Table 8.
Virus | Dose unitsa | Host type | Exposure route | No. doses | Modelb | Parametersc, d | Health endpoint/ response | N50 | Remarks | Reference |
---|---|---|---|---|---|---|---|---|---|---|
SARS-CoV-2 | - | - | Intranasal (Bao et al., 2020a, Bao et al., 2020b, Blanco-Melo et al. 2020), ocular inoculation and intratracheal (Deng et al. 2020), intratracheal and intranasal (Rockx et al. 2020) | - | - | - | - | - | Existing dosing experiments designed to infect all animals ranged from 102 TCID50 (mice)–106 TCID50 (macaques) | (Bao et al., 2020a, Bao et al., 2020b; Blanco-Melo et al., 2020; Deng et al., 2020; Rockx et al., 2020) |
SARS-CoV | PFU | Pooled transgenic mice, non-transgenic mice | Intranasal | 8 | E | k = 2.45×10-3 | Deathe | 280 | (QMRA Wiki, 2020a; Watanabe et al., 2010) | |
SARS-CoV | PFU | Transgenic mice | Intranasal | 4 | E | k = 2.97×10-3 | Death | 233 | (QMRA Wiki, 2020a; Watanabe et al., 2010) | |
SARS-CoV | PFU | Mice | Intranasal | 4 | E | k= 2.14×10-3 | Death | 324 | (QMRA Wiki, 2020a; Watanabe et al., 2010) | |
SARS-CoV | PFU | Rhesus macaques | Intratracheal | 2 | - | - | Infection | - | Monkeys: 2/2 infected at 108 PFU | (Zhou et al., 2005) |
MERS-CoV | TCID50 | Mice | Intranasal | 6 | E | k ≅ 5.71×10-3 | Shedding/ mortality | ≅ 121 | Pooled endpoint | (Lunn et al., 2019) |
MERS-CoV | PFU | Mice | Intranasal | 3 | - | - | Infection/ death | All animals infected: LD50 ~1–2×104 | (Douglas et al., 2018) | |
MERS-CoV | PFU | Mice | Intranasal | 2 | - | - | Infection/ death | - | Authors stated “sublethal” 5×103 and “lethal” 5×105 doses (no deaths in test animals observed; all sacrificed 4 days post inoculation | (Leist et al., 2019) |
MERS-CoV | TCID50 | Rhesus macaques | Intratracheal | 1 | - | - | Death | - | 0/4 died at 6.5×107 | (Yao et al., 2014) |
MERS-CoV | TCID50 | Rhesus macaques | Intratracheal | 1 | - | - | Infection | - | 4/4 infected at 6.5×107 | (Yao et al., 2014) |
Human coronavirus 229E | TCID50 | Humans | Intranasal | 4 | E | k = 5.39 ×10-2 | Illness (cold) | 13 | (Watanabe et al., 2010) | |
Animal coronaviruses (MHV-S, HEV-67N, IBVA-5968) | PFU or CD50 | Mice, rats, chicks | Intranasal | 3-6 | E | k = 8.78×10-5 - 9.16×10-2 | Death | ~8 - 5.95×105 | Various coronavirus models fit for comparison with SARS | (Watanabe et al., 2010) |
Influenza virus (H5N1) | PFU, TCID50 | Mice | Intranasal | 6 | T | α= 4.640×10-1; J0=3.015×102; J1 = 1.000; J2 =1.793 | Infection | <101.5–>107 (depending on strain) | (Kitajima et al., 2011) | |
Influenza virus (H5N1) | PFU, TCID50 | Mice | Intranasal | 7 | T | α= 2.730×10-1; J0=9.617×104; J1 = 2.7082; J2 =4.666 | Infection | <101.5–>107 (depending on strain) | (Kitajima et al., 2011) | |
Influenza virus (H5N1) | PFU, TCID50 | Ferrets | Intranasal | 2 | T | k0= -1.707×10-1; k1=-1.502×10-1 | Infection | <101.5–>107 (depending on strain) | (Kitajima et al., 2011) | |
Influenza virus (H5N1) | PFU, TCID50 | Ferrets | Intratracheal | 2 | T | k0 = -1.480×101; k1 = -7.092 | Infection | <101.5–>107 (depending on strain) | (Kitajima et al., 2011) | |
Influenza virus (H1N1) | TCID50 | Human | Intranasal | 4 | B | ɑ = 9.04×101 | Infection | 1.25×106 | (QMRA Wiki, 2020b) | |
Influenza virus (H1N1) | TCID50 | Human | Intranasal | 9 | B | ɑ = 5.81×101 | Infection | 9.45×105 | (QMRA Wiki, 2020b) | |
Influenza virus (H3N2) | TCID50 | Human | Intranasal | 5 | B | ɑ = 4.29×101 | Infection | 6.66×105 | (QMRA Wiki, 2020b) | |
Influenza virus (H5N1) | EID50 | Mice | Intranasal | 6 | E | k = 1.09×10-2, | Death | 6.38×101 | (QMRA Wiki, 2020b) | |
Influenza virus (H1N1, H3N2) | TCID50 | Human | Intranasal | 4-5 | B | ɑ= 1.57×10-1-9.05×10-1; for fixed parameters (α=2.95×10-1; N50=4.42×105) attenuation tion parameter γ=1.07e×10-3 | Infection | Children 3.3×102-1.2×105; Adults 2.7×104-1.2×106 | Pooled data analysis from 11 datasets with respect to virus subtype (H1N1 or H3N2), attenuation method (cold-adapted or avian-human gene reassortment), and human age (adults or children | (Watanabe et al., 2012) |
Influenza virus (H3N1, H1N1, influenza A, influenza B) | HI titer | Various | Various | Various | B-HI | λ= 0.002- 0.245 | Various | Depends on HI titer | Authors developed a relationship between HI titer and protection against influenza virus | (Huang et al., 2018) |
PFU, plaque forming unit; TCID50, median tissue culture infectious dose; EID50, median egg infectious dose, HI, hemagglutination inhibition.
E, exponential model; B, Beta-Poisson model; T, dose response time model; B-HI, modified Beta-Poisson model to include a parameter for hemagglutination inhibition titer.
Best fit dose response model parameters are given in table (where a model was not available, available information relating dose to an outcome in an animal or human model is provided); ID50, median infectious dose; LD50, median lethal dose.
The N50 represents the median dose associated with a particular health endpoint.
Watanabe et al. (2010) considered the animal death endpoint to be representative of a SARS-CoV human illness in the dose response model.