Disruption of Adaptive Immunity Enhances Disease in SARS-CoV-2 Infected Syrian Hamsters

Brocato, Rebecca L.; Kim, Robert K.; Zeng, Xiankun; Williams, Janice A.; Liu, Yanan; Li, Rong; Smith, Jeffrey M.; Golden, Joseph W.; Gangemi, Dave; Youssef, Sawsan; Wang, Zhongde; Glanville, Jacob; Hooper, Jay W.

doi:10.1101/2020.06.19.161612

Cited by 6 publications

(13 citation statements)

References 22 publications

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“…Studies exploring re-exposure to SARS-CoV-2 virus were limited to seven animal studies of variable quality. Broadly, two areas were explored; exposure following a primary infection with SARS-CoV-2 [89][90][91]118 and re-exposure following passive transfer of neutralising antibodies. 92,103 Following primary infection, timing of re-challenge varied between 20-43 days post inoculation.…”

Section: Re-exposure To Sars-cov-2mentioning

confidence: 99%

“…89 Similar findings were reported in a hamster model. 92,118 In a smaller ferret study, clinical findings following reinfection were mixed with the re-challenged group demonstrating increased weight loss compared to naive ferrets. However, the authors acknowledged that the sample size (n=4) was too small to draw wider inference.…”

Section: Re-exposure To Sars-cov-2mentioning

confidence: 99%

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Antibody response to SARS-CoV-2 infection in humans: a systematic review

Post

Eddy

Huntley

et al. 2020

Preprint

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Introduction Progress in characterising the humoral immune response to Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) has been rapid but areas of uncertainty persist. This review comprehensively evaluated evidence describing the antibody response to SARS-CoV-2 published from 01/01/2020-26/06/2020. Methods Systematic review. Keyword-structured searches were carried out in MEDLINE, Embase and COVID-19 Primer. Articles were independently screened on title, abstract and full text by two researchers, with arbitration of disagreements. Data were double-extracted into a pre-designed template, and studies critically appraised using a modified version of the MetaQAT tool, with resolution of disagreements by consensus. Findings were narratively synthesised. Results 150 papers were included. Most studies (75%) were observational in design, and included papers were generally of moderate quality based on hospitalised patients. Few considered mild or asymptomatic infection. Antibody dynamics were well described in the acute phase, and up to around 3 months from disease onset, although inconsistencies remain concerning clinical correlates. Development of neutralising antibodies following SARS-CoV-2 infection is typical, although titres may be low. Specific and potent neutralising antibodies have been isolated from convalescent plasma. Cross reactivity but limited cross neutralisation occurs with other HCoVs. Evidence for protective immunity in vivo is limited to small, short-term animal studies, which show promising initial results in the immediate recovery phase. Interpretation Published literature on immune responses to SARS-CoV-2 is of variable quality with considerable heterogeneity with regard to methods, study participants, outcomes measured and assays used. Antibody dynamics have been evaluated thoroughly in the acute phase but longer follow up and a comprehensive assessment of the role of demographic characteristics and disease severity is needed. The role of protective neutralising antibodies is emerging, with implications for therapeutics and vaccines. Large, cross-national cohort studies using appropriate statistical analysis and standardised serological assays and clinical classifications should be prioritised.

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Section: Re-exposure To Sars-cov-2mentioning

confidence: 99%

Section: Re-exposure To Sars-cov-2mentioning

confidence: 99%

Antibody response to SARS-CoV-2 infection in humans: a systematic review

Post

Eddy

Huntley

et al. 2020

Preprint

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“…This review has merely laid the foundation in the study of this topic. Brocato et al (35) Schlottau et al (36)…”

Section: Resultsmentioning

confidence: 99%

“…The infective dose in humans for COVID-19 was estimated as n×100 particles based on computational analysis of nasopharynx in transmission and inhalation of droplets (80). In animals the minimum dose of SARS-CoV-2 that infected immunocompromised hamsters were also 100 particles (35), whereas healthy ferrets and transgenic mice were infected at slightly higher dose of 500 particle by nasal (16) and 630 particles by aerosol route (20). Possibly the higher value of 100 particle can be used as a potential surrogate…”

Section: Discussionmentioning

confidence: 99%

“…Increased exposure to the influenza virus, presumably reflecting increased infective dose, was correlated with disease progression (55). In addition to studies of SARS-CoV-2 infected ferrets, rhesus macaques, and hamsters (16,28,32,35) studies on laboratory adapted mice infected with HCoV-OC43, SARS-CoV-1and MERS reported increased morbidity and lethality with increasing dose at exposure (6,41,42).…”

Section: Transmission Route Exposure Rate and Correlation With Outcomementioning

confidence: 96%

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Review of Infective Dose, Routes of Transmission, and Outcome of COVID-19 Caused by the SARS-CoV-2 Virus: Comparison with Other Respiratory Viruses<strong> </strong>

Karimzadeh¹,

Bhopal²,

Huy³

2020

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pandemic. Prevention and control strategies require an improved understanding of SARS-CoV-2 dynamics. We did a rapid review of the literature on SARS-CoV-2 viral dynamics with a focus on infective dose. We sought comparisons of SARS-CoV-2 with other respiratory viruses including SARS-CoV-1 and MERS-CoV. We examined laboratory animal, and human studies. The literature on infective dose, transmission, and routes of exposure was limited specially in humans, and varying endpoints were used for measurement of infection. We propose the minimum infective dose of COVID-19 in humans, is higher than 100 particles, possibly slightly lower than the 700 particles estimated for H1N1 influenza. Despite variability in animal studies, there was some evidence that increased dose at exposure correlated with higher viral load clinically, and severer symptoms. Higher viral load measures did not reflect COVID-19 severity. Aerosol transmission seemed to raise the risk of more severe respiratory complications in animals. An accurate quantitative estimate of the infective dose of SARS-CoV-2 in humans is not currently feasible and needs further research. Further work is also required on the relationship between routes of transmission, infective dose, co-infection, and outcomes.

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Review of infective dose, routes of transmission and outcome of COVID-19 caused by the SARS-COV-2: comparison with other respiratory viruses

2021

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pandemic. Prevention and control strategies require an improved understanding of SARS-CoV-2 dynamics. We did a rapid review of the literature on SARS-CoV-2 viral dynamics with a focus on infective dose. We sought comparisons of SARS-CoV-2 with other respiratory viruses including SARS-CoV-1 and Middle East respiratory syndrome coronavirus. We examined laboratory animal and human studies. The literature on infective dose, transmission and routes of exposure was limited specially in humans, and varying endpoints were used for measurement of infection. Despite variability in animal studies, there was some evidence that increased dose at exposure correlated with higher viral load clinically, and severe symptoms. Higher viral load measures did not reflect coronavirus disease 2019 severity. Aerosol transmission seemed to raise the risk of more severe respiratory complications in animals. 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. Further work is also required on the relationship between routes of transmission, infective dose, co-infection and outcomes.

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Disruption of Adaptive Immunity Enhances Disease in SARS-CoV-2 Infected Syrian Hamsters

Cited by 6 publications

References 22 publications

Antibody response to SARS-CoV-2 infection in humans: a systematic review

Antibody response to SARS-CoV-2 infection in humans: a systematic review

Review of Infective Dose, Routes of Transmission, and Outcome of COVID-19 Caused by the SARS-CoV-2 Virus: Comparison with Other Respiratory Viruses<strong> </strong>

Review of infective dose, routes of transmission and outcome of COVID-19 caused by the SARS-COV-2: comparison with other respiratory viruses

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