Abstract: Nitric Oxide 103 (2020) 1–3
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Nitric Oxide
journal homepage: www.elsevier.com/locate/yniox
Nitric oxide dosed in short bursts at high concentrations may protect
against Covid 19
€ran Hedenstierna a, *, Luni Chen b, Magnus Hedenstierna c, Robert Lieberman d, David H. Fine e
Go
a
Department of Medical Sciences, Uppsala University, Uppsala, Sweden
Department of MTC, Karolinska Institute, Solna, Sweden
c
Department of Infectious Diseases, Danderyd Hospital, Danderyd, Sweden
d
Contello Consulting LLC, New Jersey, USA
e
Pieto LLC, Florida, USA
b
A R T I C L E I N F O
A B S T R A C T
Keywords:
Nitric oxide
Smoking
Viral suppression
Covid-19
It has long been suggested that NO may inhibit an early stage in viral replication. Furthermore, in vitro tests have
shown that NO inhibits the replication cycle of severe acute respiratory syndrome coronavirus. Despite smoking
being listed as a risk factor to contract Covid-19, only a low proportion of the smokers suffered from SARS-corona
infection in China 2003, and from Covid-19 in China, Europe and the US. We hypothesize, that the intermittent
bursts of high NO concentration in cigarette smoke may be a mechanism in protecting against the virus.
Mainstream smoke from cigarettes contains NO at peak concentrations of between about 250 ppm and 1350 ppm
in each puff as compared to medicinal use of no more than 80 to a maximum of 160 ppm. The diffusion of NO
through the cell wall to reach the virus should be significantly more effective at the very high NO concentration
in the smoke, according to classic laws of physics. The only oxide of nitrogen in the mainstream smoke is NO, and
the NO2 concentration that is inhaled is very low or undetectable, and methemoglobin levels are lower in
smokers than non-smokers, reasonably explained by the breaths of air in between the puffs that wash out the NO.
Specialized iNO machines can now be developed to provide the drug intermittently in short bursts at high
concentration dose, which would then provide both a preventative drug for those at high risk, as well as an
effective treatment, without the health hazards associated with smoking.
In this commentary we present a hypothesis that inhaled nitric oxide,
iNO, delivered in short bursts at a high concentration, has a protective
effect against Covid-19.
It has long been suggested that NO may inhibit an early stage in viral
replication and thus prevent viral spread, promoting viral clearance and
recovery of the host [1]. In a recent letter, Ignarro assumed this to apply
also to inhalation of NO (iNO) [2], supported by findings in a previous
SARS-corona epidemic. One of the authors of this commentary treated
SARS patients in Beijing with iNO in a limited number of patients [3].
iNO dramatically improved arterial oxygenation, expressed as arterial
oxygen tension, PaO2, divided by the inspired oxygen fraction, FIO2,
within 2–3 days. The PaO2/FIO2 ratio increased from a mean of 97–260
mmHg and, as shown in Fig. 1, the transcutaneous O2 saturation
increased and respiratory support was at the same time reduced or
discontinued. The 270% increase in the PaO2/FIO2 ratio is many times
larger than commonly seen when treating ARDS patients with iNO,
where an improvement by 20% is considered significant [4]. A similar
low PaO2/FIO2 ratio (110 mmHg) was also reported in another study
with a larger number of patients [5]. This suggests that the SARS pa
tients benefitted more by iNO with..
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