Is the Minimum Infective Dose of COVID-19 Small?

Is the minimum infective dose of COVID-19 small?

Check out this answer from Consensus:

The minimum infective dose of SARS-CoV-2 appears to be relatively small, as evidenced by the high efficacy of vaccines in preventing infection and the significant immune responses observed even with low viral exposure. Vaccination, including booster doses, plays a critical role in reducing the risk of infection and mitigating the impact of low-dose viral exposure. Continued research is essential to refine our understanding of the MID and to develop strategies that can effectively control the spread of COVID-19.

The minimum infective dose (MID) of a pathogen is the smallest quantity of the pathogen that can cause an infection in a host. Understanding the MID of SARS-CoV-2, the virus responsible for COVID-19, is crucial for developing effective public health strategies and preventive measures. This article explores the current scientific understanding of the MID of COVID-19, drawing on data from various research studies.

Understanding the Minimum Infective Dose

The MID of a virus can vary based on several factors, including the mode of transmission, the host’s immune response, and the virulence of the virus. For respiratory viruses like SARS-CoV-2, the MID is typically measured in terms of the number of viral particles required to establish an infection.

Research Findings on SARS-CoV-2 MID

Several studies have investigated the infectivity and transmission dynamics of SARS-CoV-2, providing insights into its MID:

1. Vaccine Efficacy and Immune Response:
   • The BNT162b2 mRNA COVID-19 vaccine has shown high efficacy in preventing COVID-19, with a 95% effectiveness rate in clinical trials1. This suggests that even low doses of the virus may be sufficient to cause infection in unvaccinated individuals, highlighting the importance of vaccination in reducing susceptibility.
   • Similarly, the Ad5-vectored COVID-19 vaccine induced significant immune responses in recipients, indicating that the immune system can be primed to respond effectively to low doses of the virus2.
2. Infection in Children:
   • Studies on the mRNA-1273 and BNT162b2 vaccines in children have demonstrated robust immune responses and high efficacy, suggesting that children can be protected from infection even with low viral exposure3 4.
3. Single Dose Efficacy in Convalescents:
   • Research indicates that individuals who have recovered from COVID-19 and receive a single vaccine dose develop antibody levels comparable to those who receive a full two-dose course. This implies that prior exposure to the virus may lower the MID required to trigger an immune response5.
4. Booster Doses and Waning Immunity:
   • The effectiveness of booster doses in enhancing immunity against COVID-19, especially with the emergence of variants like Omicron, underscores the need for maintaining high antibody levels to counteract even small doses of the virus6 7 8 9.

 

 

Is the minimum infective dose of COVID-19 small?

Paul Digard has answered Uncertain

An expert from Edinburgh University in Virology

We do not yet know what the infectious dose is for SARS-CoV-2/COVID-19.

Extrapolating from influenza virus, where we know a lot more, the infectious dose by breathing it in (a direct journey from one person to another through droplets released in a cough) might be quite small. However, infection via a contaminated surface – where the virus has to survive a period of drying out, then a journey from surface to hand to face, is likely to require a lot more.

So maintain social distancing as much as possible, but following simple hand hygiene rules should take care of any risk from handling packages and groceries.

 

Is the minimum infective dose of COVID-19 small?

Mike Skinner has answered Uncertain

An expert from Imperial College London in Virology

Viruses are not poisons, within the cell they are self-replicating. That means an infection can start with just a small number of articles (the ‘dose’). The actual minimum number varies between different viruses and we don’t yet know what that ‘minimum infectious dose’ is for COVID-19, but we might presume it’s around a hundred virus particles.

When that dose reaches our respiratory tract, one or two cells will be infected and will be re-programmed to produce many new viruses within 12-24 hours (for COVID-19, we don’t yet know how many or over how long). The new viruses will infect many more nearby cells (which can include cells of our immune defence system too, possibly compromising it) and the whole process goes around again, and again, and again.

