The new coronavirus has emerged since late 2019 and spread rapidly around the world, turning to a pandemic. Medical scientists and researchers are trying to find effective drugs to treat this disease (1). Coronaviruses are named positive-sense RNA viruses because of having crown-like spikes on their surfaces. Coronaviruses are a large family of viruses belonging to the genus Nidovirales, family Coronaviridae (2, 3). On January 2nd, 2020, 41 patients were diagnosed with Coronavirus Disease 2019 (COVID-19) COVID-19 infection based on laboratory tests. Less than half of them had underlying diseases, such as diabetes, hypertension, and cardiovascular disease (4). In patients with COVID-19, the number of leukocytes in the respiratory system is abnormally high. The main pathogenesis of COVID-19 is severe pneumonia, RNAaemia, incidence of ground-glass opacities, and acute heart injury. Significantly high blood levels of cytokines and chemokines are seen in patients with COVID-19, including IL1-β, IL1RA, IL7, IL8, IL9, IL10, basic FGF2, GCSF, GMCSF, IFNγ IP10, MCP1 , MIP1α, MIP1β, PDGFB, TNFα, and VEGFA. Some severe cases admitted to the intensive care unit have been shown to have high levels of proinflammatory cytokines, including IL2, IL7, IL10, GCSF, IP10, MCP1, MIP1α, and TNFα, leading to increased disease severity (4). Tetracyclines are lipophilic compounds and have good tissue penetration; hence, there are a good concentration of this drug in the skin, nails, scalp, conjunctiva, tears, milk, saliva, and intracellular fluid (5). They are broad-spectrum bacteriostatic compounds and have activity against gram-positive, gram-negative bacteria, intracellular organisms, atypical organisms (e.g. Chlamydia and Mycoplasma Virginia) and protozoan parasites (6, 7). The mechanism of action of doxycycline is to inhibit bacterial protein synthesis through the irreversible binding of 30S and possibly S50 ribosomes as well as alterations in the cytoplasmic membrane. (5, 6, 7). Oral doxycycline is almost completely absorbed and its plasma concentration is reduced by 20% when consumed with high-fat foods or milk. It is well distributed in most body fluids, including pleural, synovial, and bronchial secretions. Its binding to proteins is more than 90%. The advantage of this drug is that it does not have hepatic metabolism; therefore, dose adjustment is not needed in patients with hepatic disease.
The bioavailability of this drug is reduced at high pH conditions, such as gastrectomy, gastric bypass surgery, or achlorhydric condition. The half-life of this drug is 18 to 22 hours. It is contraindicated in children less than 8 years of age, during pregnancy, and lactation (8, 9). The mechanism of anti-inflammatory effects of doxycycline is to inhibit bacterial products (reducing the production of chemotactic neutrophil cytokines) that stimulate inflammatory processes. Doxycycline in vitro and dermal studies inhibit leukocyte migration by chelating intracellular calcium at the onset of the inflammatory process. Tetracyclines can also suppress alpha-amylases, phospholipase A2, TNF (α), and interleukin1beta (IL-1β). Doxycycline can reduce the levels of inflammatory cytokines in neonatal rats, such as TNFα, IL-1β, and IL-6 (7, 10- 12). However, doxycycline is more effective than tetracycline in reducing pro-inflammatory cytokines (13). In this study, we evaluated the effect of doxycycline in both outpatients and inpatients with COVID-19. Patients were evaluated on the baseline day and on days 3, 7, and 14 after admission for cough, Shortness of breath (SOB), temperature and O2 sat.