Informing pandemic response in the face of uncertainty. An evaluation of the U.S. COVID-19 Scenario Modeling Hub (preprint)

Our ability to forecast epidemics more than a few weeks into the future is constrained by the complexity of disease systems, our limited ability to measure the current state of an epidemic, and uncertainties in how human action will affect transmission. Realistic longer-term projections (spanning more than a few weeks) may, however, be possible under defined scenarios that specify the future state of critical epidemic drivers, with the additional benefit that such scenarios can be used to anticipate the comparative effect of control measures. Since December 2020, the U.S. COVID-19 Scenario Modeling Hub (SMH) has convened multiple modeling teams to make 6-month ahead projections of the number of SARS-CoV-2 cases, hospitalizations and deaths. The SMH released nearly 1.8 million national and state-level projections between February 2021 and November 2022. SMH performance varied widely as a function of both scenario validity and model calibration. Scenario assumptions were periodically invalidated by the arrival of unanticipated SARS-CoV-2 variants, but SMH still provided projections on average 22 weeks before changes in assumptions (such as virus transmissibility) invalidated scenarios and their corresponding projections. During these periods, before emergence of a novel variant, a linear opinion pool ensemble of contributed models was consistently more reliable than any single model, and projection interval coverage was near target levels for the most plausible scenarios (e.g., 79% coverage for 95% projection interval). SMH projections were used operationally to guide planning and policy at different stages of the pandemic, illustrating the value of the hub approach for long-term scenario projections.

The impact of COVID-19 vaccination in the US: averted burden of SARS-COV-2-related cases, hospitalizations and deaths (preprint)

By August 1, 2022, the SARS-CoV-2 virus had caused over 90 million cases of COVID-19 and one million deaths in the United States. Since December 2020, SARS-CoV-2 vaccines have been a key component of US pandemic response; however, the impacts of vaccination are not easily quantified. Here, we use a dynamic county-scale metapopulation model to estimate the number of cases, hospitalizations, and deaths averted due to vaccination during the first six months of vaccine availability. We estimate that COVID-19 vaccination was associated with over 8 million fewer confirmed cases, over 120 thousand fewer deaths, and 700 thousand fewer hospitalizations during the first six months of the campaign.

Impact of SARS-CoV-2 vaccination of children ages 5-11 years on COVID-19 disease burden and resilience to new variants in the United States, November 2021-March 2022: a multi-model study (preprint)

Background: SARS-CoV-2 vaccination of persons aged 12 years and older has reduced disease burden in the United States. The COVID-19 Scenario Modeling Hub convened multiple modeling teams in September 2021 to project the impact of expanding vaccine administration to children 5-11 years old on anticipated COVID-19 burden and resilience against variant strains. Methods: Nine modeling teams contributed state- and national-level projections for weekly counts of cases, hospitalizations, and deaths in the United States for the period September 12, 2021 to March 12, 2022. Four scenarios covered all combinations of: 1) presence vs. absence of vaccination of children ages 5-11 years starting on November 1, 2021; and 2) continued dominance of the Delta variant vs. emergence of a hypothetical more transmissible variant on November 15, 2021. Individual team projections were combined using linear pooling. The effect of childhood vaccination on overall and age-specific outcomes was estimated by meta-analysis approaches. Findings: Absent a new variant, COVID-19 cases, hospitalizations, and deaths among all ages were projected to decrease nationally through mid-March 2022. Under a set of specific assumptions, models projected that vaccination of children 5-11 years old was associated with reductions in all-age cumulative cases (7.2%, mean incidence ratio [IR] 0.928, 95% confidence interval [CI] 0.880-0.977), hospitalizations (8.7%, mean IR 0.913, 95% CI 0.834-0.992), and deaths (9.2%, mean IR 0.908, 95% CI 0.797-1.020) compared with scenarios where children were not vaccinated. This projected effect of vaccinating children 5-11 years old increased in the presence of a more transmissible variant, assuming no change in vaccine effectiveness by variant. Larger relative reductions in cumulative cases, hospitalizations, and deaths were observed for children than for the entire U.S. population. Substantial state-level variation was projected in epidemic trajectories, vaccine benefits, and variant impacts. Conclusions: Results from this multi-model aggregation study suggest that, under a specific set of scenario assumptions, expanding vaccination to children 5-11 years old would provide measurable direct benefits to this age group and indirect benefits to the all-age U.S. population, including resilience to more transmissible variants.

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 (preprint)

What is already known about this topic?The highly transmissible SARS-CoV-2 Delta variant has begun to cause increases in cases, hospitalizations, and deaths in parts of the United States. With slowed vaccination uptake, this novel variant is expected to increase the risk of pandemic resurgence in the US in July--December 2021. What is added by this report?Data from nine mechanistic models project substantial resurgences of COVID-19 across the US resulting from the more transmissible Delta variant. These resurgences, which have now been observed in most states, were projected to occur across most of the US, coinciding with school and business reopening. Reaching higher vaccine coverage in July--December 2021 reduces the size and duration of the projected resurgence substantially. The expected impact of the outbreak is largely concentrated in a subset of states with lower vaccination coverage. What are the implications for public health practice?Renewed efforts to increase vaccination uptake are critical to limiting transmission and disease, particularly in states with lower current vaccination coverage. Reaching higher vaccination goals in the coming months can potentially avert 1.5 million cases and 21,000 deaths and improve the ability to safely resume social contacts, and educational and business activities. Continued or renewed non-pharmaceutical interventions, including masking, can also help limit transmission, particularly as schools and businesses reopen.