At some time quite early in infection, our ‘innate immune system’ detects there’s a virus infection and mounts an innate immune response. This is not the virus-specific, ‘acquired immune response’ with which people are generally familiar (i.e. antibodies) but rather a broad, non-specific, anti-viral response (characterised by interferon and cytokines, small proteins that have the side effect of causing many of the symptoms: fever, headaches, muscle pain). This response serves two purposes: to slow down the replication and spread of the virus, keeping us alive until the ‘acquired immune response’ kicks in (which, for a virus we haven’t seen, is about 2 to 3 weeks) and to call-up and commission the ‘acquired immune response’ which will stop and finally clear the infection, as well as laying-down immune memory to allow a faster response if we are infected again in the future (this is the basis of the expected immunity in survivors and of vaccination).

With COVID-19, these two arms of the immune system (innate and acquired) obviously work well for 80% of the population who recover from more or less mild influenza-like illness.

In older people, or people with immunodeficiencies, the activation of the acquired immune system may be delayed. This means that the virus can carry on replicating and spreading in the body, causing chaos and damage as it does, but there’s another consequence. Another job of the acquired immune system is to stand-down the innate immune system; until that’s done the innate immune response will keep increasing as the virus replicates and spreads. Part of the innate immune response is to cause ‘inflammation’. That is useful in containing the virus early in an infection but can result in widespread damage of uninfected tissue (we call this a ‘bystander effect’) if it becomes too large and uncontrolled, a situation named ‘cytokine storm’ when it was first seen with SARS and avian influenza H5N1. It is difficult to manage clinically, requiring intensive care and treatment and carries with it high risk of death.

The scenarios described above describe what happens following infection with ‘normal’ doses of virus, both in those who make a recovery, those who require intensive care and those (mainly elderly and/or immunosuppressed) who might succumb. Those with other comorbidities probably succumb due to additional stress of their already compromised essential systems by virus and/or cytokine storm.

It is unlikely that higher doses that would be acquired by being exposed to multiple infected sources would make much difference to the course of disease or the outcome. It’s hard to see how the dose would vary by more than 10 fold. (Although differences have been seen in lab animal infections with some viruses, those animals are inbred (genetically similar to respond in the same way). It’s unlikely that we’d see the differences as statistically significant in out-bred humans.)

We must be more concerned about situations where somebody receives a massive dose of the virus (we have no data on how large that might be but bodily fluids from those infected with other viruses can contain a million, and up to a hundred million viruses per ml), particularly through inhalation.

Unfortunately, we don’t yet know enough about the distribution of the COVID-19 virus throughout the body of the infected patients in normal, and unusual situations.

Under such circumstances the virus receives a massive jump start, leading to a massive innate immune response, which will struggle to control the virus to allow time for acquired immunity to kick-in while at the same time leading to considerable inflammation and a cytokine storm.

For most of us, it’s hard to see how we could receive such a high dose; it’s going to be a rare event. In the COVID-19 clinic, the purpose of PPE is to prevent such large exposures leading to high dose infection. Situations we should be concerned about are potential high dose exposure of clinical staff conducting procedures on patients who are not known to be infected. I read about a Chinese description of an early stage COVID-19 infection of the lung, which only came about because lung cancer patients (not known to be infected) had lobectemies. There have been suggestions that such situations contributed to the deaths of medics in Wuhan, who were conducting normal procedures (including some that could generate aerosols of infected fluids) before the spread and risk had been appreciated.

Obviously, testing of patients for infection should now be a priority for any such procedures. Some of the relevant elective procedures have been postponed or scaled back (for patient and staff safety) but we can’t do the same for non-elective procedures (especially in emergency and maternity departments).

This answer was adapted from my comments published in the Science Media Centre here.

 

Is the minimum infective dose of COVID-19 small?

Donald Schaffner has answered Uncertain

An expert from Rutgers University in Microbiology, Food Safety

First let me start by suggesting that there’s no evidence of transmission of COVID-19 from food or food packaging. There’s also no reason to disinfect food packaging after arriving home from the grocery store. But let’s say there is some theoretical risk there that we are trying to assess or manage. What would we need to know? How would we assess then manage that risk? 

