Francesco Ferrara 1*, Giovanni Granata 2, Chiara Pelliccia 3,
Raffaele La Porta PhD 4, Antonio Vitiello 1
1: Usl Umbria 1, Perugia, Italy
2: Asl Salerno, Salerno, Italy
3: Usl Umbria 2, Terni, Italy
4: Asur Marche, Ancona, Italy
*author
correspondence: francesco.ferrara@uslumbria1.it
Abstract
Reduction of pulmonary
fibrotic status and reduction of hyperinflammation is essential to
combat SARS-CoV-2 and avoid death. Many authors have divided the
SARS-CoV-2 infection into three stages, the second and third of which
are purely inflammatory and fibrotic. Waiting for the development of
antiviral drugs and vaccines to give good results, the best
pharmacological goal is the reduction of proinflammatory molecules.
This leads to less formation of fibrotic tissue and to the resolution
of the patient’s respiratory problems. In fact, in phase 3, the most
serious, there is a state of overexpression of the immune system with
consequent assault on all tissues and damage to the lungs. Sars cov 2
pneumonia is characterized by ”cytokine storm” and can lead to death.
Acting early and with pirfenidone combination therapy can be
effective. The IL-6 or IL-1 inhibitors, chloroquine /
hydroxychloroquine and colchicine, which are demonstrating their
anti-inflammatory efficacy, when combined with an anti-inflammatory
and antifibrotic agent, such as pirfenidone, can have a winning
result. The effective combined terepia allows to use non-lethal
dosages and affects all the pathological steps induced by the virus.
Pirfenidone has been used for years in lung diseases and has been
shown to have good clinical success and good safety and
tolerability.The purpose of this study is to explain the
pharmacological logic behind the use of a combination therapy as an
effective and safe remedy to reduce pneumonia and the consequent death
from Sars CoV 2.
Keywords : pirfenidone, fibrotic, inflammation, cythokine,
interleukin, Sars-CoV-2.
Introduction
Sars-CoV-2 infection leads to hyperinflammation, fibrotic and
cicatricial state, lung collapse and death of the patient if he is at
risk. This clinical picture must be contrasted to put an end to a
global pandemic that has already caused thousands of victims and this
number is expected to grow exponentially.
If the health crisis that has
hit the whole world lasts for a long time, it risks generating a deep
economic crisis with all the activities stopped and the continuous
lock dawn imposed. For these
reasons, looking for a therapy that can make the virus harmless
immediately is of fundamental importance. Avoiding death is a great
success that allows you to have the time to find a drug directed
against the virus without blocking the whole
world. Preventing patient
death is a success to be
achieved. The excessive
inflammatory state induced by the Sars-CoV-2 virus has been shown to
aggravate the patient’s clinical picture. In the most serious phases
of the pathology there is an excessive release of proinflammatory
cytokines that lead to lung damage with extensive fibrosis and
scarring of the interstitial
lungs with respiratory
impairment. The combined use
of anti-inflammatory drugs and drugs that prevent fibrotic status can
beneficially resolve the clinical
picture. Today Pirfenidone is
the only drug that has been shown to reduce the fibrotic state of the
lung tissues and is the drug of choice in many lung diseases.
Combination therapy with pirfenidone can lead, albeit indirectly, to
the defeat of the virus.
The clinical aspects of three phases SARS‐CoV‐2
infection
The SARS-Cov-2 virus caused the current global pandemic. The first cases
of SARS-Cov-2 infection were recorded in November 2019 in China and then
rapidly spread to all countries around the world causing thousands of
deaths. SARS-Cov-2 infection can rapidly cause respiratory distress
syndrome. According to observational studies conducted, the majority of
patients considered as severe cases present bilateral intestinal
pneumonia, and an overactive inflammatory state that is not only
localized to lung tissue but to all tissues of the body. SARS-Cov-2
infection has been divided by scientific opinion into three phases, the
first asymptomatic or mildly symptomatic with symptoms such as mild sore
throat and abdominal pain, phase two and three more severe than one,
presenting with a generalized inflammatory state and respiratory
distress syndrome. Evidence has shown that bilateral interstitial
pneumonia, defined in this way because it attacks the intestinal tissue
covering the lung alveoli, is associated with the presence of fibrotic
tissue caused by excess collagen (fibrosis) in the pulmonary
interstitium with hyperinflammation present. Several therapeutic
treatments have been considered, and several clinical trials are
underway to test their efficacy and safety, drugs such as antivirals,
immunomodulants, anticoagulants are being tested to best fight
SARS-Cov-2 infection.As described above, phase two and three are the
most serious, and the presence of inflammation in the lungs and scar
tissue and fibrotic tissue, requires immunomodulating and
anti-inflammatory treatment to combat these phases, although at the
moment there are no certain data that demonstrate their effectiveness
and at what time they should be used, ongoing clinical trials will give
us more evidence. However, based on the descriptions of symptomatology
and diagnostic investigations from early observational studies, one
might think that the use of a drug currently indicated for pulmonary
fibrosis such as pyrfenidone could bring great benefits. We also
consider that given the very complex nature of the pathophysiology of
SARS-Cov-2, probably a combination of several drugs (pending the
marketing of a direct and specific antiviral or vaccine) in several
steps could be the most suitable treatment (1-23).