About

Linda Simonsen is an Adjunct Professor affiliated with the Department of Mathematics at the University of Washington, with a primary affiliation at UW Bothell in the School of Science, Technology, Engineering & Mathematics. She earned her PhD from Oregon State University in 1995. Her contact email is simonse@uw.edu. Further details about her research focus or key contributions are not provided on the page.

Research topics

• Political Science
• Medicine
• Biology
• Geography

Selected publications

• Non-specific effects of vaccines on all-cause mortality: a meta-analysis of randomized controlled trials (RCTs) 2012-2025

  medRxiv · 2026-01-02

  articleOpen accessSenior authorCorresponding

  Abstract Background Early observational studies reported substantial reductions in all-cause mortality, suggesting that childhood vaccines might influence health in ways beyond their targeted disease. Such Non-Specific Effects (NSEs) of vaccines could potentially have important implications for the Expanded Programme of Immunization (EPI). In 2014 World Health Organization (WHO) Strategic Advisory Group of Experts (SAGE) commissioned a review of the NSE evidence, which called for more Randomized Controlled Trials (RCTs). We aimed to review all RCTs published after this WHO-commissioned review. Methods Following PRISMA guidelines, we searched systematically for RCTs published during 2012-2025. Inclusion criteria: children under 5 years and all-cause mortality as the primary outcome for any vaccine intervention. Risk estimates were pooled using a random effects model, reflecting the underlying hypothesis: that live-attenuated vaccines greatly reduce, and inactivated vaccines increase all-cause mortality. Results We identified seven RCTs that fit the inclusion criteria, all of them of live-attenuated vaccines (Bacillus Calmette-Guérin, measles, and oral polio vaccine). In total, 52,596 participants were included across these studies. Five were conducted in Guinea-Bissau, one in Guinea-Bissau and Burkina Faso, and one in India. The RCTs were not blinded, and no placebo was used, consistent with a moderate risk of bias. Our meta-analysis found no significant evidence of NSEs (vaccine effectiveness 5%; −16% to 22%). One study of low birthweight newborns admitted to neonatal intensive care units in India found a small but statistically significant NSE (17%; 2% to 31%); interestingly the effect primarily played out in the first 3 days of the study, raising concern of bias. Discussion The meta-analysis of seven RCTs of live-attenuated vaccines found no evidence of significant NSE on all-cause mortality. This was also true when adding RCTs from before 2012 studying NSEs. In conjunction with the WHO-SAGE review, the current body of evidence on NSEs on all-cause mortality does not warrant a paradigm shift, nor does it provide a rationale for changing vaccine programs.

  PublisherOA PDFDOI

• Modeling epidemiological patterns of smallpox in Copenhagen in the 19 ^<i>th</i> century after the introduction of the vaccine

  medRxiv · 2026-01-06

  articleOpen accessSenior author

  In 1798, Jenner’s smallpox vaccine made it possible to prevent the deadliest of childhood diseases. In Denmark the vaccine was used from 1801, and by 1810 a mandatory 1-dose childhood vaccination program was instituted, free of charge. As proof of vaccination (or natural immunity) was required for church confirmation around age 13, about 90 % of children were vaccinated and smallpox disappeared from Copenhagen after 1808. After a 16-year “honeymoon period”, it returned in 1824 with a new face: a milder disease in mostly young adults (1, 2). Here we investigate the effects of smallpox vaccination on the epidemic patterns through the post-honeymoon era (1824-1875). We accessed data from the hospital “Søkvæsthuset” where all smallpox cases, mild and severe, were hospitalized during 1824-1835 in order to contain the outbreak. We identified ∼3000 smallpox cases and four separate epidemics occurring during this period (1–3). We used a mechanistic model (SEIR) to assess factors playing a role in explaining the return of smallpox, and the changing age distribution. These factors included vaccination coverage, duration of immunity from vaccination and from natural infections, and the fate of the “lost generation” of persons born around 1800, too early to get vaccinated and too late to have been infected with smallpox. Our model tracks well the disappearance and return of smallpox in 1824, the interval between epidemic peaks, and the aging pattern. We propose vaccine waning after ∼20 years as the primary reason explaining the return of smallpox and the epidemic pattern. Significance Smallpox has played a major role in shaping modern medicine. Recently, it has received renewed attention due to fears of bioterrorism and the emergence of the closely related mpox. In this article, we use data from the carefully recorded smallpox outbreaks in Copenhagen in the 1800’s to study its dynamics following vaccine rollout. We show that the vaccine likely induced a long-lived but finite immunity and that the “lost generation” who were neither vaccinated nor had contracted smallpox in childhood continued to be plagued by the disease in the following decades. The study is relevant for understanding how smallpox was eradicated and the role of vaccination in dealing with present epidemic threats.

