Author response: Projected resurgence of COVID-19 in the United States in July—December 2021 resulting from the increased transmissibility of the Delta variant and faltering vaccination
Year: 2022
Type: peer-review
Abstract: Article Figures and data Abstract Editor's evaluation Introduction Results Discussion Materials and methods Data availability References Decision letter Author response Article and author information Metrics Abstract In Spring 2021, the highly transmissible SARS-CoV-2 Delta variant began to cause increases in cases, hospitalizations, and deaths in parts of the United States. At the time, with slowed vaccination uptake, this novel variant was expected to increase the risk of pandemic resurgence in the US in summer and fall 2021. As part of the COVID-19 Scenario Modeling Hub, an ensemble of nine mechanistic models produced 6-month scenario projections for July–December 2021 for the United States. These projections estimated substantial resurgences of COVID-19 across the US resulting from the more transmissible Delta variant, projected to occur across most of the US, coinciding with school and business reopening. The scenarios revealed that reaching higher vaccine coverage in July–December 2021 reduced the size and duration of the projected resurgence substantially, with the expected impacts was largely concentrated in a subset of states with lower vaccination coverage. Despite accurate projection of COVID-19 surges occurring and timing, the magnitude was substantially underestimated 2021 by the models compared with the of the reported cases, hospitalizations, and deaths occurring during July–December, highlighting the continued challenges to predict the evolving COVID-19 pandemic. Vaccination uptake remains critical to limiting transmission and disease, particularly in states with lower vaccination coverage. Higher vaccination goals at the onset of the surge of the new variant were estimated to avert over 1.5 million cases and 21,000 deaths, although may have had even greater impacts, considering the underestimated resurgence magnitude from the model. Editor's evaluation In this paper, the authors presented the joint efforts of nine modeling teams to provide a six-month projection of the COVID-19 pandemic across the US, in view of the circulation of the more transmissible Delta variant. The results represented a timely assessment of the risk of COVID-19 resurgence in Summer 2021 when it was conducted in July 2021, and will be of historical interest as an example of modeling efforts to inform real-time decision making during the COVID-19 pandemic. This paper will be of high interest to public health specialists, forecast modelers, and members of the general public interested in the evolution of the COVID-19 pandemic and the impact of public health interventions in the USA. https://doi.org/10.7554/eLife.73584.sa0 Decision letter Reviews on Sciety eLife's review process Introduction The rapid development, scale-up, and deployment of COVID-19 vaccines in the United States (US) has been one of the biggest public health successes in the US during this pandemic, with reported cases in a nadir in June 2021 (Centers for Disease Control and Prevention, 2021b), despite increased testing capacities. With this success, non-pharmaceutical interventions (NPIs) were lifted, including mask mandates, in almost every jurisdiction across the US in Spring 2021. However, the emergence of novel variants with increased transmissibility and /or immune escape, particularly the Delta and Omicron variants, has continually raised concern about the potential timing and magnitude of the subsequent resurgence, and the ability to mitigate it through increased uptake of vaccination. Established in December 2020, the COVID-19 Scenario Modeling Hub is an effort to apply a multiple-model approach to produce six-month projections of the state and national trajectories of cases, hospitalizations, and deaths in the US under defined scenarios (Borchering et al., 2021). Scenarios from projection rounds have focused on control measures, vaccination availability and uptake, emerging variants, and waning immunity (COVID-19 Scenario Modeling Hub, 2020). Projections are released in a timely manner to guide policy decisions and data are made publicly available on a website (COVID-19 Scenario Modeling Hub, 2020). Here, we detail results from the seventh round of projections, in which increased transmissibility variants were incorporated into projections to assess the potential impact of the Delta variant. In all scenarios, resurgences across the US were projected, with the largest resurgences occurring for scenarios with the highest variant transmissibility (60% increase over the Alpha variant, which most closely resembles estimates for the Delta variant). Corresponding increases in hospitalizations