A new virus, for which there is no previous immunity in the population, which is transmitted by air, whose disease has a period of a few days in which the patient may be presymptomatic but contagious and in which there are also asymptomatic people who can transmitting the disease is simply the worst nightmare for an epidemiologist trying to control an epidemic.
Although there are already more than 42,000 articles on COVID-19 and SARS-CoV-2 in PubMed and obviously I have not read all of them, not even a small representation, here is a short summary of ten ideas of what we know and what is missing to know about SARS-CoV-2.
What we know
1. We know who it is
The first cases of AIDS were described in 1980 and it took two years to discover who was the causative agent, the HIV virus. Now, in just a matter of days, it was known who he was: a new coronavirus, SARS-CoV-2. Obtaining its complete genome has made it possible to investigate its origin and its relationship with other coronaviruses, develop molecular detection systems such as RT-PCR, identification and tracking systems such as Next-Strain, which allows to follow the evolution of the virus in real time , and even pre-alert systems through wastewater monitoring.
All this is allowing the detection and tracking of new cases and outbreaks as never before in history.
Early diagnosis together with the tracking of cases and quarantine of contacts is what can prevent us from confining the population.
2. We know their biological cycle, how they enter cells
We know how the SARS-CoV-2 virus uses the S protein ( spike ) of its envelope to bind to the ACE2 receptor of our cells and that cellular proteases (furin and TMPRSS2) facilitate its entry into the interior. As this receptor and these proteases are in a large number of tissues in the human body, the virus can infect many different types of cells: pneumocytes, enterocytes, nasal secretory cells, kidney, endothelium, heart.
This information has been essential in proposing possible treatments and the development of vaccine candidates.
3. COVID-19 is much more than pneumonia
We know the disease much better. Although COVID-19 was initially described as a severe atypical pneumonia, unlike many other respiratory diseases, this coronavirus generates silent hypoxemia , deprives the patient of oxygen without affecting respiration, reaching saturations of 70%.
In addition, a high number of patients suffer clotting problems (due to affecting the endothelium) and an exaggerated immune response (cytokine storm) that end in pulmonary embolisms, heart attacks, strokes, liver and kidney problems, and even alterations in the system highly strung.
In addition, risk groups are now better identified: older people, patients with comorbidity, diabetics, obese … and the influence of hormonal factors and sex is known. This has meant that the treatments, still experimental, and the care of patients have improved, because patients are better monitored and the evolution of the disease is better understood.
4. We better understand the dynamics of virus transmission
SARS-CoV-2 is transmitted primarily from person to person through respiratory droplets, airways, and physical contact.
Droplet transmission occurs when a person comes into close contact (less than 1 meter) with an infected individual and is exposed to the droplets that they expel, for example, by coughing, sneezing, or getting too close, resulting in entry of the virus through the nose, mouth or eyes.
The virus can also be transmitted by contaminated objects (fomites) present in the immediate environment of the infected person.
We know that asymptomatic patients may have the same viral load as symptomatic patients and that they can be an important transmitting vector, although we still do not know if in the same way.
We also know that there are “super contagion” people and events, situations in which contagion is much easier: 10-20% of those infected who act as “super contagion”, in closed, crowded and poorly ventilated places, with people very close to each other. , and where you yell, sing, cough or sneeze frequently and without precautions.
5. A milestone in international cooperation
International cooperation between public and private entities, research centers, governments and companies that has never before taken place at this level is being essential: from the development of clinical trials to achieve medicines promoted by the WHO and other countries, to the design , evaluation, manufacture and distribution of future vaccines , very varied and with very different technologies.
What remains for us to know
1. Why do many people have no symptoms?
It has been suggested that it may be due to developing a rapid immune response, due to previous immunity due to a cross reaction with other coronaviruses, due to genetic factors or because the viral load is very low at the time of infection.
In young children, it has also been suggested that they may have an immature immune system that does not develop that cytokine storm that seems to be one of the factors that aggravates the disease, or that the frequency of immunological stimuli received by childhood vaccines has a certain protective role nonspecific against coronavirus. But we still don’t know for sure.
2. What role do cross immunity and reinfections play?
Although it is a weight-gaining hypothesis (people not exposed to SARS-CoV-2 who have a memory T cell immunity by cross-reacting with coronaviruses responsible for colds), we do not yet know what influence this has on COVID-19.
