Coronaviruses pathogenesis, comorbidities and multi-organ damage - A review

Abstract

Human coronaviruses, especially COVID-19, is an emerging pandemic infectious disease with high morbidity and mortality. Coronaviruses are associated with comorbidities, along with the symptoms of it. SARS-CoV-2 is one of the highly pathogenic coronaviruses that causes a high death rate compared to the SARS-CoV and MERS. In this review, we focused on the mechanism of coronavirus with comorbidities and impairment in multi-organ function. The main dysfunction upon coronavirus infection is damage to alveolar and acute respiratory failure. It is associated with the other organ damage such as cardiovascular risk via an increased level of hypertension through ACE2, gastrointestinal dysfunction, chronic kidney disease, diabetes mellitus, liver dysfunction, lung injury, CNS risk, ocular risks such as chemosis, conjunctivitis, and conjunctival hyperemia, cancer risk, venous thromboembolism, tuberculosis, aging, and cardiovascular dysfunction and reproductive risk. Along with this, we have discussed the immunopathology and coronaviruses at a molecular level and therapeutic approaches for the coronavirus infection. The comorbidities and multi-organ failure of COVID-19 have been explained at a molecular level along with the base of the SARS-CoV and MERS-CoV. This review would help us to understand the comorbidities associated with the coronaviruses with multi-organ damage.

Keywords: COVID-19; Comorbidities; Multi-organ failure and immunopathology; SARS-CoV-2.

Graphical abstract

Fig. 1

The abnormal activation of the Renin-Angiotensin-Aldosterone system (RAAS) pathway via the ACE-AngII-AT1R axis results in vasoconstriction (hypertension) which is treated by the usage of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). Since ACE2 is also the binding receptor for SARS-CoV-2 and enhances the viral entry, replication decreases the level of the ACE2, leading to reduced anti-atrophy and anti-fibrosis anti-inflammation, anti-oxidant, and vasodilation further leads to decreased tissue protection. On the other hand, there is a pro-atrophy, pro-fibrosis, pro-inflammation, vasoconstriction, pro-oxidant, and acute lung injury via angiotensin II type 1 receptor which leads to tissue injury.

Fig. 2

SARS-CoV-2 enters into the host cell via binding with the cellular receptor ACE-2. It undergoes the fusion with the joining of the plasma membrane and the virus. Then it undergoes the process of the proteolytic cleavage; further, it will undergo replication and lead to the formation of the proteins. This process activates the signaling pathway, such as the NF-kB pathway, via TRIF. The interaction between the cells and the virus activates many cytokine storms. On the other hand, once the virus enters into the cell, the antigen present in that would undergo the antigen presentation cells (APC); further, this stimulates the humoral and cellular immunity. COVID-19 infects the macrophage cells, which presents to the T cell, further, which leads to the activation, differentiation of T-cells, along with the production of cytokines. This shows the negative action on the activation of CD8 T cells. Thus the mediator produced by the CD8+ T cells clears the infection of SARS-CoV. Upon COVID-19 infection, there is a reduced CD4+ and CD8+ cell level, further increasing the cytokine level in the cells, which triggers the inflammation. This mediates the production of the cytokine storm via secreting chemokine and cytokines such as IL-1β, IL-6, TNF-α, IL-8, IL-21, CCL2, CCL3, CCL5, CXCL10, TNF-β, and MCP-1 and triggers the tissue injury. On the other hand, based on the weight of the protein of SARS-CoV2, there is an activation of Th1/Th17 (boosts immune system) when the spike protein is >70 kDa. In case of the Th2 (anti-inflammatory) is activated by the majority of the protein with <70 kDa, then the activation of the B-cell receptor, which causes activation-induced cell death such as apoptosis and lymphopenia which is by releasing IL-10, shifting of Th1 to Th2 immune response, suppression of the immune system and further leads to the COVID-19 sepsis. The role of IL-4 has not been elucidated yet. It remains unanswerable upon COVID-19 condition with the mechanism of Th2 and Th1/Th17.

Fig. 3

The symptoms due to the SARS-CoV-2 in normal patients and patients with other co-morbid conditions. The symptoms found SARS-CoV-2 in normal patients and patients with other co-morbid conditions. The typical symptoms that emerged due to SARS-CoV-2 include dry cough, sneezing, and difficulty in breathing, which eventually leads to severe acute respiratory syndrome (SARS). The severity of the SARS not only depends upon the person's age and immunity but also various other co-morbid conditions such as cardiac issues, diabetes mellitus, hypertension, tuberculosis, cancer, and venous thromboembolism. The pre-existing co-morbid conditions deteriorate the patient health upon SARS-CoV-2 entry. Also, the SARS-CoV-2 have different effects on different organs which include elevated troponin levels in the cardiac tissue, acute kidney injury, proteinuria and hematuria in the kidney, elevated ALT, AST levels indicating liver damage, conjunctivitis and conjunctival hyperemia in the eye, the intrauterine transmission of the SARS-CoV-2 from mother to the fetus, vomiting, and diarrhea.