Positive association between COVID-19 deaths and influenza vaccination rates in elderly people worldwide

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Author and article information

 
 
Instituto de Silvicultura e Industria de la Madera, Universidad Juárez del Estado de DurangoDurangoMexico
DOI
10.7717/peerj.10112
Academic Editor
Antonio Palazón-Bru
Subject Areas
EpidemiologyGlobal HealthImmunologyInfectious DiseasesPublic Health
Keywords
SARS-CoV-2Global health crisisRisk factorsVirus interferenceGeographical longitudeLockdownFace mask use
Copyright
© 2020 Wehenkel
Licence
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
Cite this article
Wehenkel C. 2020Positive association between COVID-19 deaths and influenza vaccination rates in elderly people worldwidePeerJ 8:e10112 https://doi.org/10.7717/peerj.10112
The author has chosen to make the review history of this article public.
 

Abstract

 
 

Background

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing global health crisis, directly and indirectly impacting all spheres of human life. Some pharmacological measures have been proposed to prevent COVID-19 or reduce its severity, such as vaccinations. Previous reports indicate that influenza vaccination appears to be negatively correlated with COVID-19-associated mortality, perhaps as a result of heterologous immunity or changes in innate immunity. The understanding of such trends in correlations could prevent deaths from COVID-19 in the future. The aim of this study was therefore to analyze the association between COVID-19 related deaths and influenza vaccination rate (IVR) in elderly people worldwide.

Methods

To determine the association between COVID-19 deaths and influenza vaccination, available data sets from countries with more than 0.5 million inhabitants were analyzed (in total 39 countries). To accurately estimate the influence of IVR on COVID-19 deaths and mitigate effects of confounding variables, a sophisticated ranking of the importance of different variables was performed, including as predictor variables IVR and some potentially important geographical and socioeconomic variables as well as variables related to non-pharmaceutical intervention. The associations were measured by non-parametric Spearman rank correlation coefficients and random forest functions.

Results

The results showed a positive association between COVID-19 deaths and IVR of people ≥65 years-old. There is a significant increase in COVID-19 deaths from eastern to western regions in the world. Further exploration is needed to explain these findings, and additional work on this line of research may lead to prevention of deaths associated with COVID-19.

Cite this as

Wehenkel C. 2020Positive association between COVID-19 deaths and influenza vaccination rates in elderly people worldwidePeerJ 8:e10112 https://doi.org/10.7717/peerj.10112
 
 

Main article text

 
 

