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, Volume: 5( 1)

Cellular and Molecular Pathways of COVID-19 and Ability Points of Therapeutic Intervention

Brynjolf Bjarme, Department of Molecular Biology, University of Cologne, Cologne, Germany; E-mail: [email protected]

Received: January 25, 2022, Manuscript No. TSBMBL-22-153; Editor assigned: January 27, 2022, Pre QC No. TSBMBL-22-153(PQ); Reviewed: February 10, 2022, QC No. TSBMBL-22-153; Revised: February 16, 2022, Manuscript No: TSBMBL-22-153(R); Published: February 23, 2022, DOI: 10.37532/ tsbmbl.2022.5.153.

Citation: Bjarme B. Cellular and Molecular Pathways of COVID-19 and Ability Points of Therapeutic Intervention. Biochem Mol Biol Lett. 5(1):153


COVID-19 is a severe acute respiratory disorder due to the unconventional coronavirus SARS-CoV-2, which emerged in Wuhan, China in overdue 2019, quick turning into a worldwide pandemic, with over 10 million suggested cases and 500,000 fatalities attributed to the sickness via June 2020. Lots of the response to the novel coronavirus has relied, through necessity, on a vast variety of early reviews regarding medical features, organic markers, and candidate therapeutics. at the identical time, many traits of the SARS-CoV-2 coronavirus and the acute breathing misery produced through intense cases of COVID19 infection reflect the ones determined in in advance coronavirus outbreaks, together with SARS (severe acute breathing syndrome, due to SARS-CoV) and MERS (middle-East breathing syndrome, due to MERS-CoV). Different conditions with informative overlap include ARDS (acute respiratory distress syndrome, because of pulmonary edema) and dengue hemorrhagic fever (DHF), which functions severe and regularly deadly secondary immunopathology following dengue virus infection involving rapidly extended cytokine expression, pulmonary edema, and acute respiratory failure.

The SARS-CoV-2 epidemic has emerged in the context of a wealthy current literature detailing elements of cell and molecular pathways suffering from earlier CoV serotypes and related situations. Tons of the emerging literature particular to SARS-CoV-2 not most effective is strongly constant with those findings however also capabilities informative variations, especially in lung tissue (e.g., weaker type III and type I interferon reaction, suppressed epithelial defense, and improved pulmonary infectivity)  [1].

With the objective of linking early findings regarding the novel SARS-CoV-2 coronavirus with potentially informative findings from prior studies literature and to promote research towards healing reaction, a coherent cellular and molecular pathway is proposed for COVID-19. The pathway is steady with a huge variety of located medical features and biological markers and captures key mediators of pathophysiology. In this proposed pathway, membrane fusion and cytoplasmic access of SARS-CoV-2 virus through ACE2 and TMPRSS2-expressing respiration epithelial cells, including pulmonary type-II pneumocytes, provokes an preliminary immune reaction featuring inflammatory cytokine production coupled with a vulnerable interferon reaction, especially in IFN-λ–based epithelial protection [2].

Differentiation of non-traditional pathogenic T-cells and seasoned-inflammatory intermediate monocytes contributes to a skewed inflammatory profile, mediated by way of membrane-sure immune receptor subtypes (e.g., FcγRIIA) and downstream signaling pathways (e.g., NF-κB p65 and p38 MAPK), observed through chemotactic infiltration of monocytederived macrophages and neutrophils into lung tissue. Endothelial barrier degradation and capillary leakage contribute to alveolar cellular harm. Inflammatory cytokine launch, delayed neutrophil apoptosis, and NETosis make a contribution to pulmonary thrombosis and cytokine hurricane. these mechanisms are concordant with determined clinical markers in COVID-19, which includes high expression of inflammatory cytokines at the TNF-α/IL-6 axis, increased neutrophil-tolymphocyte ratio (NLR), diffuse alveolar harm via mobile apoptosis in breathing epithelia and vascular endothelia, extended lactate dehydrogenase (LDH) and C-reactive protein (CRP), excessive manufacturing of neutrophil extracellular traps (NETs), depressed platelet remember, and thrombosis.

Even though sure factors are in all likelihood to be revised as new findings emerge, the proposed pathway suggests multiple points of research for capability therapeutic interventions. These encompass prophylaxis to enhance epithelial defense, lessen viral load, and temper inflammatory harm, in addition to therapeutics targeted in the direction of molecular mediators of the COVID-19 immune response .

