Science-informed policy: considerations in support of judicious, circumspect changes to Aotearoa/NZ alert levels during the COVID-19 pandemic

Posted on by

Prof John D Potter (Centre for Public Health Research, Massey University)

There are a number of characteristics of the novel SARS-CoV-2 virus and the COVID-19 pandemic that make deciding when and how to change the rules regarding lock-down and physical distancing less than straightforward. In this very brief commentary, these considerations do not include the pressures from those who are more concerned with the economy than with human individual, whanau, and population health.


It has been clear from the earliest days of the pandemic that this virus is highly infectious, with estimates of the basic reproduction number (R0) of greater than 21,2 (ie, the average infected case will typically infect more than two other people). A tight estimate of R0 is difficult in the absence of a good understanding of the prevalence and incidence of disease but the early rapid spread, the nature and size of clusters, especially in residential facilities and resulting from social functions, and the effectiveness of physical distancing all attest to this high infectivity, even in the absence of an exact measure of R0.

Severity and lethality

Equally obvious from the earliest reports is the lethal nature of the virus, particularly among older individuals and those with existing chronic conditions, including heart disease, diabetes, cancer, etc3-6.

Silent transmission

Infection with SARS-CoV-2 manifests across a very wide spectrum – from individuals who are asymptomatic through increasing severity of disease to a need for critical care and, finally, death. The asymptomatic and mildly affected are clearly, nonetheless, capable of spreading the virus to others7, as also evidenced by the emergence of disease without a clear transmission path8 and by the population pattern of virus mutations. Indeed, the time of early low-symptom infection is probably the period of greatest infectivity (shedding of the virus9-11). Routine screening of asymptomatic pregnant women has been shown to reveal a high proportion of infected individuals; not all of these women eventually showed symptoms12. In a study of virus transmission, He et al concluded that infectivity probably peaked at or before symptom onset and estimated that 44% (95% CI: 25–69%) of secondary cases were infected during the index cases’ presymptomatic stage13.

It is silent transmission, coupled with the highly infective nature of the virus, that makes lifting restrictions on physical distancing and social contacts most problematic. It speaks to the need for a better understanding of the prevalence of infection in asymptomatic individuals, best accomplished by widening testing out from individuals who present with symptoms, as has now begun in some New Zealand centres14. We will eventually know the extent of asymptomatic disease by virtue of establishing retrospectively the immune status of the population, but that does not answer the exigent need to know the prevalence in order to better plan the management of the degree of restriction of non-bubble contact.

Re-emergence of infection?

There are data from China15, Japan16, and South Korea17 attesting to the re-emergence of infection in individuals who were reported to have been COVID-19 positive and, later, negative. One possible explanation is obviously the presence of errors in the testing system18. However, others have asked the question as to whether reinfection can occur19 (which means that immunity is not 100% following infection – see below). A third possibility is reactivation, whereby a virus emerges from a latent state in a host cell and undergoes productive replication and shedding20. This occurs particularly among herpes viruses but is currently under investigation as a possible explanation for the apparent behaviour of SARS-CoV-219. Finally, given the widespread list of SARS-CoV-2 target organs (see below), it seems possible that an individual may harbour the virus (undetected by upper-respiratory testing) in, say, the kidney, which later emerges, for a second time, in the respiratory tract.

Whatever the explanation of apparent reinfection, it identifies yet another source of transmission in the population and, again, argues for a careful approach to lifting physical distancing restrictions.

Target organs

COVID-19 has been largely identified as a respiratory viral disease (and can present with a loss of the sense of smell – anosmia21); indeed, SARS-CoV-2 is most likely to be fatal as a result of its impact on the lungs. Nonetheless, it has been shown to target an extensive list of organs, some of which also contribute to the mortality associated with infection. The immune system (see also below) is central to an elevated risk of mortality as a consequence of a cytokine storm22, a condition (associated with a wide variety of viral infections and auto-immune disorders) in which the immune response is no longer targeting an invading organism but rather acts to induce widespread inflammation and organ damage. The COVID-19 version of the cytokine storm may respond to treatment with an anti-cytokine antibody23,24. The difficulty of establishing, in any individual case, exactly how SARS-CoV-2 is threatening life makes decisions about letting natural immunity control the virus versus suppressing an over-reacting immune system very problematic25. Other organ systems affected by SARS-CoV-2 include the kidney26, the cardiovascular system27-30, the eye31 and the gastrointestinal tract32,33, which can also act as a source of viral spread.

