The future of pandemics


How do we get ready for the next one?

CLINICAL MATTERS

The World Health Organization (WHO) is meeting this month to determine whether the current characterization of Covid-19 as a global pandemic will change. Earlier in September, WHO director general Tedros Ghebreyesus hinted that the end of the pandemic was “in sight,” amid the sustained global decline in cases and deaths.

Many countries have moved on from mobility restrictions, mask mandates, and vaccine certificates, and have decided to treat Covid-19 like the flu. Denmark ended all pandemic measures as far back as February this year once they determined that vaccination rates were high enough to keep deaths and hospitalization rates stable even as widespread transmission continued.

Monkeypox, which was declared a Public Health Emergency of International Concern (PHEIC) in July 2022, seems to be fizzling out. The PHEIC declaration worried many people, since the previous PHEIC that was announced in January 2022 was for the current Covid-19 pandemic. Fortunately, monkeypox does not seem to be following in the footsteps of Covid-19 for now. While many countries including the Philippines have reported their first-ever monkeypox cases, there has not been enough widespread community transmission to establish endemicity in most places. The US saw the biggest monkeypox outbreak globally, with cases in all 50 states. Fortunately, it too is seeing a sustained decrease in daily reported cases.

Monkeypox does not seem to be on the same level of danger of Covid-19. It is a DNA virus, which means it is not prone to rapid mutation compared to SARS-CoV-2. Vaccines against smallpox work against it, and there are already effective antivirals. It is not efficiently transmitted between humans, and the rashes and vesicles are easy to identify. Specific groups are at higher risk and the mode of transmission has been predominantly through sexual spread rather than via a respiratory route. Covid-19 measures such as masking and contact tracing that are already in place also work well in preventing and containing monkeypox. Finally, the case fatality rate of monkeypox has been very low, much lower than historical case fatality rates in endemic areas in Africa.

Prior to the arrival of Covid-19, most scientists and physicians believed that the next big pandemic was going to be influenza. After all, the Spanish flu of 1918 was such a globally devastating event, and we did have an influenza pandemic as recently as 2009. Given the propensity of the human influenza virus to reassort its genes and recombine with animal influenza viruses, the risk of an influenza pandemic is a clear and present danger that needs to be continuously monitored. The next influenza pandemic can still happen out of nowhere. Influenza’s deadliness, however, has been tempered by vaccines and effective antivirals. Despite an increase in oseltamivir resistance, there are other effective options for prevention and treatment in the event of a new global outbreak.

It took three tries for coronavirus to become a pandemic in the modern era. Several types of coronaviruses have historically infected humans, but typically cause mild symptoms that are indistinguishable from the common cold. There is evidence that one or more of these human coronaviruses caused a Covid-19-like outbreak in the past, but there were no tools to detect or document those events. More likely it was assumed to be the flu or another viral illness and it became less virulent as it established itself in the human population. The original SARS outbreak in 2003 was the first significant documented zoonotic (from animals) outbreak of a coronavirus in humans. Like the initial presentation of Covid-19, it had a very high mortality rate of up to 11 percent.

Unlike SARS-CoV-2, SARS-CoV was not significantly transmitted among asymptomatic patients. This allowed effective containment of the outbreak, and SARS did not progress to a full-blown pandemic nor did it become endemic.

The second coronavirus outbreak to threaten to become a full-scale pandemic was MERS. MERS-CoV was first identified in 2012 and led to several large-scale outbreaks. MERS has been the deadliest zoonotic coronavirus so far, with up to a 35 percent death rate among infected patients. Human to human transmission does not seem to be very efficient and has not been documented from asymptomatic patients. Two cases were identified in the Philippines but there were no onward transmissions. Both patients survived. Low level transmission in the several hundreds of cases continues to occur every year and MERS-CoV continues to circulate in camels and animal hosts. Large scale outbreaks like those that occurred in South Korea and Saudi Arabia have been rare and not sustained.

With the occurrence of Covid-19 and the unprecedented vaccination program against it, there is now a significant level of immunity against coronaviruses in the population. It is likely that vaccination against SARS-CoV-2 will provide at least partial protection against SARS and MERS, and so the threat of these coronavirus infections becoming the next pandemic is unlikely. Emergence of a new variant of concern is possible, but protection from severe disease from the current vaccines will likely persist. With the availability of bivalent vaccines and the ability to quickly produce updated ones, it is unlikely that a coronavirus pandemic of the magnitude of Covid-19 will occur any time soon.

As for influenza, the lessons learned during the Covid-19 pandemic have also tempered the risk of a future influenza pandemic. The rapid development and deployment of mRNA vaccines for SARS-CoV-2 can likely be replicated for influenza. Medications developed for Covid-19 may have some activity against influenza, and the extensive pipeline of antivirals in development because of Covid-19 will also yield more anti-influenza treatments. Molecular diagnostic tools and rapid sequencing methodologies that were widely deployed for Covid-19 are now also being applied to influenza and will enable healthcare workers to quickly detect and characterize outbreaks.

The last two years of the Covid-19 pandemic have been among the most challenging in our recent history. The economic fallout of the lockdowns continues to disrupt our lives. The lessons learned should not be forgotten and should be institutionalized to ensure that the threat of future pandemics can be mitigated. We must never again underestimate the impact of an infectious virus on humanity. The unimaginable has happened, and we need to make sure it doesn’t happen again.