Clinical Features

Amongst sufferers with COVID-19 contamination, mobile biomarkers in extreme instances consist of accelerated leukocyte and neutrophil counts, alongside suppressed lymphocyte remember, resulting in a substantially better NLR ratio relative to non-excessive cases. In a meta-evaluation of 9 studies along with 1779 patients, 399 with severe sickness, low platelet count number was extensively associated with ailment severity and mortality. Platelet count (thrombocytopenia) under the locally defined reference variety is related to a five-fold increase within the hazard of extreme sickness.

Experimental evolution in analyzing pathway evolution

Molecular biomarkers of excessive disorder encompass elevated procalcitonin, serum ferritin, D-dimer, C-reactive protein (CRP), and inflammatory cytokines which include IL-6, IL-2R, IL-7, IL-eight/CXCL8, IP10, MCP-1/CCL2, MIP1A/CCL3, GM-CSF, and TNF-α, as well as IL-10. However, the level of IL-10, a terrible regulator of immune response, is pronounced to differ with COVID-19 severity and development, with lower preliminary levels and next decline related to milder instances and likely more a hit viral clearance. Speedy respiratory rate and extended tiers of lactate dehydrogenase (LDH), a marker of cell loss of life, also are expecting severity [3].

Elevated inflammatory markers including IL-6, CRP, procalcitonin (PCT), and erythrocyte sedimentation charge (ESR) are found in fatal instances. Deadly acute lung injury is related to T-lymphocyte dysregulation and cytokine-driven inflammation, with diffuse pulmonary thrombosis and damage to endothelial cells.

In exam of post-mortem tissue from all fundamental organs of COVID-19 subjects, the primary finding is diffuse alveolar harm (DAD), proposing marked contamination and viral burden in type II pneumocystis, in conjunction with pulmonary oedema. CT examination is stated to have excessive diagnostic fee, with multiple ground glass opacities being a prominent characteristic of ailment development. COVID-19 functions infiltration of macrophages into lung tissue, with apoptosis of epithelial cells and pneumocytes. Infiltration of macrophages into alveolar cavities may be triggered with the aid of MCP-1, with TGF-β1 and TNF-α contributing to proliferation and amplified cytokine manufacturing. Markers of infiltration include the neutrophil chemokine receptor CXCR2, alongside monocyte chemotactic protein MCP-1/CCL2 and its receptor CCR2. Genes up regulated in extreme and critically unwell patients are enriched with individuals belonging to the NF-κB pathway. Improved expression of TGF-beta in COVID-19 patients might also sell fibroblast proliferation and make contributions to pulmonary fibrosis.

Several comorbid situations are cited as danger-elements for development and case fatality, inclusive of age, diabetes, vascular disease, cardiac disorder, high blood pressure, and cancer Fever is the maximum common initial symptom, observed with the aid of cough, with most frame temperature at admission, breathing rate, CRP, and albumin notably associated with progression in severity. Gastrointestinal symptoms are also suggested however with decrease frequency than in SARS or MERS.

The situations related to excessive COVID-19 aren't as it should be described as “compromised immunity.” among 5700 hospitalized patients within the NY area with showed sickness, the maximum frequent comorbidities suggested have been hypertension (56.6%), obesity (41.7%), diabetes (33.eight%), and coronary artery disease (eleven.1%), all of which may be higher defined as situations proposing predisposition to inflammation. Indeed, numerous key inflammatory cytokines related to high blood pressure (TNF-α, MCP-1, and IL-6) overlap those expanded in COVID-19 [4].


  1. Al-Rasheed NM, Fadda L, Attia HA, et al.Pulmonary prophylactic impact of melatonin and/or quercetin: A novel therapy for inflammatory hypoxic stress in rats. Acta Pharmace. 2017; 67(1):125-35.
  2. Indexed, Google Scholar, Cross Ref

  3. Alsamman AM, Zayed H. The transcriptomic profiling of SARS-CoV-2 compared to SARS, MERS, EBOV, and H1N1. PLoS One. 2020; 15(12):e0243270.
  4. Indexed, Google Scholar, Cross Ref

  5. Anft M, Paniskaki K, Blazquez-Navarro A, et al. COVID-19 progression is potentially driven by T cell immunopathogenesis. Medrxiv. 2020.
  6. Google Scholar, Cross Ref

  7. Ansari MA, Marchi E, Ramamurthy N, Aschenbrenner D, et al. A gene locus that controls expression of ACE2 in virus infection. MedRxiv.2020.
  8. Google Scholar

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Biochemistry & Molecular Biology Letters received 17 citations as per Google Scholar report

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