Original research: Cost of the COVID-19 pandemic versus the cost-effectiveness of mitigation strategies in EU/UK/OECD: a systematic review (2024)

Strengths and limitations of this study

• The systematic review is adhering to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) framework.

• The risk of bias was assessed using the Consensus on Health Economic Criteria (CHEC) checklist.

• Studies were searched in two databases, Ovid MEDLINE and EMBASE.

• The population of interest is restricted to the European Union (EU)/UK/European Economic Area (EEA)/Organisation for Economic Co-operation and Development (OECD).

Search strategy and selection criteria

A systematic review was conducted to identify peer-reviewed articles published from 1 January 2020 through 22 April 2021 in Ovid MEDLINE and EMBASE. The review is reported adhering to the PRISMA framework (Preferred Reporting Items for Systematic Reviews and Meta-analyses)¹⁴ available in online supplemental appendix 1. Two sets of inclusion criteria were used to determine the eligibility of the studies based on the two objectives; however, a single search strategy was used to capture eligible studies. The complete search strategy and search terms are available in online supplemental appendix 2.

To summarise the total direct and indirect costs of the COVID-19 pandemic, the inclusion criteria for Objective 1 were as follows:

• Population: EU/EEA/UK and remaining OECD countries.

• Exposure: COVID-19 outbreak or public health preparedness measures or interventions.

• Outcome measures: direct and indirect costs for disease and preparedness and/or response.

• Study designs: We included all relevant analytical epidemiological designs which estimate cost, including partial cost evaluation studies, cost studies, cost-outcome description studies, cost-description studies, and economic modelling studies.

• Perspective: All direct and indirect costs were considered pertaining to all relevant perspectives (eg, individual, health and social care, and societal including national and regional).

In particular:

• The individual perspective refers to considering the costs and outcomes experienced by individuals directly affected by the issue being studied. It focuses on understanding how the issue impacts individuals in terms of their personal expenses, quality of life and health outcomes.

  See Also

  Is COVID-19 Still a Pandemic?

• The health and social care perspective involves examining the costs and outcomes associated with healthcare services and social support systems. It considers the financial implications and health-related consequences for healthcare providers, institutions, and social care organisations involved in addressing the issue.

• The societal perspective considers the broader societal impact of the issue under investigation. It considers not only the direct costs and outcomes for individuals and healthcare systems but also the economic costs to society as a whole. This perspective includes factors such as productivity loss, resource allocation and the overall impact on the well-being and functioning of society at large.

To contrast with the costs and the cost-effectiveness of public health surveillance, preparedness and response measures in averting and/or responding to COVID-19, the inclusion criteria for Objective 2 were as follows:

• Population: EU/EEA/UK and remaining OECD countries.

• Intervention: Public health preparedness measures or interventions.

• Comparator: (i) No intervention (cost of inaction) or current practice; (ii) cost of preparedness versus cost of response (for studies reporting cost and benefit of public health preparedness).

• Outcome measures: Cost-benefit and cost-effectiveness outcomes (eg, cost per life-year saved). Studies that use other methods to formally combine cost and clinical outcome data (pertinent to infectious diseases) were also included. Typical outcome measures of economic evaluations include: Life years gained (or cost per life-year achieved with the intervention under investigation when incremental costs are combined), Quality-Adjusted Life Years (QALY; cost per QALY gained), Cases averted (eg, cost per case that is averted with the intervention vs the comparator) and monetary outcomes (in the case of a cost-benefit analysis). Where available, the incremental cost-effectiveness ratio (ICER) was also provided.

• Study designs: We included all designs specific to cost-benefit questions either as full economic evaluation studies, including cost-minimisation, cost-effectiveness, cost-utility and cost-benefit analyses; cost-outcome and economic modelling studies; or partial economic evaluations.

• Perspective: All direct and indirect costs were considered pertaining to all relevant perspectives (eg, individual, health and social care, and societal, a detailed explanation of which is provided in the inclusion criteria for Objective 1).

Data analysis and extraction

Studies identified from the searches were uploaded into a bibliographic database (Covidence) in which duplicate entries were removed. Initially, a random sample of 100 titles and abstracts were screened independently for eligibility by two reviewers to enable consistency in screening and identify areas for amendments in the inclusion criteria. Since a high measure of inter-rater agreement was achieved (inter-rater agreement=88.7%), the remaining titles and abstracts were screened for eligibility by one reviewer. Full-text articles of potentially eligible studies were retrieved and screened independently by two reviewers (inter-rater agreement=89.3%). Data were extracted with the use of a predefined data extraction sheet. Initially, two reviewers piloted the data extraction template independently on a random sample of five included studies and given the high consistency in data extraction, the remaining studies were extracted only by one reviewer. Disagreements in every step of the process were subsequently discussed with a third reviewer and agreed on.

