COVID-19 - A clinical update

Coronaviruses infect many species of animal including the bat. These RNA viruses frequently mutate particularly in bats, and chance mutations rendered the SARS-CoV-2 capable of readily infecting humans. The bat virus infected an intermediate host, possibly the Pangolin that was sold in the live fish and animal market in China. A key virulence (characteristic that allows a pathogen to cause disease) factor is the S protein which was the likely primary target of the mutations. This protein forms knobs on the outer surface of the virus that bind strongly to the ACE2 receptor on human respiratory epithelial cells. Binding is followed by internalization and within the cell the virus replicates its RNA using a replicase and assembles into a nuclear capsid in the host cell cytoplasm RNA is also translated into proteins that coat the outer surface of the virus. Once fully assembled the virus is exocytosed (released) from vesicles. The new viral particles can infect other cells and spread to other humans. The virus first replicates in the throat and nasal passages and then spreads to the trachea, bronchi and alveoli where it induces inflammation and damage to the alveolar walls causing fluid to leak into the air exchanging sacks and interfering with oxygen exchange. If inflammation continues the alveolar walls become fibrosed (scarred) and further compromising oxygen exchange resulting in decreases in oxygen saturation (hypoxia). SARS-CoV-2 is able to spread efficiently from person to person primarily by droplets and aerosol (tiny particles that stay in the air for hours). Infection quickly spread throughout the world and caused a pandemic within 3 months. Humans were infected at the Huanan live fish and animal market. The infection initially was confined to workers in the market (point source) but then quickly spread person to person within the first 10 days. Because of the lack of travel restrictions early in the outbreak Chinese traveling from the area quickly spread the virus to many other countries. The lack of therapy or vaccine has allowed the virus to move from person to person unchecked with a steep exponential curve with a doubling of cases every 2-3 days. This virus is one of the most infectious ever reported each infected person on average infecting 2.2 to 2.7 people. Another characteristic that has allowed rapid spread is the existence of 40-60% asymptomatic or minimally symptomatic carriers. 10% are superspreaders infecting on average 10-30 others.

COVID-19 presents similarly to influenza. The most common symptoms are fever (>100.4 °F or 38°C), dry cough, and shortness of breath. Other common symptoms include marked fatigue, myalgias (muscle aches), headache, and sorethroat. Chest tightness can develop early in severe cases. Diarrhea and vomiting less commonly can be presenting complaints. Physical exam is usually unremarkable with the exception of fever, tachycardias (elevated pulse), an elevated respiratory rate and low oxygen saturation on room air. Lymphadenopathy is usually not present and pulmonary exam is unremarkable. Laboratory studies are nonspecific with a low lymphocyte count, low platelets, elevated CRP, and normal procalcitonin level. CXR is insensitive (60% sensitivity) chest CT being more sensitive and highly specific and is the study of choice in patients being considered for admission to the hospital.

Treatment consists of supportive care by administering nasal O2 to maintain saturation above 92%. If nasal O2 fails to achieve appropriate oxygenation intubation and mechanical ventilation with PEEP (positive end expiratory pressure) is recommended and standard ARDS protocols should guide care. Septic shock with end organ damage can develop and standard sepsis protocols are recommended with the exception of fluid administration which should be cautious. The critical management tool for this disease is prevention through infection control methods. The 5 tactics for preventing the spread of infection are 1. Identification and isolation of infected individuals. 2. Quarantining all contacts of infected patients 3. Social (or physical) distancing of individuals >70 yo, 4. Social distancing by everyone and 5. Closing of schools, universities, and nonessential businesses. Modeling by the Imperial College reveal that suppression (instituting all 5 tactics) is the only way to reduce R sub 0 to <1. Mitigation ( lowering the R sub0 but remaining > 1 will allow the infection to continue and demands for treatment will outstrip the capacity of each country's health system. Campaign methods will need to be used to encourage social distancing by everyone.