coronaviruses (hCoVs) is regulated by various host factors and immune interaction (
Besides activation, hCoVs can also inhibit the innate immune response by shielding viral RNA from host cell sensors to inhibit IFN induction (
Furthermore, coronaviruses induce the production of chemokines and cytokines other than IFN in the innate immune system. SARS-CoV infection can result in the moderate upregulation of inflammatory cytokine such as tumor necrosis factor (TNF) and interleukin (IL)-6 and significant upregulation of the chemokine ligand (CCL) 3, CCL5, CCL2 and chemokine (C-X-C motif) ligand (CXCL) 10 in macrophages and dendritic cells (
Previous reports have demonstrated that the acute phase in patients with SARS-CoV infection is associated with leukopenia and severe lymphopenia in >80% patients, involving a marked loss of 90–100 and 80–90% in CD4+ T and CD8+ T-cells, respectively (
Two Chinese studies reported impaired CD4+ and CD8+ T-cell activation in patients with SARS-CoV (
Several studies have previously identified virus-specific memory CD4+ and CD8+ T-cells in patients who recovered from SARS (
A recent meta-analysis compiled >600 studies to report a full clinical profile of COVID-19 (
In addition to virological tests, CT scans served vital roles for early detection and disease evaluation (
Previous histological reports of patients who succumbed to COVID-19 revealed extensive infiltration of immune cells, including CD4+ helper T lymphocytes and CD163+ M2 macrophages (
Immune damage results in thromboembolism in the lungs, heart and brain (
Activation of coagulation and thrombin generation results from the interaction between pathogens and host innate immunity (
Besides thromboinflammation, endotheliopathy also contributes to coagulation disorders in patients with COVID-19 (
In conclusion, the current review compiled available data concerning COVID-19, which were then compared with SARS and MERS to profile the molecular characteristics of SARS-CoV-2 and the immune response against the virus. As a novel CoV originating from β-CoVs, SARS-CoV-2 infects alveolar cells and other cells in which ACE2 is highly expressed, causing damage to target organs. Host immunity is crucial for viral replication and sequential pathogenesis. However, the comprehensive underlying mechanisms are yet to be fully elucidated. Based on the current data, it can be hypothesized that patients with SARS-CoV-2 infection may have insufficient antiviral T-cell responses, resulting in disorders of the innate immune response. To a certain degree, this may explain why this type of CoV triggers excessive inflammatory responses and immune damage due to COVID-19 and its associated complications.
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The current study was supported by Special Funds for Prevention and Control of COVID-19 of Sichuan University (grant no. 2020scunCoVyingji10004) and the Scientific and Technological Project for Prevention and Control of COVID-19 of West China Hospital of Sichuan University (grant no. HX-2019-nCoV-010).
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HT and LB conceptualized and designed the current work. LD, JS, NH, DL and JW researched and evaluated the literature obtained from the database. LD and JS drafted the manuscript. LD, LB, HT and HY revised the manuscript. All authors read and approved the final manuscript.
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The authors declare that they have no competing interests.
Schematic of the SARS-CoV-2 RNA genome. SARS, severe acute respiratory syndrome; CoV, coronavirus; UTR, untranslated region; ORF, open reading frame; S, spike; E, envelope; M, membrane; N, nucleocapsid.