Seasonal trends in COVID-19 cases, hospitalizations, and deaths in the United States and Europe

doi:10.21203/rs.3.rs-2037950/v1

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Seasonal trends in COVID-19 cases, hospitalizations, and deaths in the United States and Europe

https://doi.org/10.21203/rs.3.rs-2037950/v1

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Journal Publication

published 08 Mar, 2023

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Determining whether SARS-CoV-2 exhibits seasonality like other respiratory viruses is critical for public health planning. We evaluated whether COVID-19 rates follow a seasonal pattern using time series models. We used time series decomposition to extract the annual seasonal component of COVID-19 case, hospitalization, and death rates from March 2020 through July 2022 for the United States and Europe. Models were adjusted for a country-specific stringency index to account for confounding by nonpharmaceutical interventions. Despite year-round disease activity, we identified seasonal spikes in COVID-19 from approximately November-April for all outcomes and in all countries. Our results support employing annual preventative measures against SARS-CoV-2, such as administering seasonal booster vaccines in a similar timeframe as those in place for influenza. Whether certain high-risk individuals may need more than one COVID-19 vaccine booster dose each year will depend on factors like vaccine durability against severe illness and levels of year-round disease activity.

SARS-CoV-2

winter

fall

autumn

surge

The Coronavirus Disease 2019 (COVID-19) pandemic has caused unprecedented worldwide morbidity, mortality, and social and economic disruption.¹ Globally, waves of infection, hospitalization, and death have paralleled the emergence of new variants of concern which have shown increased transmissibility² and improved ability to evade vaccine- and infection-induced immunity.³ Vaccination strategies to date have struggled to keep pace, and booster doses have been deployed to bolster protection against infection and symptomatic disease and maintain peak protection against severe disease throughout the pandemic.^4–8

Many respiratory viruses show distinct seasonal patterns and result in waves of illness during the winter months.^9,10 These patterns are likely caused by a combination of host, pathogen, and environmental factors, including increased indoor activity and seasonal weather fluctuations known to impact viral stability outside the host.^9,11−13 To date, there is still discussion about whether SARS-CoV-2 currently follows, or will follow in the future, similar seasonal patterns to these other respiratory viruses.^14–16 Determining whether SARS-CoV-2 exhibits seasonal spikes in disease activity is critical for public health planning, including informing vaccination policy about the optimal timing for deploying additional doses. To help answer this urgent public health question, we used time series models to evaluate the seasonal patterns of COVID-19 cases, hospitalizations, and deaths in the United States and Europe.

Primary analysis

We followed Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for our ecological study. Daily rates of COVID-19 cases, hospitalizations, and deaths per million population by country for the United States, all countries in the European Union, and the United Kingdom were obtained from the public-use Our World in Data (OWID) GitHub repository.^17,18 OWID sources case and death data from Johns Hopkins University¹⁹ and hospitalization data from various official country-specific sources.¹⁸ Data were included from 01 Mar 2020 through 31 Jul 2022, as available by country. If daily data were missing or unavailable, data were substituted from that country’s corresponding weekly data.

Statistical Analysis

We used a Prophet time series model to decompose daily country-specific time series rates of COVID-19 cases, hospitalizations, and deaths separately and adjusted for the country stringency index in an additive, linear time series.^20,21 In these models, we decomposed the observed data into a trend component and weekly and annual seasonal components and included the country-specific stringency index as a regressor to account for potential confounding by nonpharmaceutical interventions. The stringency index was developed by the Oxford Coronavirus Government Response Tracker project and is a composite of nine metrics, including school closures; workplace closures; cancellation of public events; restrictions on public gatherings; closures of public transport; stay-at-home requirements; public information campaigns; restrictions on internal movements; and international travel controls.²² Uncertainty interval widths for computed point estimates were set to 95%, with 2,000 uncertainty samples used to compute the intervals. Bayesian sampling was performed with 2,000 Markov Chain Monte Carlo samples to obtain uncertainty intervals for seasonality estimates. In our models, we focused our analysis on the annual seasonal component only, which models the annual seasonal changes in observed rates after any long-term trends. The estimated rate is the sum of the long-term trend, weekly, and seasonal components, as well as the estimated effect of the country-specific stringency index. Positive values for the seasonal component indicate rates during that time of year are higher than during other parts of the year, while negative values indicate decreased rates during that season.

In addition to extracting the decomposed trend, annual seasonal component, weekly seasonal component, and the estimated effect of the stringency index, the monthly median value of the annual seasonal component was computed and displayed in a country-level heatmap to depict the month's driving annual seasonal increases more clearly.