  PublisherOA PDFDOI

• Relationship dynamics and behavioral adaptations in the control of the 2022 mpox epidemic

  medRxiv · 2025-05-06

  preprintOpen access

  We analyzed the patterns of transmission in the 2022 mpox epidemic as it unfolded in the European population of MSM (men who have sex with men). We developed an agent-based model that simulates sexual pair formation, incorporating both brief and longer-term sexual relationships. The model implements survey data on the sexual behavior of MSM and accounts for the highly heterogeneous nature of the sexual contact network within this community. When simulating the mpox epidemic, the model reproduces the reported numbers of sexual partners of mpox-infected patients. We find that natural herd immunity had little impact on ending the European outbreak. Instead, we suggest that the marked decrease in serial interval observed across the epidemic reflects a dramatic increase in self-isolating behavior amongst infected and that this is sufficient to explain the early control of the epidemic. Our work highlights the critical interplay between relationship dynamics and adaptive behaviors in shaping mpox epidemic patterns and achieving control in 2022. Now that the virus is endemic, the European MSM population remains protected by a combined effect of increased awareness and immunity, both natural and vaccine-induced. Significance Statement The waning of smallpox immunity since its elimination around 1980 leaves an immunological opening to emerging poxviruses. We have witnessed two major mpox outbreaks – clade IIb in 2022 and the ongoing clade Ib in Central Africa – both concentrated in a subpopulation with high-risk sexual behavior. Clade IIb is now endemic and recently surged among Australian MSM. Despite parallels with HIV, particularly its disproportionate burden on MSM, the short infection cycle and subsequent lifelong immunity of mpox imply distinct transmission dynamics. These novel outbreaks demand new modeling approaches and a deeper grasp of herd immunity in highly heterogeneous sexual networks.

  PublisherOA PDFDOI

• Relationship dynamics and behavioral adaptations in the control of the 2022 mpox epidemic

  Proceedings of the National Academy of Sciences · 2025-09-10 · 1 citations

  articleOpen accessCorresponding

  We analyzed the patterns of transmission in the 2022 clade IIb mpox epidemic as it unfolded in the European population of men who have sex with men (MSM). We developed an agent-based model that simulates sexual pair formation, incorporating both brief and longer-term sexual relationships. The model implements survey data on the sexual behavior of MSM and accounts for the highly heterogeneous nature of the sexual contact network within this community. When simulating the mpox epidemic, the model reproduces the reported numbers of sexual partners of mpox-infected individuals. We find that infection-derived immunity had little impact on ending the European outbreak. Instead, we suggest that the marked decrease in serial interval observed across the epidemic reflects a substantial increase in self-isolating behavior among infected persons and that this is sufficient to explain the early control of the epidemic. Our work highlights the critical interplay between relationship dynamics and adaptive behaviors in shaping mpox epidemic patterns and achieving control in 2022. Despite continued propagation of clade IIb mpox, the European MSM population remains protected by immunity, primarily vaccine-induced.

  PublisherOA PDFDOI

• A disease suppression strategy in action: The impact of non-pharmaceutical interventions in the COVID-19 pandemic in Denmark

  International Journal of Infectious Diseases · 2025-09-02 · 1 citations

  reviewOpen access1st authorCorresponding

  When a new pandemic virus emerges in a naive population, the only control options are non-pharmaceutical interventions (NPIs) until vaccines or effective treatments become available. Here, we report on the Danish suppression strategy and use of a combination of NPIs with a notable absence of extremely strict measures (such as stay-at-home orders). Only 7% of Danes were infected (serological evidence) in the first year of the pandemic, compared with 50% in Lombardy in the first wave alone. This low attack rate was accomplished by initial rapid intervention with a free-of-charge mass testing program beginning in October 2020, a strong digital data infrastructure, timely contact tracing and voluntary home isolation, real-time reporting of surveillance data, and a high degree of public trust. The individual contribution of each NPI to the pandemic control is difficult to assess; yet, evidence points to the mass testing program as being particularly effective in removing infected individuals from the pool. In January 2021, vaccines became available, and 96% of Danes over 50 years of age were vaccinated twice with an mRNA vaccine by summer. On February 1, 2022, while facing the Omicron variant and with the older adult newly boosted, Denmark became the first country to drop all NPIs. A few months later, 70% of the population had been infected with the Omicron variant, showing the SARS-CoV-2 transmission potential when unmitigated. Denmark was only close to intensive care unit capacity during the second wave in winter 2020-2021, when 5% of the population was infected. In conclusion, the effectiveness of the combined NPIs is evident due to the low (<10%) attack rate in the first two waves before vaccines became available, far from the experience of unmitigated COVID-19 in Lombardy in spring 2020, with a 50% attack rate and catastropic levels of severe morbidity and mortality.