Appraisal of methodological quality

The Consensus on Health Economic Criteria (CHEC) checklist was used¹⁵ to evaluate the methodological quality of full health economic evaluations, which comprises 19 questions with answers of ‘Yes’ or ‘No’. For each positive response of full health economic evaluations, a single point was assigned for the methodological quality, with a maximum score of 19. For the quality appraisal of partial economic evaluations, we used items from the CHEC checklist that were applicable—hence the maximum score was 17. In cases of insufficient information or details reported in both full and partial economic evaluation studies, with regard to a specific item, no point was awarded for that question. Studies were categorised as high (>80%), good (60%–80%), medium (40%–60%) or low (<40%) quality. The quality appraisal process was completed by one reviewer since piloting of three studies by two independent reviewers had an inter-rater agreement of 85.6%.

Comparative economic analysis approach

All cost data were adjusted to a common currency (Euro in 2021) and price year, using the Campbell and Cochrane Economics Methods Group–Evidence for Policy and Practice Information and Coordinating Centre cost converter.¹⁶ A two-stage computation is used, where the 2021 implied conversion factor is US$1=€0.88. The 2021 implied conversion factor of British pounds is £1=€1.18. In our study, we first inflated the cost from the original price year to 2021, using a GDP deflator index (GDP values), obtained from the International Monetary Fund World Economic Outlook Database GDP deflator index data set. After that, we converted the original currency to the next rounded 2021 Euros, using conversion rates based on Purchasing Power Parities for GDP (PPP values). For studies that did not state the year of cost calculation, the costs were calculated 1 year before the publication year.

Synthesis of cost-effectiveness

The Dominance Ranking Matrix (DRM) was used to assess the cost-effectiveness of the interventions noted within the identified studies.¹⁷ The DRM is a three-by-three matrix with the following classification options:

1. Strong dominance for the intervention when the incremental cost-effectiveness measure shows that the intervention versus the comparator is (a) more effective and less costly; or (b) as effective and less costly; or (c) equally costly and more effective. Strong dominance suggests that under similar circ*mstances, the intervention is preferable to the comparator.

2. Weak dominance for the intervention versus the comparator is noted when the measure shows the intervention as (d) equally costly and effective; or (e) more effective and more costly; or (f) less effective and less costly. In principle, weak dominance indicates that no conclusion can be drawn and hence judgement by policymakers is required on whether the intervention is preferable when taking into consideration whether the cost/benefit trade-offs are worth the introduction of the intervention within the particular context.

3. Non-dominance for the intervention versus the comparator when the measure shows the intervention as (g) more costly and less effective; or (h) equally as costly and less effective; or (i) more costly and as effective. In this case, the comparator is preferable to the measured intervention, at least under the circ*mstances of the specific study.

Patient and public involvement

This study was performed under contract for the ECDC. Patients or the public were not explicitly involved in the design, or conduct, or reporting, or dissemination plans of our research.

Objective 1: economic impact of COVID-19 infection on healthcare systems and societies

Ten studies evaluated the cost of the COVID-19 pandemic within EU/EEA/UK and OECD countries (table 1), among which eight studies used a cost of illness analysis approach.^18–25 The direct medical costs were presented in 7 out of 10 studies,^{18–20 22 23 25 26} while in 8 studies the costs were estimated for a time horizon shorter than 1 year,^{19–21 23–27} and specific discount rates were not applied in 7 studies.^{18–20 23 25–27} With regard to the country of origin, 5 out of the 10 studies took place in the European region, including in the UK and Turkey,^{19–21 24 26} 3 were from the USA,^{22 25 27} 1 from Korea²³ and 1 from Australia.¹⁸ Six of the 10 studies were observational,^{21 23–27} while a few used modelling techniques^18–20 or simulation methods.²² Furthermore, it should be noted that the healthcare system perspective was included in the analysis of four studies,^{19 20 22 25} the societal in two,^{21 24} the third payer perspective was assessed in three^{22 23 26} and one study¹⁸ assessed data from the public health payer perspective. The perspective considered within one study was unclear.²⁷

Objective 2: economic evaluation of strategies for the mitigation of COVID-19 virus transmission

Our systematic review identified 31 studies assessing the cost-effectiveness of interventions for reducing SARS-CoV-2 transmission within EU/EEA/UK and OECD countries (online supplemental appendix 5). We identified studies that assessed isolation, lockdown policies, physical distancing scenarios,^28–38 testing/screening policies,^39–45 personal protective equipment intervention,⁴⁶ vaccinations^47–50 and pharmaceutical treatment strategies (n=4).^50–53 Multiple strategies were evaluated by four studies,^54–57 which mainly assessed the combination of testing, isolation and vaccinations, and one study⁵⁸ that analysed an ICU bed provision scenario.

