“Novel Coronavirus SARS-CoV-2” by NIAID is licensed under CC BY 2.0 (Virus emerging from the surface of an infected cell)
We have heard about a new virus that was causing pneumonia since December 2019; the virus was spreading in China and it was temporarily called 2019-nCoV.
On February 11th, 2020, the International Committee on Taxonomy of Viruses (ICTV)officially named it SARS-CoV-2, and the World Health Organization (WHO) established the name of the associated disease: COVID-19. The clinical manifestations of the infection are heterogeneous, varying from asymptomatic carriers to acute respiratory disease and pneumonia.
On March 11th, 2020, the WHO declared that, with more than 118.000 cases in 114 countries, COVID-19 could be defined as a pandemic.
From the report of the first case of atypical pneumonia in Wuhan to March 22nd, 2020, 494 scientific papers were produced about clinical features of patients, transmission route of the virus, its persistence in aerosol and surfaces, its molecular characterisation, mathematical models of its spreading, pathogenesis, possible treatments and vaccines.
Here I report some of the central pieces of knowledge from a selection of the so far published articles.
Origin of the virus. SARS-CoV-2 is the seventh coronavirus known to infect humans. Its Spike protein (S), as the S protein of SARS-CoV, binds to the human protein ACE-2 as well as to similar proteins of other animal species. The binding site between the new virus S protein and human ACE-2 is however different and less efficient than the already known binding site of SARS-CoV, indicating that the virus was not intentionally created in a laboratory, but is the result of natural random mutations.
The virus as it is currently spreading among the human population could have arisen in two ways:
1) by natural selection in an animal host (probably present in the Wuhan wet market) before the host shift,
2) by natural selection in humans after the host shift.
According to the first hypothesis, the analysis of the SARS-CoV-2 genome revealed important similarities with a related virus infecting bats, and another one infecting pangolins. However, none of the viruses so far isolated from these animals is similar enough to be the direct progenitor of the human virus, but we have to keep in mind that not all the viruses that infect these animals are known or characterized. We would need to identify a bat or pangolin species with an ACE-2 protein extremely similar to the human one, in which SARS-CoV-2 could have acquired its characteristics before being transmitted to humans.
The second hypothesis is that the virus was first transmitted from animals to humans, and then it spread undetected from human to human, and that during these passages it accumulated mutations that improved the ability of the S protein to bind human ACE-2. The high similarity between the S protein of the pangolin virus and that of the human virus suggests that the virus firstly originated in the pangolins, and that acquired favourable mutations in the human host.
Further studies are needed to determine which hypothesis is the correct one.
The fact that some sequences within the SARS-CoV-2 genome are similar to those of other known viruses, other coronaviruses as well as non-related viruses like HIV, does not mean that the virus was created in a laboratory. On the contrary, this indicates its natural origin: as similar sequences are shared between human genes and genes of other animals, in the same way, similar sequences are shared between different viruses, because evolution selects similar sequences for similar functions in different organisms. Moreover, if the virus was intentionally created in a laboratory, the sequences “taken” from other viruses would have been identical (“copied and pasted”) rather than simply similar.
TraNsmission and incubation period. The ACE-2 protein, to which the virus binds, is present in many tissues of the human bodies, particularly in the oral mucosa, considered the most important entry way for SARS-CoV-2. The virus can likely entry also through the conjunctival membrane of the eyes since it has been reported that doctors wearing face masks that covered mouth and nose, but not wearing protective goggles, acquired the virus while attending positive patients.
Being a virus that infects the airways, the presence of the virus is usually detected on oropharyngeal and nasal swabs, sputum, bronchoalveolar lavage fluid and in the biopsies of patients with more severe symptoms. One study analysed different sample types collected from 205 patients in three hospitals in China, and in some cases, the virus was found also in the blood and feces (1% and 29% of cases respectively). The presence of vital virus in these sample types suggests that the infection can be systemic (not limited to the respiratory tract) and that it could be transmitted by the fecal-oral route.
Several studies have calculated the incubation time, the period between the exposure to the infectious agent and the onset of the symptoms, obtaining variable results: it seems to be around 5 days, but it can range between 2 and 14 days (this is way a quarantine of 14 days is required after being in contact with infected subjects). The analysis of more cases is necessary to achieve a more precise determination of the incubation time.