  PublisherDOI

• The disappearance of malaria from Denmark, 1862–1900

  The Economic History Review · 2025-05-24

  articleOpen access

  Abstract The reason for malaria's disappearance from northwestern Europe in the early twentieth century has long been discussed but remains an unresolved conundrum. This is partially due to a previous focus on the early modern era, and partially because various theories have never been tested against each other. In this study, we test some of the proposed hypotheses using nineteenth‐century Denmark as a case. We found that the accelerating agricultural improvements with drainage and increasing livestock per km 2 explained much of the declining incidence rates, whilst other factors such as household size, temperatures, and precipitation did not seem to matter. Increased drainage meant dryer surface environment, and this led to a reduced size of the mosquito populations and therefore fewer malaria infections, and increased access to livestock led to changes in the mosquitoes’ feeding preferences. Whilst drainage may have played a key role, it is possible that improvements in housing and clothing materials as well as use of quinine could also have affected malaria trends, although this could not be tested. We conclude that the disappearance of malaria was likely an unanticipated benefit of the agricultural developments related to the modernization of rural Denmark during the nineteenth century.

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• Implications of the 2023–2024 MPXV clade I outbreak in the Democratic Republic of Congo to global public health

  Clinical Microbiology and Infection · 2024-04-30 · 15 citations

  letterOpen access

  Mpox, a zoonotic disease resulting from infection with monkeypox virus (MPXV), was previously considered endemic to central- and west Africa. However, an ongoing global outbreak of clade IIb (previously known as West African clade) MPXV associated with human-to-human transmission primarily through sexual contact has occurred since May 2022, with introduction of MPXV to regions and countries that had previously only reported sporadic imported cases [ 1 Thornhill J.P. et al. Monkeypox Virus Infection in Humans across 16 Countries - April-June 2022. N. Engl. J. Med. Jul. 2022; Crossref Scopus (1114) Google Scholar ], [ 2 Laurenson-Schafer H. et al. Description of the first global outbreak of mpox: an analysis of global surveillance data. Lancet Glob. Health. Jul. 2023; 11: e1012-e1023 Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar ].

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• Disentangling the relationship between cancer mortality and COVID-19 in the US

  eLife · 2024-07-18 · 3 citations

  articleOpen accessSenior author

  Cancer is considered a risk factor for COVID-19 mortality, yet several countries have reported that deaths with a primary code of cancer remained within historic levels during the COVID-19 pandemic. Here, we further elucidate the relationship between cancer mortality and COVID-19 on a population level in the US. We compared pandemic-related mortality patterns from underlying and multiple cause (MC) death data for six types of cancer, diabetes, and Alzheimer’s. Any pandemic-related changes in coding practices should be eliminated by study of MC data. Nationally in 2020, MC cancer mortality rose by only 3% over a pre-pandemic baseline, corresponding to ~13,600 excess deaths. Mortality elevation was measurably higher for less deadly cancers (breast, colorectal, and hematological, 2–7%) than cancers with a poor survival rate (lung and pancreatic, 0–1%). In comparison, there was substantial elevation in MC deaths from diabetes (37%) and Alzheimer’s (19%). To understand these differences, we simulated the expected excess mortality for each condition using COVID-19 attack rates, life expectancy, population size, and mean age of individuals living with each condition. We find that the observed mortality differences are primarily explained by differences in life expectancy, with the risk of death from deadly cancers outcompeting the risk of death from COVID-19.

