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Why is COVID-19 so hard to treat?

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How viruses attack our bodies and spread usually determines a course of treatment. While coronavirus (COVID-19) is no different in that sense, researchers likely will need to rely on a combination of approaches to launch an effective counterattack, explained Michael Oglesbee, director of Ohio State’s Infectious Diseases Institute.

Why is it so hard to treat COVID-19? While morbidity rates may be lower than other outbreaks of recent history, its spread seems much more pernicious.

Let’s start with how this is spread.

There are two basic relationships between a virus and host: 1) get in, get out (acute infection); 2) take your time — shed viral progeny over a prolonged period, either continuously or in periodic bursts.

In acute infection, clinical disease occurs early, and the immune system generally clears the infection shortly after clinical signs present. In chronic/persistent infection, clinical disease is delayed, and viruses do a good job of avoiding immune system clearance.

Acute infections generally hit an organ system where viral progeny can be readily shed — gastrointestinal and respiratory tracts, for example. Coughing, sneezing and diarrhea are great vehicles for shedding and spreading. The idea is the virus gets in and makes a lot of progeny before the immune system kicks in and clears it out.

When introduced into a population with no immunity, the infection has potential to spread rapidly, particularly for those viruses infecting the respiratory tract. Irritating your respiratory tract can increase secretions, and droplets released by breathing, sneezing or coughing can propel the virus for significant distances. Infections spread best if they don’t kill you — because you are the factory.

But for a new virus in a new host, the balance can be tipped toward more severe disease outcomes in a larger number of infected individuals. One problem we see with COVID-19 is that the host inflammatory response can be excessive to the point of damaging tissues, such as your lungs. The more virus in your lungs, the greater the inflammatory response and thus the greater damage done.

How do you treat this?

Antivirals (drugs designed to inhibit virus replication) generally don’t work well on their own once the infection is fully established because there is simply too much virus on board at that point, and they are all replicating like crazy. Antivirals work best in the early stages of infection and so you might use these prophylactically for those most at risk of severe disease outcomes.

Mostly we focus on providing supportive care until the immune system can clear the virus, and we might try to rein in the inflammatory response in the event that this is the major problem (as in influenza, and likely also the case with the virus causing COVID-19). The latter is particularly relevant for hospitalized COVID-19 patients.

Can you explain how antibodies could be the possible key to treatment?

When your immune system responds to an infection, you produce antibodies that bind the surface of the virus and prevent it from infecting new cells. You also produce a group of lymphocytes that remove virus infected cells. In short, your body eliminates the factories and neutralizes any product that the factories made.

If someone has recovered from a virus infection, they should have neutralizing antibodies in their serum.

The most straightforward approach to immunotherapy is to harvest serum from patients with high concentrations of neutralizing antibodies and administer that serum to a patient suffering from severe disease outcomes. We have proof of concept that this works for other coronaviruses, and there is very good reason to believe it can help with COVID-19.

Does this scientific approach pave the way for a vaccine?

The vaccine approach builds off these principles, although here it is all about protecting the individual that is susceptible to infection.

The goal is to express key coronavirus proteins in ways that induce both a protective antibody response (i.e., neutralizing antibodies) and a cell-mediated immune response (i.e., the lymphocytes that can eliminate virus infected cells — the viral factories).

Recovery from a natural virus infection is a form of vaccination, in that infection can induce a protective immunity — prevention of reinfection, although we are unsure of the duration of that immunity and there are obvious adverse health outcomes.

We are looking at approaches where only a subset of coronavirus proteins are expressed through a vaccination strategy. The challenge is that we are at least a year away from having a vaccine in hand.

Infections spread best if they don’t kill you — because you are the factory.
Michael Oglesbee, Director of The Ohio State University's Infectious Diseases Institute
Are there other kinds of treatments that you’re hearing about that give you hope?

There is no silver bullet.

The approaches that work usually employ a combination of approaches. This could include passive immune therapy, blunting aspects of the inflammatory response that are harmful to the patient, and possible addition of an antiviral.

Used alone, the antiviral would not be expected to have much effect, but in combination there may be benefit.

There is a lot of talk about people returning to their more normal routines. Does that pose a risk of the virus mutating further and undoing researchers’ work as they try to outsmart it?

Our ability to safely return to more normal routines will be defined by the number of people with protective immunity.

That is obviously the goal of vaccination, but it can also be defined by the number of people who have recovered from natural infection. If you have protective immunity, you could return to the workforce, for example, without significant risk to you or others. Ultimately, when we have enough people with protective immunity, the chance of virus spreading within a community is blocked so that even those lacking protective immunity are not at significant risk of infection. We call this herd immunity.

The challenge: We need to be able to measure protective antibodies in serum of people on a large scale — serologic surveillance (or serologic monitoring). We are not currently testing in this way, although we are working hard to develop and then deploy those tests.

In the meantime, we can expect periodic outbreaks of disease in specific locations, also known as “hot spots.” But if our monitoring systems are in place, we should be able to contain those outbreaks by strategically focusing on that location and/or individuals that have been in contact with an infected person.

Does the virus change with time?

Yes, there are genetic changes that allow us to determine if two separate outbreaks are caused by the same or related virus. But there is no evidence at present that these genetic changes have occurred to a level where we have unique viral behaviors — or strains.

Protective immunity against the virus that started this mess should be effective against the virus at the close of this pandemic.