SARS-CoV-2: What do we know so far?

SARS-CoV-2: What do we know so far?

How will the SARS-CoV-2 emergency end? Will we be immunized after the disease has passed? Will a vaccine be developed?

We don’t have all the answers, but published research can give us some clues. In February, we published this infographic but right now we have more information to put you up to date. Let’s go through it.

If you haven’t read them yet, you can go through our posts about seasonal flu and vaccines. They will help you understand some concepts that we will mention next.

COVID-19, SARS-CoV-2? What does it mean?

COVID-19 is the name given to the disease caused by the virus SARS-CoV-2. The name SARS comes from Severe Acute Respiratory Syndrome. We already knew about coronavirus causing epidemics, specifically SARS-CoV and MERS-CoV (Middle East Respiratory Syndrome). Published research regarding these two viruses could help us find new ways to stop the current pandemic.

Which virus family does it belong to?

Within the coronavirus family 4 genera are known: α, β, γ, δ. Currently, only virus from genera α and β are known to infect humans. MERS-CoV and SARS-CoV are both part of genus β, as it is this newly found SARS-CoV-2. We know that the SARS-CoV-2, as all the virus belonging to this family, it is a single strand RNA virus.

Where does the virus come from?

The virus isolated from the first patients shows 88% identity in sequence with two other viruses that infect bats. This phenomena is known as species jump. Scientists think that it could have passed through another mammal before, but it is still unidentified. The WHO has said, by now, is that it seems that pets such as cats and dogs cannot spread the disease.

What shall we do to prevent infection?

Virus are generally build of genetic material (DNA or RNA) wrapped up in a protein capsid. Additionally, some of them have an extra layer made up of membrane fragments from the host cell they infect. In plain terms, these viruses “steal” some membrane from their victim when they leave the cell. SARS-CoV-2 is one of this viruses, and for this reason our main recommendation is to frequently wash hands with soap. Celular membranes (and virus which have them) are made of lipids. Lipids are what we commonly know as fat, and are highly hydrophobic (waterproof). As we know, soap dissolves fats and so does the same with the virus envelope. This way the virus stops being infective.

How does the virus infect us?

We currently know that SARS-CoV needs a protein known as ACE2 (angiotensin-converting enzyme 2) that uses as a receptor to enter the cell. Viral receptors are molecules found in the membranes of our own cells with other functions that virus can use at their favor to enter.

Knowing the entry mechanisms of virus is important so we can use them as therapeutic targets. For example, HIV can enter through a receptor named CCR5 (among others). There are preople with mutations causing this CCR5 protein to be slightly different, disabling the viral infection pathway. These days you might have read about another patient recovered from HIV and what exactly was done was a bone marrow transplant with the particularity that the donor had this CCR5 mutation. This way, the virus suddenly finds itself without a receptor to enter the cells, ceases to be infective, and thus ends up being eliminated.

Aside from knowing which receptors a virus uses in humans, having information about its receptors in other species can help us predict whether the virus could be capable of infecting humans based on whether we have potential receptors that resemble it.

What pathology does the virus cause?

As it has been said a lot in the media, the main symptoms of the disease are fever, dry cough, dyspnea, myalgia, fatigue and pneumonia. The mechanisms of the pathogenesis of the virus are still unknown, but given that the symptoms are very similar to those produced by the SARS-CoV and MERS-CoV viruses, the study of these can give us information.

How does our immune system respond to the virus? Why don’t we respond all the same?

To answer this we have to talk about different phases of response.

Antigenic presentation

An important stage of the immune response is the antigen presentation. The cells in our body have a mechanism that is used to “show” to the cells of the immune system what they have inside. The molecules that do this function are known as MHC (Major Histocompatibility Complex). In humans, these molecules are known as HLA (Human Leukocyte Antigen), and we talked a little about them here.

What happens is that parts of the protein (peptides) inside the cell bind to HLA molecules, which present the peptides outside. If the cell is not infected it will present only peptides of its own, but if an intracellular pathogen (i.e. virus) is present, the HLA molecules will present peptides from the pathogen. Adaptive immunity cells will interact with these molecules to identify what’s going on. If they only see peptides in principle they will not act, but if they find peptides that they do not identify, an adaptive response will be initiated.

