CLINICAL MATTERS

Before the arrival of effective vaccines, Covid-19 treatment was the only thing doctors could offer patients who were infected with SARS-CoV-2. At the start of the pandemic, the mortality rate for those in the vulnerable population who developed Covid-19 was 10 percent or more. One out of 10 elderly patients and those with comorbid conditions were going to die without medical intervention. The big question at the onset was what was going to work, and what might harm patients?

As we learned more about SARS-CoV-2, it became clear that death from Covid-19 was due to disordered immune responses in different parts of the body. SARS-CoV-2 caused exuberant inflammation in the lungs leading to acute respiratory distress syndrome, which has a high fatality rate. It also predisposed to blood clots, causing strokes and heart attacks. 

Treating Covid-19 therefore involved two approaches: targeting the virus and targeting the inflammatory mechanisms. As cases mounted, doctors and scientists scrambled to come up with new medicinal compounds or tried to repurpose old ones. Medications could be used either to treat severe disease or to prevent the progression from moderate disease to severe disease. Mild disease, which did not involve the lungs, did not seem to need treatment as most people recovered without any intervention.

Many antivirals were tried for severe disease, including those used for flu and other viruses. The first antiviral to show efficacy in rigorous clinical trials was remdesivir. This was an intravenous only medicine and so it was difficult to give and could only be offered to hospitalized patients. The United States National Institutes of Health included remdesivir in their guidelines for treatment of severe Covid-19 early on in the pandemic. Unfortunately, the World Health Organization (WHO) inexplicably recommended against its use even in the face of good quality evidence. As more trials showed improved outcomes with remdesivir, WHO quietly changed its guidelines and now recommends remdesivir for severe Covid-19.

Two other antivirals eventually showed efficacy against moderate Covid-19, but not severe disease. These were oral medications and so they were easier to administer. Molnupiravir showed utility in decreasing the risk of progression to severe disease among unvaccinated patients. Unfortunately, this did not carry over to vaccinated patients, probably because the risk of progression was substantially much less when one is vaccinated. It still seemed, however, to decrease the risk of viral shedding and time to recovery and so it remains as an alternative drug to nirmatrelvir-ritonavir, better known as Paxlovid. Paxlovid has shown efficacy in preventing progression to severe disease even among those who are vaccinated. It is the first choice for Covid-19 patients with moderate disease. Remdesivir works just as well as Paxlovid in preventing the progression of moderate disease to severe disease. The intravenous route of administration of remdesivir, however, is a significant barrier to its use as an outpatient treatment.

The latest WHO guidelines recognize the evolving risk of disease as more and more people are vaccinated, vis-à-vis the emergence of new, potentially immune-evading variants. A new risk stratification category has been introduced in patients with non-severe Covid-19, whether or not they have been vaccinated. For severe disease, the only recommended antiviral remains to be remdesivir. For non-severe disease, they have divided the categories into risk of hospitalization: low, moderate, and high. This should not be confused with the categories of disease severity, which are mild, moderate, and severe. Risk of hospitalization only applies to non-severe Covid-19, and the new guidelines state that those with moderate to high risk of hospitalization should be preferentially treated with Paxlovid. If Paxlovid is not available, then molnupiravir and remdesivir can be used. It goes the extra step of explicitly recommending against the use of ivermectin because there is strong evidence that ivermectin is completely useless against Covid-19.

Other proven medications that target the inflammatory cascade are typically used in severe disease only. These include dexamethasone, tocilizumab, and baricitinib. Non-invasive high flow oxygen has for the most part replaced mechanical ventilation as the main mode of addressing low oxygen levels.

In the meantime, there are sinister forces that are trying to link excess deaths seen in the Philippines in 2021 to the rollout of vaccines. The reasoning is extremely faulty and does not reflect the reality in other countries that had worse deaths than us and did not lock down. It also does not reflect the lack on any death spikes upon mass vaccination in countries with late increases in Covid cases, way after most of their populations got their shots.

Excess deaths in the Philippines were in fact negative (i.e., there were fewer than expected deaths compared to past years) in 2020 because of the strict lockdowns. The lockdowns prevented widespread deaths from Covid-19 and also impacted the transmission of pneumonia, TB, influenza, and other communicable diseases.  We started to see excess deaths show up in 2021, mostly from non-Covid causes as early as January (vaccine program started in March and two doses were completed for a substantial number of the population much later around July/August) because of missed clinic visits for chronic illnesses along with missed cancer screening and treatment. The Commission on Population and Development (POPCOM) showed that data from the Philippines on non-Covid-19 causes of death in 2021 compared to 2020 showed increases in deaths due to ischaemic heart disease (30 percent), cerebrovascular disease (15 percent), diabetes mellitus (21 percent), hypertensive disease (32 percent), and malnutrition (47 percent). Only a small number of these excess deaths were uncounted Covid-19 deaths. The government advisers were acutely aware of this and this is why we strongly advocated transitioning to granular lockdowns even as the vaccines were about to be rolled out. It is expected that deaths will increase as we relax restrictions because more people are expected to get infected.

If we look at countries that had relatively controlled Covid-19 and did not resort to lockdowns early on since they just closed their borders to the world like Australia, there is no such increase in excess deaths even as they were rolling out their vaccines. Malaysia and Australia, which vaccinated faster than us, only saw excess deaths rise when Delta and Omicron came along, way after they had vaccinated the majority of their populations.

The assertion that the purported increase in excess deaths in the Philippines is somehow linked to the vaccination program is unfounded. Closer examination of these deaths clearly shows most of these were from chronic illnesses such as heart disease while a few were from undetected Covid-19 deaths. There is no evidence any of these deaths were from the vaccines. 

Vaccines, especially the Covid-19 vaccines, have saved millions of lives and continue to do so. The unprecedented rollout of Covid-19 vaccines has enabled us to open up safely and continued to protect us from severe disease from Covid-19 even as new variants crop up. Coupled with the judicious use of proven antivirals and ancillary medications, the threat of Covid-19 is now at its lowest since the start of the pandemic. Nevertheless, we need to remain vigilant for new variants. New vaccine development and research into effective treatment needs to continue as a form of insurance against reemergence of SARS-CoV-2.