Virology

The Coronavirus Disease 2019 (COVID-19) is a respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). By late March 2020, the viral infection, originally detected in China, had expanded into a worldwide pandemic.

Reservoir and strains: The viral strain was first discovered in the city of Wuhan, Hubei province of China in November, 2019. It is believed to be a zoonotic virus, related to coronavirus species found in bats with an intermediate animal reservoir that remains to be determined, although pangolins have been suspected. Features of the SARS-CoV-2 genome, including mutations in the receptor binding sites and subunit spikes, support the view that this is a novel virus that evolved through natural selection during the process of zoonotic transfer and that it is not derived from any previously known virus. Extensive mapping and tracking of the viral strains is currently underway through projects such as Nextstrain

It is still unknown whether SARS-CoV-2 was transmitted to human through an intermediate host.

Viruses change through mutation, and new variants can occur. There are three variants circulating globally. The United Kingdom first identified a variant called B.1.1.7 in the fall of 2020. This variant has a large number of mutations, and spread more easily and quickly than other variants. The variant called B.1.351 emerged independently of B.1.17 in South Africa, and was originally detected in October 2020. B.1.1.7 and B.1.351 doe share some mutations. Japan detected a variant called P.1 in travelers from Brazil. This variant contains more mutations that may affect its ability to be recognized by antibodies. All three new variants have been detected in the United States.

Viral characteristics: SARS-CoV-2 is a positive-sense, linear, single-stranded RNA virus from the coronaviridae family, specifically the betacoronavirus genus. Other viruses in coronaviridae family were responsible for the SARS-CoV outbreak in 2003 and the MERS-CoV outbreak in 2012. The viral infection commences with the attachment of the viral spike glycoprotein (S) to the receptor, which is suspected to be the angiotensin converting enzyme 2 (ACE2) receptor. Once in the cell, the virus is translated using the host ribosome. The virus also carries its own RNA-dependent RNA polymerase used to replicate the RNA for progeny viruses. The virus also has a number of virulence factors (Nsp1, Nsp3c, ORF7a) that interfere with host immunity. These virulence factors may be potential targets for effective anti-viral therapy.

Transmission: The virus is transmitted via the respiratory route by human-to-human contact, largely via respiratory droplets. These droplets have an effective range for infectivity of about two meters, but the virus may also be aerosolized and may be acquired from fomites (contaminated surfaces), both of which would extend the range of transmissibility beyond that possible by droplets alone. The virus has been found in blood and stool samples, but fecal-oral transmission has not yet been determined to be a major source of spread.

Incubation Period: The incubation period is around 5 days, with severe symptoms usually developing around 8 days after symptoms and set, and critical disease and death occur at around 16 days. This suggests that little infection occurs beyond 14 days of exposure.

Infectivity: The period of disease infectivity following infection remains uncertain. The basic reproductive number (R0) of the virus is not entirely clear and likely to vary by population density and other factors.An estimated R0 of 2.5 (1.8-3.6) has been proposed for SARS-CoV-2, which suggest a very highly transmissible virus. Findings regard the role of viral load in determining the severity and prognosis of the disease have been mixed. More recent studies have shown that the viral load is higher in non-hospitalized patients and has a significant inverse correlation with duration of symptoms. Viral loads have been shown to be inversely correlated with disease severity. Viral load appears to peak within the first week that symptoms develop.

Immunity: Following infection with the virus, antibodies are induced in those infected. However, how protective the response is, and how long the immunity lasts, is not securely known. Researchers have found durable immune responses in the majority of people that were previously infected with SARS-CoV-2. While the number of antibodies ranged between the study populations, the levels stayed relatively consistent until the 6-8 month mark after infection. 95% of individuals in one study had at least 3 of 5 immune-systems components that could recognize SARS-CoV-2 up to eight months after infection.  The risk of reinfection can occur with the circulation of new strains. What we know of antibody status in this disease can be found here.

Monoclonal Antibody: Monoclonal antibodies have been predicted to reduce viral load, decrease symptoms, and prevent hospitalization. In a recent trial, one of three doses of neutralizing LY-CoV555 appeared to accelerate the decline in viral load over time. The percentage of those hospitalized that were treated with monoclonal antibodies was 1.6% while those in the placebo group was 6.3%. In another recent study, REGN-CVO2 antibody cocktail reduced viral load, having a larger effect in patients whose immune response had not been initiated or who had a viral load at baseline. A 22% reduction in progression to ventilation was reported in regards to hospitalized patients with oxygen dependent COVID-19. Both of these clinical trials have received EUA’s from the FDA.