Introduction

Materials and Methods

Table 1:
Raw data (part 1).
Countries with their influenza vaccination rate (IVR) (%) of people aged 65 and older in 2019 or latest available, COVID-19 deaths per million inhabitants (DPMI), COVID-19 Case Fatality Ratio (CFR) based on documented COVID-19 cases per million inhabitants (CPMI) in 2020, COVID-19 tests per million inhabitants.
CountryIVR*
(%)
Year of
IVR
DPMI+
(N per M)
CPMI+
(N per M)
CFR+COVID-19 tests+Continent
Australia 73.0 2018/2019 6 547 0.011 151,037 Australia and
Ozeanien
Belgium 59.1 2019 847 5,624 0.151 130,601 Europe
Brazil 71.8 2018/2019 402 11,078 0.036 23,094 America
Canada 59.0 2019 235 3,006 0.078 98,442 America
Chile 68.3 2019 472 17,964 0.026 78,678 America
China 7.0 2018/2019 3 58 0.052 62,814 Asia
Croatia 23.0 2017 31 1,168 0.027 26,932 Europe
Czech Republic 21.5 2019 34 1,413 0.024 61,332 Europe
Denmark 52.0 2019 106 2,319 0.046 243,677 Europe
Estonia 10.2 2019 52 1,532 0.034 87,692 Europe
Finland 49.5 2019 59 1,333 0.044 59,654 Europe
France 51.0 2019 462 2,765 0.167 45,683 Europe
Germany 34.8 2019 110 2,460 0.045 88,528 Europe
Greece 56.2 2019 19 400 0.048 42,244 Europe
Hungary 24.1 2019 62 458 0.135 33,116 Europe
Ireland 68.5 2019 357 5,235 0.068 121,496 Europe
Israel 59.8 2019 49 6,577 0.007 173,662 Europe
Italy 53.1 2019 581 4,067 0.143 107,848 Europe
Japan 48.0 2019 8 221 0.036 5,516 Asia
Latvia 11.7 2019 16 640 0.025 100,009 Europe
Lithuania 14.8 2019 29 736 0.039 182,847 Europe
Luxembourg 39.8 2019 179 9,665 0.019 618,326 Europe
Mexico 82.3 2018/2019 331 2,932 0.113 6,946 America
Netherlands 62.7 2019 358 3,077 0.116 49,709 Europe
New Zealand 62.0 2019 4 311 0.013 90,746 Australia and
Ozeanien
Norway 38.2 2019 47 1,677 0.028 77,531 Europe
Portugal 60.8 2019 168 4,900 0.034 149,941 Europe
Romania 16.1 2017 112 2,272 0.049 56,571 Europe
Singapore** 14.0 2016/2017 5 8,523 0.001 199,896 Asia
Slovak Republic 12.5 2019 5 392 0.013 46,285 Europe
Slovenia 12.9 2019 55 994 0.055 61,108 Europa
South Korea 85.1 2019 6 275 0.022 29,619 Asia
Spain 54.9 2019 608 6,833 0.089 135,188 Europe
Sweden 52.2 2019 562 7,819 0.072 74,353 Europe
Thailand 12.0 2018/2019 0.8 47 0.017 9,817 Asia
Turkey 7.0 2019 66 2,668 0.025 53,707 Europe
United Kingdom 72.0 2019 673 4,398 0.153 214,532 Europe
United States 68.7 2019 450 12,929 0.035 159,672 America
Vietnam*** 12.0 2017 0 4 0.000 2,824 Asia
DOI: 10.7717/peerj.10112/table-1
Table 2:
Raw data (part 2).
Countries with their centroid coordinates (longitude (Long) and latitude (Lat)), Degree of urbanization in 2020, Human Development Index (HDI) in 2018, Percent elder people in 2019 and Population density in 2018.
CountryLong (°)Lat
(°)
Degree of urbanization
(2020)*
HDI
(2018)**
Percent elder people (%) (2019)***Population density (people per km2 of land area) (2018)****
Australia 134.5 −25.7 86.2 0.938 15.92 3.2
Belgium 4.6 50.6 98.1 0.919 19.01 377.4
Brazil −53.1 −10.8 87.1 0.761 9.25 25.1
Canada −98.3 61.4 81.6 0.922 17.65 4.1
Chile −71.4 −37.7 87.7 0.847 11.88 25.2
China 103.8 36.6 61.4 0.758 11.47 148.3
Croatia 16.4 45.1 57.6 0.837 20.86 73.0
Czech Republic 15.3 49.7 74.1 0.891 19.80 137.7
Denmark 10.0 56.0 88.1 0.930 19.97 138.0
Estonia 25.5 58.7 69.2 0.882 19.99 30.4
Finland 26.3 64.5 85.5 0.925 22.14 18.1
France 2.5 46.2 81.0 0.891 20.39 122.3
Germany 15.3 49.7 77.5 0.939 21.56 237.3
Greece 23.0 39.1 79.7 0.872 21.94 83.3
Hungary 19.4 47.2 71.9 0.845 19.69 108.0
Ireland −8.1 53.2 63.7 0.942 14.22 70.7
Israel 35.0 31.5 92.6 0.906 12.21 410.5
Italy 12.1 42.8 71.0 0.883 23.01 205.4
Japan 138.0 37.6 91.8 0.915 28.00 347.1
Latvia 24.9 56.9 68.3 0.854 20.34 31.0
Lithuania 23.9 55.3 68.0 0.869 20.16 44.7
