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. 2020 Apr 30;739:139076. doi: 10.1016/j.scitotenv.2020.139076

Table 8.

Dose-response parameters available and sporadic dose-response data where there are limited models and gaps.

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)
a

PFU, plaque forming unit; TCID50, median tissue culture infectious dose; EID50, median egg infectious dose, HI, hemagglutination inhibition.

b

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.

c

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.

d

The N50 represents the median dose associated with a particular health endpoint.

e

Watanabe et al. (2010) considered the animal death endpoint to be representative of a SARS-CoV human illness in the dose response model.