and deaths were also projected. In scenarios with higher vaccine coverage, the size and duration of this resurgence was notably smaller. Cases were projected to increase in early July 2021 at the national level and peak in mid to late September 2021. Corresponding increases in hospitalizations and deaths were also projected. The resurgence was projected to be geographically heterogeneous; although most states were projected to experience some degree of rebound, those having higher vaccine coverage were projected to experience less severe increases in incidence relative to prior observed peaks. However, while the timing of these projected resurges was relatively accurate compared to what has since been reported, the magnitude of reported cases, hospitalization, and deaths far surpassed what was projected. Here, we describe our experience with multi-model projections of the Delta variant to highlight both the value of scenario-based projections for planning, but also the challenges to understand and predict the constantly evolving COVID-19 pandemic. Results In the two scenarios with high Delta variant transmissibility (60% more transmissible than Alpha), we projected a national wave of cases to continue to grow over the summer and peak in mid- to late September 2021. In the scenario that assumes lower vaccination coverage among eligible individuals (70%) and higher variant transmissibility (the most pessimistic scenario), this resurgence was projected to peak at 414,000 weekly cases (95% projection interval (PI): 140,000–1,525,000) and 5900 weekly deaths (95% PI: 900–30,000) nationally. Overall, this scenario projected 7,554,000 (95% PI: 3,294,000–28,399,000) cumulative cases and 96,000 (95% PI: 27,000–476,000) cumulative deaths during July 4, 2021–Jan 1, 2022 (Figure 1). Figure 1 with 3 supplements see all Download asset Open asset Historical data and weekly ensemble projections of reported numbers of COVID-19 cases. (A) Hospitalizations (B) and deaths (C) under four scenarios representing different levels of vaccination and Delta variant transmissibility increase — United States, October, 2020–December, 2021.Projections are ensemble estimates of 9 models projecting four 6-month scenarios with 95% prediction intervals (the grey shading encompasses the prediction intervals from all four scenarios). Projections used empirical data from up to July 3, 2021, to calibrate models (black filled dots). The vertical lines indicate the beginning of each projection, with only data available prior to that point used to fit the projections. Observations available after the projection start are displayed as open dots. With higher variant transmissibility, increasing national vaccination coverage was projected to temper the fall wave slightly and cause it to drop more quickly, but not prevent it. With an increase in national vaccine coverage to 80% by January 1, 2022, the ensemble projected 65,000 (16%) fewer cases and 1300 (21%) fewer deaths per week at the peak, and 1,525,000 (20%) and 21,000 (22%) fewer cumulative cases and deaths, respectively, during July 4, 2021–January 1, 2022, when compared to the scenario where vaccination saturated at 70% nationally (Figure 1). The projected national resurgence in COVID-19 cases in the higher transmissibility variant scenarios was composed of highly heterogeneous state-level resurgences. The ten states with the largest projected increases in incidence relative to their winter 2020–21 peak were, in descending order, Louisiana, Hawaii, Nevada, Arkansas, Florida, Missouri, Georgia, Alabama, Alaska, and Arizona. The ensemble estimates projected these states to experience median peak levels of weekly incident cases that were 18–69% (95% PI: 1%–541%) of their (smoothed) winter peak, although this was exceeded in many states. The 10 states with the lowest projected resurgences were, in ascending order, Massachusetts, Rhode Island, Vermont, Maine, Minnesota, Pennsylvania, North Dakota, Wisconsin, Tennessee, and South Dakota. The 10 states with the smallest projected resurgence had a median first-dose vaccine coverage of 70% among the eligible population (ages 12+) on July 3, 2021, compared to 56% in the ten states with the highest projected resurgence. We find a high negative correlation (Pearson's r=–0.66, Figure 2) between projected cumulative deaths per population and vaccination coverage on July 3, 2021 (NCIRD, 2021). In all states, even those with low overall vaccination coverage, at least 76% of people 65+had received at least one dose of the vaccine, which was expected to have a major effect in limiting mortality from Delta (Centers for Disease Control and Prevention, 2021b). Figure 2 Download asset Open asset Projected cumulative cases and mortality in the most pessimistic scenario (low vaccination, high variant transmissibility) and