Luxembourg 6.1 49.8 91.5 0.909 14.27 250.2
Mexico −102.5 23.9 80.7 0.767 7.42 64.9
Netherlands 5.3 52.1 92.2 0.933 19.61 511.5
New Zealand 171.5 −41.8 86.7 0.921 15.99 18.4
Norway 15.3 68.8 83.0 0.954 17.27 14.5
Portugal −8.5 39.6 66.3 0.850 22.36 112.3
Romania 25.0 45.9 56.4 0.816 18.79 84.6
Singapore 103.8 1.4 100.0 0.935 12.39 7953.0
Slovak Republic 19.5 48.7 53.8 0.857 16.17 113.3
Slovenia 14.8 46.1 55.1 0.902 20.19 103.0
South Korea 127.8 36.4 81.4 0.906 15.06 529.4
Spain −3.6 40.2 80.8 0.893 19.65 93.7
Sweden 16.7 62.8 88.0 0.937 20.20 25.0
Thailand 101.0 15.1 51.4 0.765 12.41 135.9
Turkey 35.2 39.1 76.1 0.806 8.73 107.0
United Kingdom −2.9 54.1 83.9 0.920 18.51 274.7
United States −112.5 45.7 82.7 0.920 16.21 35.7
Vietnam 106.3 16.6 37.3 0.693 7.55 308.1
DOI: 10.7717/peerj.10112/table-2
Table 3:
Raw data (part 3).
Countries with some Covid-19 measures (degree of mask requirements in public, lockdown degree and lockdown beginning).
CountryDegree of mask requirement*Lockdown degreeLockdown beginningSources about lockdown
(retrieved on Aug 13, 2020)
Australia Parts of Country Lockdown 3/23/20 https://www.straitstimes.com/asia/australianz/australia-starts-lockdown-measures-as-coronavirus-cases-jump
Belgium Full Country Lockdown 3/17/20 https://www.euractiv.com/section/coronavirus/news/belgium-enters-lockdown-over-coronavirus-crisis-until-5-april/
Brazil Parts of Country Lockdown 5/5/20 https://www.reuters.com/article/us-health-coronavirus-brazil-lockdown/major-brazilian-cities-set-lockdowns-as-virus-spreads-idUSKBN22H2V3
Canada Parts of Country Partial lockdown 3/17/20 https://www.manitoulin.ca/updated-canada-goes-on-covid-19-lockdown/
Chile Full Country Partial lockdown 3/25/20 https://www.gob.cl/noticias/ministerio-de-salud-anuncia-cuarentena-total-para-siete-comunas-de-la-region-metropolitana/
China None, but voluntary Universal Mask Usage Lockdown 1/23/20 https://www.who.int/bulletin/volumes/98/7/20-254045/en/
Croatia Full Country Lockdown 3/18/20 https://www.telegram.hr/zivot/koronavirus-krizni-stozer-danas-ce-objaviti-sto-se-sve-zatvara-u-hrvatskoj/https://m.vecernji.hr/vijesti/oxford-hrvatska-ima-najstroze-mjere-u-europi-iza-su-samo-srbija-i-sirija-1389281
Czech Republic Full Country Lockdown 3/16/20 https://archiv.radio.cz/en/section/breaking/czech-republic-severely-limits-freedom-of-movement-in-order-to-slow-down-coronavirus-spread
Denmark None Lockdown 3/13/20 https://nyheder.tv2.dk/samfund/2020-03-11-danmark-lukker-ned-her-er-regeringens-nye-tiltag
Estonia None, but Recommends Masks No lockdown   https://www.euronews.com/2020/05/13/coronavirus-lockdown-latvia-lithuania-and-estonia-re-open-borders-to-each-other
Finland None, but Recommends Masks Partial lockdown 3/28/20 https://newseu.cgtn.com/news/2020-04-16/Finland-to-lift-coronavirus-lockdown-in-region-around-capital--PIiAE4MM36/index.html
France Full Country Lockdown 3/17/20 https://www.leparisien.fr/societe/coronavirus-etat-d-urgence-aux-etats-unis-800-nouveaux-cas-en-france-79-morts-au-total-suivez-notre-direct-14-03-2020-8279826.php
Germany Full Country Lockdown 3/23/20 https://www.welt.de/politik/deutschland/article206725829/Coronavirus-Deutschland-Kontaktverbote-zu-mehr-als-zwei-Personen-Friseure-zu.html
Greece Full Country Lockdown 3/23/20 https://www.in.gr/2020/04/23/politics/se-ekseliksi-enimerosi-tou-kyvernitikou-ekprosopou-steliou-petsa-2/
Hungary Parts of Country Lockdown 3/28/20 https://www.theguardian.com/world/2020/mar/30/hungary-jail-for-coronavirus-misinformation-viktor-orban
Ireland No, but Recommends Masks Lockdown 3/12/20 https://www.irishtimes.com/news/health/coronavirus-schools-colleges-and-childcare-facilities-in-ireland-to-shut-1.4200977