But things are a little trickier as there are different HLA molecules and each person has a specific combination, a combination inherited from father and mother. In practice, what this implies is that each HLA molecule presents different peptides even though they come from the same proteins, and this conditions the ensuing response. We know from SARS-CoV and MERS-CoV that some specific HLA polymorphisms correlate more with their susceptibility to the diseases they cause, while others appear to have a more protective effect. This could happen in a similar way to SARS-CoV-2 and it would be one of the answers to why it does not affect everyone equally.

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Adaptive humoral response

Antigen presentation activates adaptive response, involving T and B lymphocytes. Viral infections typically trigger a first response in which B cells secrete IgM and IgG antibodies (we talked about immunoglobulins here). The antibody-mediated response is what we call the humoral response. In SARS-CoV infection, it is known that IgM-type antibodies disappear after about 12 weeks, whereas IgG-type antibodies may remain in the body for longer, so it could be that immunological memory exists and these IgG protect us from future infections. However, it is still unclear and it is not yet known whether the response to SARS-CoV-2 is similar.

Adaptive cellular response

The cellular adaptive response is the T lymphocyte-mediated response. At the moment, we know that people infected with the virus have lower than normal levels of T-lymphocytes in the blood, but that they are over-activated. It is known from studies in SARS-CoV and MERS-CoV that these virus-specific cells (those that specifically recognize these viruses) persist for up to 4-6 years after the disease has passed. This could also be similar to SARS-CoV-2 and could help design treatments.

Does the immune response protect us after the illness has passed?

The main cause of death of COVID19 is what is known as ARDS (Acute respiratory distress syndrome). Unlike you might think, the main cause of this syndrome is the immune system. The thing is, you give yourself such a strong immune response that the inflammation itself causes respiratory failure. One of the mechanisms that lead to this syndrome is known as cytokine storm. Cytokines are soluble molecules that are released and regulate the function of cells. They create a kind of communication between cells and have very different functions: activation of cells, recruitment of cells to sites of infection…

Image from Osterholm, 2005

Pro-inflammatory cytokines are responsible for inflammation. An inflammation is defined in Latin as heat, pain, flushing, tumor. This is fever, pain, redness and swelling. It is usually one of the first responses that occur but then the immune system is also responsible for stopping the inflammation. Maintaining this inflammation over time can cause organ failure. In general, we do not see exacerbated inflammations but in those cases where the disease is fatal, the main reason is that the immune system cannot stop the inflammation.

We do not yet have enough information about whether we become immunized once the disease has passed. Similarly we also don’t know if this immunological memory (which would activate the immune system in a faster wat) could also lead to these fatal consequences.

Why doesn’t the disease threat children so much as the elderly?

It is not very clear why children are infected with almost no symptoms or completely asymptomatically. We know, however, that children do not have a highly developed immune system and if the primary cause of the most severe symptoms is the immune system itself, some scientists point out that this could be the explanation. In contrast, the elderly are a risk group, as with seasonal flu. In this case, a weakened immune system could not be able to cope the infection. Moreover, they usually have other previous pathologies which can complicate if they have an infection.

What previous pathologies make us more vulnerable to disease?

At the moment, with the available data, we know that the most frequent previous pathologies in the fatal cases of the disease are: cardiovascular diseases, diabetes, chronic respiratory diseases, high blood pressure and cancer.

Why is it spreading so fast?

Everything indicates that SARS-CoV-2 can be transmitted not only during the symptomatic phase, in which we notice symptoms, but also during the asymptomatic phase. Due to its long incubation time, we can be unknowingly infected for days and infect other people. This makes the spread extremely fast in the population.

Is it like a flu?

If you heard that COVID-19 is like a flu, it probably was regarding people with previous illnesses or the elderly were susceptible to serious illness or even death. But keep in mind that the flu does generate immune memory and, although it may mutate every year, many of us will not become infected since our immune system will recognize the virus anyway, so we will be immunized.

