Public Health Intervention Framework for Reviving Economy (2): Use of Personalized Measures Beyond the Epidemiological Model Limits

Jianqing Wu, Ping Zha


We previously proposed a public intervention framework concept that would allow people to resume personal and economic activities. We showed that intervention measures are used in a quantitative scale to reduce transmission probabilities and disease severity. In this article, we systematically examine the origin, assumptions, performance and limitations of epidemiological models from different angles used in published researches. We found that nearly all model assumptions fail to hold or are remote from reality; R0 is a variable depending on a large number of factors or has no utility in guiding treatment options; personalized intervention measures are vitally important due COVID-19 transmission characteristics, but current epidemiological models are unable to accurately assess the true benefits of personalized intervention measures. We found that poor performance of the models are attributed to flawed assumption that health/disease properties can be treated as transferable properties. The flaw creates a fiction that disease properties such as infection probabilities and death risks can be transferred from any vulnerable person to any other person in the population, and thus severely limits societal ability to fight the pandemic. We finally show that the benefits of personalized mitigation measures could be determined directly by using variable Ri values for infected persons (or nodes) together with assessment of death rate and disability rate; the attempt of avoiding the disease by defeating all potential transmission probabilities is unrealistic; but mitigating disease severity for specific persons is more feasible and reliable. A most reliable strategy for reviving economy should include personalized protective and mitigation measures for improving personal health.

Full Text:



Wu, JQ, and Zha P. Public Health Intervention Framework for Reviving Economy Amid the COVID-19 Pandemic (1): A Concept. Preprint ( 2019 Available from

b. Wu J, Zha P. Clinical Trials and Reductionist Approach Preclude Cures for Chronic Diseases Due to Flawed Presumptions. Preprints 2020, 2020090572 Doi: 10.20944/preprints202009.0572.v1.

Heesterbeek JAP. A brief history of R0 and a recipe for its calculation. Acta Biotheor. 2002;50:189–204.

MacDonald G. The analysis of equilibrium in malaria. Trop Dis Bull. 1952;49:813–29.

MacDonald G. The epidemiology and control of malaria. London: Oxford University Press;1957.

Fine PEM. Herd immunity: history, theory, practice. Epidemiol Rev. 1993;15:265–302.

Dietz K. The estimation of the basic reproduction number for infectious diseases. Stat Methods Med Res.1993;2:23–41.

Diekmann O, Heesterbeek JAP, Metz JAJ. On the definition and the computation of the basic reproduction ratio R0 in models for infectious diseases in heterogeneous populations. J Math Biol. 1990;28:365–82.

Li J, Blakeley D, Smith RJ. The failure of R0. Comput Math Methods Med. 2011;2011:527610.

CDC, Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) — United States, February 12–March 16, 2020. The report was posted online on March 18, 2020 as an MMWR Early Release. Weekly/March 26, 2020/69(12);343-346.

Verity R, Okell LC, Dorigatti I et al. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infect Dis 2020. Published Online March 30, 2020. Available from

Devine M. Another blow dealt to public faith in scientific models: Devine. Apil 25, 2020. Available from

Pennisi E. The human genome. Science. February 2001;291 (5507): 1177–80.

Misteli T. Beyond the sequence: cellular organization of genome function. Cell. February 2007;128 (4): 787–800.

Bernstein BE, Meissner A, Lander ES. The mammalian epigenome. Cell. February, 2007;128 (4): 669–81.

Segerstrom SC, Miller GE. Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychol Bull. 2004 Jul;130(4):601–30.

Steptoe A, Hamer M, Chida Y. The effects of acute psychological stress on circulating inflammatory factors in humans: a review and meta-analysis. Brain Behav Immun. 2007 Oct;21(7):901–12.

McCann SM. Neuroimmunomodulation: Molecular aspects, integrative systems, and clinical advances. Ann N Y Acad Sci, 840,1-1998 May 1.

Dhabhar FS. Effects of stress on immune function: the good, the bad, and the beautiful. Immunol Res. 2014 May;58(2-3):193–210.

Webster Marketon JI, Glaser R. Stress hormones and immune function. Cell Immunol. 2008 Mar-Apr;252(1-2):16–26.

Allen AP, Kennedy PJ, Cryan JF, Dinan TG, Clarke G. Biological and psychological markers of stress in humans: focus on the Trier Social Stress Test. Neurosci Biobehav Rev. 2014 Jan;38:94–124.

Bakunina N, Pariante CM, Zunszain PA. Immune mechanisms linked to depression via oxidative stress and neuroprogression. Immunology. 2015 Mar; 144(3): 365–373.

