The present study is a randomized, double-blind, placebo-controlled, clinical trial, with the approval of the ethics committee will be conducted on patients who have a positive test confirming COVID-19 in Loghman Hakim Medical Education Center in Tehran. Patients will be randomly assigned to the two arms of the study and after completing the course of treatment and collecting and analyzing the necessary information from each patient, the results of the study will be published both on this site and in the form of an article in a reputable international journal.

According to previous studies, IFN-β, amongst IFN-1s, has strong antiviral activity and also has an acceptable safety profile. Based on possible therapeutic effects, We decided to lead An Investigation into Beneficial Effects of Interferon Beta 1a, Compared to Interferon Beta 1b And The Base Therapeutic Regiment in Moderate to Severe COVID-19. In a 2003 study, SARS was treated with different human interferons and found that IFN-β was 5 to 10 times more effective than other types of interferons and the strongest antiviral drug possible against SARS-CoV.

Chloroquine has been a broadly-utilized anti-malaria agent which back in 2006, had been proved to be a powerful wide-spectrum antiviral. Moreover, Chloroquine has the characteristics of anti-inflammatory and immune-modulatory by inhibiting the production of TNF-α along with IL-6. In the first half of February, Wang et al illustrated puissant inhibition of SARS-CoV-2 by Chloroquine, when taking two 500-mg tablets of it by mouth per day; similar to some clinical studies in China through this outbreak. According to the news briefing of works of Per Gao et al., it was indicated that chloroquine phosphate actually outdo the control treatment in inhibition of pneumonia exacerbation, improving lung imaging findings, and curtailing the disease course. X. Yao et al. evaluated the possible doses of CQ and HCQ to find the optimized dose in treatment of COVID-19. They revealed that while within in-vitro settings Hydroxychloroquine is more potent than chloroquine. As a conclusion, they suggested a 800 mg daily dose of hydroxychloroquine, followed by an overall maintenance dose of 400 mg per day divided in two separate doses, which was three-fold more potent compared to the 500 mg twice daily administration of chloroquine in 5 days. The new study of Gautret et al. published in 16th March, pointed out that hydroxychloroquine was notably effectual in eradicating SARS-CoV-2 from the nasopharynx. Currently the evidence is quite inconclusive about the effectiveness or comparative effectiveness of either HCQ or CQ. Moreover, CQ has recently become scarce and even unavailable for ordering due to a huge demand for it, all because of a significant interest gained as a potential medicinal alternative for the management of COVID-19. In spite of all, the primary experience in China and France is propitious for the potential role of chloroquine, or alternatively hydroxychloroquine, for managing COVID-19.

Lopinavir, classified in the drug group of protease inhibitors, is utilized for the treatment of patients affected prolongedly with HIV-1. The mechanism by which Lopinavir acts is blocking the main protease of SARS-CoV-1, resulting in inhibition of viral replication. Real-world information supporting the treatment of COVID-19 with LPV/r keep coming out. Chu et al. have discovered that LPV/r has an anti-SARS-CoV effect within both in-vitro settings and clinical studies. In disclosed results of Young and colleagues' research on COVID-19 patients in Singapore, 5 cases received LPV/r monotherapy. Among those 5 patients, 3 had decrease in oxygen requirements after treatment, while the other 2 had their conditions worsened to the point of respiratory failure. Other published evaluations from Korea and China made up of a total of 6 patients, show reduced viral load, and clinical improvement after onset of LPV/r treatment. Latterly, Cao and colleagues illustrated the results of comparing twice a day use of LPV/r 400/100 mg to standard care, for treating the pneumonia caused by SARS-CoV-2. This study's upshot, demonstrated no benefit regarding a lopinavir-ritonavir treatment beyond standard care. Considering the currently available data, it is yet to be determined whether LPV/r could significantly affect the status of COVID-19 patients, either as monotherapy or in combination-therapy. Moreover, close monitoring is needed during the administration of this drug, because particularly elevated levels of AST or ALT suggesting the gastrointestinal complications and hepatoxicity may exclude patients with COVID-19 from clinical trials.

The present study is a randomized, double-blind, placebo-controlled, clinical trial, with the approval of the ethics committee will be conducted on patients who have a positive test confirming COVID-19 in Loghman Hakim Medical Education Center in Tehran. Patients will be randomly assigned to the two arms of the study and after completing the course of treatment and collecting and analyzing the necessary information from each patient, the results of the study will be published both on this site and in the form of an article in a reputable international journal.

Inclusion Criteria:

• Age ≥ 50
• COVID-19 Confirmed Cases (Either RT-PCR or CT Scan Confirmed).
• Tympanic Temperature of ≥37.5 AND at least one of the following: Cough, Sputum production, nasal discharge, myalgia, headache or fatigue) on admission.
• Time of onset of the symptoms should be acute ( Days ≤ 10).
• SpO2 ≤ 88%
• Respiratory Rate ≥ 24

Exclusion Criteria:

• Refusal to participate expressed by patient or legally authorized representative if they are present.
• Patients with prolonged QT or PR intervals, Second or Third Degree heart block, Arrhythmias including torsade de pointes
• Patients using drugs with potential interaction with Umifenovir Hydroxychloroquine, Lopinavir/Ritonavir or Interferon-β 1a.
• Pregnant or lactating women.
• History of alcohol or drug addiction in the past 5 years.
• Blood ALT/AST levels > 5 times the upper limit of normal on laboratory results.

There is no further information.