SARS-CoV-2, the agent causing COVID-19 has ignited a global health crisis unparalleled since the 1918 influenza pandemic. The virus emerged in late 2019 from live animal markets in Wuhan, China and on March 11, 2020, COVID-19 was declared a pandemic by the WHO.
There are seven human coronaviruses including SARS-CoV-2 with an RNA genome surrounded by a protein coat and lipid envelope studded with a corona (Latin for crown) of spikes projecting from the surface. The virus was introduced by zoonotic transmission from bats and is highly pathogenic and transmissible to humans, primarily through large respiratory droplets that enter the body through the eyes, nose, or mouth. If an infected individual coughs or sneezes without containing the droplets, the virus can spread >2 m. Even talking or singing can spread the virus, the reason why it is important to maintain social distancing of at least 2 m. SARS-CoV-2 may also be present in faeces, a potential source of transmission from aerosols generated when flushing toilets without first closing the lid. To prevent infection, it is important to wash your hands with soap and water after using the toilet and before eating.
Infections depend on binding virion spike (S) protein primed by host cell TMPRSS2 enzymes to ACE2-receptors on respiratory and small intestine cells. The average incubation period is 5 days after exposure. Unlike influenza, symptoms begin gradually and include flu-like and GI symptoms, purple toes, loss of smell and taste. Infections range from asymptomatic to severe/critical, mainly in individuals > 65 yr., obese, with co-morbidities, and in nursing homes.
Infected individuals are generally infectious for 2-3 days before symptoms to >=20 days post-infection. Complications include systemic infection, endotheliosis, hypercoagulability, co-infections, and lung fibrosis with bilateral diffuse ground-glass infiltrates. Some cases elicit a ‘cytokine storm’ due to immune hyperactivation and interleukin production (e.g., IL-6) with increased severity. The recently described multisystem inflammatory syndrome in children (MIS-C) follows exposure to SARS-CoV-2 with persistent fever and organ dysfunction.
PCR tests using nasal swabs are generally positive ~ 1-d before onset. Rapid tests include ID NOW with results within 13 min and GeneXpert within 45 min. Other automated molecular tests, batch specimens with longer turnaround times. Antibody tests detect past infections and are generally positive within 2-week post-exposure. Results must be interpreted with caution due to false (+) and (-) reactions. Many tests are designated Emergency Use Authorization (EUA) not cleared by FDA but can be performed for the duration of the pandemic.
The Reproductive Number (Ro, pronounced R naught) refers to the number of new cases that occur from one infected person in a population with no immunity, that can be used to justify mitigation strategies to decrease cases and deaths during a pandemic. The higher the Ro, the more rapid the spread of the disease. If the Ro=4, a single infected person can transmit the virus to four non-immune individuals and so on. In the U.S., the Ro ranges between ~2 – 6 depending on adherence to social distancing. Decreasing the number of cases requires immunity of a significant percentage of people either by ‘herd immunity’ or by immunisation. The U.S. is estimated to need immunity in 70 per cent of the population. This will take a concerted effort of the entire population and contact tracing for an extended period. If not, we likely will see infection rates rising and falling due to relaxed social distancing.
Populations at greatest risk include prolonged exposure to infected individuals (e.g., low income, minority communities with high rates of chronic illnesses). The disparities in testing for marginalised communities cannot be ignored and is critical for control of COVID-19.
Interventions include social distancing, staying home when sick, frequent hand washing or 70 per cent alcohol hand sanitizing, correctly donning and doffing masks, coughing/ sneezing into your elbow, et al. Scientists are racing to provide safe and effective COVID-19 vaccines using mRNA, DNA, and adenovirus vectors.
1) Remdesivir has been rationed under EAU for 5-10-day IV treatment of hospitalised patients with severe COVID-19 disease.
2) Recently, FDA has revoked the EAU of hydroxychloroquine and chloroquine for treating COVID-19.
3) Tocilizumab anti-IL-6 monoclonal antibodies are used to interrupt hyperinflammation due to cytokine release.
4) Anti-SARS-CoV-2 blocking antibodies are currently in development to prevent virus spike (S1) protein from binding to host cell ACE-2 receptors.
5) Mayo Clinic is spearheading a clinical trial using convalescent plasma transfusions containing SARS-CoV-2 antibodies from patients who recovered from COVID-19.
What should we expect in the coming months? Until herd immunity can be established in a population, or a vaccine(s) is available, physical distancing measures will need to continue. As all countries come together to contain COVID-19, we must work to contain misinformation.
References available upon request.