Hu D, Wan L, Chen M, Caudle Y, LeSage G, Li Q, Yin D. Essential role of IL-10/STAT3 in chronic stress-induced immune suppression. Brain Behav Immun. 2014 Feb; 36:118–127.

Cohen S, Janicki-Deverts D, Doyle WJ, Miller GE, Frank E, Rabin BS, et al. Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk. Proc Natl Acad Sci USA. 2012 Apr;109(16):5995–9.

Schakel L, Veldhuijzen DS, Crompvoets PI, et al. Effectiveness of Stress-Reducing Interventions on the Response to Challenges to the Immune System: A Meta-Analytic Review. Published online 2019 Aug 6. doi: 10.1159/000501645: 10.1159/000501645

Cross J, Emotional expression in cancer onset and progression, Soc. Sci. Med. Vol. 28. No. 12 pp. 1239-1248, 1989.

Moreno-Smith M, Lutgendorf SK, Sood AK. Impact of stress on cancer metastasis. Future Oncology 2010;6(12):1863-1881.

Sloan EK, Priceman SJ, Cox BF, et al. The sympathetic nervous system induces a metastatic switch in primary breast cancer. Cancer Research 2010;70(18):7042-7052.

Lutgendorf SK, Sood AK, Anderson B, et al. Social support, psychological distress, and natural killer cell activity in ovarian cancer. Journal of Clinical Oncology 2005;23(28):7105-7113.

Lutgendorf SK, DeGeest K, Dahmoush L, et al. Social isolation is associated with elevated tumor norepinephrine in ovarian carcinoma patients. Brain, Behavior, and Immunity 2011;25(2):250-255.

Brydon L, Magid K, Steptoe A. Platelets, coronary heart disease, and stress. Brain Behav Immun (2006) 20: 113–119.

Sundquist J, Li X, Johansson SE, Sundquist K. Depression as a predictor of hospitalization due to coronary heart disease. Am J Prev Med (2005) 29: 428–433.

Kiecolt-Glaser JK, Marucha PT, Malarkey WB, Mercado AM, Glaser R (1995) Slowing of wound healing by psychological stress. Lancet 346: 1194–1196.

Walburn J, Vedhara K, Hankins M, Rixon L, Weinman J. Psychological stress and wound healing in humans: a systematic review and meta-analysis. J Psychosom Res. 2009 Sep;67(3):253–71.

Kiecolt-Glaser JK, Preacher KJ, MacCallum RC, Atkinson C, Malarkey WB, Glaser R (2003). Chronic stress and age-related increases in the proinflammatory cytokine IL-6. Proc Natl Acad Sci USA 100: 9090–9095.

Pedersen AF, Zachariae R, Bovbjerg DH. Psychological stress and antibody response to influenza vaccination: a meta-analysis. Brain Behav Immun. 2009 May;23(4):427–33.

Pedersen A, Zachariae R, Bovbjerg DH. Influence of psychological stress on upper respiratory infection—a meta-analysis of prospective studies. Psychosom Med. 2010 Oct;72(8):823–32.

Hawryluck L, Gold WL, Robinson S, Pogorski S. Galea S, Styra R. SARS Control and Psychological Effects of Quarantine, Toronto, Canada. Emerg Infect Disv. 10(7); 2004 Jul;10(7),1206-12.

Peña J, Chen-Harris H, Allen JE, et al. Sendai virus intra-host population dynamics and host immunocompetence influence viral virulence during in vivo passage. Virus Evol. 2016 Jan; 2(1): vew008.

Monteiro R, Azevedo I. Chronic Inflammation in Obesity and the Metabolic Syndrome, Mediators of Inflammation, 2010, pii:289645.

Nieman DC, Henson DA, Nehlsen-Cannarella SL, et al. Influence of Obesity on Immune Function, Journal of the American Dietetic Association, 1999; 99: 294–9.

Kanneganti TD, Dixit VD. Immunological Complications of Obesity, Nat Immunol, 2012;13:707–12.

Smith AG, Sheridan PA, Harp JB, et al. Diet-Induced Obese Mice have Increased Mortality and Altered Immune Responses when Infected with Influenza Virus, Journal of Nutrition, 2007;37:1236–43.

Levander OA. Nutrition and Newly Emerging Viral Diseases: An Overview, Journal of Nutrition, 1997;127: 948S–50S.

Beck MA, Williams-Toone D, Levander OA. Coxsackievirus B3-Resistant Mice Become Susceptible in Se/Vitamin E Deficiency, Free Radical Biology and Medicine, 2003;34:1263–70.

Beck MA. Selenium and Vitamin E Status: Impact on Viral Pathogenicity, Journal of Nutrition, 2007;137: 1338–40.

