Covid-19: A review of three medical approaches
As the cases of Covid-19 increase, many are wondering what they can do if they or someone close to them gets the infection. First, some reassurance. A vast majority of those infected with SARS-CoV2 is asymptomatic or have minimal symptoms which require no treatment. This proportion is highest among the young, more than 90% in children and young adults, but is less in older adults with co-morbidities such as diabetes and hypertension. In seroprevalence studies, where we look for the presence of antibodies in people’s blood, indicating they have been infected and are recovering or have recovered, most who test positive do not recall any unusual symptoms. This indicates widespread asymptomatic or minimally symptomatic infection and recovery.
While this is good at a population level and should reduce the panic associated with Covid-19, the more symptomatic patients should not think of this as just another flu. In this group, especially for the elderly or those having diabetes, hypertension or other co-morbidities, there is a small but real risk of severe illness which could be fatal.
What are the available treatments for those with moderate to severe disease and when or to whom should they be administered? The answers are still evolving. The treatment can be broken down into three categories. First, general supportive care targeted at managing the symptoms and general complications. Second, antiviral treatment directed at killing or limiting the growth of the virus. Third, modulating the immune response of the infected person such that it is strong enough to clear the virus, but not so much that it kills the host.
The first category, access to good quality supportive care, is simple in concept but needs a strong public health focus. There must be timely testing so that people are diagnosed early, with simple monitoring for common danger signals such as low oxygen levels in the blood that can be monitored by a simple pulse oximeter. If this is done, patients likely to become more ill can get necessary care in time — oxygen supplementation, with face down positioning (proning) and ventilator support, if needed, preferably non-invasive. Attention can also be paid to preventing, detecting and treating blood clots.
The second category is antiviral treatment. This ranges from true antiviral drugs, such as favipiravir and remdesivir, to commonly available medicines that may additionally reduce viral entry or replication such as zinc, vitamin C, chloroquine/hydroxychloroquine, azithromycin, doxycycline, ivermectin, niclosamide, ciclesonide and indomethacin. There is no authentic evidence that any of these are effective, but data so far offers some hope. Remdesivir seemed to accelerate recovery in one randomised controlled trial (RCT). In moderately ill patients, it may reduce death. Favipiravir is cheaper, has fewer side effects, and can be given orally, making it more attractive but lacks any quality RCT data and is thus used for mild to moderate illness only. Zinc and vitamin C are being commonly used by patients with mild illness, due to lack of any known or postulated side effects, with some observational data of zinc being potentially useful. Treatment with chloroquine or hydroxychloroquine has not been very promising so far. While recent reports of high toxicity turned out to be false, side effects may occur at high doses, especially in those with existing heart disease.
The last category, immune modulation, looks promising since much of the severe disease is either due to uncontrolled viral infection in people with compromised immunity, or due to an exaggerated immune response causing damage to the lungs and other tissues.
Increasing natural immunity through vaccines appears distant at the moment and externally providing antibodies via the plasma of recovered patients (plasma therapy) is neither risk-free, nor easy to do at scale. The only published RCT for plasma therapy was inconclusive. In fact, the first clear winner in immune modulation is the widely available and cheap steroid, dexamethasone. It is expected that when used correctly, steroids will dampen excessive immune response, limit damage, and promote recovery. However, it also suppresses immunity and should not be used early in the disease. More sophisticated immune modulators like tocilizumab that can selectively block cytokine storms, without compromising immunity, have also shown promising results. Many other approaches have been suggested for immune modulation, ranging from mycobacterium w vaccine to traditional remedies that boost immunity. What works remains to be seen.
Currently, we have both a shortage of proven treatments and an excess of unproven ones. With exaggerated claims from every quarter, it is difficult to subjectively determine the best treatment. Objectively, uncomplicated disease in otherwise healthy subjects usually requires no specific treatment beyond general support. In fact, such support is probably both necessary and sufficient to prevent most Covid-19 deaths. More specific treatment, including new antivirals and targeted immune modulators, will certainly be beneficial in specific settings but are not required for everyone. We should treat based on what we have learnt and keep learning as we treat. For this, patients, doctors and researchers must come together and share information at covbase.igib.res.in, a site meant for this specific collaborative purpose.