@ducky

Hamster models may not reflect humans, but

Six hamsters per group were intranasally inoculated with 100, 10, and 1 PFU of WT/D614G and Alpha variants. All hamsters became infected. [12]

that same study tried smaller doses:

To determine the smallest dose capable of causing robust infection, we next inoculated hamsters with 10, 1, and 0.1 PFU of Alpha and Delta variants, with four hamsters per group. In the 10 and 1 PFU groups, all hamsters (4/4) were infected and shed infectious virus (Table 1 and Fig. S3a, b). In the 0.1 PFU Alpha group, three hamsters (3/4) were infected, with viral shedding starting on 1 dpi, and comparable virus titres observed on day 3. In the 0.1 PFU Delta group, only one hamster (1/4) was infected, with delayed viral shedding and a half-log lower virus titre [12]

and finding an

ID50 of 0.304 PFU for Delta

but you'll note no quantification of viral particles per PFU, and obviously 0.1 PFU in that procedure must have had at least 1 full copy of viral RNA and almost certainly a full and intact virus.

[12] https://www.nature.com/articles/s44298-025-00120-1

#COVID #COVID19 #SARSCoV2

@ducky

First off this thread is excellent: https://mastodon.social/@jmcrookston/111205323609496167 - I never found the source for https://mastodon.social/@jmcrookston/111205339806125850 though

One early result estimated:

an infectious dose on the order of 10 aerosol-borne virions [1]

And another reported that

An accurate quantitative estimate of the infective dose of SARS-CoV-2 in humans is not currently feasible and needs further research. Our review suggests that it is small, perhaps about 100 particles [6]

One paper found 102 - 104 RNA copies / PFU, depending on variant [13], and they point out that RNA copies overcount viable virus particles:

The observed discrepancies between RNA copies/mL and PFU/mL are likely attributable to difference in the virus’ ability to form plaques and varying ratios of infectious particles to RNA copies present. Whilst the PFU/mL measures infectious virus present, RNA copies/mL encompasses all SARS-CoV-2 RNA present including non-infectious or dead virus.

Elsewhere PFUs are described as:

each plaque in a layer of host cells indicating colonisation by a single virus particle (plaque forming unit - PFU) [6]

but that doesn't necessarily mean that 1 PFU could systemically infect, and I'm not sure why they say a single viral particle without physically explanation. They and 2/2 mice infected from 630 PFU SARS2 and:

The human ID50 for seasonal coronavirus subtype 229E that causes mild common cold in humans was reported to be 13 TCID50 [6]

Experimentally, pre-Omicron,

The relation between PFU/mL and RNA copies/mL was 1:29800 for D614G strain, 1:11700 for Alpha, 1:8930 for Gamma, 1:12500 for Delta, and 1:2950 for Mu [5]

Suggesting 103 to 104 viral copies per PFU for older strains.

The minimum infective dose of SARS-CoV-2 causing COVID-19 in humans in assessed cross-sectional and case-series studies was low; in a case-series study that investigated infective dose in 273 specimens from 15 SARS-CoV-2-positive patients, detected minimum infective dose was 1.26 PFU in vitro in the COVID-19-RdRp/Hel assay. In another study, 248 oro-nasopharyngeal samples of COVID-19 individuals were assessed, and infective dose was reported to be 364 PFU [2]

Giving a range of 100 to 103 PFU to a minimum infectious dose.

A survey (2022) found:

The range of minimum infective was 1.26-7 × 106.25 PFU [3]

The reasoning behind "one single viral particle might be infectious" is:

The independent action hypothesis (IAH) states that each virion has an equal, nonzero probability of causing an infection. Validity of IAH was demonstrated for infection of insect larvae by baculovirus (15), and of plants by Tobacco etch virus variants that carried green fluorescent protein markers (16). IAH applies to systems where the host is highly susceptible, but the extent to which IAH is valid for humans and SARS-CoV-2 has not yet been firmly established. For COVID-19, with an oral fluid average virus RNA load of 7 × 106 copies per milliliter (maximum of 2.35 × 109 copies per milliliter) (7), the probability that a 50-µm-diameter droplet, prior to dehydration, contains at least one virion is ~37%. For a 10-µm droplet, this probability drops to 0.37%, and the probability that it contains more than one virion, if generated from a homogeneous distribution of oral fluid, is negligible. Therefore, airborne droplets pose a significant risk only if IAH applies to human virus transmission. Considering that frequent person-to-person transmission has been reported in community and health care settings, it appears likely that IAH applies to COVID-19 and other highly contagious airborne respiratory diseases, such as influenza and measles. [4]

In 2021, a summary of low quality evidence concluded

the total number of virions to establish a COVID-19 infection in susceptible individuals is likely to be in the order of hundreds, taken from modelling and microbiological perspectives [11]

From the Skagit Valley Choir event, in immune-naive people (rare now!)

Basu (2021) quantified the number of virions that can initiate an infection in susceptible individuals and the author concluded that 330 virions may be considered a conservative upper estimate of the COVID-19 infective dose in humans [11]

[1] https://www.pnas.org/doi/full/10.1073/pnas.2018995118
[2] https://journals.sagepub.com/doi/full/10.1177/20503121221115053
[3] https://pubmed.ncbi.nlm.nih.gov/35983085/
[4] https://www.pnas.org/doi/10.1073/pnas.2006874117
[5] https://pubmed.ncbi.nlm.nih.gov/37124861/
[6] https://www.cambridge.org/core/journals/epidemiology-and-infection/article/review-of-infective-dose-routes-of-transmission-and-outcome-of-covid19-caused-by-the-sarscov2-comparison-with-other-respiratory-viruses/8607769D2983FE35F15CCC328AB8289D
[11] https://edwebcontent.ed.ac.uk/sites/default/files/atoms/files/uncover_029-01_review_infectious_dose_of_covid-19.pdf
[13] https://www.medrxiv.org/content/10.1101/2023.07.24.23293072v3.full

#COVID #COVID19 #SARSCoV2