**2. Comorbidities and their drug treatments**

#### **2.1 COVID-19**

COVID-19 is a respiratory infection caused by the virus named "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2) [8]. COVID-19 is a novel disease officially declared as a pandemic on March 11th, 2020 [9, 10]. SARS-CoV-2 has infected 98.2 million people worldwide and caused 2.1 million deaths as of January 24th, 2021 [11]. COVID-19 is characterized by dry cough, fever, and fatigue symptoms in adults while in children rhinorrhea, abdominal pain, and diarrhea are also present [10]. SARS-CoV-2 binds directly to angiotensin converting enzyme 2 (ACE2) for subsequent entry into cells [10, 12]. Infected cells respond to the virus by generating pro-inflammatory cytokines and chemokines that sometimes lead to a cytokine storm which aggravates the disease [10, 12, 13]. Those with certain underlying health conditions such as respiratory disease, cardiovascular disease, and diabetes as well as older individuals seem to be at a higher risk for developing severe complications from the infection [14, 15]. Because SARS-CoV-2 has approximately 80% genomic homology with SARS-CoV-1, the virus that caused the 2002–2003 epidemic, many research studies have proposed the use of treatments that were effective against SARS-CoV-1 [9]. Current treatments for COVID-19 used in the clinics are ACE2 inhibitors, corticosteroids, chloroquine, anti-inflammatory tocilizumab, comostat, protease inhibitors (lopivavir and ritonavir), and RNA polymerase inhibitors (remdesivir, favipiravir) [16]. Some of the established protocols are: no treatment for mild cases besides acetaminophen for fever; hydroxychloroquine + azithromycin for moderate cases; tocilizumab or sarilumab for worsening respiratory function; and remdesivir, convalescent plasma, corticosteroids for respiratory failure. NSAIDs such as ibuprofen are not recommended

due to potential increase in ACE2 expression [17]. Lastly, it has been suggested that reduction in cholesterol decreases viral mRNA [18]. Thus, treatments that reduce cholesterol in addition to antivirals, anti-inflammatories, and respiratory support should be beneficial in managing COVID-19.
