COVID-19: disease, or no disease? - that is the question. It’s the dose stupid!

Sehrawat, Sharvan; Rouse, Barry T.

doi:10.1016/j.micinf.2021.104779

Cited by 8 publications

(5 citation statements)

References 26 publications

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“…On the surface, our findings of higher protection in older university employees relative to younger university students appear to contradict evidence that Covid-19 vaccines are (relatively) less protective in older adults [36,37]. However, the risk of infection is dependent on the size of the infecting dose of the virus (i.e., viral load) [38][39][40][41][42][43]. Compared to the average adult, university students typically engage in more frequent and higher-density social interactions [27,44].…”

Section: Plos Global Public Healthcontrasting

confidence: 68%

Covid-19 vaccine effectiveness against general SARS-CoV-2 infection from the omicron variant: A retrospective cohort study

Rennert

McMahan

et al. 2023

PLOS Glob Public Health

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We aim to estimate the effectiveness of 2-dose and 3-dose mRNA vaccination (BNT162b2 and mRNA-1273) against general Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (asymptomatic or symptomatic) caused by the omicron BA.1 variant. This propensity-score matched retrospective cohort study takes place in a large public university undergoing weekly Coronavirus Disease 2019 (Covid-19) testing in South Carolina, USA. The population consists of 24,145 university students and employees undergoing weekly Covid-19 testing between January 3rd and January 31st, 2022. The analytic sample was constructed via propensity score matching on vaccination status: unvaccinated, completion of 2-dose mRNA series (BNT162b2 or mRNA-1273) within the previous 5 months, and receipt of mRNA booster dose (BNT162b2 or mRNA-1273) within the previous 5 months. The resulting analytic sample consists of 1,944 university students (mean [SD] age, 19.64 [1.42] years, 66.4% female, 81.3% non-Hispanic White) and 658 university employees (mean [SD] age, 43.05 [12.22] years, 64.7% female, 83.3% non-Hispanic White). Booster protection against any SARS-CoV-2 infection was 66.4% among employees (95% CI: 46.1–79.0%; P < .001) and 45.4% among students (95% CI: 30.0–57.4%; P < .001). Compared to the 2-dose mRNA series, estimated increase in protection from the booster dose was 40.8% among employees (P = .024) and 37.7% among students (P = .001). We did not have enough evidence to conclude a statistically significant protective effect of the 2-dose mRNA vaccination series, nor did we have enough evidence to conclude that protection waned in the 5-month period after receipt of the 2nd or 3rd mRNA dose. Furthermore, we did not find evidence that protection varied by manufacturer. We conclude that in adults 18–65 years of age, Covid-19 mRNA booster doses offer moderate protection against general SARS-CoV-2 infection caused by the omicron variant and provide a substantial increase in protection relative to the 2-dose mRNA vaccination series.

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Section: Plos Global Public Healthcontrasting

confidence: 68%

Covid-19 vaccine effectiveness against general SARS-CoV-2 infection from the omicron variant: A retrospective cohort study

Rennert

McMahan

et al. 2023

PLOS Glob Public Health

View full text Add to dashboard Cite

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“…The efficacy of masks in reducing infection risk has been shown in the context of SARS-CoV-2 1 and for other respiratory viruses , masking on the part of a contact also reduces infection risk. During the COVID-19 pandemic, an additional benefit of masking has been hypothesized: that masks can reduce disease severity in individuals who become infected despite masking [4][5][6] . The initial articles arguing that 'masks do more' than reduce viral transmission have been heavily cited 4,5,7 , with several follow-up articles that either express support of this hypothesis 6,8 or are critical of it based on the extent of evidence presented [9][10][11] or on findings from subsequent studies 12 .…”

Section: Introductionmentioning

confidence: 99%

Masks Do No More Than Prevent Transmission: Theory and Data Undermine the Variolation Hypothesis