This together creates what is known as collective immunity. In other words, the contagion is much more difficult because in many of us the virus cannot develop. In this case we are dealing with a new virus and this effect does not occur, therefore there is an increased risk of infection.

Will this transmission stop some day?

As it’s already happening in China, the number of infected during the first days approaches exponential growth (corresponding to the first section of a curve named “sigmoid”) and then the growth rate decreases until the growth stops.

Logistic-curve

This is going to be the behavior  everywhere, but as has been discussed about a lot, what is now being sought is to smooth the curve. This means that if the number of infected people occurs in a short period of time, the health care system will not be able to deal with them. However, if we try to delay the infections, the healthcare system will not be saturated. This is why the most important thing is for everyone to move as little as possible and stay home as long as possible. If the highest-risk people are infected all at once, they may not be treated properly and this will result in more deaths.

 

It is important to keep in mind that not all the countries of the world have an efficient health system and if the virus arrives to these countries and can be maintained in there, it can have much worse consequences than in our country.

Why is the lethality rate varying so much between countries?

With the data that we have right now, we are observing that the lethality rate is very variable. The answer is probably in whether how many people is being diagnosed; in those countries in which lots of people is being diagnosed, the lethality will probably be lower. Thus, by now, lethality rate data in different countries cannot be compared.

Will the virus stop being dangerous?

Virus-host evolutions are processes that occur in parallel. In general, the tendency is for viruses to become less virulent and for hosts to develop immunity mechanisms to survive. This is beneficial for both species so they can survive through the passing of time. For example, lots of people are infected with the Epstein-Barr virus or the Cytomegalovirus without serious symptoms. This process, however, does’t happen overnight; it is instead a result of thousands of years of co-evolution. Thus, we won’t be seeing anytime soon a less pathogenic SARS-CoV-2, but we have to remember that it is not a really virulent virus.

Are there any vaccines or treatments under investigation?

At this moment we have no reliable treatment. Current research lines are divided into three main possible treatments:

  • Antiviral treatments: These treatments are based on intervention in the virus cycle, disabling any of its main functions, such as the replication of its RNA or the production/ensambling of the capsid proteins. We can also intervene in the viral evasion mechanisms.
  • Antibodies and plasma therapy: Tests are being performed using plasma from patients that have recovered well and seems that promising results are achieved in patients undergoing severe symptoms. Similarly, monoclonal antibodies are being studied to neutralize the virus.
  • Vaccines: Vaccines take from months to years to be developed, made safe, and effective. While it might be far,  promising results were obtained in animals when testing SARS-CoV and MERS-CoV vaccines.

The WHO is currently working in partnership with Chinese scientists to begin clinical trials with 80 potential candidates.

Finally, some links of interest:

On these days, there is a lot of people on social media writing twitter threads or in blogs about the SARS-CoV-2. We want to make a list of those contents which we think that can be interesting.

  • Information is beautiful: COVID-19 #CoronaVirus Infographic Datapack. In this website with lots of infographics about general interest topics, they have created infographics with data about the COVID-19. You can see percentages of numbers of infected people, recovered people, deaths by country and much more.
  • Microbiología para humanos: Los microvillanos: Coronavirus“Microbiology for humans” is the Marçal Arumí blog about microbiology. Here you can find a post with information of the SARS-CoV-2, characteristics, infectious cycle… If you want to know more about the virus, go and visit this blog.
  • Interview with Dr. Ignacio López Goñi from the NavarraTV: Navarra TV has done this interview with Dr. Ignacio López Goñi, Professor of Microbiology at the UNAV and author of the blog of scientific outreach microBIO. In this interview he answers many questions that we have these days.
  • Marta Llorens’ Twitter thread: Marta, one of the scientists writing in this blog, made a Twitter thread with the information about the investigations that are occuring in Catalunya and Spain. If you want to know which scientific investigations are taking place, don’t miss it.
  • Manuel F. Herrador’s Twitter thread: We want to share with you this twitter thread in which the engineer Manuel F. Herrador explained why we cannot say that the growth of the SARS-CoV-2 infections is an exponential growth, as it is being said by some people.

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