It typically only takes a few viral particles to enter your body to trigger an infection. But if the initial invasion is triggered by a larger number of viruses, the infection can also be more severe.

We don’t yet know just how much the initial viral load (also called the infectious dose) matters for COVID-19, or whether more severe cases manifest themselves through a larger viral load inside the body.

However, there are already a few studies on this issue, and researchers are starting to suspect that this parameter might play a more important role than was initially suspected.

The initial load

“In general with respiratory viruses, the outcome of infection – whether you get severely ill or only get a mild cold – can sometimes be determined by how much virus actually got into your body and started the infection off. It’s all about the size of the armies on each side of the battle, a very large virus army is difficult for our immune systems army to fight off,” says Professor Wendy Barclay, Head of Department of Infectious Disease, Imperial College London.

It’s not a novel concept. For influenza, a higher infectious dose has been associated with worse symptoms. However, the influenza studies were carried out by exposing volunteers to escalating doses of the virus, in a carefully monitored and controlled setting. This is very unlikely to happen with COVID-19, considering its severity, so we will have to look for evidence in other studies.

Animals infected with higher doses of SARS and MERS (two coronaviruses which also triggered severe outbreaks) also experienced worse outcomes. Of course, this is no guarantee that the same would happen in humans, or even that the same would happen with the novel coronavirus. However, it is a strong indication that that might be the case — and this is what most epidemiologists seem to be thinking at the moment.

“On the basis of previous work on SARS and MERS coronaviruses, we know that exposure to higher doses are associated with a worse outcome and this may be likely in the case of Covid-19 as well,” says Professor Willem van Schaik, Professor in Microbiology and Infection at the University of Birmingham.

This would also help explain why some healthcare workers seem to exhibit more severe infections than average — it’s not just that they are risking infection, but they are probably getting a larger infection dose.

“The amount of virus we are exposed to at the start of an infection is referred to as the ‘infectious dose’. For influenza, we know that that initial exposure to more virus – or a higher infectious dose – appears to increase the chance of infection and illness. Studies in mice have also shown that repeated exposure to low doses may be just as infectious as a single high dose,” adds Dr. Edward Parker, Research Fellow in Systems Biology at the London School of Hygiene and Tropical Medicine,

Reducing the frequency and intensity of exposure to SARs-CoV-2 might reduce the infectious dose and result in less severe cases — this is what we should be doing anyway to reduce the risk of transmission.

The infected viral load

The discussion about viral load sometimes gets murky as the two viral loads get confused — the initial viral load (the infectious dose) and the viral load taken from bodily samples of infected patients. When someone says, for instance, that “a higher viral load can be associated with more severe cases” they could, reasonably, mean both (and there is a case to be made for both), but they are not the same.

Viral load refers to the number of viral particles that an individual is carrying (and shedding into the environment). Essentially, the more a virus has multiplied inside the body, the higher the viral load is.

Intuitively, it might seem that the higher the viral load, the more severe the case would be, but this is not always so. The severity of an infection is governed by a number of bio-physical parameters. So what do we know about viral load and COVID-19?

When someone is tested for COVID-19, a swab is taken from their nose and throat. In addition to carrying a simple yes/no diagnostic, some tests can also analyze the viral load — how much virus is on the swab.

The initial studies coming out of China and Italy seem to indicate that viral load is not a factor in severity. Doctors at the Guangzhou Eighth People’s Hospital in China took throat swabs from 94 COVID-19 patients on the day people became ill and repeated the sample when 14 days later. They found no obvious difference in viral load between milder cases and more severe ones.

But there is a catch, and a big one at that. Not only were those studies preliminary and carried on small sample sizes, but they were also not peer-reviewed yet. The Italian study, in particular, makes no claims about a lack of correlation between viral load and case severity, it merely reports a large variation in patients’ viral load. The paper from China makes a solid, but not a compelling case for a lack of correlation.

Meanwhile, two peer-reviewed papers published in The Lancet (one of the most high-profile medical journals) suggest that there is a correlation between viral load and case severity. It’s still far from providing a clear and unequivocal answer, but the weight of evidence seems to lean heavier here, as peer-reviewed science is still the gold standard for scientific evidence, and these studies are generally regarded with far more trust.

This debate might be highly consequential. For one, doctors detecting patients with a higher viral load could pay extra attention to these patients, as they might be more likely to develop a severe case. But in addition, this could also help explain why testing negative for COVID-19 might not necessarily mean you don’t have the disease: if the viral load is small enough and not captured on the swab, the virus can simply escape detection. Even if a case is mild or asymptomatic it can still pass the virus on.

These are just a few of the complex aspects of COVID-19 that researchers are working frantically to uncover in this period.

It’s not surprising that the evidence is not always clear, and sometimes even conflicting, but with every published study, we get one step closer to understanding this disease — and one step closer to defeating it.