  PublisherDOI

• Disentangling the relationship between cancer mortality and COVID-19 in the US

  medRxiv · 2024-01-03

  preprintOpen accessSenior author

  Abstract Several countries have reported that deaths with a primary code of cancer did not rise during COVID-19 pandemic waves compared to baseline pre-pandemic levels. This is in apparent conflict with findings from cohort studies where cancer has been identified as a risk factor for COVID-19 mortality. Here we further elucidate the relationship between cancer mortality and COVID-19 on a population level in the US by testing the impact of death certificate coding changes during the pandemic and leveraging heterogeneity in pandemic intensity across US states. We computed excess mortality from weekly deaths during 2014-2020 nationally and for three states with distinct COVID-19 wave timing (NY, TX, and CA). We compared pandemic-related mortality patterns from underlying and multiple cause (MC) death data for six types of cancer and compared to that seen for chronic conditions such as diabetes and Alzheimer’s. Any death certificate coding changes should be eliminated by study of MC data. Nationally in 2020, we found only modest excess MC cancer mortality (∼13,600 deaths), representing a 3% elevation over baseline level. Mortality elevation was measurably higher for less deadly cancers (breast, colorectal, and hematologic, 2-7%) than cancers with a poor 5-year survival (lung and pancreatic, 0-1%). In comparison, there was substantial elevation in MC deaths from diabetes (37%) and Alzheimer’s (19%). Homing in on the intense spring 2020 COVID-19 wave in NY, mortality elevation was 1-16% for different types of cancer and 128% and 49% for diabetes and Alzheimer’s, respectively. To investigate the peculiar absence of excess mortality on deadly cancers, we implemented a demographic model and simulated the expected covid-related mortality using COVID-19 attack rates, life expectancy, population size and mean age for each chronic condition. This model indicates that these factors largely explain the considerable differences in observed excess mortality between these chronic conditions during the COVID-19 pandemic, even if cancer had increased the relative risk of mortality by a factor of 2 or 5. In conclusion, we found limited elevation in cancer mortality during COVID-19 waves, even after considering MC mortality, and this was especially pronounced for the deadliest cancers. Our demographic model predicted low expected excess mortality in populations living with certain types of cancer, even if cancer is a risk factor for COVID-19 fatality, due to competing mortality risk. We also find a moderate increase in excess mortality from hematological cancers, aligned with other types of observational studies. While our study concentrates on the immediate consequences of the COVID-19 pandemic on cancer mortality in 2020, further research should consider excess mortality in the complete pandemic period. Also, a study of the delayed impact of the pandemic on cancer mortality due to delayed diagnosis and treatment during the pandemic period is warranted.

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• Severity of respiratory tract infections depends on the infectious dose. Perspectives for the next pandemic

  Frontiers in Public Health · 2024-04-30 · 4 citations

  articleOpen access

  During the COVID-19 pandemic, much has been said about the importance of host-specific and virus-specific factors as predictors of the risk of infection and severity of disease. For example, host factors such as increased age, male gender, ethnicity, and comorbidities such as metabolic and pulmonary disorders have been recognized as risk factors for severe disease, whereas host immunity stemming from prior infection or vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with reduced severity. Similarly, the viral evolution of SARS-CoV-2 over the past 4 years has been scrutinized to estimate changes in the relative transmissibility, virulence and vaccine-match of each emerging variant over time during the COVID-19 pandemic. However, despite this scrutiny, variation in transmissibility and severity of disease remain imperfectly understood.<br/><br/>An aspect that has been comparatively ignored is the importance of transmission factors such as the size of viral inoculation and the duration of exposure, i.e., the dose of exposure (see Figure 1). The dose of exposure is determined by human behavior, environmental conditions and mitigation strategies, such as indoor versus outdoor exposure, indoor crowding, indoor air ventilation and physical distancing. As observed for a range of pathogens, the risk of getting infected, and in some studies, also the disease severity and post infection sequelae depend on the dose encountered (1–10). In 2021, Van Damme et al. (11) postulated that the dose of SARS-CoV-2 at infection was an important missing factor in understanding several incompletely explained observations in the epidemiology of COVID-19. Nevertheless, epidemiological models (and common thinking) continue to parameterize exposure as a dichotomous phenomenon, where the susceptible host is being considered as either exposed (and at risk of infection and severe disease) or unexposed (and therefore not at risk). We hypothesize that a quantitative exposure approach, where dose of exposure is included as a factor that determine important factors such as risk of infection, incubation period, outcome of infection and transmissibility, may be helpful for our understanding of the epidemiology of COVID-19, also in the ongoing transition of the pandemic to endemicity. But more importantly, if this hypothesis can be generalized across other pathogens, a quantitative exposure approach to infection epidemiology may open new options for mitigation of a future severe pandemic, Disease X, and point a way forward to a control strategy with a gentler impact on society.

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Frequent coauthors

• Cécile Viboud

  527 shared

• Gerardo Chowell

  Arizona State University

  263 shared

• Mark A. Miller

  Reckitt Benckiser (United States)

  152 shared

• C. Hansen

  National Institutes of Health

  99 shared

• Bryan T. Grenfell

  Princeton Public Schools

  93 shared

• Thea Kølsen Fischer

  University of Copenhagen

  85 shared

• Robert J. Taylor

  Texas A&M University

  67 shared

• Vivek Charu

  Stanford University

  66 shared

Education

• Epidemic Intelligence Program Certificate, National Institute of Infectious Diseases

  Centers for Disease Control and Prevention

  1994

• PhD, Department of Zoology

  University of Massachusetts Amherst

  1992

• BS, MA, Life Sciences

  Roskilde Universitet

  1985