Beck MA, Handy J, Levander OA. Host Nutritional Status: The Neglected Virulence Factor, Trends in Microbiology, 2004;12:417–23.

Beck MA, Levander OA, Handy J. Selenium Deficiency and Viral Infection, Jourrnal of Nutrition, 2003;133: 1463S–7S.

Beck MA, Nelson HK, Shi Q, et al. () Selenium Deficiency Increases the Pathology of an Influenza Virus Infection, The FASEB Journal 2001;15: 1481–3.

Nelson HK, Shi Q, Van Dael P, et al. Host Nutritional Selenium Status as a Driving Force for Influenza Virus Mutations, The FASEB Journal, 2001; 15: 1846–8. 10.1096/fj. 01-0115fje.

Alice M, Tang ES, Semba RD. Nutrition and Infection, in: Kenrad E., Nelson CMW, editors. (edn.) Infectious Disease Epidemiology: Theory and Practice, 3rd eds. Burlington, MA: Jones & Bartlett Learning; 2013.

Chandra RK. Nutrition and The Immune System: An Introduction, American Journal of Clinical Nutrition. 1997;66: 460S–3S.

Keusch GT. The History of Nutrition: Malnutrition, Infection and Immunity, Journal of Nutrition.2003;133: 336S–40S.

Ritz BW, Gardner EM. Malnutrition and Energy Restriction Differentially Affect Viral Immunity, Journal of Nutrition. 2006;136:1141–4.

Schaible UE, Kaufmann SH. Malnutrition and Infection: Complex Mechanisms and Global Impacts. PLoS Medicine. 2007;4: e115.

Ogino S, Fuchs CS, Giovannucci E. How many molecular subtypes? Implications of the unique tumor principle in personalized medicine. Expert Rev Mol Diagn. 2012;12(6): 621–8.

Ogino S, Lochhead P, Chan AT, et al. Molecular pathological epidemiology of epigenetics: Emerging integrative science to analyze environment, host, and disease. Mod Pathol. 2013;26(4): 465–84.

Anderson RM. Directly transmitted viral and bacterial infections of man. In: Anderson RM, editor. The population dynamics of infectious diseases: theory and applications. London: Chapman and Hall; 1982. p.1–37.

Guerra FM, Bolotin S, Lim G, Heffernan J, Deeks SL, Li Y, et al. The basic reproduction number (R0) of measles: a systematic review. Lancet Infect Dis. 2017;17:e420–8.

Nishiura H, Chowell G. The effective reproduction number as a prelude to statistical estimation of time-dependent epidemic trends. In: Chowell G, Hyman JM, Bettencourt LMA, Castillo-Chavez C, editors. Mathematical and statistical estimation approaches in epidemiology. Dordrecht (the Netherlands): Springer Netherlands; 2009. p.103–21.

Mercer GN, Glass K, Becker NG. Effective reproduction numbers are commonly overestimated early in a disease outbreak. Stat Med. 2011;30:984–94.

Associated Press. Coronavirus outbreaks like 'wildfire' at US nursing homes under lockdowns: Measures including a ban on visits and daily health screenings of staffers either came too late or were not rigorous enough. Thu 2 Apr 2020. Accessed from

Janney E, MD Coronavirus: Nearly 48 Percent Of Deaths Are In Nursing Homes: Nursing homes are a hot spot for the new coronavirus in Maryland, according to new data provided by the Maryland Department of Health. Apr 29, 2020. Accessed at

Heesterbeek JAP, Dietz K. The concept of R0 in epidemic theory. Stat Neerl. 1996;50:89–110.

Handfield C, Kwock J, and MacLeod AS. Innate Antiviral Immunity in the Skin. Trends Immunol. 2018 April; 39(4): 328–340.

Yoo J-K, Kim TS, Hufford MM, Braciale TJ. Viral infection of the lung: Host response and sequelae. J Allergy Clin Immunol. 2013 December; 132(6): doi:10.1016/j.jaci.2013.06.006.

Nutt, SL, Hodgkin, PD, Tarlinton, DM, Corcoran, LM. The generation of antibody-secreting plasma cells. Nature Reviews Immunology. 2015;15 (3): 160–71.

Park WB, Perera RA, Choe PG, et al. Kinetics of serologic responses to MERS coronavirus infection in humans, South Korea. Emerg. Infect. Dis. 2015;21:2186–2189.

MacLennan, ICM; Toellner, K-M; Cunningham, AF, et al. Extrafollicular antibody responses. Immunological Reviews. 2003,194:8–18.

Shlomchik, MJ, Weisel, F. Germinal center selection and the development of memory B and plasma cells. Immunological Reviews. 2012; 247 (1): 52–63.