Concerning study characteristics, 13 out of 31 studies were from the USA,^{28 29 39 41 43 44 47–49 51 53 55 57} seven from the UK,^{33–36 45 52 56} three from Germany,^{31 54 58} one from Switzerland,⁵⁰ Israel³⁷ and Wales,⁴⁰ while five studies included analyses from multiple OECD countries.^{30 32 38 42 46} The societal perspective was followed in 14 studies,^{29 31 33 34 36 37 39 42 44 46 54 55 57 58} while ten studies performed an analysis via a healthcare perspective.^{28 30 40 41 43 45 49 50 52 56} Various perspectives were included in four studies,^{47 48 51 53} including the payer for some of them,^{48 51 53} while the perspective considered was unclear in three studies.^{32 35 38}

Seven studies (online supplemental appendix 6) assessed the cost-effectiveness of testing and screening interventions, a synthesis of which is in figure 2. Stevenson et al⁴⁵ compared 30 interventions and found that the least costly testing intervention was testing on hospital admission, and routine retesting following hospital admission. The authors noted that strategies with shorter times to test results were more cost-effective, all other things being equal, as were SARS-CoV-2 tests with greater diagnostic accuracy. Strategies that included saliva sampling and nasopharyngeal have been assessed within the systematic review and meta-analysis by Bastos et al.⁴² The incremental cost per additional SARS-CoV-2 infection detected with nasopharyngeal swabs versus saliva sampling was €6427 if the prevalence was 1%, and the cost-savings of saliva sampling were estimated at €505 177 € (95% CI 371 217 to 660 568) if 100 000 persons are tested. The clinical and economic value of PCR testing was investigated by Neilan et al,⁴¹ who showed that under all epidemic growth scenarios considered, testing people with any COVID-19-consistent symptoms would be cost-saving compared with restricting testing to only those with symptoms severe enough to warrant hospital care, leading to lower costs and reducing infections and deaths. According to their results, and within the context of the first wave of the pandemic, the symptomatic and asymptomatic monthly testing scenario was a cost-effective strategy only with an (R_e)>1.6 but would be no longer a cost-effective option for lower reproduction scenarios, unless testing cost was lower. A cost-minimisation analysis performed by Currie et al⁴⁰ comparing community testing undertaking swabbing of suspected cases in Wales with standard hospital testing showed that community testing for COVID-19 was a superior strategy, resulting in significant benefits for the healthcare system. Two studies appraised the cost-effectiveness outcomes of different testing strategies within specific settings. Baggett et al⁴³ investigated the clinical outcomes, costs and cost-effectiveness associated with strategies for COVID-19 management among adults experiencing sheltered homelessness in Boston, USA. Daily symptom screening with subsequent PCR testing of individuals who screened positively was the most efficient strategy and was cost-saving relative to no intervention in all epidemic scenarios.

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Figure 2

ICER results for testing and screening strategies. ACS, alternative care site; ICER, incremental cost-effectiveness ratio; QALY, Quality-Adjusted Life Years.

Paltiel et al⁴⁴ examined the SARS-CoV-2 screening performance standards that would permit the safe return of students to US residential college campuses for the fall semester of 2020 and noted that screening with a less expensive, less sensitive test dominated the intervention of screening with more expensive, more accurate tests. Paltiel et al,³⁹ assessed the clinical and economic effects of widespread home-based SARS-CoV-2 antigen testing and noted that the cost per infection averted was €6266.

Cost-effectiveness of quarantine, isolation, physical distancing and physical restriction policies

Twelve studies were included to assess the cost-effectiveness across different strategies to prevent or mitigate SARS-COV-2 transmission (online supplemental appendix 6).

