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. 2021 Dec 23;10(1):3.
doi: 10.3390/medsci10010003.

Nitric Oxide: The Missing Factor in COVID-19 Severity?

Alexandros Nikolaidis  1 , Ron Kramer  2 , Sergej Ostojic  3
Affiliations

Nitric Oxide: The Missing Factor in COVID-19 Severity?

Alexandros Nikolaidis et al. Med Sci (Basel). .

Abstract

Coronavirus disease 2019 (COVID-19) is a contagious respiratory and vascular disease that continues to spread among people around the world, mutating into new strains with increased transmission rates, such as the delta variant. The scientific community is struggling to discover the link between negative COVID-19 outcomes in patients with preexisting conditions, as well as identify the cause of the negative clinical patient outcomes (patients who need medical attention, including hospitalization) in what seems like a widespread range of COVID-19 symptoms that manifest atypically to any preexisting respiratory tract infectious diseases known so far. Having successfully developed a nutritional formulation intervention based on nitrate, a nitric oxide precursor, the authors hypothesis is that both the comorbidities associated with negative clinical patient outcomes and symptoms associated with COVID-19 sickness are linked to the depletion of a simple molecule: nitric oxide.

Keywords: COVID-19; NO; SARS-CoV-2; comorbidities; etiology; nitric oxide.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Number of COVID-19-associated hospitalizations for the period of 7 March 2020–22 May 2021 in the USA, categorized by age group. Source: US CDC https://gis.cdc.gov/grasp/covidnet/COVID19_5.html, accessed on 5 June 2021.
Figure 2
Figure 2
Underlying medical conditions and pregnancy by percentage in patients with COVID-19-related hospitalizations in the USA. Data are restricted to cases reported during 1 March 2020–31 March 2021, due to delays in reporting.
Figure 3
Figure 3
Biological pathways of nitric oxide generation in vivo in the body. Image created by authors.
Figure 4
Figure 4
Molecular targets and biological effects of Nitric Oxide. Source: Lundberg et al., The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Image reproduced with author’s and Nature publishing group’s permission.
Figure 5
Figure 5
Activation of soluble guanylyl cyclase by nitric oxide. Source: https://commons.wikimedia.org/w/index.php?curid=15680898, accessed on 22 June 2021.
Figure 6
Figure 6
Cells were infected with SARS-CoV-1 at an MOI of 1.0. At 1 hpi, the cells were treated with different concentrations of SNAP (•) and NAP (○). (A) Supernatants were harvested at 24 hpi and titers were determined. (B) Nitrite concentrations produced at 24 h posttreatment with different concentrations of SNAP and NAP. (C) Cell viability, as determined by MTT assays. The mean values from two experiments are indicated. Source: [21].
Figure 7
Figure 7
Disulfide bond forming on COVID-19 spike protein and ACE2 during oxidative stress. Both ACE2 and CoV-2 possess four disulfide bridges, equaling 8 cysteine residues. Source: [82].
Figure 8
Figure 8
Reaction of nitric oxide with the cysteine sulfhydryl group. Source: [85].
See this image and copyright information in PMC

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Supplementary concepts

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