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Does the severity of the COVID disease depend on the dose of virus received?

Text updated on 2021-04-18


Many observations suggest that the severity of COVID disease is dependent on the infectious dose. Wearing a mask appears to not only decrease transmission, but also the intensity of symptoms in the event of infection. It is important to wear a mask to protect others, to reduce the risk of getting COVID, and also to reduce the risk of developing severe COVID disease in the event of infection.

The severity of the disease COVID depends on the infectious dose.

The idea that the severity of a viral disease depends on the infectious dose or viral inoculum (which is the amount of absorbed virus particles that triggered the infection) is not new. It has been demonstrated in the laboratory in mice for Influenza A, SARS-CoV-1 or MERS-CoV and in humans for non-lethal viruses such as seasonal influenza A. An experiment in hamsters showed that those who received a smaller amount of virus SARS-CoV-2 developed less severe forms of the disease than others. Recent studies on patients with COVID-19 confirm these results.

If the inoculum is reduced, the immune system is less likely to be overwhelmed by the infection, and the symptoms of the COVID-19 disease will be mild or non-existent. It will develop into a mild or even an asymptomatic form of the disease. On the contrary, if the viral inoculum is large, it will immediately infect a large number of cells and the immune system may be overwhelmed. The sick person will develop a severe form of COVID-19.

These observations on the relationship between infectious dose and severity of COVID-19 helps to explain why in the summer of 2020, despite a significant number of new daily cases of SARS-CoV-2, the percentage of hospitalizations due to COVID-19 hospitalizations among vulnerable individuals has not increased significantly. In the summer, the warmer, sunnier, more airy environments than in the winter have surely reduced the amount of virus in our environment. It can be assumed that in a large proportion of cases of infection this summer, the infectious dose was lower, which may have led to a decrease in the number of severe forms of COVID-19. Another explanation for the low proportion of hospitalizations during the summer is that it was mainly the 20-40 year olds who were infected in July-August, whereas in the over 70 year olds the positive tests tended to increase after the summer.

The mask is a filter that reduces the infectious dose.

The mask is a filter that works both ways. The aerosols and droplets we breathe out are largely stopped by the mask, so we don't infect others. But more importantly, the mask also filters out aerosols and droplets that are present in the environment around us. It reduces the amount of coronavirus SARS-CoV-2 that we are likely to inhale and therefore reduces the infectious dose. See the question Why put on a mask?.

A distinction must be made between the infectious dose or viral inoculum (which is the amount of absorbed viral particles that triggered the infection) and the viral load (which is the number of viral particles carried by an infected individual at a given time and that can be spread in the environment). Wearing a mask reduces the infectious dose received when interacting with a person with a high viral load.

The mask reduces the symptoms of COVID-19.

In the laboratory on hamsters, it has been shown that the mask protects against severe forms of COVID-19. Another argument supporting the protective role of the mask comes from the cruise ships stuck at sea at the beginning of the epidemic of COVID-19. In February 2020, the "Diamond Princess", was the first cruise ship to be stranded at sea for 2 weeks after a case of a patient with the COVID-19. The recommendations were still unclear on how to proceed and passengers were only told to stay in their cabins. On this ship, not all passengers were tested but the percentage of symptomatic infected individuals was estimated by a statistical model to be 82%. A month later, another cruise ship, the "Greg Mortimer", suffered a similar fate. This time, however, the guidelines for dealing with the epidemic had evolved and as soon as the first case of a patient with COVID-19 was reported, masks were distributed to all passengers, including the crew. All passengers were tested and on this ship, where passengers were masked, only 19% of the 128 passengers infected with the SARS-CoV-2 coronavirus developed symptoms and only one died. This suggests that wearing masks reduced the symptoms of COVID-19.

The mask is an essential barrier to reduce the inoculum and thus protect us from a severe form of COVID-19 .


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Sources

Clinical study in human volunteers that shows that in the case of influenza, the symptoms presented by patients are dependent on the viral dose that infected them: the higher the infectious dose, the greater the symptoms.

Memoli, M. J., Czajkowski, L., Reed, S., Athota, R., Bristol, T., Proudfoot, K., ... & Davey, R. T. (2015). Validation of the wild-type influenza A human challenge model H1N1pdMIST: an A (H1N1) pdm09 dose-finding investigational new drug study. Clinical Infectious Diseases, 60(5), 693-702.

In the case of the influenza A virus, it has been shown in mice that the greater the volume of the inoculum, the more severe the form of the disease.

Miller, D. S., Kok, T., & Li, P. (2013). The virus inoculum volume influences outcome of influenza A infection in mice. Laboratory animals, 47(1), 74-77.

Laboratory experiment in mice showing that the severity of infection with a virus derived from human SARS-CoV (containing 6 mutations that make it more lethal in mice) is dependent on the dose of the inoculum.

Roberts, A., Deming, D., Paddock, C. D., Cheng, A., Yount, B., Vogel, L., ... & Zaki, S. R. (2007). A mouse-adapted SARS-coronavirus causes disease and mortality in BALB/c mice. PLoS Pathog, 3(1), e5.

Laboratory experiments in transgenic mice expressing the human CD26 receptor show that the severity of infection with human MERS-CoV coronavirus is dose-dependent.

Tao, X., Garron, T., Agrawal, A. S., Algaissi, A., Peng, B. H., Wakamiya, M., ... & Couch, R. B. (2016). Characterization and demonstration of the value of a lethal mouse model of Middle East respiratory syndrome coronavirus infection and disease. Journal of virology, 90(1), 57-67.

This laboratory study showed, using a device that simulated the effect of the mask, that hamsters wearing masks have a lower risk of being infected with the SARS-CoV-2 coronavirus and that those who become ill have less severe forms of the disease than those who do not wear masks.

