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1. SARS-CoV-2 variants of concern Alpha and Delta show increased viral load in saliva

   https://doi.org/10.1371/journal.pone.0267750  

   King, Kylie L. ; Wilson, Stevin ; Napolitano, Justin M. ; Sell, Keegan J. ; Rennert, Lior ; Parkinson, Christopher L. ; Dean, Delphine ( May 2022 , PLOS ONE)

   Abd El-Aty, A. M. (Ed.)

   Background Higher viral loads in SARS-CoV-2 infections may be linked to more rapid spread of emerging variants of concern (VOC). Rapid detection and isolation of cases with highest viral loads, even in pre- or asymptomatic individuals, is essential for the mitigation of community outbreaks. Methods and findings In this study, we analyze Ct values from 1297 SARS-CoV-2 positive patient saliva samples collected at the Clemson University testing lab in upstate South Carolina. Samples were identified as positive using RT-qPCR, and clade information was determined via whole genome sequencing at nearby commercial labs. We also obtained patient-reported information on symptoms and exposures at the time of testing. The lowest Ct values were observed among those infected with Delta (median: 22.61, IQR: 16.72–28.51), followed by Alpha (23.93, 18.36–28.49), Gamma (24.74, 18.84–30.64), and the more historic clade 20G (25.21, 20.50–29.916). There was a statistically significant difference in Ct value between Delta and all other clades (all p.adj<0.01), as well as between Alpha and 20G (p.adj<0.05). Additionally, pre- or asymptomatic patients (n = 1093) showed the same statistical differences between Delta and all other clades (all p.adj<0.01); however, symptomatic patients (n = 167) did not show any significant differences between clades. Our weekly testing strategy ensures that cases are caught earlier in the infection cycle, often before symptoms are present, reducing this sample size in our population. Conclusions COVID-19 variants Alpha and Delta have substantially higher viral loads in saliva compared to more historic clades. This trend is especially observed in individuals who are pre- or asymptomatic, which provides evidence supporting higher transmissibility and more rapid spread of emerging variants. Understanding the viral load of variants spreading within a community can inform public policy and clinical decision making. 

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2. Quantifying asymptomatic infection and transmission of COVID-19 in New York City using observed cases, serology, and testing capacity

   https://doi.org/10.1073/pnas.2019716118  

   Subramanian, Rahul ; He, Qixin ; Pascual, Mercedes ( February 2021 , Proceedings of the National Academy of Sciences)

   null (Ed.)

   The contributions of asymptomatic infections to herd immunity and community transmission are key to the resurgence and control of COVID-19, but are difficult to estimate using current models that ignore changes in testing capacity. Using a model that incorporates daily testing information fit to the case and serology data from New York City, we show that the proportion of symptomatic cases is low, ranging from 13 to 18%, and that the reproductive number may be larger than often assumed. Asymptomatic infections contribute substantially to herd immunity, and to community transmission together with presymptomatic ones. If asymptomatic infections transmit at similar rates as symptomatic ones, the overall reproductive number across all classes is larger than often assumed, with estimates ranging from 3.2 to 4.4. If they transmit poorly, then symptomatic cases have a larger reproductive number ranging from 3.9 to 8.1. Even in this regime, presymptomatic and asymptomatic cases together comprise at least 50% of the force of infection at the outbreak peak. We find no regimes in which all infection subpopulations have reproductive numbers lower than three. These findings elucidate the uncertainty that current case and serology data cannot resolve, despite consideration of different model structures. They also emphasize how temporal data on testing can reduce and better define this uncertainty, as we move forward through longer surveillance and second epidemic waves. Complementary information is required to determine the transmissibility of asymptomatic cases, which we discuss. Regardless, current assumptions about the basic reproductive number of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) should be reconsidered. 

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3. Booster vaccination protection against SARS-CoV-2 infections in young adults during an Omicron BA.1-predominant period: A retrospective cohort study

   https://doi.org/10.1371/journal.pmed.1004153  

   Wan, Jiayue ; Cazer, Casey L. ; Clarkberg, Marin E. ; Henderson, Shane G. ; Lee, Scarlett E. ; Meredith, Genevive R. ; Osman, Marwan ; Shmoys, David B. ; Frazier, Peter I. ( January 2023 , PLOS Medicine)

   Low, Nicola (Ed.)