 We should start with the idea that virus inactivation is dependent on temperature. Inactivation happens faster at higher temperatures and slower at lower temperatures. I took data from a couple of different papers to try to figure out the effect of temperature on the rate of reduction of the virus. Here’s the paper on the original SARS virus. And then there’s this pre-print on the new SARS-CoV-2. And the data do lineup pretty well. From the data in these two papers I was able to construct a table which shows the relationship between temperature and rate of reduction.

There’s also some other data that I’ve gotten a lot of attention. These come from the NEJM here and those authors report a worst case half-life of 6.8 hours on plastic. Let’s round up to seven hours for simplicity. 

I should also note that the NEJM paper does not mention experiment temperature, so let’s assume room temperature (~72 F). These data don’t line up exactly with the earlier data, but they’re in the right ballpark. 

What does it mean to have a “half life”? 

It means that the viable virus concentration drops by 50% every seven hours. Food microbiologists reading this may see that it’s possible to convert “half-life” to “log reduction rate”, that we commonly use. 

 In this case a half-life of seven hours corresponds to roughly a one log reduction per day (actually about 23.26 hours, but you get the idea). That’s actually slightly faster then the rate I calculated in the table above. 

Next, let me suggest that you stop thinking about the amount of “time” needed to make something safe. It’s not about *time* it’s about rate. What do I mean by that? 

“Inactivation time” is a function of the starting concentration, the rate of reduction, and the growth sensitivity of your method (i.e. detection limit), so any mention of “time” presupposes those three values. 

What would be a logical starting concentration? 

We know based on research with and without face masks, that 30 minutes of breathing without a mask gives about 10,000 virus particles from some individuals. Those virus particles spread throughout a store are mostly going to end up on the floor, but even if they end up on food they will gradually inactivate overtime and as you’ll see below transfer rate to hands would be low. 

From the same paper swab samples of nose and throat (unknown volume) give ~1M virus particles, which might be a worst case sneeze or cough. But what does any of this mean in terms of risk? 

It means based on the NEJM letter that your chance of finding an infectious virus particle someone has sneezed, coughed or breathed on food drops by 50% every seven hours, or by one order of magnitude (1 logarithm) every day. 

So what’s the risk of sick from different doses?

To answer this question we need a dose response model. We don’t have a dose response model SARS-CoV-2, but we do have one that’s been estimated for the original SARS. Based on that model if you ingest 10,000 virus particles the odds of getting sick are 100%. If you ingest 284 particles your odds are about 50-50, and if you ingest a single viral particle your risk is just a fraction of 1% (0.24% to be exact). 

But what happens when the predicted number of virus particles on a surface is less than one? Does it mean there’s no virus particles? No. 

If we predict that the number of virus particles is 0.1, another way of thinking about that is if we tested 10 surfaces, we would expect to find a single virus particle on one of them. 

I think it’s pretty unlikely that those hypothetical virus particles sitting there on packages of food are going to suddenly jump off and aerosolize, but they could get on your fingers. 

We don’t have data on cross-contamination for the virus that causes COVID-19, but based on our research on cross contamination with other organisms, I’d estimate about 1% of the virus particles (plus or minus) will transfer to the hand. 

Of course at this point it would be a really good time to wash your hands or use hand sanitizer. Probably not a good idea to stick your finger in your nose. 

So where does this leave us? 

If you think about the math, what it means is that nothing is ever completely safe. Sorry if that freaks you out a little bit, but that’s the nature of risk and probabilities. 

So what to do? 

Well, start by not leaving your groceries on your porch… if it’s cold outside, it won’t help. I’m still not planning on disinfecting my groceries either, because the risk is very low. 

The real risk is other people coughing/sneezing/breathing one *you* in the grocery store. Now that CDC is recommending face covers (i.e. masks) that risk should be less too. 

I will keep washing my hands and using hand sanitizer, especially when returning from the store or any other trip. 

If it makes you feel better to sanitize your groceries (or for that matter wash your produce in soap), go for it, but I don’t want to know. Stay home if you can, wash your hands and use hand sanitizer, and take care of those who need it most.