current vaccination coverage by state — United States, July 4, 2021–January 1, 2022. (A) Correlation between cumulative projected cases per 10,000 population during the 6-month period and proportion of the eligible population vaccinated with at least one COVID-19 vaccine dose by July 3, 2021, by state. Circle sizes represent population size. Single dose coverage was used as data reporting were most reliable for the first dose at the time of this analysis; yet second dose coverage is highly correlated with first dose coverage (Pearson rho = 0.92 on July 3, 2021, p<10–15). (B) Cumulative projected cases per 10,000 population during the 6-month period, by state. (C) Correlation between cumulative projected deaths per 10,000 population during the 6-month period and proportion of the eligible population vaccinated with at least one COVID-19 vaccine dose by July 3, 2021, by state. Circle sizes represent population size. (D) Cumulative projected deaths per 10,000 population during the 6-month period, by state. The impact of vaccination was already being observed early in the Delta wave: in the 10 states with the largest projected resurgence there was a 9% reduction in the observed case fatality ratio (CFR) comparing August–December 2020 and January–July 2021; in the 10 states with the smallest projected resurgence a 21% reduction in CFR was observed. During the projection period, we projected CFR reductions of 15% and 14%, as compared to August-December 2020. Lower transmissibility variant scenarios projected significantly reduced resurgence, projecting cumulative national cases of only 9% and 13% compared to the winter 2020–21 peak. Similarly, in the previous projection round (Round 6), which similar to the 7th round except it assumed only a 20% transmissibility increase from a novel variant, resurgence was expected to produce only 8% of the cases reported during the winter 2020–21 peak nationally (COVID-19 Scenario Modeling Hub, 2020). Weekly case observations exceeded our 95% projection interval in the first 9 weeks of the projection period in all scenarios, including those assuming 60% increased transmissibility of the Delta variant (Figure 1). Our projections also tended to underestimate hospitalizations and deaths in the ascending phase of the Delta wave, although to a lesser degree. We compared weekly incident and cumulative cases during the first four weeks after the projection date (July 4–31, 2021). The total median projected number of cases underestimated the observed cases overall during this 4-week period (1,256,000 observed vs 516,000 projected); however, we find a strong correlation between ranking of observed and projected total cases per 100,000 during the first four weeks of the projection period, at the state level (Spearman's ⍴=0.87, Figure 3). Seven of the ten states with greatest projected incidence rank in the ten worst observed incidence states. Hence while projections did not capture the full scope of the rise in incidence due to the Delta variant, these projections reflected the expected severity ranking among state projections well. Figure 3 Download asset Open asset Comparison of the median projected and observed state-level total COVID-19 case incidences occurring during July 4–31, 2021, United States. Comparison is based on ranking of incidence per capita in 50 states + DC (Spearman's rank correlation = 0.867). The grey solid line represents perfect agreement between ranks (y=x), which overlays a regression line fitted to the data (dashed line) and 95% confidence intervals (grey shaded area). The two high variant transmissibility scenarios, which most closely resembled the characteristics of the circulating Delta variant, projected the timing of the Delta resurgence, projecting deaths to increase simultaneously with reported cases and peak one week after reported cases (Figure 1). However, all scenarios substantially underestimated the magnitude of the Delta wave for all outcomes. Among the two high variant transmissibility scenarios, at the national level the peak cases were under-projected by 70% (95% PI: −25–91%) and 64% (95% PI: −49–88%) (349,183 and 413,733 vs 1.15 M peak reported weekly cases), though the 95% projection interval did capture the reported magnitude of the peak (Figure 1). Similarly, hospitalizations and deaths were also under-projected by 47% (95% PI: −184–84%) and 36% (95% PI: −230–82%) (46,000 and 56,000 vs 87,000 peak reported hospitalizations) and 67% (95% PI: −77–93%) and 59% (95% PI: −120–93%) (4700 and 6000 vs 14,000 peak reported deaths), respectively; both also captured the reported magnitude within projection intervals. Discussion Prevalence of the SARS-CoV-2 Delta variant rose quickly in the US between May and June 2021, with the variant achieving dominance by late June 2021, and accounting for over 