   Background While booster vaccinations clearly reduce the risk of severe Coronavirus Disease 2019 (COVID-19) and death, the impact of boosters on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections has not been fully characterized: Doing so requires understanding their impact on asymptomatic and mildly symptomatic infections that often go unreported but nevertheless play an important role in spreading SARS-CoV-2. We sought to estimate the impact of COVID-19 booster doses on SARS-CoV-2 infections in a vaccinated population of young adults during an Omicron BA.1-predominant period. Methods and findings We implemented a cohort study of young adults in a college environment (Cornell University’s Ithaca campus) from a period when Omicron BA.1 was the predominant SARS-CoV-2 variant on campus (December 5 to December 31, 2021). Participants included 15,800 university students who completed initial vaccination series with vaccines approved by the World Health Organization for emergency use, were enrolled in mandatory at-least-weekly surveillance polymerase chain reaction (PCR) testing, and had no positive SARS-CoV-2 PCR test within 90 days before the start of the study period. Robust multivariable Poisson regression with the main outcome of a positive SARS-CoV-2 PCR test was performed to compare those who completed their initial vaccination series and a booster dose to those without a booster dose. A total of 1,926 unique SARS-CoV-2 infections were identified in the study population. Controlling for sex, student group membership, date of completion of initial vaccination series, initial vaccine type, and temporal effect during the study period, our analysis estimates that receiving a booster dose further reduces the rate of having a PCR-detected SARS-CoV-2 infection relative to an initial vaccination series by 56% (95% confidence interval [42%, 67%], P < 0.001). While most individuals had recent booster administration before or during the study period (a limitation of our study), this result is robust to the assumed delay over which a booster dose becomes effective (varied from 1 day to 14 days). The mandatory active surveillance approach used in this study, under which 86% of the person-days in the study occurred, reduces the likelihood of outcome misclassification. Key limitations of our methodology are that we did not have an a priori protocol or statistical analysis plan because the analysis was initially done for institutional research purposes, and some analysis choices were made after observing the data. Conclusions We observed that boosters are effective, relative to completion of initial vaccination series, in further reducing the rate of SARS-CoV-2 infections in a college student population during a period when Omicron BA.1 was predominant; booster vaccinations for this age group may play an important role in reducing incidence of COVID-19. 

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4. Estimating unobserved SARS-CoV-2 infections in the United States

   https://doi.org/10.1073/pnas.2005476117  

   Perkins, T. Alex ; Cavany, Sean M. ; Moore, Sean M. ; Oidtman, Rachel J. ; Lerch, Anita ; Poterek, Marya ( September 2020 , Proceedings of the National Academy of Sciences)

   null (Ed.)

   By March 2020, COVID-19 led to thousands of deaths and disrupted economic activity worldwide. As a result of narrow case definitions and limited capacity for testing, the number of unobserved severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during its initial invasion of the United States remains unknown. We developed an approach for estimating the number of unobserved infections based on data that are commonly available shortly after the emergence of a new infectious disease. The logic of our approach is, in essence, that there are bounds on the amount of exponential growth of new infections that can occur during the first few weeks after imported cases start appearing. Applying that logic to data on imported cases and local deaths in the United States through 12 March, we estimated that 108,689 (95% posterior predictive interval [95% PPI]: 1,023 to 14,182,310) infections occurred in the United States by this date. By comparing the model’s predictions of symptomatic infections with local cases reported over time, we obtained daily estimates of the proportion of symptomatic infections detected by surveillance. This revealed that detection of symptomatic infections decreased throughout February as exponential growth of infections outpaced increases in testing. Between 24 February and 12 March, we estimated an increase in detection of symptomatic infections, which was strongly correlated (median: 0.98; 95% PPI: 0.66 to 0.98) with increases in testing. These results suggest that testing was a major limiting factor in assessing the extent of SARS-CoV-2 transmission during its initial invasion of the United States. 

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5. The implications of silent transmission for the control of COVID-19 outbreaks

   https://doi.org/10.1073/pnas.2008373117  

   Moghadas, Seyed M. ; Fitzpatrick, Meagan C. ; Sah, Pratha ; Pandey, Abhishek ; Shoukat, Affan ; Singer, Burton H. ; Galvani, Alison P. ( July 2020 , Proceedings of the National Academy of Sciences)

   null (Ed.)

   Since the emergence of coronavirus disease 2019 (COVID-19), unprecedented movement restrictions and social distancing measures have been implemented worldwide. The socioeconomic repercussions have fueled calls to lift these measures. In the absence of population-wide restrictions, isolation of infected individuals is key to curtailing transmission. However, the effectiveness of symptom-based isolation in preventing a resurgence depends on the extent of presymptomatic and asymptomatic transmission. We evaluate the contribution of presymptomatic and asymptomatic transmission based on recent individual-level data regarding infectiousness prior to symptom onset and the asymptomatic proportion among all infections. We found that the majority of incidences may be attributable to silent transmission from a combination of the presymptomatic stage and asymptomatic infections. Consequently, even if all symptomatic cases are isolated, a vast outbreak may nonetheless unfold. We further quantified the effect of isolating silent infections in addition to symptomatic cases, finding that over one-third of silent infections must be isolated to suppress a future outbreak below 1% of the population. Our results indicate that symptom-based isolation must be supplemented by rapid contact tracing and testing that identifies asymptomatic and presymptomatic cases, in order to safely lift current restrictions and minimize the risk of resurgence. 

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