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. Because of the inaccuracy of the viral replicase as the virus actively grows it produces point mutations. Some of these mutant virus more effectively infect cells. The alpha variant became prominent in the Winter and Spring of 2021 subsequently a more highly infectious variant the Delta variant that originated in India has become the dominant strain in the U.S. and the U.K. 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, the alpha variant can infect 3.0-5.0 and for the Delta variant one person on average infects 5-8 individuals. Another characteristic that has allowed rapid spread is the existence of 40-60% asymptomatic or minimally symptomatic carriers. 10% are superspreaders infecting on average 10-60 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 were promoted from the very beginning of the pandemic 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 revealed that suppression (instituting all 5 tactics) was the only way to reduce R sub 0 to <1. Mitigation ( lowering the R sub0 but remaining > 1 allows the infection to continue and demands for treatment then outstrip the capacity of each country's health system. Campaign methods will need to be used to encourage effective infection control practices by everyone. A major challenge particularly in the United States disinformation. If people don't believe the disease is a concern they will resist following the 5 practices. Another major issue has been the socioeconomic consequences of closing schools, universities and businesses. The blunt approach of shelter in place should be avoiding whenever possible. A combination of infection control practices best described using the Swiss cheese analogy should allow a partial opening. However, this approach requires consensus and alignment. Each individual must agree to 1. wear a face mask in any potential infectious environment. 2. Avoid crowds and when necessary limit the duration of exposure. 3. Avoid closed poorly ventilated spaces , outdoor gathering being preferred. 4. Practice 6 foot physical distancing. 5. Practice good hand hygiene 6. Avoid touching your face and eyes. and 7. Ignore rumors and conspiracy theories and listen to acknowledged experts. Governments and institutions must provide adequate supplies of Personal Protective Equipment (PPE), provide accessible, timely and effective testing, respond to positive tests by contact tracing and appropriate quarantine and isolation procedures, create consistent scientifically based messages about infection control, treatment and vaccination. Create effective supply chains to provide PPE, medications, and vaccines. Vaccination will provide the ultimate solution and efficacious vaccines will soon be available. If enough individuals receive the vaccine herd immunity can be achieved and the pandemic will end.