90% of all SARS-CoV-2 infections for an extended period from late July to early December 2021 (Centers for Disease Control and Prevention, 2021b). This variant prompted concerns about the scale of the COVID-19 resurgence in the US in the summer and fall of 2021, especially in the midst of decreased NPIs and slowing vaccination rates. Projections combining insights from multiple models suggested sizable resurgences of COVID-19 across the US, assuming growth of a variant that is 60% more transmissible than the Alpha variant (an assumption aligned with most estimates of the relative transmissibility of the Delta variant) (Allen et al., 2022). In scenarios with higher vaccination coverage, the magnitude of the resurgence in cases and deaths was substantially lower than in the lower coverage scenarios. Efforts to increase vaccination rates are critical and will save lives before and during future resurgences. At the outset of the Delta wave on July 1, 2021, only 13 states and Washington, D.C. had accomplished President Biden's goal for vaccination coverage among eligible populations at or above 70%. The rapid case growth observed in July 2021 in multiple US states was surprising, tracking with or above the projections from our worst-case scenario. Scenarios were designed at the end of June 2021 based on information available at that time about the transmissibility of the Delta variant, vaccine effectiveness, and vaccine coverage; projections were generated on or before July 4, 2021. Our data should not be understood as forecasts, but as projections conditional on the scenarios and assumptions; several reasons could explain why case growth was faster than expected, including key epidemiological and behavioral aspects that may have affected the disease dynamics. Possible mechanisms driving the underestimation of the observed Summer 2021 resurgence may include inaccurate assumptions about the transmissibility and severity of Delta (including changes in serial interval or severity of infection relative to other variants), the effectiveness of the vaccines against infection and transmission, waning of natural and vaccine-derived immunity, changes in testing practices, and the interaction of these factors with NPIs and behavior change (Li et al., 2021; Elliott et al., 2021; Puranik et al., 2021). Assumptions regarding these factors were left to the discretion of the teams and therefore vary across models. Critically, eight of the nine teams did not include waning of natural or vaccine-derived immunity, an assumption that we now know is incorrect. (Higdon et al., 2021) Subsequent rounds of projection have focused on different scenarios of waning immunity. Yet in this round, absence of waning resulted in a much smaller population susceptible to infection with Delta, thus reducing the overall potential magnitude that could be projected by these models. Use of NPIs has been substantially reduced across the US, with a lapse in mask mandates in most states. Although modeled use of NPIs was left to the discretion of individual modeling teams and did not vary between scenarios, results of prior rounds underscore the effectiveness of NPIs, in combination with increasing vaccination, to moderate the spread of a highly transmissible variant (Borchering et al., 2021). The extent to which NPIs may be necessary will vary across states, as those states with high levels of vaccination coverage or natural immunity may be at lower risk for an increase in cases. The impact of the resurgence on severe disease and mortality was expected to vary substantially across states; states with younger populations and higher vaccination coverage among older and high-risk populations were expected to experience a relatively lower burden of severe disease, even with resurgences in cases. Several states (for example, South Dakota, North Dakota) with low vaccination coverage were not projected to experience major resurgences, likely because of high naturally acquired immunity. In addition, as the projected resurgence continued throughout the summer and into the beginning of the school year, efforts to promote vaccination among eligible school-aged children and college students and to maintain key prevention strategies in schools (for example, mask-wearing among the unvaccinated, physical distancing, screening programs) likely helped reduce risks with a safe return to in-person instruction (Centers for Disease Control and Prevention, 2021a). Observed increases in new vaccinations, particularly among young age groups and in jurisdictions most severely impacted by the Delta variant, was a positive step in this direction (Centers for Disease Control and Prevention, 2021b). The findings in this report are subject to several limitations. First, considerable uncertainty is inherent to long-term projections. This has