New Corona virus (COVID-19) has made a horrible situation for all of the countries. This disease is not only a health problem but also economy, culture and the whole entity of the countries is under attack by the virus. This disease seems to affect the body in two different pathology pathways. From one side virus can decrease activity of immune system in the blood stream and whole body and from other side it can attack the respiratory cells. Tissue biopsy shows that immune cells penetrate into the Lung tissue and we have accumulation and over activity of Immune cells in the lung. This inflammation in respiratory tract probably is the major cause of Cytokine storm and release of TNF-α and IL-6 into the blood. It seems that by three strategy disease can be treated. 1- By using systemic immune simulators. 2- By using topical anti-inflammatory drug in the respiratory system (Steroids or NSAIDs) 3- By inhibition of replication of the virus in the attacked cells.
Looking at the pathology of this disease shows that COVID-19 virus binds to the Angiotensin
converting enzyme II (ACE II) which is located on the surface of different cells in the body
and specially on the cells of respiratory system. This enzyme is responsible to turn
angiotensin II into angiotensin1-7. It is also turns angiotensin I into angiotensin 1-9.
When ACEII would be blocked by virus level of angiotensin II will be increased and this
enzyme along with vasoconstriction, makes cells to manufacture TNF α and IL-6 which are
responsible for cytokine storm and Lymphopenia. Also presence of virus and virus shell on the
surface of the infected cells make immune system to attack to the respiratory system hence
effect of angiotensin II inside the cell causes fibrosis of the respiratory cells. This
inflammation and tissue damage make Acute Respiratory Distress syndrome (ARDS) which is
lethal for patients. There is a dilemma in treatment of this infection. From one side it
doesn't make sense to decrease the immune response hence it will make the infection worse.
And from other side stimulation of the immune response because of respiratory inflammation
can expedite process of lethal ARDS. A new strategy for treatment of this disease which
consists of local anti- inflammatory and systemic immune stimulant drugs can be considered as
a reasonable strategy.As immunostimulator, Levamisole can increase Lymphocytes and empower
the immunity of the body. This drug can also bind to Papaine Like Protease(PL-pro) of the
shell of the virus which is necessary for virulence of COVID-19. It also can decrease level
of TNF α and IL-6, and as a chemical adjutant can introduce the virus to the immune system.
In addition to Levamisole, Formoterol+Budesonide inhaler can be used in this protocol.
Budesonide is a steroid and can suppress the immune reaction locally in the respiratory
system. Formoterol is β2 agonist and can open airways. It also can bind to PL-pro and can
neutralize the virus according to the published articles.
Drug: Levamisole Pill + Budesonide+Formoterol inhaler
Levamisole 50 mg tablet has to be taken 1-2 tablets every 8 hours Budesonide+Formoterol has to be inhaled 1-2 puff every 12 hours
Other Name: Levamisole and Budesonide+Formoterol inhaler both are generic drugs.
Drug: Lopinavir/Ritonavir + hydoxychloroquine
Hydroxy Chloroquine 200mg single dise Lopinavir/Ritonavir 2 tablets every 12 hours
Other Name: Kaletra+ Generic Hydroxy Chloroquine( Generic Drug)
Inclusion Criteria:
Definitely positive COVID-19 patients
Exclusion Criteria:
Patients with acute respiratory problems including patients with:
1. Spo2<60%
2. Severe respiratory distress
3. Heamodynamic instabilitty
4. Acid base disturbance
5. Severe Anemia Patients with severe hepatic diseases Patients with Nurvous system
diseases
Vali-Asr Hospital
Fasa, Fars, Iran, Islamic Republic of
Investigator: Jalal Karimi, PhD
Contact: +987153314026
info@fums.ac.ir
Siamack Afazeli, Pharm.D
+989121392982
Dr.afazeli@gmail.com
Mojtaba Farjaam, MD
+989177104789
farjam.md@gmail.com
Siamack Afazeli, Principal Investigator
Fasa University of Medical Sciences