Understanding SARS-CoV-2 and COVID19

Image Source: Ann Kiernan for “The Washington Post”, June 18, 2020

Here we go: another blog post on the coronavirus pandemia that is ongoing globally. The race to a vaccine continues (will discuss a little about that below), however this post will be focused on the virus that caused the disease COVID19 (Coronavirus Disease 2019), named SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), its biology, complexity, how changes in its genetic material could make harder to develop vaccines against it, the latest reports on tropism to specific human cells and organs and how the outlook for the near future looks like. In addition, I will discuss cases being reported of secondary infections in the same person and people that was “cured” from a first infection developing complex syndromes (especially children) and long-term neurological problems in older people. This pandemia is ongoing for more than 6 months, and I am very happy with how the scientific community is collaborating worldwide (collaboration in science is key, totally opposite to the system we were used to before) accelerating our understanding on the invisible enemy we are dealing with. Unfortunately, it is still not enough to eliminate it yet, but we are on the right track.

Biology of the Virus

What is the best way to understand a virus and its biology? First, we need to isolate the virus from patients and sequence its genetic material. With this information, we can use the databases available to scientists to compare its sequence and even identify how it is evolving comparing different strains in different places of the globe. The second thing to do is to study how the virus “attacks” the host (yes, us, humans). The good news are that both information is getting out fast with several scientists studying both topics very deeply. There is already a catalogue of SARS-CoV-2 mutations available and comparisons to see which genetic changes facilitate the infection and how it will affect the disease course (for more information check the article describing it here). To date, more than 100,000 isolates have been sequenced and made public (www.gisaid.org). Two SARS-CoV-2 viruses collected from anywhere in the world differ by an average of just 10 genetic letters out of 30,000 (the virus genome has 30 Kilobases or 30,000 bases) that could confer evolutionary advantages. Based on these studies, it is a possibility that the virus will acquire mutations that could change its susceptibility to antibodies and immunity affecting treatment and vaccination. The second way to understand the disease is to analyze the the tropism of the virus when it enters the human body. Tropism is which cells it binds to and in which organs it affects when inside the body. A recent report just released from a group that evaluated thousands of cell types (a type of “coronavirus cell atlas”) and organs from patients infected identified that the virus enters our respiratory system, however it has tropism to several other cell types and organs – see the Figure below. The idea here is that all these cell types in different organs in the human body have a protein (lock) that binds to the virus “spike” protein (key). When the key unlocks that lock the virus enters the cell and multiply, killing it and causing all the signs and symptoms that we see in the disease. Based on this study, we can tell how complex is the spread of the virus in the human body and why each person has a different reaction to the disease.

Source: Figure from article entitled “A single-cell RNA expression map of human coronavirus entry factors” published in the journal “Cell Reports”

Re-infection Cases

Another problem that worries the research community, especially for a successful vaccine to work, is the recent reports of cases of re-infection with the virus. Most of these are probably re-infection with other strains, very similar to the common cold or flu virus that we can get it more than once in a year, for example. The first report was in Hong Kong (see article here) and now we see a lot of reports with cases of re-infection. Most people who are infected with the coronavirus produce detectable antibodies that would be expected to protect against a second infection by the virus. Even people who had only mild symptoms may also have immune “memory” that prevent symptoms on a second exposure. It is clear now that is not the case. Even though it is early to make conclusions, this could impact vaccination when a vaccine is ready.

Post-COVID19 Syndrome

The last important issue that have been reported since April of this year when the spread of the virus started and now it is much clearer is that people considered cured developed neurological problems and other signs and symptoms that persist until today. Remember (check the Figure above) that the virus infects cells from the brain and the nervous system, so neurological problems would be expected. For the sickest patients, infection with the new coronavirus is proving to be a full-body assault, causing damage well beyond the lungs. And even after patients who become severely ill have recovered and cleared the virus, physicians have begun seeing evidence of the infection’s lingering effects (check the article for more information here). Another worrying post-coronavirus effect that has been reported is a mysterious, new disease called multisystem inflammatory syndrome in children (MIS-C, and also known as pediatric multisystem inflammatory syndrome or PIMS). It has affected hundreds of children around the world since it was first discovered earlier this year. Other syndromes have been reported everywhere now and that is concerning. What is causing these post-COVID19 syndromes? Why in children? We still do not have the answers to these questions. Let’s hope the scientists can uncover this mystery.

Updates on the Vaccine Race

Finally, let me discuss a bit about the “pause” that the AstraZeneca/Oxford University vaccine had last week because of a severe side-effect in one patient that had inflammation in the central nervous system. First, that is common to happen, especially when you are dealing with a fast-track vaccine trials and with people with different genetic backgrounds. Second, the “pause” was important to show to the world that this vaccine is trustworthy since the researchers from both places coordinating it are using the best scientific guidelines with very strict rules (trust is important!). Third, side-effects will happen, the severity of them that will be key for a successful vaccine. Finally, the vaccine race continues and I just read that AstraZeneca and the University of Oxford is going forward with their trial after the “pause”.

Final remarks

All the information I just discussed here is just the tip of the iceberg on the complexity of this virus and how it infects humans. We are starting to understand several processes on how the virus infects human cells, which cells and organs have the tropism for it and how people with different genetic backgrounds from different places react to it. Post-COVID19 effects are getting clear (it happens) but we still have lots of WHYs to focus on right now. I always finalize my posts with some advices: the best thing to do now is still social isolation, take the measures to avoid getting infected and stay mentally sane. I confess that I am already having mental issues (don’t leave the house for almost 4 months!). Stay strong. We will overcome this crazy pandemia. And let’s thank the scientists and healthcare professionals everywhere that are making it possible to gather all the information we have to date on this disease. A brighter future is closer… I hope!

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