been repeatedly illustrated throughout the COVID-19 pandemic, with rapid changes in behavior, deployment of vaccines and boosters, and the emergence of novel variants, each of which has the capacity to drastically shift the epidemic trajectories. Uncertainty may arise from three main sources: specification of the scenarios (for example, uncertainty in transmissibility); errors in the structure or assumptions of individual models given a specific scenario (for example, variations in assumptions about vaccination uptake); and inaccurate calibration based on incomplete or biased data (for example, reporting backlogs). None of the four scenarios considered here were likely to precisely reflect the future reality over a 6-month period. As a case in point the emergence of the Omicron variant in December 2021, at the end of our projection period, could not have been predicted when scenarios were designed in June 2021 (Borchering et al., 2021). Similarly, a resurgence in Delta variant incidence was observed in mid-fall 2021, possibly due to changes in behavior and waning immunity, and is not captured in scenarios or model projections. Further, for a given scenario, there is notable variation among individual model projections with regard to both the timing and the magnitude of the resurgence (Figure 1—figure supplements 1–3). Variation likely reflects differences in model structure, projected vaccine coverage, projected variant growth, and importance of seasonal effects. Some of these variations reflect true scientific uncertainty, making ensemble projections particularly useful to integrate uncertainty between and within individual models. In addition, these scenarios do not specify considerations of Delta infecting previously immune individuals due to moderate antigenic changes, the waning of existing immunity, increases in NPIs, or vaccination among children aged <12 years starting in November 2021, all of which were expected to be important drivers of dynamics in the subsequent months. In the same vein, model estimates are dependent on assumptions about vaccine hesitancy, which are informed in part by large-scale surveys of vaccine sentiments (Carnegie Mellon University Delphi Group, 2021; Estimates of Vaccine Hesitancy for COVID-19, 2021). These surveys may underestimate vaccine hesitancy, as coverage estimates among survey respondents are substantially higher than measured among the overall US population. Additionally, there are limitations to individual component models, although these concerns are tempered by analyzing ensembles of the nine different models. Overall, a full evaluation of our projections and sources of uncertainty is particularly difficult in a scenario context and is beyond the scope of this paper. However, it is worth noting that in this particular round of projection, the relationship between projection accuracy and time horizon is not straightforward (e.g. refer to Figure 1 for a visual assessment of coverage). Conclusions The emergence and introduction of more transmissible SARS-CoV-2 variants like the Delta variant was projected to lead to a substantial resurgence of COVID-19 in the US, which was observed in every state across the country. The high variant transmissibility scenarios, which more accurately represented the characteristics of the Delta variant, both in transmissibility and in current case trajectories, projected a significant national resurgence with substantial variation in magnitude across states. Resurgences were expected to be more pronounced in low-vaccination jurisdictions. The projections indicated that even with substantial vaccination coverage, the increased transmissibility of new variants like Delta can continue to challenge our ability to control this pandemic. efforts to increase vaccination coverage are critical to limiting transmission and disease, particularly in states with low natural immunity and lower current vaccination, in to control like when Projections of Delta resurgence presented in this paper were made publicly available in early July 2021 (COVID-19 Scenario Modeling Hub, 2 of the peak of the Delta wave, is a between projections in a timely manner to guide and projection accuracy and uncertainty that with of these projections underestimated the magnitude of the Delta resurgence, the challenges to predict this continually evolving pandemic, did provide value in projecting the timing and the importance of vaccination. ensemble efforts as the COVID-19 Scenario Modeling Hub are particularly to provide disease projections to inform the pandemic response under epidemiological and behavioral Materials and methods The COVID-19 Scenario Modeling Hub (COVID-19 Scenario Modeling Hub, nine modeling teams in an open to provide six-month (July 3, 1, COVID-19 projections in the US data available through July 3, 