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With a new position from the LSE professor Elijah Mosialos refers to everything that has occupied us lately about the new coronavirus.
Professor Mosialos answers questions like what a positive test means, what is the development rate of the vaccine, and how the coronavirus is transmitted.
Read the full announcement from Elias Mosialos:
Knowledge, uncertainty, and coronavirus disease
Dealing with a new virus, the scientific community since the beginning of the pandemic has been trying to address the clinical questions that arise in real time.
Let’s look again at some of these complex issues that have preoccupied us all this time by focusing on the range of contrasts.
• Patients and variety of symptoms
There are some clear factors about who is at higher risk for serious illness, but it is not entirely clear why some people without an underlying illness suffer and others do not. The wide range of symptoms for people with COVID-19, from a truly asymptomatic case to mild symptoms, a moderate illness that leads to complications lasting many months, up to death, still worries researchers in all specialties.
• A positive test does not always mean symptoms: asymptomatic but also over-scattering
The US Centers for Disease Control and Prevention estimated in July that at least 40% of people infected with COVID-19 are asymptomatic. The probability of transmission from asymptomatic patients appears to be slightly lower than the probability of transmission from symptomatic patients (75% vs 100%). The data also show that contagion increases in symptomatic patients for 2-3 days before they show symptoms. At the same time, however, a certain percentage of infected people, perhaps 10-20%, are found to be responsible for about 80% of new cases, often through indoor events. Whether this transmission occurs depends on a number of variables: how many people are in a particular place, how the room is ventilated, and of course, if there is someone with a COVID-19 carrier in the room.
• A negative test does not always mean recovery: children and patients with long-term Covid-19 symptoms
Children generally do not show the severe symptoms that send adults to the hospital. They contribute to the transmission of SARS-CoV-2, although it is often unclear why they do not develop symptoms. Like adults, children with other health conditions – obesity, chronic lung disease, or premature babies – are at higher risk than healthy children. Perhaps most concerning is that a small percentage of children infected with COVID-19 continue to develop a condition in which many organs are attacked by their own immune systems. It’s called multi-organ inflammatory syndrome, or MIS-C, and it appears to occur two to four weeks after COVID-19 infection. Most children who develop this syndrome recover.
Deaths among children and adolescents are rare, but children are not invulnerable, just as those who recover are not. Doctors are concerned that the pandemic will lead to a significant increase in people struggling with the long-term impact of the disease. But the disease is new and no one yet knows what the long-term effects will be. Some of the problems will come from the side effects of intensive care, such as intubation, while other long-term problems could be caused by the virus itself. However, preliminary studies and existing research on other coronaviruses suggest that the virus can damage many organs and, sadly, cause a wide range of pathologies. That is why many follow-up studies of people infected with SARS-CoV-2 have already begun.
• Levels of infection affecting antibody production: pre-existing immunoprotection but also immunity
We know that in the case of immunity, for example in Iceland, the vast majority of evaluated patients had developed antibodies at least four months after diagnosis. Immunity may last longer, but most – as is well known – have not contracted the virus. Up to half of the population may have immune system T cells that were originally created in response to infection by one of the other common viruses that cause colds, but they can also recognize SARS-CoV-2. These “reactive” T cells could help give the immune system the boost it needs to prevent severe symptoms, but researchers are not sure what their function is and how long this immune protection lasts, if any.
• Global and pandemic mortality, but also significant differences by country
The infection mortality rate (IFR), although initially estimated at 0.5-1.2, will probably be between 0.4 and 0.8 at the end of the pandemic, but with significant variations by country. Certainly 0.1-0.2 will not be what those who insisted that there is no problem and that it is a flu would say.
Why do we expect to have a lower IFR? The IFR is higher in the US and in some other countries, such as Brazil, where a recent previous publication, for example, refers to IFR 1.05 (95% CI nationwide: 0.96-1.17). It will be less because we now have a drug that reduces mortality in severe cases and that in itself significantly reduces IFR. ICU hospital management has also been improved (due to the knowledge of the most favorable position of intubated patients (prone position), the correct choice of ventilator patients. This affects the world average because the population of China is approximately 18, 5% of the world’s population, so in countries that do not have significant spread control, the IFR may be near the upper limit of initial estimates, perhaps even higher, while the world average is lower than the original, but much higher than the flu.
• Conditions of coexistence and coexistence
Research has shown that 97% of “over-transmission” cases occur indoors and external transmission is minimal. Transmission is easier indoors and where there are crowds and large concentrations. But now we know that transmission is also high in homes. And remember again that in sparsely populated Sweden, nearly 50% of the population lives alone and the elderly do not live with their children and grandchildren. Let’s go out as much as possible when we meet other people. If an enclosed space is not well ventilated, not crowded, and nobody wears masks, it is best avoided. Now is the time to avoid unnecessary travel and support local businesses.
• Initial reports, preprints and large randomized clinical trials
Remember that at the beginning of the pandemic, while we had a large flow of information and publications, we had multiple clinical protocols but results from a small sample of patients. Now, large randomized clinical trials have been published and others are ongoing.
• Growth rate and efficacy of the vaccine
Is it realistic to think that at that time of year we will have approved vaccines? We will likely have vaccine approvals in the coming months, but we will have the first doses for use in the general population, if all goes well, in the spring of 2021. But let’s not take that for granted from now on. The huge growth numbers are optimistic and we will have several vaccines approved, but the question that really arises and still has no answer is how well they will work. Of course, this does not mean that it is not safe. However, clinical studies have not currently evaluated vaccines in terms of their ability to protect against the virus or the transmissibility of those who do. At the moment, the results we have refer to the safety of vaccines and the immune response of those who make them. But, the immune response and / or immunity to the virus itself has not been clarified, as I said, to those who have gotten sick. No company or specialist will ever bet that we will have 70% protection, and most likely the first generation of vaccines will give us 50% protection. But also remember that even protecting some people really helps and impacts the community, because these people are unlikely to pass the virus on to other people.
Sufficient time should be devoted to vaccine clinical trials to answer questions about vaccination of vulnerable groups and the elderly. It’s also important that clinical trials focus on the right clinical questions and outcomes – that is, will vaccines protect us from mild to severe Covid-19 disease. We can use a combination of different vaccines to improve the effect in the community or do booster doses.
Our immune system may recognize the type of vaccine we receive if we get vaccinated a second time, so in theory a different vaccine could be used as a ‘booster’. Booster doses may also be needed for the elderly, whose immune systems weaken with age and are at increased risk of contracting the virus. As for the negatives and skeptics, my opinion is that most people will wait in line to get the vaccine.
• Dynamics of coronavirus transmission and high-risk activities
The risk of transmission is complex and multidimensional. It depends on many factors, as discussed in the figure: contact patterns (and their duration or proximity), individual factors per person, spaces and environment (i.e. outdoors, outdoors, etc.) but also socio-economic factors (such as co-housing with many people, job insecurity, etc.). As I often say, we know that constant close contact leads to most infections and outbreaks. For example, close contact, such as at home or with friends, and large gatherings carry a higher risk of transmission than brief outdoor gatherings.
We hear every day that it takes time to clear up other scientific and clinical uncertainties. And we all live in extremely difficult times and it’s perfectly normal to be angry about our lost normality. All of us, young and old.
Although it is very common to say that all young people outgrow the virus, remember that SARS-COV-2 is a virus that all the evidence shows that it is best not to contract it. None of us know how a mild or asymptomatic coronavirus infection can develop over time. Let’s not challenge our luck.
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