The Science

Medical updates regarding Coronavirus testing

How similar is SARS-CoV-2 to the common cold and flu viruses?


Coronavirus: is caused by the virus SARS-CoV-2 whose genome is a single strand of RNA. One interesting facet of coronaviruses is that they have the largest genomes of any known RNA viruses ( ≈ 30 kb). These large genomes led researchers to suspect the presence of a “proofreading mechanism” to reduce the mutation rate and stabilize the genome. This relatively low mutation rate will be of interest for future studies predicting the speed with which coronaviruses can evade our immunization efforts, such as vaccines.

Flu: is caused by an entirely different family of RNA viruses called influenza viruses. Flu viruses have smaller genomes encoded in 8 distinct strands of RNA, and they infect human cells in a different manner than coronaviruses.

“Common cold”: is caused by a variety of viruses, including some coronaviruses and rhinoviruses. Cold-causing coronaviruses (e.g. OC43 and 229E strains) are quite similar to SARS-CoV-2 in genome length and gene content, but different from SARS-CoV-2 in sequence and infection severity.

How stable and infectious is the virion on surfaces?


SARS-CoV-2 RNA has been detected on various surfaces several weeks after they were last touched (Moriarty et al. 2020). The probability of human infection from such exposure is not yet characterized as experiments to test this are very challenging. Nevertheless, caution and protective measures must be taken. More details on the risk of infection from touching surfaces urgently awaits study.

How do N95 masks block SARS-CoV-2?


N95 masks likely protect against several modes of viral transmission. Measurements of the particle filtration efficiency of N95 masks show that they are capable of filtering ≈99.8% of particles with a diameter of ~0.1 μm (Regnasamy et al. 2017) . SARS-CoV-2 is an enveloped virus ~0.1 μm in diameter, so N95 masks are capable of filtering most free virions.

N95 masks do more than just block viral particles. Viruses are often transmitted through droplets produced by coughing and sneezing.

These droplets are can be large droplets that fall rapidly to the ground and are thus transmitted only over short distances, or small droplets that evaporate and remain suspended in the air for significant periods of time. At present there is no direct evidence showing SARS-CoV-2 transmission by small evaporated droplets. Rather, larger droplets are believed to be the main vector of SARS-CoV-2 transmission, usually by settling onto surfaces that are touched and transported by hands onto mucosal membranes such as the eyes, nose and mouth (CDC 2020). Therefore, N95 masks likely protect against several modes of viral transmission.

How long does it take a single infected person to yield one million infected people?


The basic reproduction number, R0, suggests each infection directly generates 2-4 more infections in the absence of countermeasures like social distancing. Once a person is infected, it takes a period of time known as the latent period before they are able to transmit the virus. The current best-estimate of the median latent time is ≈3 days followed by ≈4 days of close to maximal infectiousness (Li et al. 2020, He et al. 2020). The exact durations vary among people, and some are infectious for much longer. Using R0 ≈4, the number of cases will quadruple every ≈7 days or double every ≈3 days.

Therefore, going from one case to 1000 requires about one month. So we expect one million cases in two months, and a billion cases in three months. Even though this calculation is highly simplified, ignoring the effects of “super-spreaders”, herd-immunity and incomplete testing, it emphasizes the fact that viruses can spread at a bewildering pace when no countermeasures are taken. This illustrates why it is crucial to limit the spread of the virus by social distancing measures.

Why is the quarantine period two weeks?


The period of time from infection to symptoms is termed the incubation period. The median SARS-CoV-2 incubation period is estimated to be roughly 5 days (Lauer et al. 2020) . Yet there is much person-to-person variation. Approximately 99% of those showing symptoms will show them before day 14, which explains the two week confinement period.

Importantly, this analysis neglects infected people who never show symptoms. Since asymptomatic people are not usually tested, it is still not clear how many such cases there are or how long asymptomatic people remain infectious for.

What is the effect of social distancing?


Suppose that you are infected and you encounter 50 people over the course of a day of working, commuting, socializing and running errands. To make the numbers round, let’s further suppose that you have a 2% chance of transmitting the virus in each of these encounters, so that you are likely to infect 1 new person each day. If you are infectious for 4 days, then you will infect 4 others on average.

With social distancing measures, you instead see 5 people each day (preferably fewer) then you will infect 0.1 people per day, or 0.4 people before you become less infectious. The desired effect of social distancing is to make each current infection produce less than 1 new infection.

What is the difference between the case fatality rate and the infection fatality rate?


Global statistics on new infections and fatalities are pouring in from many countries, providing somewhat different views on the severity and progression of the pandemic. Assessing the severity of the pandemic is critical for policy making and thus much effort has been put into quantification. The most common measure for the severity of a disease is the fatality rate.

One commonly reported measure is the case fatality rate (CFR), which is the proportion of fatalities out of total diagnosed cases. The CFR reported in different countries varies significantly, from 0.3% to about 10%. Several key factors affect the CFR. First, demographic parameters and practices associated with increased or decreased risk differ greatly across societies.

For example, the prevalence of smoking, the average age of the population, and the capacity of the healthcare system. Indeed, the majority of people dying from SARS-CoV-2 have a pre-existing condition such as cardiovascular disease or smoking (China CDC 2020).

There is also potential for bias in estimating the CFR. For example, a tendency to identify more severe cases (selection bias) will tend to overestimate the CFR. On the other hand, there is usually a delay between the onset of symptoms and death, which can lead to an underestimate of the CFR early in the progression of an epidemic.

Even when correcting for these factors, the CFR does not give a complete picture as many cases with mild or no symptoms are not tested. Thus, the CFR will tend to overestimate the rate of fatalities per infected person, termed the infection fatality rate (IFR). Estimating the total number of infected people is usually accomplished by testing a random sample for anti-viral antibodies, whose presence indicates that the patient was previously infected.

As of writing, such assays are not widely available, and so researchers resort to surrogate datasets generated by testing of foreign citizens returning home from infected countries (Verity et al. 2020), or epidemiological models estimating the number of undocumented cases (Li et al. 2020). These methods provide a first glimpse of the true severity of the disease.

Disclaimer: The above section have been modified from eLife 2020;9:e57309 doi: 10.7554/eLife.57309

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