Wu, JQ and Zha, P. Treatment Strategies for Reducing Damages to Lungs in Coronavirus and Other Lung Infections. Preprint( February 6, 2020. Available from

Delamater PL, Street EJ, Leslie TF, Yang YT, Jacobsen KH. Complexity of the Basic Reproduction Number (R0). Emerging Infectious Diseases January 2019; Vol. 25, No. 1.

Wu, JQ and Zha, P. Association of COVID-19 Disease Severity with Transmission Routes and Suggested Changes to Community Guidelines. March 13, 2020. Preprint ( Available from

Wu, JQ and Zha, P. Randomized Clinical Trial Is Biased and Invalid In Studying Chronic Diseases, Compared with Multiple Factors Optimization Trial. November 4, 2019. Preprint ( Available from

Ridenhour B, Kowalik JM, Shay DK. Unraveling R0: considerations for public health applications. Am J Public Health. 2014;104: e32–41.

Anderson RM, May RM. Infectious diseases of humans: dynamics and control. Oxford: Oxford University Press; 1991.

Anderson RM. The concept of herd immunity and the design of community-based immunization programmes. Vaccine. 1992;10:928–35.

Plans Rubió P. Is the basic reproductive number (R0) for measles viruses observed in recent outbreaks lower than in the pre-vaccination era? Euro Surveill. 2012;17:22.

Tang B, Wang X, Li Q, et. al. Estimation of the transmission risk of 2019-nCov and its implication for public health interventions. 27 Jan 2020. Preprint ( Available from

Yang Y, Yang M, Shen C, et al. Evaluating the accuracy of different respiratory specimens in the laboratory diagnosis and monitoring the viral shedding of 2019-nCoV infections. medRxiv preprint. Available from doi:

Ma J, Lew L, Jeong-ho L. A third of coronavirus cases may be ‘silent carriers’, classified Chinese data suggests. 22 Mar, 2020. South China Morning Post. Accessed from

Arons MM, Hatfield, KM, Reddy SC, et al. Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility. April 24, 2020. Available from DOI: 10.1056/NEJMoa2008457

Lauer SA, Grantz KH, Bi, Q, et al. The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application. Ann Intern Med. 2020;172(9):577-582. doi:10.7326/M20-0504

Bao L, Deng W, Gao H, et al. Reinfection could not occur in SARS-CoV-2 infected rhesus macaques. March 14, 2020. Preprint at bioRxiv. Available from

Chen D, Xu W, Lei Z, et al. Recurrence of positive SARS-CoV-2 RNA in COVID-19: A case report. Int J Infect Dis. 2020 Apr; 93: 297–299.

Keeling MJ, Grenfell BT. Individual-based perspectives on R0. J Theor Biol. 2000; 203:51–61.

Breban R, Vardavas R, Blower S. Theory versus data: how to calculate R0? PLoS One. 2007;2:e282.

Artalejo JR, Lopez-Herrero MJ. On the exact measure of disease spread in stochastic epidemic models. Bull Math Biol. 2013;75:1031–50.

Khan A, Naveed M, Dur-E-Ahmad M, Imran M. Estimating the basic reproductive ratio for the Ebola outbreak in Liberia and Sierra Leone. Infect Dis Poverty. 2015;4:13.

Roberts M, Heesterbeek H. Bluff your way in epidemic models. Trends Microbiol. 1993;1:343–8.

Bani-Yaghoub M, Gautam R, Shuai Z, van den Driessche P, Ivanek R. Reproduction numbers for infections with free-living pathogens growing in the environment. J Biol Dyn. 2012;6:923–40.

Nishiura H. Correcting the actual reproduction number: a simple method to estimate R0 from early epidemic growth data. Int J Environ Res Public Health. 2010;7:291–302.

Roberts MG. The pluses and minuses of R0. J R Soc Interface. 2007;4:949–61.

Pellis L, Ball F, Trapman P. Reproduction numbers for epidemic models with households and other social structures. I. Definition and calculation of R0. Math Biosci. 2012;235:85–97.

Lloyd-Smith JO, Schreiber SJ, Kopp PE, Getz WM. Superspreading and the effect of individual variation on disease emergence. Nature. 2005;438:355–9.

Howard J, Huang A, Li Z, et al. Face Masks Against COVID-19: An Evidence Review. Preprint ( 12 April 2020. Available from doi:10.20944/preprints202004.0203.v1

Wu, JQ and Zha, P. Mask Is a Double-edged Sword in the Fight Against COVID-19 Pandemic. Preprint ( March 28, 2020. Available from

Johnson R. The 10 epidemics that almost wiped out mankind. Business Insider. 2011 Sep 19. Accessed on May 1, 2020. Available from


  • There are currently no refbacks.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.