2021. a model to weekly reported cases, hospitalizations, and deaths, both nationally and by jurisdiction states and the of for four different epidemiological scenarios. were against data from the for and and US of and 2020). The four scenarios low and high vaccination assuming national vaccination coverage at 80% and respectively, based on surveys (Carnegie Mellon University Delphi Group, 2021; Estimates of Vaccine Hesitancy for COVID-19, 2021). teams for vaccination rates by and (for example, older and health vaccine levels were across the scenarios and were based on against disease in and effectiveness for effectiveness against transmission, and to severe (for example, were left to be by each (COVID-19 Scenario Modeling Hub, 2020). the scenarios were designed in late June 2021, information was available on vaccine specific to the Delta variant and on waning immunity. on individual model see 1 COVID-19 projection — United States, July 4, 2021–January 1, 2022. Scenarios defined for projection of COVID-19 cases, hospitalizations, and deaths for the round of projections through the COVID-19 Scenario Modeling impact transmissibility impact transmissibility at 80% nationally among the by December is for against circulating variants and 60% for increased transmissibility as compared with Alpha for Delta variant. estimated at state-level by at 80% nationally among the by December is for against circulating variants and 60% for increased transmissibility as compared with Alpha for Delta variant. estimated at state-level by at 70% nationally among the by December is for against circulating variants and 60% for increased transmissibility as compared with Alpha for Delta variant. estimated at state-level by at 70% nationally among the by December is for against circulating variants and 60% for used increased transmissibility as compared with Alpha for Delta variant. estimated at state-level by The population is to be individuals aged years and older through the end of the projection period. Vaccine expected to cause vaccination coverage to and at some level The levels in these scenarios are to guide hesitancy, though the of that and between states other age groups are at the discretion of the modeling (COVID-19 Scenario Modeling Hub, 2020). The high vaccination 80% is defined the current estimates from the Delphi from (Carnegie Mellon University Delphi Group, 2021). The low of 70% is the lowest from the US from May 2021 data of Vaccine Hesitancy for COVID-19, 2021). the models and future projections of vaccine it was assumed continued of the vaccine not occur on or after the projection date July 4, 2021) due to the previously in the US of 4, 2021 million since 2021 compared to million for and (Centers for Disease Control and Prevention, 2021b). COVID-19 Scenario Modeling Scenarios assumed one of two levels of increased transmissibility for the Delta or 60% more transmissible than the Alpha variant. in new variant over time were by each modeling and were estimated at the state models substantially in structure and see 1 and the COVID-19 Scenario Modeling Hub website for more (COVID-19 Scenario Modeling Hub, 2021). modeling teams projections of incident and
Source: eLife
Authors: Shaun Truelove, Claire P Smith, Michelle Qin, Luke C Mullany, Rebecca K Borchering, Justin Lessler, Katriona Shea, Emily Howerton, Lucie Contamin, John Levander, Jessica Kerr, Harry Hochheiser, Matt Kinsey, Kate Tallaksen, Shelby Wilson, Lauren Shin, Kaitlin Rainwater-Lovett, Joseph C Lemairtre, Juan Dent, Joshua Kaminsky, Elizabeth C Lee, Javier Perez-Saez, Alison Hill, Dean Karlen, Matteo Chinazzi, Jessica T Davis, Kunpeng Mu, Xinyue Xiong, Ana Pastore y Piontti, Alessandro Vespignani, Ajitesh Srivastava, Przemyslaw Porebski, Srinivasan Venkatramanan, Aniruddha Adiga, Bryan Lewis, Brian Klahn, Joseph Outten, Mark Orr, Galen Harrison, Benjamin Hurt, Jiangzhuo Chen, Anil Vullikanti, Madhav Marathe, Stefan Hoops, Parantapa Bhattacharya, Dustin Machi, Shi Chen, Rajib Paul, Daniel Janies, Jean-Claude Thill, Marta Galanti, Teresa K Yamana, Sen Pei, Jeffrey L Shaman, Jessica M Healy, Rachel B Slayton, Matthew Biggerstaff, Michael A Johansson, Michael C Runge, Cecile Viboud
Institutions: Johns Hopkins University, Harvard University, Johns Hopkins University Applied Physics Laboratory, Pennsylvania State University, University of North Carolina at Chapel Hill, University of Pittsburgh, École Polytechnique Fédérale de Lausanne, University of Victoria, Northeastern University, University of Southern California, University of Virginia, University of North Carolina at Charlotte, Columbia University, United States Geological Survey, Fogarty International Center
Language: English
Subfield: Modeling and Simulation
Field: Mathematics
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $2,500
OpenAlex ID: W4283370221