Israel Full Country Lockdown 4/1/20 https://www.haaretz.com/israel-news/coronavirus-israeli-health-minister-netanyahu-mossad-chief-quarantine-1.8720108https://www.timesofisrael.com/israelis-will-be-required-to-wear-face-masks-outdoors-under-new-order/
Italy Full Country Lockdown 2/25/20 https://metro.co.uk/2020/02/25/towns-italy-lockdown-coronavirus-12298246/
Japan No, but Universal Mask Usage No lockdown   https://asia.nikkei.com/Spotlight/Coronavirus/Japan-quietly-reopens-as-much-of-world-locks-down
Latvia Full Country No lockdown   https://www.euronews.com/2020/05/13/coronavirus-lockdown-latvia-lithuania-and-estonia-re-open-borders-to-each-other
Lithuania Full Country No lockdown   https://www.euronews.com/2020/05/13/coronavirus-lockdown-latvia-lithuania-and-estonia-re-open-borders-to-each-other
Luxembourg Full Country Lockdown 4/15/20 https://www.tageblatt.lu/headlines/pressekonferenz-nach-dem-regierungsrat-kommt-das-ende-des-lockdowns/
Mexico Full Country Lockdown 3/23/20 https://www.eluniversal.com.mx/english/mexico-city-closes-museums-bars-nightclubs-and-movie-theaters-bid-halt-coronavirus-spread
Netherlands Full Country Lockdown 3/12/20 Maarten Keulemans (12 March 2020). "Are we doing enough? RIVM boss Van Dissel: ’As soon as something indicates infection in the family: isolation’". de Volkskrant (in Dutch). Retrieved 13 March 2020.
New Zealand None Lockdown 3/26/20 https://www.newstalkzb.co.nz/news/national/coronavirus-covid-19-state-of-emergency-declared-in-new-zealand-50-new-cases-confirmed/
Norway None Lockdown 3/12/20 https://www.nrk.no/norge/alle-utdanningsinstitusjoner-stenges-_-flere-arrangementer-og-virksomheter-far-forbud-1.14940952
Portugal Full Country Lockdown 3/19/20 http://www.presidencia.pt/?idc=22&idi=176060
Romania Full Country Lockdown 3/25/20 http://www.ms.ro/2020/03/25/buletin-informativ-25-03-2020/
Singapore Full Country Lockdown 4/7/20 https://www.channelnewsasia.com/news/business/suntec-city-waives-april-rent-for-tenants-covid-19-12614802
Slovak Republic Full Country Lockdown 3/12/20 https://spectator.sme.sk/c/22356193/emergency-situation-applies-from-thursday-morning.html?ref=njctse
Slovenia Full Country Lockdown 3/13/20 https://www.rtvslo.si/zdravje/novi-koronavirus/katalonija-zeli-razglasiti-karanteno-za-celotno-pokrajino/517068
South Korea None, but voluntary Universal Mask Usage No lockdown   https://www.sciencemag.org/news/2020/03/coronavirus-cases-have-dropped-sharply-south-korea-whats-secret-its-success
Spain Full Country Lockdown 3/14/20 https://administracion.gob.es/pag_Home/atencionCiudadana/Estado-de-alarma-crisis-sanitaria.html#.Xn3xj0dKjIU
Sweden None No lockdown   Sayers, Freddy (17 April 2020). Swedish expert: why lockdowns are the wrong policy—The Post. UnHerd.
Thailand Full Country Lockdown 4/3/20 https://www.bangkokpost.com/thailand/general/1891910/curfew-starts-today
Turkey Full Country Partial lockdown 3/21/20 ttps://www.bbc.com/news/world-europe-52831017https://www.aa.com.tr/tr/koronavirus/cumhurbaskanligi-sozcusu-kalin-ilk-orta-ve-liseler-1-hafta-universiteler-3-hafta-tatil-edilecek/1763918
United Kingdom Full Country Lockdown 3/23/20 https://www.thesun.co.uk/news/11304061/uk-coronavirus-lockdown-month-lasted-start-end/
United States Parts of Country Lockdown 3/19/20 https://www.wsj.com/articles/china-reports-no-new-domestic-coronavirus-infections-for-the-first-time-since-outbreak-started-11584611233
Vietnam Full Country Lockdown 4/1/20 https://e.vnexpress.net/news/news/covid-19-lockdown-hanoi-hospital-lacks-food-necessities-for-3-500-inmates-4077071.html
DOI: 10.7717/peerj.10112/table-3