Chan, J. F. W., Yuan, S., Zhang, A. J., Poon, V. K. M., Chan, C. C. S., Lee, A. C. Y., ... & Tang, K. (2020). Surgical mask partition reduces the risk of non-contact transmission in a golden Syrian hamster model for Coronavirus Disease 2019 (COVID-19). Clinical Infectious Diseases.

Study on the Diamond Princess, a cruise ship that remained at sea for 15 days in February 2020 without being able to dock after the discovery of cases of patients with COVID-19 among the 3711 passengers. On this boat, there were no special instructions on the wearing of masks. Not all the passengers were tested and based on a statistical model the number of asymptomatic individuals among those infected with SARS-CoV-2 was estimated to be 17.9%.

Mizumoto K, Kagaya K, Zarebski A, Chowell G. Estimating the asymptomatic proportion of coronavirus disease (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020. Euro Surveill 2020; 25(10).

On a cruise ship, the Greg Mortimer, which was cruising off Antarctica in March 2020, an individual reported having  COVID-19 on the 8th day of the cruise. All passengers and crew members were given masks and began to wear them. For 28 days, the ship remained at sea without permission to disembark and the passengers remained isolated from the rest of the world. Of the 217 passengers, 128 were infected with SARS-CoV-2. However, only 24 passengers (19%) infected with SARS-CoV-2 showed symptoms of COVID-19 and only one died. All the other 104 passengers infected with SARS-CoV-2 (81%) were asymptomatic.

Ing, A. J., Cocks, C., & Green, J. P. (2020). COVID-19 in the footsteps of Ernest Shackleton. Thorax.

In hospitalized patients infected with SARS-CoV-2, the viral load detected at the time of diagnosis is a predictor of the risk of mortality. The higher the viral load, the greater the risk of dying from the COVID-19 disease.

Pujadas, E., Chaudhry, F., McBride, R., Richter, F., Zhao, S., Wajnberg, A., ... & Cordon-Cardo, C. (2020). SARS-CoV-2 Viral Load Predicts COVID-19 Mortality. The Lancet Respiratory Medicine, Volume 8, Issue 9, e70

Among 76 hospitalized patients, 46 developed a moderate form of COVID-19 and 30 a severe form. This study shows that patients who develop a severe form have a higher viral load on admission than patients who develop a moderate form.

Liu, Y., Yan, L. M., Wan, L., Xiang, T. X., Le, A., Liu, J. M., ... & Zhang, W. (2020). Viral dynamics in mild and severe cases of COVID-19. The Lancet Infectious Diseases.

30 patients infected with SARS-CoV-2 and isolated in a quarantine centre were followed up. Of these individuals, 13 (43%) were asymptomatic. At the time of management, the presence of SARS-CoV-2 is more difficult to detect in asymptomatic individuals. The viral load of SARS-CoV-2 disappears more rapidly in asymptomatic individuals than in symptomatic individuals.

Chau, N. V. V., Lam, V. T., Dung, N. T., Yen, L. M., Minh, N. N. Q., Ngoc, N. M., ... & Hong, N. T. T. (2020). The natural history and transmission potential of asymptomatic SARS-CoV-2 infection. Clinical Infectious Diseases, ciaa711.

Modelling study showing that transmission of SARS-CoV-2 is attributable in only 3.4% to 6.6% of cases to SARS-CoV-2 infected individuals who are asymptomatic. On the other hand, in 46%-47% of the cases, the contamination occurs in individuals who are presymptomatic, in the days preceding the onset of symptoms of COVID disease.

Moghadas, S. M., Fitzpatrick, M. C., Sah, P., Pandey, A., Shoukat, A., Singer, B. H., & Galvani, A. P. (2020). The implications of silent transmission for the control of COVID-19 outbreaks. Proceedings of the National Academy of Sciences, 117(30), 17513-17515.

In France, the number of daily cases of people infected with SARS-CoV-2 increased during the summer (partly also because the number of tests performed also increased during this period). At the beginning of July, the number of daily cases detected was less than 1000. Between early and late August, it rose from 2000 cases per day to almost 8000 cases per day. At the same time, the daily number of people hospitalized for the COVID-19 disease did not increase in the same proportions. It was around 100 per day in early July and 250 at the end of August.

Public Health Data France.

Study that followed patients with COVID-19 patients and their contacts whose viral load was measured on day 1 and day 14 and, if applicable, on the day of onset of symptoms. This study shows that the viral load of the index cases (the individuals who infected the contact cases) is one of the main factors in the transmission of SARS-CoV-2: the higher the viral load of the index case, the higher the risk of contagion. In the infected contact case, the initial viral load is correlated with the incubation time: the higher the viral load, the shorter the incubation time. In the infected contact case, a higher viral load level on day 1 was associated with an increased risk of developing symptomatic disease. Among contacts, the risk of developing symptomatic disease was approximately 38% for those with an initial viral load of less than 1 × 107 copies per mL, compared with a risk of more than 66% for those with an initial viral load of 1 × 11010 copies per mL or greater.

Marks, M., Millat-Martinez, P., Ouchi, D., h Roberts, C., Alemany, A., Corbacho-Monné, M., ... & Mitjà, O. (2021). Transmission of COVID-19 in 282 clusters in Catalonia, Spain: a cohort study. The Lancet Infectious Diseases.

Further reading

Where and when should I put on a mask?

Why put on a mask?

How do you put on and take off your mask?

Can a mask be reused?

Do I have to wear a mask if I already had COVID-19?

Do I have to wear a mask if I don't have any symptoms?

What are the symptoms of COVID-19 ?