Non-pharmaceutical interventions and inoculation rate shape SARS-COV-2 vaccination campaign success (preprint)

Nearly one year into the COVID-19 pandemic, the first SARS-COV-2 vaccines received emergency use authorization and vaccination campaigns began. A number of factors can reduce the averted burden of cases and deaths due to vaccination. Here, we use a dynamic model, parametrized with Bayesian inference methods, to assess the effects of non-pharmaceutical interventions, and vaccine administration and uptake rates on infections and deaths averted in the United States. We estimate that high compliance with non-pharmaceutical interventions could avert more than 60% of infections and 70% of deaths during the period of vaccine administration, and that increasing the vaccination rate from 5 to 11 million people per week could increase the averted burden by more than one third. These findings underscore the importance of maintaining non-pharmaceutical interventions and increasing vaccine administration rates.

Overall burden and characteristics of COVID-19 in the United States during 2020 (preprint)

The COVID-19 pandemic disrupted health systems and economies throughout the world during 2020 and was particularly devastating for the United States. Many of epidemiological features that produced observed rates of morbidity and mortality have not been thoroughly assessed. Here we use a data-driven model-inference approach to simulate the pandemic at county-scale in the United States during 2020 and estimate critical, time-varying epidemiological properties underpinning the dynamics of the virus. The pandemic in the US during 2020 was characterized by an overall ascertainment rate of 21.6% (95% credible interval (CI):18.9-25.5%). Population susceptibility at year end was 68.8% (63.4-75.3%), indicating roughly one third of the US population had been infected. Community infectious rates, the percentage of people harboring a contagious infection, rose above 0.8% (0.6-1.0%) before the end of the year, and were as high as 2.4% in some major metropolitan areas. In contrast, the infection fatality rate fell to 0.3% by year end; however, community control of transmission, estimated from trends of the time-varying reproduction number, Rt, slackened during successive pandemic waves. In the coming months, as vaccines are distributed and administered and new more transmissible virus variants emerge and spread, greater use of non-pharmaceutical interventions will be needed.

The importance of continued non-pharmaceutical interventions during the upcoming SARS-COV-2 vaccination campaign (preprint)

In this communication we assess the potential benefit of SARS-COV-2 pandemic vaccination in the US and show how continued use of non-pharmaceutical interventions (NPIs) will be crucial during implementation.

Direct observation of repeated infections with endemic coronaviruses (preprint)

Background: While the mechanisms of adaptive immunity to pandemic coronavirus SARS-CoV-2 are still unknown, the immune response to the widespread endemic coronaviruses HKU1, 229E, NL63 and OC43 provide a useful reference for understanding repeat infection risk. Methods: Here we used data from proactive sampling carried out in New York City from fall 2016 to spring 2018. We combined weekly nasal swab collection with self-reports of respiratory symptoms from 191 participants to investigate the profile of recurring infections with endemic coronaviruses. Results: During the study, 12 individuals tested positive multiple times for the same coronavirus. We found no significant difference between the probability of testing positive at least once and the probability of a recurrence for the beta-coronaviruses HKU1 and OC43 at 34 weeks after enrollment/first infection. We also found no significant association between repeat infections and symptom severity but strong association between symptom severity and belonging to the same family. Conclusion: This study provides evidence that re-infections with the same endemic coronavirus are not atypical in a time window shorter than 1 year and that the genetic basis of innate immune response may be a greater determinant of infection severity than immune memory acquired after a previous infection.

Virome of New York Presbyterian Hospital pediatric emergency (preprint)

Background Viral infection of the respiratory tract is one of the major causes of hospital visits for young children. In this study, we report the occurrence and co-occurrence of different virus types and subtypes among the patients arriving at the pediatric emergency room of New York Presbyterian Hospital, a major urban hospital. Methods We collected nasal swabs from the patients and their accompanying persons. We also recorded the levels (None, Mild, High, and Severe) of their symptoms (Fever, Chill, Muscle Pain, Watery Eye, Runny Nose, Sneezing, Sore throat and Cough). The collected swabs were tested for the presence of common viruses infecting the respiratory tract. Results Human Rhinovirus was the most common virus among the patients, followed Influenza and Respiratory Syncytial Virus. Human Rhinovirus was most common in summer, autumn and spring. In contrast, influenza was more common in winter. Further, Influenza A virus was more likely to co-occur with Corona Virus 229E. In comparison, Influenza was less likely to co-occur with Human Rhinovirus. Moreover, Influenza, Parainfluenza and Corona virus were associated with more severe symptoms, while Human Rhinovirus was associated with less severe symptoms. In addition, we observed that Influenza and Respiratory Syncytial Virus were more likely to infect a patient when these viruses also infected the accompanying person. We also found that it was difficult to distinguish among viruses based on the symptoms. The inability to distinguish among different virus types and subtypes is explained by the fact that multiple viruses lead to similar symptoms. Conclusions The findings of this study provide a better understanding of respiratory viral infections in small children presenting at a pediatric emergency room in New York.

Direct Measurement of Rates of Asymptomatic Infection and Clinical Care-Seeking for Seasonal Coronavirus (preprint)

The pandemic potential of the novel coronavirus (nCoV) that emerged in Wuhan, China, during December 2019 is strongly tied to the number and contagiousness of undocumented human infections. Here we present findings from a proactive longitudinal sampling study of acute viral respiratory infections that documents rates of asymptomatic infection and clinical care seeking for seasonal coronavirus. We find that the majority of infections are asymptomatic by most symptom definitions and that only 4% of individuals experiencing a seasonal coronavirus infection episode sought medical care for their symptoms. These numbers indicate that a very high percentage of seasonal coronavirus infections are undocumented and provide a reference for understanding the spread of the emergent nCoV.