SARS-CoV-2 infection: molecular mechanisms of severe outcomes to suggest therapeutics

ABSTRACT

Introduction:The year 2020 was defined by the 29,903 base pairs of RNA that codes for the SARS-CoV-2 genome. SARS-CoV-2 infects humans to cause COVID-19, spreading from patient-to-patient yet impacts patients very divergently.

Areas covered: Within this review, we address the known molecular mechanisms and supporting data for COVID-19 clinical course and pathology, clinical risk factors and molecular signatures, therapeutics of severe COVID-19, and reinfection/vaccination. Literature and published datasets were reviewed using PubMed, Google Scholar, and NCBI SRA tools. The combination of exaggerated cytokine signaling, pneumonia, NETosis, pyroptosis, thrombocytopathy, endotheliopathy, multiple organ dysfunction syndrome (MODS), and acute respiratory distress syndrome (ARDS) create a positive feedback loop of severe damage in patients with COVID-19 that impacts the entire body and may persist for months following infection. Understanding the molecular pathways of severe COVID-19 opens the door for novel therapeutic design. We summarize the current insights into pathology, risk factors, secondary infections, genetics, omics, and drugs being tested to treat severe COVID-19.

Expert opinion: A growing level of support suggests the need for stronger integration of biomarkers and precision medicine to guide treatment strategies of severe COVID-19, where each patient has unique outcomes and thus require guided treatment.

KEYWORDS:

• SARS-CoV-2
• COVID-19
• acute respiratory distress syndrome

Article highlights

• In some individuals COVID-19 causes severe lung infections associated with pneumonia.

• Severe COVID-19 is associated with lymphopenia and systemic immune activation.

• Immune activation can result in neutrophil extracellular traps and platelet activation associated with coagulation, endotheliopathy, and vascular dysfunction.

• Alterations of the immune system from genetics to secondary infections can yield elevated risk of immune pathology for COVID-19.

• Many of these immune activations can be targeted with therapies on the market, with testing underway to validate their usage in Patients with COVID-19 .

• Ongoing strategies are needed to mitigate vaccine evasion by SARS-CoV-2 variants.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial or other relationships to disclose.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.