Koelle

Lin

Zhu

et al. 2022

Preprint

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Background. Masking serves an important role in reducing the transmission of respiratory viruses, including SARS-CoV-2. During the COVID-19 pandemic, several perspective and review articles have also argued that masking reduces the risk of developing severe disease by reducing the inoculum dose received by the contact. This hypothesis, known as the variolation hypothesis, has gained considerable traction since its development. Methods. To assess the plausibility of this hypothesis, we develop a quantitative framework for understanding the relationship between (i) inoculum dose and the risk of infection and (ii) inoculum dose and the risk of developing severe disease. We parameterize the mathematical models underlying this framework with parameters relevant for SARS-CoV-2 to quantify these relationships empirically and to gauge the range of inoculum doses in natural infections. We then identify and analyze relevant experimental studies of SARS-CoV-2 to ascertain the extent of empirical support for the proposed framework. Results. Mathematical models, when simulated under parameter values appropriate for SARS-CoV-2, indicate that the risk of infection and the risk of developing severe disease both increase with an increase in inoculum dose. However, the risk of infection increases from low to almost certain infection at low inoculum doses (with <1000 initially infected cells). In contrast, the risk of developing severe disease is only sensitive to dose at very high inoculum levels, above 106 initially infected cells. By drawing on studies that have estimated transmission bottleneck sizes of SARS-CoV-2, we find that inoculum doses are low in natural SARS-CoV-2 infections. As such, reductions in inoculum dose through masking or greater social distancing are expected to reduce the risk of infection but not the risk of developing severe disease conditional on infection. Our review of existing experimental studies support this finding. Conclusions. We find that masking and other measures such as distancing that act to reduce inoculum doses in natural infections are highly unlikely to impact the contact's risk of developing severe disease conditional on infection. However, in support of existing empirical studies, we find that masking and other mitigation measures that reduce inoculum dose are expected to reduce the risk of infection with SARS-CoV-2. Our findings therefore undermine the plausibility of the variolation hypothesis, underscoring the need to focus on other factors such as comorbidities and host age for understanding the heterogeneity in disease outcomes for SARS-CoV-2.

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“…29,30 However, the risk of infection is dependent on the size of the infecting dose of the virus (i.e., viral load). [31][32][33][34][35][36] Compared to the average adult, university students typically engage in more frequent and higher-density social interactions. 18,37 Such social behavior increases exposure to higher viral loads and subsequently impacts the protective effect of vaccines.…”

Section: Discussionmentioning

confidence: 99%

Covid-19 vaccine effectiveness against general SARS-CoV-2 infection from the omicron variant: A retrospective cohort study

Rennert

McMahan

et al. 2022

Preprint

View full text Add to dashboard Cite

ObjectiveTo estimate the effectiveness of 2-dose and 3-dose mRNA vaccination (BNT162b2 and mRNA-1273) against general SARS-CoV-2 infection (asymptomatic or symptomatic) caused by the omicron variant.DesignPropensity-score matched retrospective Cohort Study.SettingLarge public university undergoing weekly Covid-19 testing in South Carolina, USA.ParticipantsPopulation consists of 24,145 university students and employees undergoing weekly Covid-19 testing between January 3rd and January 31st, 2022. The analytic sample was constructed via propensity score matching on vaccination status: Unvaccinated, completion of 2-dose mRNA series within previous 5 months, and receipt of mRNA booster dose within previous 5 months. The resulting analytic sample consists of 1,944 university students and 658 university employees.InterventionVaccination with a two dose or 3 dose regimen of the BNT162b2 or mRNA-1273 vaccine.ResultsBooster protection against any SARS-CoV-2 infection was 66.4% among employees (95% CI: 46.1-79.0%; P<.001) and 45.4% among students (95% CI: 30.0-57.4%; P<.001). Compared to the 2-dose mRNA series, estimated increase in protection from the booster dose was 40.8% among employees (P=.024) and 37.7% among students (P=.001). We did not have enough evidence to conclude a statistically significant protective effect of the 2-dose mRNA vaccination series, nor did we have enough evidence to conclude that protection waned in the 5-month period after receipt of the 2nd or 3rd mRNA dose. Furthermore, we did not find evidence that protection varied by manufacturer.ConclusionsCovid-19 mRNA booster doses offer moderate protection against any SARS-CoV-2 infection caused by the omicron variant and provide a substantial increase in protection relative to the 2-dose mRNA vaccination series.

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COVID-19: disease, or no disease? - that is the question. It’s the dose stupid!

Cited by 8 publications

References 26 publications

Covid-19 vaccine effectiveness against general SARS-CoV-2 infection from the omicron variant: A retrospective cohort study

Covid-19 vaccine effectiveness against general SARS-CoV-2 infection from the omicron variant: A retrospective cohort study

Masks Do No More Than Prevent Transmission: Theory and Data Undermine the Variolation Hypothesis

Covid-19 vaccine effectiveness against general SARS-CoV-2 infection from the omicron variant: A retrospective cohort study

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