Copyright ©The Author(s) 2022.
World J Gastroenterol. Jan 21, 2022; 28(3): 275-289
Published online Jan 21, 2022. doi: 10.3748/wjg.v28.i3.275
Table 1 COVID-19 and endothelium/blood vessels
COVID-19 and endothelium/blood vessels
Endothelium and blood vessels are integral parts of COVID-19-induced tissue injury. Their injury is likely due to either direct viral infection and/or cytokine storm triggered by infection of adjacent epithelial cells and inflammatory response[18].
Blood vessels are critical for virus dissemination to distant organs.
Preexisting-impaired endothelial function, e.g., in aging or diabetes are likely predisposing factors COVID-19. Our studies demonstrated that aging gastric mucosa has increased susceptibility to injury and prominent EC abnormalities (decreased VEGF, NGF and impaired mitochondrial function)[19-21].
ECs are critical for vascular regeneration (through angiogenesis and vasculogenesis) during injury/lesions healing and therefore are essential for the delivery of oxygen and nutrients to the healing site[22, 23].
Several growth factors e.g., NGF, IGF-1, HGF and BMD-stem cells may facilitate tissue regeneration in the healing phase[20,24,25].
Long-term effects of COVID-19, its vaccines and treatment on endothelium and vasculature remain to be determined.
Recently, new oral drugs inhibiting viral replication–Molnupiravir (Merck) and Paxlovid (Pfizer) showed significant efficacy in controlling severe COVID-19 infection by inhibiting viral replication. The interim analysis of the latter drug showed an 89% reduction in risk of COVID-19-related hospitalization or death from any cause compared to placebo in patients treated within three-five days of symptom onset[26].
Table 2 Scenarios by which SARS-CoV-2 elicits endothelial damage
Scenario A: SARS-CoV-2 infection
Scenario B: Cytokine storm
SARS-CoV-2 infects and replicates within vascular ECs and new virus particles are released into the blood vessel. These virions can infect neighboring cells or are carried to distant organs via circulation↑ IL-6, IL-1β, and TNFα release (cytokine storm) → endothelial damage
↑ vascular permeability → plasma extravasation
↑ vWF & FVIII (promote clot formation) and ↑ PAI-1 (inhibits clots lysis) → hypercoagulation
Table 3 Summary of the investigational interventions/treatments for COVID-19 in clinical trials
Intervention/ Treatment
Mode of action
Route Identifier
Ronapreve/REGN-COV2 (REGN10933 and REGN10987) Monoclonal antibodies against spike proteins8 g once, or 4 g twiceIVNCT04425629
Lopinavir/RitonavirInhibitor of the HIV protease and cytochrome P-450 CYP3A 200/ 50 mg; (4 tablets twice a day on day 1 followed by 2 tablets twice a day for 9 d)OralNCT04403100
Remdesivir (RDV, GS-5734, Veklury)Inhibitor of RNA-dependent RNA polymerase200 mg on day 1 followed by 100 mg for 4-9 dIVNCT04292899
Hyperimmune Plasma (COV19-PLASMA)Immunotherapy 250-300 mL up to 3 times over 5 dIVNCT04321421
Tocilizumab (TCZ, ROACTEMRA)Humanized anti-IL6 receptor monoclonal antibody8 mg/kg single infusion, up to 800 mgIVNCT04320615
Sarilumab (Kevzara, REGN88, SAR153191)Monoclonal antibody against IL-6 receptor alpha200 mg or 400 mg; single dose and multiple dosesIVNCT04315298
Anakinra (KINERET)Monoclonal antibody against the IL-1 receptor100 mg daily up to 28 dSCNCT04330638
Siltuximab (SYLVANT)Chimeric anti-IL-6 antibody11 mg/kg single infusionIVNCT04330638
Eculizumab Monoclonal antibody against complement protein C5900 mg every 7 dIVNCT04288713
Methyl-prednisolone (MP)Immunosuppression against cytokine storm80 mg/kg IV bolus, followed by infusion of 80 mg/d for at least 8 d and then oral MP 16 mg or 20 mg IV twice dailyOral-IVNCT04323592
HeparinAntithrombotic agents10 units/kg/hIVNCT04367831
Enoxaparin (Lovenox)Antithrombotic agents1 mg/kgSCNCT04367831
DexamethasoneImmunosuppression against cytokine storm20 mg/d (5 d) then 10 mg/d (5 d)IVNCT04325061
Vitamin CAntioxidant12 g infusion twice a day for 7 dIVNCT04264533
MelatoninAntioxidant3 or 30 mg three times a day for 14 dOralNCT04784754
CoQ10Antioxidant500 mg/day for 6 wkOralNCT04960215