Results

Association of COVID-19 deaths per million inhabitants (DPMI) up to July 25, 2020 with influenza vaccination rate (IVR) of people aged 65 and older in 2019 or latest data available in Europe.

Figure 1: Association of COVID-19 deaths per million inhabitants (DPMI) up to July 25, 2020 with influenza vaccination rate (IVR) of people aged 65 and older in 2019 or latest data available in Europe.

Association of COVID-19 deaths per million inhabitants (DPMI) up to July 25, 2020 with influenza vaccination rate (IVR) of people aged 65 and older in 2019 or latest data available in Europe (26 countries with more than 0.5 million inhabitants). The mean (blue line) and standard deviation (grey area) are based on generalized additive models (GAM); rs (IVR × DPMI) = +0.687 with p = 0.00015.
Association of COVID-19 Case Fatality Ratio (CFR) up to July 25, 2020 with influenza vaccination rate (IVR) of people aged 65 and older in 2019 or latest data available in Europe.

Figure 2: Association of COVID-19 Case Fatality Ratio (CFR) up to July 25, 2020 with influenza vaccination rate (IVR) of people aged 65 and older in 2019 or latest data available in Europe.

Association of COVID-19 Case Fatality Ratio (CFR) up to July 25, 2020 with influenza vaccination rate (IVR) of people aged 65 and older in 2019 or latest data available in Europe (26 countries with more than 0.5 million inhabitants). The mean (blue line) and standard deviation (grey area) are based on generalized additive models (GAM); rs(IVR × CFR) = +0.629 with p = 0.00075.
Table 4:
Spearman correlations (rs) of COVID-19 deaths per million inhabitants (DPMI) with nine predictor variables.
Spearman correlations (rs) of COVID-19 deaths per million inhabitants (DPMI) with the variables (var): IVR = influenza vaccination rate (IVR, %) of people aged 65 and older in 2019 or latest data available, Long and Lat = Longitude and Latitude of the country centroid (°), DUR = Degree of urbanization in 2020, HDI = Human Development Index in 2018, PEP = Percent elder people in 2019, PD = Population density in 2018, Mask = the requirement degree of using masks in public (with three degrees: none, parts of country, full country), Lockdown = lockdown degree (with three levels: no lockdown, partial lockdown, nationwide lockdown) and their p values based on 26 countries in Europe (Tables 13).
varrs (DPMI × var)p value
Long −0.65 0.0003
IVR 0.62 0.0008
DUR 0.43 0.0273
PD 0.41 0.0375
HDI 0.38 0.0533
Lockdown 0.25 0.2146
PEP −0.07 0.7387
Lat (abs) −0.02 0.9313
Mask 0 0.9949
DOI: 10.7717/peerj.10112/table-4

Note:

Bold values statistically significant after Bonferroni correction (α = 0.0019).

Association of COVID-19 deaths per million inhabitants (DPMI) up to July 25, 2020 with influenza vaccination rate of people aged 65 and older in 2019 or latest data available worldwide.

Figure 3: Association of COVID-19 deaths per million inhabitants (DPMI) up to July 25, 2020 with influenza vaccination rate of people aged 65 and older in 2019 or latest data available worldwide.

