skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


Title: Estimating unobserved SARS-CoV-2 infections in the United States
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.  more » « less
Award ID(s):
2027718
PAR ID:
10221400
Author(s) / Creator(s):
; ; ; ; ;
Date Published:
Journal Name:
Proceedings of the National Academy of Sciences
Volume:
117
Issue:
36
ISSN:
0027-8424
Page Range / eLocation ID:
22597 to 22602
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. null (Ed.)
    Abstract We use COVID-19 case and mortality data from 1 February 2020 to 21 September 2020 and a deterministic SEIR (susceptible, exposed, infectious and recovered) compartmental framework to model possible trajectories of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the effects of non-pharmaceutical interventions in the United States at the state level from 22 September 2020 through 28 February 2021. Using this SEIR model, and projections of critical driving covariates (pneumonia seasonality, mobility, testing rates and mask use per capita), we assessed scenarios of social distancing mandates and levels of mask use. Projections of current non-pharmaceutical intervention strategies by state—with social distancing mandates reinstated when a threshold of 8 deaths per million population is exceeded (reference scenario)—suggest that, cumulatively, 511,373 (469,578–578,347) lives could be lost to COVID-19 across the United States by 28 February 2021. We find that achieving universal mask use (95% mask use in public) could be sufficient to ameliorate the worst effects of epidemic resurgences in many states. Universal mask use could save an additional 129,574 (85,284–170,867) lives from September 22, 2020 through the end of February 2021, or an additional 95,814 (60,731–133,077) lives assuming a lesser adoption of mask wearing (85%), when compared to the reference scenario. 
    more » « less
  2. Abstract BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has spread globally. However, the contribution of community versus household transmission to the overall risk of infection remains unclear. MethodsBetween November 2021 and March 2022, we conducted an active case-finding study in an urban informal settlement with biweekly visits across 1174 households with 3364 residents. Individuals displaying coronavirus disease 2019 (COVID-19)–related symptoms were identified, interviewed along with household contacts, and defined as index and secondary cases based on reverse-transcription polymerase chain reaction (RT-PCR) and symptom onset. ResultsIn 61 households, we detected a total of 94 RT-PCR–positive cases. Of 69 sequenced samples, 67 cases (97.1%) were attributed to the Omicron BA.1* variant. Among 35 of their households, the secondary attack rate was 50.0% (95% confidence interval [CI], 37.0%–63.0%). Women (relative risk [RR], 1.6 [95% CI, .9–2.7]), older individuals (median difference, 15 [95% CI, 2–21] years), and those reporting symptoms (RR, 1.73 [95% CI, 1.0–3.0]) had a significantly increased risk for SARS-CoV-2 secondary infection. Genomic analysis revealed substantial acquisition of viruses from the community even among households with other SARS-CoV-2 infections. After excluding community acquisition, we estimated a household secondary attack rate of 24.2% (95% CI, 11.9%–40.9%). ConclusionsThese findings underscore the ongoing risk of community acquisition of SARS-CoV-2 among households with current infections. The observed high attack rate necessitates swift booster vaccination, rapid testing availability, and therapeutic options to mitigate the severe outcomes of COVID-19. 