Modeling Validation

To validate our modeling approach, we applied the same Prophet model (excluding the stringency index regressor) to pre-pandemic country-level influenza data from the World Health Organization.²³ This approach was used to assess whether the model would predict well-documented annual seasonal patterns for influenza and if those patterns matched those we documented for SARS-CoV-2. Influenza positivity rates were defined by computing the percent positive specimens of all respiratory specimens processed from 04 Oct 2009 through 19 Dec 2021 using the same countries (the United States, European Union countries, and the United Kingdom). Malta was not evaluated as influenza data were not available from the World Health Organization.

Human Subjects Protection

All data used in this study were publicly available and de-identified and therefore did not constitute human subjects research per 45 CFR 46.102. Due to this, the study did not require IRB registration or review.

R version 4.2.0 (R Foundation for Statistical Computing, Vienna, Austria) was used for all analyses.

Our model showed distinct annual seasonality consistent across COVID-19 case (Fig. 1a), hospitalization (Fig. 1b), and death (Fig. 1c) rates from approximately November through April. The additional impact of the annual seasonal component for cases was most substantial in January through March, with the maximum additional seasonal rate value of 905 per 1,000,000 population. The annual seasonal component for hospitalizations indicated a clear differentiation between seasons, with up to 100 per 1,000,000 additional seasonal hospitalizations from November through April. COVID-19-associated mortality showed a similar trend in the annual seasonal component, with an additional two deaths per 1,000,000 population due to the annual seasonal effect primarily focused from November through February. These trends were consistent in all countries evaluated.

Country-specific time-series annual seasonal components not aggregated by month, along with other individual decomposed components (trend, weekly seasonality, and stringency index), can be seen in supplementary Figures s1-s4 (cases), s5-s8 (hospitalizations), and s9-s12 (deaths). Most of the positive annual seasonality values were within the typical respiratory viral season in the Northern Hemisphere and are indicated with a purple highlight in the annual seasonal component Figures s1, s5, and s9.

Our analyses using the exact model specifications described for rates of COVID-19 (excluding the stringency index regressor) also documented the well-established annual seasonality of pre-pandemic influenza between December and April over twelve US influenza seasons (Fig. 2), consistent with current knowledge regarding annual influenza patterns in the Northern Hemisphere temperate regions.²⁴

Although SARS-CoV-2 continues to cause infections, hospitalizations, and deaths throughout the year, we identified additional seasonal impact on these rates in the United States and Europe. Since the beginning of the pandemic, COVID-19 has spiked in the months of November through April, consistent with the typical months of seasonal respiratory virus epidemics in the northern hemisphere.²⁵ Although we documented apparent winter increases in COVID-19 burden, there remain steady rates of cases, hospitalizations, and deaths throughout the year, with various smaller waves in the summer months.²⁴ Our results indicating seasonal spikes are consistent with seasonal patterns seen for influenza,²⁵ respiratory syncytial virus (RSV),²⁶ and other coronaviruses,²⁷ and are compatible with mathematical simulations of COVID-19 activity.^14,15

There are many possible reasons for the seasonality of respiratory viruses, including climate-related changes in viral transmissibility, modified host factors (e.g., waning of infection- or vaccine-induced immunity), and changes in human behavior during the winter months.^9,16 Regardless of the mechanisms, knowledge of pathogen seasonality is imperative for instituting targeted interventions to lessen the impact when the burden on our healthcare infrastructure is the greatest.

Accordingly, our findings have important vaccine policy implications. Additional doses of COVID-19 vaccines or modified versions of the vaccines administered before the winter months will likely have the most significant public health impact on the COVID-19 burden. This is analogous to providing influenza vaccine before peak flu activity each year to mitigate the largest spikes in disease burden. Because SARS-CoV-2 appears to be more transmissible than influenza and other seasonal respiratory viruses, it seems likely that year-round SARS-CoV-2 activity will remain elevated compared to other pathogens.²⁸ However, providing more than one dose of COVID-19 vaccines each year has proven programmatically challenging, and concerns regarding “booster fatigue” are increasing.^29,30 Thus, timing the administration of an annual COVID-19 vaccine just prior to peak COVID-19 activity (i.e., the winter viral respiratory season based on our results) may be the most prudent approach for the general population in the near term as we continue to learn from this pandemic.

Despite evidence that protection provided by current mRNA COVID-19 vaccines wanes significantly against omicron infection and symptomatic disease after only 3 to 4 months, even after a booster,^5,8,31 this short-term protection could still provide meaningful defense against SARS-CoV-2 infection if deployed just before seasonal waves which last 3 to 4 months on average. Moreover, it remains unknown whether variant-adapted or other modified vaccines may improve the durability of protection against infection and symptomatic disease for longer than current wild-type formulations.