The latency time, that is the period between getting the virus and becoming contagious, is another important characteristic: the analysis of asymptomatic positive patients and patients with mild symptoms, suggests that is shorter than the incubation time, meaning that an infected person can be contagious before having developed the symptoms.
PERSISTENCE ON SURFACES. It has been shown that SARS-CoV-2 remains stable in the air for up to 3 hours. It can persist in a vital form (capable to infect) as long as 72 hours on plastic, 48 hours on stainless steel, 8 hours on cardboard and 4 hours on copper. These data mean that the virus is transmitted through aerosol and by physical contact with contaminated objects. Objects can be decontaminated using reagents proven to be efficient with other coronaviruses, containing the proper concentration of one of the following chemicals: ethanol 62-71%, hydrogen peroxide 0.5% or sodium hypochlorite 0.1%.
Vaccine development. To date, it is not clear whether SARS-CoV-2 infection induces the production of antibodies, whether such antibodies are protective against a second infection, and for how long they can persist in our body. Several research centres and pharmaceutical companies are working on the development of an efficient vaccine against SARS-CoV-2. The first step in this process is to identify the viral proteins that can induce antibody production (antigens). For a vaccine to be effective the induced antibodies must be able to “intercept” the virus; for some viral infection, however, the antibodies produced by the immune system do not block the virus, as in the case of antibodies against the antigene e of the hepatitis B virus (the topic of a previous post). Once the antigen with the necessary characteristics has been identified, the vaccine composition is studied and its safety (absence of adverse effects) and efficacy need to be assessed, first in animal models, and then in humans.
The viral protein that is being currently studied is the S protein, exposed on the viral surface and responsible for its attachment to the human cells. On March 16th, 2020 the American company Moderna started the first clinical test to access the safety of a potential vaccine against SARS-CoV-2; the company expects that if the vaccine results safe and effective, it could available in 12-18 months.
These are only some of the aspects of the virus and the disease investigated by the scientists all over the world. If you have any other questions about SARS-CoV-2 or COVID-19 please leave a comment and I will find the answer for you.
BIBLIOGRAPHY:
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/events-as-they-happen
The species Severe acute respiratory syndrome related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2, Coronaviridae Study Group of the International Committee on Taxonomy of Viruses, Nature microbiology 2020 http://doi.org/10.0.4.14/s41564-020-0695-z
The proximal origin of SARS-CoV-2, Andersen K.G et al., Nature 2020 https://doi.org/10.1038/s41591-020-0820-9
No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2, Shan-Lu L. et al., Emerging microbes and infections 2020 http://doi.org/10.1080/22221751.2020.1733440
Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis, Hamming I. et al, Journal of Pathology 2004 http://doi.org/10.1002/path.1570
High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa, Xu H. et al., International journal of oral science 2020 http://doi.org/10.1038/s41368-020-0074-x
2019-nCoV transmission through the ocular surface must not be ignored, Cheng-wei Lu et al., The Lancet 2020 https://doi.org/10.1016/S0140-6736(20)30313-5
Detection of SARS-CoV-23 in Different Types of Clinical Specimens, Wang W. at al., Journal of the American Medical Association, 2020 http://doi.org/10.1001/jama.2020.3786
Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths, Lai C-C et al., Journal of Microbiology, Immunology and infection 2020 https://doi.org/10.1016/j.jmii.2020.02.012
The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application, Lauer S.A. et al., Annals of Internal Medicine 2020 http://doi.org/10.7326/M20-0504
Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1, van Doremalen N. et al., The New Egland Journal of Medicine 2020 http://doi.org/10.1056/NEJMc2004973
Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents, Kampf G. et al., Journal of Hospital Infection 2020. https://doi.org/10.1016/j.jhin.2020.01.022
Coronavirus vaccines: five key questions as trials begin, Callaway E., https://www.nature.com/articles/d41586-020-00798-8
https://www.modernatx.com/modernas-work-potential-vaccine-against-covid-19
A Sequence Homology and Bioinformatic Approach Can Predict Candidate Targets for Immune Responses to SARS-CoV-2, Grifoni A. at al., Cell Host & Microbe 2020 https://doi.org/10.1016/j.chom.2020.03.002
Development of epitope‐based peptide vaccine against novel coronavirus 2019 (SARS‐COV‐2): Immunoinformatics approach, Bhattacharya M. et al., Journal of Medical Virology 2020 http://doi.org/10.1002/jmv.25736
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