The same happens with the possibility of being reinfected: how long does the immunity last? What does it depend on in this specific case? Does having passed the disease protect, how long, how long? Is reinfection possible? What happens with those patients who improve, are even days without symptoms and relapse again? Are they reinfections, relapses, poorly cured, misdiagnosed? What is the viral load, the amount of virus necessary for the infection? that in the symptoms or in the severity of the disease?
3. What is the long-term effect of COVID-19?
A percentage of patients suffer more or less important sequelae, ranging from dyspnea and fatigue, to damage to tissues and organs such as lungs, joints and heart, neurological disorders and hypertension. Can COVID-19 end up being a chronic disease?
4. Rapid and differential diagnosis
We have the technology but we need it to reach the citizen. To control outbreaks, we need to finish implementing quick, simple and cheap self-diagnosis systems that do not require blood samples, from saliva for example, that do not need health personnel and that you can perform them yourself in your own home or place work and repeatedly.
This would allow individual monitoring for possible infection. Although the sensitivity is lower than molecular techniques such as PCR, the simplicity and the possibility of repeating the test frequently could make these types of tools very useful for population screening. This technology is already developed, you just have to implement it.
In the same way, as it is very likely that SARS-CoV-2 will coexist with other respiratory pathogens in the coming years, it is necessary to have differential diagnosis systems that allow us to quickly distinguish whether it is a SARS-CoV-2 infection. , other coronaviruses, influenza, respiratory syncytial virus, or others. This technology is also developed: the CARMEN diagnostic platform that combines microfluidics with detection technology based on CRISPR.
5. Transparency, truthfulness and coordination are still pending subjects
It is surprising that there are still no reliable, coordinated and immediate data on the number of CRPs that are done, how many are positive, number of hospitalized patients, ICU patients and deaths. Without data it is very difficult to govern a pandemic.
On the other hand, truthful and transparent information about the virus and the disease is still essential to avoid the proliferation of false news, misinterpretations or hoaxes. The lack of coordination is exasperating.
Is the virus changing?
Finally, a frequently asked question: now that many more asymptomatic patients are detected, is the virus weakening?
The virus is neither weakening nor becoming more virulent, we have no evidence at this time that there are more or less virulent strains. SARS-CoV-2 is relatively stable, at least much more so than other viruses like the flu, which is the champion of variability. This is because it has a mutation control mechanism, a protein (nsp14-ExoN) that acts as an enzyme capable of repairing errors that can occur during genome replication.
What is happening now, the feeling that there are fewer serious cases, is not due to a mutation of the virus, because it is less virulent. It is due to other factors extrinsic to the virus: we are detecting many more asymptomatic cases because more PCR is being done and outbreaks are being tracked; the measures we have taken (mask, hygiene, distancing…) are preventing the virus from reaching the most susceptible people, who are protecting themselves much better and taking precautions; perhaps these measures also contribute to a lower viral load; medical treatment has improved, we now know more about the disease and doctors know what they are dealing with and start treatments sooner; the health system is no longer collapsed and the cases that come to be admitted and to the ICUs can be cared for much better. But as I said, the virus does not seem to have been attenuated and if it now infected a susceptible person (older than 75 years with previous pathologies, for example), in principle the disease would be just as serious.
However, this does not mean that there are no mutations. A mutation has been identified that may affect the infectivity of the virus.
Specifically, for months a greater presence of coronavirus isolates that carry a mutation called D614G has been described. It is so named because the amino acid at position 614 of the coronavirus protein S has mutated from an aspartic acid (Asp or D) to a glycine (Gly or G). Studies in in vitro models, in cell cultures, show that the new strain with the G614 mutation infects cells more efficiently than the original strain. It seems that the mutant has a greater amount of S proteins on its surface, thus facilitating entry into cells.
People infected with the G614 mutant variant have also been shown to have a higher viral load (measured as viral RNA) in the upper respiratory tract than those infected with the parent variant. In addition, this variant began to circulate frequently from February of this year and is already predominant in Europe, the United States and also in South America.
However, while this suggests that the mutant variant may be more infectious, this does not mean that it is more virulent, more pathogenic, or causes more serious disease. They are two different things, the ability to transmit and be contagious, and the virulence and severity of the infection. The mutation is not associated with an increase in the severity of the disease.
Ignacio López-Goñi, Professor of Microbiology, University of Navarra
This article was originally published on The Conversation. Read the original.