    more » « less
  3. Abstract Objective: Current guidance states that asymptomatic screening for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) prior to admission to an acute-care setting is at the facility’s discretion. This study’s objective was to estimate the number of undetected cases of SARS-CoV-2 admitted as inpatients under 4 testing approaches and varying assumptions. Design and setting: Individual-based microsimulation of 104 North Carolina acute-care hospitals Patients: All simulated inpatient admissions to acute-care hospitals from December 15, 2021, to January 13, 2022 [ie, during the SARS-COV-2 ο (omicron) variant surge]. Interventions: We simulated (1) only testing symptomatic patients, (2) 1-stage antigen testing with no confirmatory polymerase chain reaction (PCR) test, (3) 1-stage antigen testing with a confirmatory PCR for negative results, and (4) serial antigen screening (ie, repeat antigen test 2 days after a negative result). Results: Over 1 month, there were 77,980 admissions: 13.7% for COVID-19, 4.3% with but not for COVID-19, and 82.0% for non–COVID-19 indications without current infection. Without asymptomatic screening, 1,089 (credible interval [CI], 946–1,253) total SARS-CoV-2 infections (7.72%) went undetected. With 1-stage antigen screening, 734 (CI, 638–845) asymptomatic infections (67.4%) were detected, with 1,277 false positives. With combined antigen and PCR screening, 1,007 (CI, 875–1,159) asymptomatic infections (92.5%) were detected, with 5,578 false positives. A serial antigen testing policy detected 973 (CI, 845–1,120) asymptomatic infections (89.4%), with 2,529 false positives. Conclusions: Serial antigen testing identified >85% of asymptomatic infections and resulted in fewer false positives with less cost per identified infection compared to combined antigen plus PCR testing. 
    more » « less
  4. Abstract Contact tracing forms a crucial part of the public-health toolbox in mitigating and understanding emergent pathogens and nascent disease outbreaks. Contact tracing in the United States was conducted during the pre-Omicron phase of the ongoing COVID-19 pandemic. This tracing relied on voluntary reporting and responses, often using rapid antigen tests due to lack of accessibility to PCR tests. These limitations, combined with SARS-CoV-2’s propensity for asymptomatic transmission, raise the question “how reliable was contact tracing for COVID-19 in the United States”? We answered this question using a Markov model to examine the efficiency with which transmission could be detected based on the design and response rates of contact tracing studies in the United States. Our results suggest that contact tracing protocols in the U.S. are unlikely to have identified more than 1.65% (95% uncertainty interval: 1.62-1.68%) of transmission events with PCR testing and 1.00% (95% uncertainty interval 0.98-1.02%) with rapid antigen testing. When considering a more robust contact tracing scenario, based on compliance rates in East Asia with PCR testing, this increases to 62.7% (95% uncertainty interval: 62.6-62.8%). We did not assume presence of asymptomatic transmission or superspreading, making our estimates upper bounds on the actual percentages traced. These findings highlight the limitations in interpretability for studies of SARS-CoV-2 disease spread based on U.S. contact tracing and underscore the vulnerability of the population to future disease outbreaks, for SARS-CoV-2 and other pathogens. 
    more » « less
  5. Funk, Sebastian (Ed.)
    Simultaneously controlling COVID-19 epidemics and limiting economic and societal impacts presents a difficult challenge, especially with limited public health budgets. Testing, contact tracing, and isolating/quarantining is a key strategy that has been used to reduce transmission of SARS-CoV-2, the virus that causes COVID-19 and other pathogens. However, manual contact tracing is a time-consuming process and as case numbers increase a smaller fraction of cases’ contacts can be traced, leading to additional virus spread. Delays between symptom onset and being tested (and receiving results), and a low fraction of symptomatic cases being tested and traced can also reduce the impact of contact tracing on transmission. We examined the relationship between increasing cases and delays and the pathogen reproductive number R t , and the implications for infection dynamics using deterministic and stochastic compartmental models of SARS-CoV-2. We found that R t increased sigmoidally with the number of cases due to decreasing contact tracing efficacy. This relationship results in accelerating epidemics because R t initially increases, rather than declines, as infections increase. Shifting contact tracers from locations with high and low case burdens relative to capacity to locations with intermediate case burdens maximizes their impact in reducing R t (but minimizing total infections may be more complicated). Contact tracing efficacy decreased sharply with increasing delays between symptom onset and tracing and with lower fraction of symptomatic infections being tested. Finally, testing and tracing reductions in R t can sometimes greatly delay epidemics due to the highly heterogeneous transmission dynamics of SARS-CoV-2. These results demonstrate the importance of having an expandable or mobile team of contact tracers that can be used to control surges in cases. They also highlight the synergistic value of high capacity, easy access testing and rapid turn-around of testing results, and outreach efforts to encourage symptomatic cases to be tested immediately after symptom onset. 
    more » « less