Association of COVID-19 deaths per million inhabitants (DPMI) up to July 25, 2020 with influenza vaccination rate of people aged 65 and older in 2019 or latest data available worldwide (39 countries with more than 0.5 million inhabitants). The mean (blue line) and standard deviation (grey area) are based on generalized additive models (GAM); rs (IVR × DPMI) = +0.487 with p = 0.0017.
Table 5:
Spearman correlations (rs) of COVID-19 deaths per million inhabitants (DPMI) and COVID-19 Case Fatality Ratio (CFR) with nine predictor variables.
Spearman correlations (rs) of COVID-19 deaths per million inhabitants (DPMI) and COVID-19 Case Fatality Ratio (CFR) with the variables: IVR = influenza vaccination rate (%) of people aged 65 and older in 2019 or latest available, Long = Longitude of the centroid of the country (°), Latitude of the centroid of the country (°), DUR = Degree of urbanization in 2020, HDI = Human Development Index in 2018, PEP = Percent elder persons in 2019, PD = Population density in 2018, Mask = the requirement degree of using masks in public (with three degrees: none, parts of country, full country), Lockdown = lockdown degree (with three levels: no lockdown, partial lockdown, nationwide lockdown), based on 39 countries worldwide (Tables 13).
rsDPMICFR
Long −0.81 −0.56
IVR 0.49 0.25
DUR 0.32 0.39
Lat (abs) 0.32 0.03
HDI 0.20 0.10
PEP 0.15 0.38
Mask 0.14 −0.01
Lockdown 0.08 0.09
PD −0.07 −0.01
p values    
Long 0 0.0002
IVR 0.0016 0.1275
DUR 0.0436 0.8698
Lat (abs) 0.0451 0.0155
HDI 0.2167 0.5529
PEP 0.3523 0.0174
Mask 0.3819 0.9436
Lockdown 0.6448 0.5980
PD 0.6713 0.9347
DOI: 10.7717/peerj.10112/table-5

Note:

Bold values statistically significant after Bonferroni correction (α = 0.0019).

Unbiased Conditional variables importance ranking to predict COVID-19 deaths per million inhabitant.

Figure 4: Unbiased Conditional variables importance ranking to predict COVID-19 deaths per million inhabitant.

Unbiased conditional variables importance ranking (%) to predict COVID-19 deaths per million inhabitants using the package “party” and the non-parametric random forest function “cforest” in the software R; IVR = influenza vaccination rate, Long = centroid longitude (°), Lat = centroid latitude (°), DUR = degree of urbanization in 2020, HDI = Human Development Index in 2018, PEP = percent of elder people in 2019, PD = population density in 2018, mask = the requirement degree of using masks in public (with three degrees: none, parts of country, full country), lockdown = lockdown degree (with three levels: no lockdown, partial lockdown, nationwide lockdown) of each country, at worldwide level (39 countries studied).
Conditional variables importance ranking to predict COVID-19 Case Fatality Ratio.

Figure 5: Conditional variables importance ranking to predict COVID-19 Case Fatality Ratio.

Unbiased conditional variables importance ranking (%) to predict COVID-19 Case Fatality Ratio using the package “party” and the non-parametric random forest function “cforest” in the software R; IVR = influenza vaccination rate, Long = centroid longitude (°), Lat = centroid latitude (°), DUR = degree of urbanization in 2020, HDI = Human Development Index in 2018, PEP = percent of elder people in 2019, PD = population density in 2018, mask = the requirement degree of using masks in public (with three degrees: none, parts of country, full country), lockdown = lockdown degree (with three levels: no lockdown, partial lockdown, nationwide lockdown) of each country, at worldwide level (39 countries studied).

Discussion

Conclusions

Additional Information and Declarations

Competing Interests

Christian Wehenkel is an Academic Editor for PeerJ.

Author Contributions

Christian Wehenkel conceived and designed the experiments, performed the experiments, analyzed the data, prepared figures and/or tables, authored and reviewed drafts of the paper, and approved the final draft.

Data Availability

The following information was supplied regarding data availability:

The raw data is available in Tables 13.

Funding

The author received no funding for this work.

 

Acknowledgements

 
 

I am grateful to María del Socorro González-Elizondo and José Ciro Hernández-Díaz for their comments on the manuscript, and to Dr. Daniela Marín-Hernández and an anonymous reviewer for their careful review and insightful comments.

 

References