Kouidere et al³⁸ conducted a mathematical compartmental modelling to assess three different strategies for diabetics and concluded that awareness programmes and quarantine for those infected having symptoms as well as those having complications in hospital treatment was the most effective strategy and was associated with an ICER of −0.6951 (cost per infection averted) compared with sensitisation and prevention.

The cost-effectiveness of comparing the national lockdown policy for the susceptible population with the isolation of those infected or being at high risk in Israel returning to the workforce under social distancing measures after a 14-day isolation period was appraised by Shlomai et al.³⁷ The national lockdown of the susceptible population was associated with a higher economic burden but contributed to a reduction in deaths making this intervention superior to the comparator only in terms of health outcomes but was not cost-effective since it contributed to high economic costs, estimated at €36 568 451 costs per death averted, and €3.6 million costs per QALY gained. Furthermore, Keogh-Brown et al³⁶ assessed the direct and indirect costs of three different strategies in the UK and indicated that although mitigation and suppression policies contribute to lower mortality rates, the economic impact of COVID-19 is likely to be dominated by public prevention measures rather than the direct health costs of the disease and indicated that a 3-month mitigation scenario resulted in a prediction of 13.5% loss to GDP with the direct-health related economic impact of 2% of the GDP while the suppression scenario was associated with an approximately 22% loss in GDP. Furthermore, Miles et al within the context of a cost-benefit analyses³⁵ noted that a full lockdown policy for 4 months followed by an extension for 3 months showed that net extra economic costs of the lockdown relative to the easing of restrictions were estimated at €116.2 billion with the best scenario of lives not lost at €96.5 billion. The main factors of the substantial costs of the lockdown policy were associated mainly with employment restrictions and physical restrictions. Miles et al³⁴ also conducted an additional modelling and simulation study to assess a few physical restriction scenarios in a time frame of 6 months in the UK and found that the strategy of relatively slowly easing restrictions comes at a cost in terms of GDP reduction of up to €697 121/life‐year saved. Moreover, the cost per life-year saved with a short transition physical restriction policy (8 weeks medium then 18 weeks low) was associated with a cost of per life-year saved at €206 888 while keeping the policies strict for 26 weeks was estimated at a cost of per life-year saved of €1 553 988.

Suppression and physical distancing interventions were assessed by Zala et al³³ and Barnett-Howell et al.³² Zala et al³³ noted that suppression policies compared with an unmitigated scenario strategy were associated with an ICER below €56 972, while all of the four suppression policies presented ICER results. Barnett-Howell et al³² investigated five physical distancing strategies, including an unmitigated intervention, to assess the value of statistical life lost. Full lockdown policies were associated with lower Value of Statistical Life (VSL) in the USA, UK and Mexico countries (USA: €23 billion, UK: €4.76 billion, Mexico: €794 million) while the no-action scenario, which was the unmitigated spread of COVID-19, contributed to higher VSL in those countries (USA: €38.9 billion, UK: €7.1 billion, Mexico: €1.58 billion).

Additional studies focusing on policies related to stay-home and shutdown orders were investigated by Gandjour³¹ and Thom et al.³⁰ Gandjour³¹ assessed the clinical and economic cost of a shutdown during the SARS-CoV-2 pandemic in Germany to estimate the cost of life-years gained per capita estimating the indirect costs for 1 year. The results showed that the economic cost of the lockdown intervention was associated with €3472 or extrapolated to the total population, 8% of Germany’s GDP in 2019 (ranging from 1% to 12% in the sensitivity analysis). Thom et al³⁰ provided an exploratory comparison of health-related benefits and costs saved by government mitigation measures across European countries (UK, Ireland, Germany, Spain and Sweden) over a time frame of 7 months, where the authors concluded that the benefit of government COVID-19 responses might outweigh their economic costs, saving millions of QALYs (0.5 million for Sweden to approximately 5 million for Germany) and ideally those countries with more mask-wearing and testing, had better outcomes.

The last studies focusing on stay-home policies were by the same authors, Chen et al.^{28 29} Their first study, Chen et al²⁸ estimated the total medical costs by keeping the US economy open and assessed 13 interventions with different stay-home isolation and voluntary home isolation compliance rates for 1 year. Without mitigation, the total medical costs would be 5% of the US GDP. In their second study, Chen et al²⁹ compared the epidemiological and economic impact of SARS-CoV-2 spread in the USA under different mitigation scenarios, comprising NPIs including stay-home with varying compliance rates.