Viral load

The body’s burden of virus – the viral load – is an established risk factor for the severity of viral infections generally, eg, influenza34. This probably provides an explanation for the particular risk of healthcare workers35 who spend many hours in close contact with multiple infected individuals in settings where the virus is airborne and on multiple surfaces36. This particular risk can be mitigated with widespread and well trained use of PPE.

Antibody-dependent enhancement

As already noted, the immune system is not always on our side when it comes to fighting infection, particularly viral infection. It has been known since the 1960s37 that sometimes the immune system acts in a way that facilitates infection in a variety of ways and across a wide spectrum of viral agents. The phenomenon is associated with the development of antibodies that are not neutralising antibodies and that can actually facilitate the subsequent entry of a different but related virus38,39. Known as antibody-dependent enhancement (ADE), its best-known deleterious consequences are described around the development of dengue haemorrhagic fever38,40-43. The list of viruses that are associated with ADE includes the coronavirus that causes feline peritonitis44.

The phenomenon of ADE has not been established for SARS-CoV-2, but it is clear that a cytokine storm can be severe to lethal in COVID-1923. This raises yet more questions to which we do not yet have answers but which, again, give us pause in relation to rapidly changing the rules around physical distancing and lock-down. For example, are asymptomatic and low-symptomatic infection associated with an immune response that does not produce neutralising antibodies and that may lay the groundwork for a subsequent more severe infection? Even more speculatively, is the higher risk in older individuals the result of previous multiple exposures and weak responses to other coronaviruses, perhaps those associated with the common cold? ADE is one of the problems associated with the development of a safe and effective vaccine.

Co-infection with other respiratory viruses

An early report from Wuhan suggested that those infected with SARS-CoV-2 were only rarely co-infected with other respiratory pathogens45. A very recent study from Northern California found that more than 20% of samples that were positive for SARS-CoV-2 were also positive for other respiratory viruses46, suggesting higher rates of co-infection than those previously reported. The Southern Hemisphere is rolling into Winter – colds and influenza season – so it is additionally problematic that establishing the presence of a non–SARS-CoV-2 pathogen provides little reassurance that an individual is not also infected with SARS-CoV-2.


A final problem for population and individual management of COVID-19 is the ubiquity of misinformation — from the US White House, from social media both as a result of ignorance and malice47, and from deliberate campaigns designed to discredit science and the effectiveness of medical practice48. It is not clear whether, as a society, we can ever develop an effective immune response – but we need to work harder at it.

Final thought

Given the complexity of COVID-19, when it comes to establishing policy, it is better to follow those with manifest leadership skills, brightened further by clarity, compassion, and informed counsel, than to follow those with only modest public-health knowledge and even less understanding of infectious disease.


