In the third part of Online Kapehan, we discussed how South Korea addresses the issue of “reinfection” and the possible modes of treatment for COVID-19. I am joined by Ph. D. candidates and fellow PIKO members Erica Españo (Life Science in Pharmacy, Korea University Sejong Campus), Paula Cammayo (Preventive Veterinary Medicine, Gyeongsang National University), and Rey Anthony Sanjorjo (Applied Life Science, Gyeongsang National University). WATCH HERE.

Jubert: As other countries still grapple with the first phase of this problem, Korea is already preparing for the next phase: reinfection. A small percentage of patients in Korea retest positive for the virus after a couple of weeks. What could be the science behind this?

Pau: I’m not so sure if the proper term would be reinfection because they are also looking into the possibility that the virus may have been reactivated. The mechanism for this is that a virus that might have remained dormant for some time, but once the immunity of the recovered person got compromised again, then there is the possibility of the disease to resurface again. This would be the case for other enveloped viruses like herpes virus and retrovirus. They remain latent up to a certain period that when the host’s immunity is down they start to replicate and take over the host again. Probably researchers and scientists are also looking at that angle too.

Rey: Upon infection, our body produces different immune cells as a response. Neutralizing antibodies are one of these immune cells that can block viral entry. Pre-print studies point out that there are individuals that have failed to develop high titers of neutralizing antibodies that could pose a higher risk of reinfection. In one study, around 10-20% of symptomatically infected people have shown little or no detectable antibody. There are also discussions that low antibody titers could be correlated to the severity of the infection, which means that those who are asymptomatic or who have developed milder disease might not yield the specific or the appropriate antibody levels to mount optimal immunity. There is an on-going seroprevalence study in various countries in the world or how many might have already developed antibodies since they have already been infected and then recovered but was never tested. This will be an interesting development to look out for in the upcoming days.

Erica: We’ll have to wait for a few months and for the KCDC study to actually understand what is happening. KCDC is looking at a possible latency, where the virus hides for some time, so the people test positive, and then it appears again. But this is still just speculation. There is also the problem with some of the human common-cold coronaviruses not triggering long-lasting protection. But this is usually in the duration of 3-6 months, so we’ll only find out after then to know what’s really happening. This is something that we have to follow closely because this would help us guide vaccine design. Current vaccine designs and strategies might have to be readjusted to address this issue.

Jubert: I remember previously we have discussed the transmissibility of COVID-19. Have there been any updates regarding newly-discovered routes of transmission?

Erica: I think so far, it’s still really the respiratory route. The fecal-oral route of transmission is still suspect but has not quite gained traction. I guess because if you’re observing proper hygiene, this route can also be cut off.

Pau: Still via oro-nasal route so we need to be careful with the aerosol droplets

Jubert: Let’s now discuss treatment options. New details have emerged that one of the drugs scientists were hoping can address the virus is remdesivir, but recent data show that the drug failed to have any effect in the patients. Why do you think is that?

Erica: There’s been conflicting data about remdesivir, actually, because we are yet to see a full official report. But I think this (or any candidate failing) reminds us that the race to find a drug (or even a vaccine) is really hard. From the perspective of someone who works with antivirals, this is actually normal. Some drugs that perform well in the lab (in cells or animals) do not necessarily perform well in the human body simply because the human system is more complex and cannot easily be represented by tests in the lab. Butas ng karayom talaga ang pinagdadaanan ng drugs to get to the finish line, for good (safety and effectivity) reasons, which is why we have very few approved antivirals. If finding a drug were so easy, we wouldn’t have a lot of diseases to deal with. But that doesn’t mean we should lose hope. Occasionally, we hit the jackpot so, hopefully, we’ll get lucky with one candidate (any candidate) for COVID-19.

Jubert: What other “candidates” do you think have the potential for human use?

Pau: On how FDA approves drugs for human use, it is a tedious process. It starts with the drug in vitro testing thru cell cultures and primary cells, followed by testing in animal models if it passes that it undergoes phases 2-4 of drug safety and efficiency assessment before it finally gets approved.

Probably to determine the drug that could help cure COVID-19, scientists and researchers are looking into the pathophysiology of the virus and possible areas that could disrupt or delay its replication. Based on these, they have identified some promising drugs. However the results either didn’t cause much clinical improvement to treated patients or have undesirable side effects. This includes remdesivir, an antiviral used to treat Ebola it works by interfering with the RNA dependent RNA polymerase (rdrp) essential for viral replication; hydrochloroquine-chloroquine combination, an antimalarial drug known for its immunomodulatory effects, studies also says that it reduces the acidity of organelles of cells resulting to a delay in viral replication; lopinavir/ritonavir combination, used for treating HIV, they are protease inhibitors which prevents cleaving of protein chains into peptides. So again, these drugs haven’t been approved so they are still looking for other treatment options. Other drugs they have been looking into are ivermectin, an antiparasitic drug we use in the veterinary field but so far, it’s effectivity was only checked up to in vitro level. Then also favipiravir, an influenza drug which also inhibits viral rdrp discovered back in 2017 in japan is gaining attention right now.

Jubert: More recently, even the Philippine General Hospital is conducting tests regarding the use of plasma therapy. Why or why not is this better than the drugs we are testing now?

Rey: Convalescent blood plasma therapy has shown to be a promising option for severe COVID-19 in various trials in China and Korea, and this has already been implemented in various controlled studies in the US and in the Philippines as well. In one PNAS study, SARS-CoV-2 became undetectable after 2-6days of blood plasma treatment along with increased neutralizing antibody levels improving clinical symptoms with low adverse risk or side effects among 10 patients. This is a very old tool but it is considered to be an option of last resort due to many variabilities and limitations. For example, how many recovered could actually donate, some might be too weak to donate, and if the donor has enough neutralizing antibodies to provide adequate protection to the recipient. Also, plasma transfusions can only be done in a hospital and may require large volumes of the plasma for one patient. The recipient might also develop mild to fatal allergic reactions or transmit other infectious diseases that the donor may have.