Cost-effectiveness of vaccination measures

Three included studies^47–49 focused on vaccination interventions and used modelling and simulation methods to assess the cost-effectiveness of the included interventions (online supplemental appendix 6) and synthesised in figure 3. Shaker et al⁴⁷ appraised the universal COVID-19 vaccination versus the risk-stratified vaccination approach over the time frame of 1 year, and they found that the universal COVID-19 vaccination dominates the risk-stratified approach, making it a cost-effective strategy for the US population from the societal perspective and the healthcare perspective. ICER analyses indicated that in the case of societal perspective, the universal approach presents a cost of €52 033 per death averted compared with the risk-stratified vaccination, with cost-savings estimated at €395 million. When considering the healthcare perspective, the cost per death averted by the risk-stratified approach was €52 575 making it the dominant option. Bartsch et al⁴⁸ noted that NPI implementation before vaccination was associated with less total costs compared with the case of non-implementation of NPIs. Finally, Kohli et al⁴⁹ conducted a cost utility analysis (CUA) to assess the COVID-19 vaccine versus no vaccine for the US population over 1 year. Base case analysis presented good value for money outcomes where the ICER per age was found to be €74 652 for ages 18–49 years, €6353 for 50–64 years, while for ages 65+ the COVID-19 vaccine dominates. This strategy was also cost-effective under additional scenarios, such as with the per-risk-based prioritisation scheme.

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Figure 3

ICER results for vaccination and treatment strategies. FFS, fee for service payment; ICER, incremental cost-effectiveness ratio; QALY, Quality-Adjusted Life Years.

Strengths and limitations

This review provides several strengths, including covering within one review both the economic burden of COVID-19 and the cost-effectiveness of the strategies and programmes implemented to mitigate the pandemic. Moreover, this review followed a systematic approach to study identification, data extraction and quality appraisal with most of the included studies of good or high quality. Furthermore, this study used the DRM approach, which summarised and interpreted the results of economic evaluation studies. On the other hand, there are some limitations, as publication bias can not be excluded and as our search was performed up to the end of April 2021 it only reflects the cost-effectiveness of interventions assessed during the first waves of the pandemic when the majority of the populations were unvaccinated, and while most of the included studies have a short duration on which modelling was performed. A further limitation is that most studies estimate costs and benefits based on a healthcare perspective, excluding wider societal effects, with a time horizon of 1 year. As we restricted our search to EU/UK/EEA/USA and OECD countries, the studies primarily refer to high-income countries. In addition, our literature search was conducted through two databases, Ovid MEDLINE and EMBASE and consequently any information available in other databases or in the grey literature may have been overlooked. Finally, as costs and resources varied between different countries, different pandemic settings and over time, and as indicated in this review depended on multiple other factors including population vaccination status, pre-existing healthcare capacity and the infectivity of the SARS-CoV-2 variant at each time point, the comparison of cost-effectiveness measures is a complex process to interpret and the cost-effectiveness of each intervention should be weighed by policymakers against the regional circ*mstances. Moreover, as the complete economic and health consequences are yet unknown, further research is needed on the cost-effectiveness of NPIs, while the cost of the long-term effects of COVID-19 (both physical and mental) should also be assessed in future analyses.

Reviewer comments:

Author'smanuscript:

Twitter: @stvfdz

Contributors: CV, KZ, JL-B and JES designed the study. KZ and KN undertook the systematic review and extracted the data with help from KAs. JL-B and RP developed the search strategy and JL-B ran the searches. KZ and KN analysed and interpreted the economic data. OC, FL, FS, AP, CD, and JES participated in data evaluation and interpretation along with JL-B, RP, JES, VM, KAt, KAs, EF, and FS. The first draft of the manuscript was written by CV, KN, and KZ with input from all authors with further revisions by VM. Figures have been prepared by KZ. All authors reviewed and revised subsequent drafts. CV is responsible for the overall content as guarantor.

Funding: This report was commissioned by the European Centre for Disease Prevention and Control (ECDC), to the PREP-EU Consortium, coordinated by CV under specific contract ECD. 11986 within Framework contract ECDC/2019/001. The information and views in this manuscript are those of the authors and do not necessarily reflect the official opinion of the Commission/Agency. The Commission/Agency does not guarantee the accuracy of the data included in this study. Neither the Commission/Agency nor any person acting on the Commission’s/Agency’s behalf may be held responsible for the use which may be made of the information contained in that regard.

Competing interests: None declared.

Patient and public involvement: Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

Provenance and peer review: Not commissioned; externally peer reviewed.

Data availability: No new data was generated.

Supplemental material: This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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