There has been much debate about whether the goal of vaccination programs should be only to prevent severe disease or if it should include preventing infection and reducing transmission.³² We now know that vaccination alone is unlikely to lead to eradicating or eliminating SARS-CoV-2. However, deploying vaccines on a schedule that aligns the timing of peak protection with peak disease activity can still have a meaningful impact on flattening future waves of infection and disease, in addition to ensuring protection against severe illness is maintained year-over-year. Lessening the burden of SARS-CoV-2 infection remains an important goal and corresponds with fewer long-term consequences of infection such as post-acute sequelae^33–35 and other disruptive societal and economic consequences.³⁶

Although our study suggests that SARS-CoV-2 follows a seasonal pattern like other viral respiratory pathogens, COVID-19 continues to cause substantial morbidity and mortality throughout the year, including outside of the traditional viral respiratory season. Thus, additional COVID-19 vaccine booster doses may be needed at a frequency greater than once annually for certain high-risk individuals. This determination will be a careful balance between epidemiological, benefit-risk, and programmatic considerations moving forward and will likely depend primarily on COVID-19 vaccine durability against severe illness and levels of year-round disease activity.

Our methodology also detected the annual seasonality of influenza virus in the same countries, corresponding to known annual seasonal patterns of influenza,^25,26 underscoring the utility of this method for detecting seasonal patterns in common respiratory viruses. Regardless, our results have limitations. First, we could not account for potential underreporting of cases, which may have a large effect more recently with increases in at-home SARS-CoV-2 testing that may not be reported.³⁷ Further, statistical modeling may not fully reflect the intricacies of preventing transmissible infectious diseases, such as the impact of waning immunity or changes in testing, nonpharmaceutical interventions, or healthcare-seeking behavior over time. Although the pandemic is in its third year, the longitudinal data available for modeling was limited compared to other common seasonal viruses. Because of this, similar models created in the future may illustrate different outputs given variable prevention behaviors, vaccines and vaccine uptake, and novel SARS-CoV-2 variants. Another limitation is that our findings are not generalizable beyond the United States and Europe. More research is needed to understand if the same annual seasonal patterns in SARS-CoV-2 activity are seen in the Southern Hemisphere or Asia-Pacific regions. Finally, with SARS-CoV-2, there is always the potential for new variants to emerge that could meaningfully escape prior vaccine- or infection-induced immunity and cause significant epidemics outside of regular seasonal patterns identified thus far in the pandemic. Therefore, the public health community should continue to plan and maintain the capability for sufficient response in the event of this possibility.

In conclusion, our study suggests that COVID-19 activity and associated hospitalization and death in the United States and Europe peaks during the traditional winter viral respiratory season despite continual transmission throughout the year. Thus, employing annual protective measures against SARS-CoV-2 such as administering seasonal booster vaccines or other non-pharmaceutical interventions for the general population in a similar timeframe as those already in place for influenza prevention (i.e., beginning in early autumn) is a prudent strategy to stay ahead of likely forthcoming seasonal waves of COVID-19. However, whether certain high-risk individuals may need more than one booster dose each year will depend on factors like vaccine durability against severe illness and levels of year-round disease activity. Additional confirmatory studies are needed, including those conducted in the Southern Hemisphere and other regions outside the United States and Europe.

Acknowledgments

Author Contributions: Dr. Wiemken had full access to all the data in the study and took responsibility for the integrity and data analysis accuracy. All authors had full access to all data and accepted responsibility for submitting it for publication.

Concept and design: All Authors.

Accessed and verified data and analysis: TLW, FK

Interpretation of data: All authors.

Drafting of the manuscript: TLW, JMM

Critical revision of the manuscript for important intellectual content: All Authors

Obtained funding: N/A.

Administrative, technical, or material support: All Authors

Supervision: JMM

Conflict of Interest Disclosures: TLW, LP, JMM, LJ, JN, and FK are employees and shareholders of Pfizer Inc.

Funding/Support: Pfizer, Inc

Role of the Funder/Sponsor: This study was sponsored by Pfizer.

Data Sharing: All data utilized in this study are open and available to the public, as referenced in the manuscript. Reasonable requests for programming scripts can be made to the corresponding author.

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Competing interest reported. Conflict of Interest Disclosures: TLW, LP, JMM, LJ, JN, and FK are employees and shareholders of Pfizer Inc.

Funding/Support: Pfizer, Inc

Role of the Funder/Sponsor: This study was sponsored by Pfizer.

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You are reading this latest preprint version

Seasonal trends in COVID-19 cases, hospitalizations, and deaths in the United States and Europe

Status:

Journal Publication

Version 1

Abstract

Figures

Introduction

Methods

Primary analysis

Statistical Analysis

Modeling Validation

Human Subjects Protection

Results

Discussion

Declarations

References

Additional Declarations

Supplementary Files

Status:

Journal Publication

Version 1