  1. Ferguson NM, Laydon D, Nedjati-Gilani G, et al. Impact of non-pharmaceutical interventions (NPIs) to reduce COVID-19 mortality and healthcare demand 16 March, 2020, 2020. (accessed 18 March, 2020).
  2. Wang Y, Teunis PFM. Strongly heterogeneous transmission of COVID-19 in mainland China: local and regional variation. medRxiv 2020: 2020.03.10.20033852.
  3. Bialek S, Boundy E, Bowen V, et al. Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) — United States, February 12–March 16, 2020. MMWR Morbidity and Mortality Weekly Report 2020; 69(12).
  4. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395(10223): 497-506.
  5. Xie J, Tong Z, Guan X, Du B, Qiu H. Clinical Characteristics of Patients Who Died of Coronavirus Disease 2019 in China. JAMA Network Open 2020; 3(4): e205619-e.
  6. Guan WJ, Ni ZY, Hu Y, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med 2020.
  7. National Academies of Sciences Engineering and Medicine. Rapid Expert Consultation on SARS-CoV-2 Viral Shedding and Antibody Response for the COVID-19 Pandemic (April 8, 2020). Washington, DC: The National Academies Press, 2020.
  8. Li R, Pei S, Chen B, et al. Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV2). Science 2020: eabb3221.
  9. Zou L, Ruan F, Huang M, et al. SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. N Engl J Med 2020; 382(12): 1177-9.
  10. To KK-W, Tsang OT-Y, Leung W-S, et al. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. The Lancet Infectious Diseases 2020.
  11. Wolfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with COVID-2019. Nature 2020.
  12. Breslin N, Baptiste C, Gyamfi-Bannerman C, et al. COVID-19 infection among asymptomatic and symptomatic pregnant women: Two weeks of confirmed presentations to an affiliated pair of New York City hospitals. American Journal of Obstetrics & Gynecology MFM 2020: 100118.
  13. He X, Lau EHY, Wu P, et al. Temporal dynamics in viral shedding and transmissibility of COVID-19. Nat Med 2020: doi: 10.1038/s41591-020-0869-5.
  14. Hayward M. Coronavirus: First random Covid-19 tests conducted as screening ramps up. Stuff, 19:59, Apr 16 2020, 2020. (accessed.
  15. Ye G, Pan Z, Pan Y, et al. Clinical characteristics of severe acute respiratory syndrome coronavirus 2 reactivation. J Infect 2020.
  16. DeGregorio E. Questions raised over COVID-19 reinfection after Japanese woman develops illness again. Japan Times. 2020 2020/02/28.
  17. Hyun-ju O. 91 recovered COVID-19 patients test positive again: KCDC. Korea Herald, Apr 10, 2020 – 18:05, 2020. (accessed April 11, 2020).
  18. Hu E. COVID-19 Testing: Challenges, Limitations and Suggestions for Improvement. Preprints 2020; 2020040155.
  19. Lipsitch M. Who Is Immune to the Coronavirus? New York Times. 2020 April 13, 2020.
  20. Traylen CM, Patel HR, Fondaw W, et al. Virus reactivation: a panoramic view in human infections. Future Virol 2011; 6(4): 451-63.
  21. Hopkins C, Kumar N. Loss of sense of smell as marker of COVID-19 infection.
  22. Behrens EM. Cytokines in Cytokine Storm Syndrome. In: Cron RQ, Behrens EM, eds. Cytokine Storm Syndrome. Cham: Springer International Publishing; 2019: 197-207.
  23. Zhang C, Wu Z, Li J-W, Zhao H, Wang G-Q. The cytokine release syndrome (CRS) of severe COVID-19 and Interleukin-6 receptor (IL-6R) antagonist Tocilizumab may be the key to reduce the mortality. International Journal of Antimicrobial Agents 2020: 105954.
  24. Xu X, Han M, Li T, al e. Effective Treatment of Severe COVID-19 Patients with Tocilizumab. ChinaXiv 2020: 202003.00026v1.
  25. Ledford H. How does COVID-19 kill? Uncertainty is hampering doctors’ ability to choose treatments. Nature 2020; 580(7803): 311-2.
  26. Su H, Yang M, Wan C, et al. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney International 2020.
  27. Shi S, Qin M, Shen B, et al. Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. JAMA Cardiology 2020.
  28. Zhou B, She J, Wang Y, Ma X. The Clinical Characteristics of Myocardial injury 1 in Severe and Very Severe Patients with 2019 Novel Coronavirus Disease. J Infect 2020.
  29. Clerkin KJ, Fried JA, Raikhelkar J, et al. Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease. Circulation 2020; 0(0).
  30. Cui S, Chen S, Li X, Liu S, Wang F. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost 2020; n/a(n/a).
  31. Chen L, Liu M, Zhang Z, et al. Ocular manifestations of a hospitalised patient with confirmed 2019 novel coronavirus disease. Br J Ophthalmol 2020: bjophthalmol-2020-316304.
  32. Tian Y, Rong L, Nian W, He Y. Review article: gastrointestinal features in COVID-19 and the possibility of faecal transmission. Aliment Pharmacol Ther 2020; 51(9): 843-51.
  33. Du M, Cai G, Chen F, Christiani DC, Zhang Z, Wang M. Multi-omics Evaluation of Gastrointestinal and Other Clinical Characteristics of SARS-CoV-2 and COVID-19. Gastroenterology 2020.
  34. Yu L, Wang Z, Chen Y, et al. Clinical, Virological, and Histopathological Manifestations of Fatal Human Infections by Avian Influenza A(H7N9) Virus. Clinical Infectious Diseases 2013; 57(10): 1449-57.
  35. Zhan M, Qin Y, Xue X, Zhu S. Death from Covid-19 of 23 Health Care Workers in China. New England Journal of Medicine 2020.
  36. van Doremalen N, Bushmaker T, Morris DH, et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. N Engl J Med 2020; 382(16): 1564-7.
  37. Hawkes RA. Enhancement of the Infectivity of Arboviruses by Specific Antisera Produced in Domestic Fowls. Australian Journal of Experimental Biology and Medical Science 1964; 42(4): 465-82.
  38. Halstead SB, O’Rourke EJ. Dengue viruses and mononuclear phagocytes. I. Infection enhancement by non-neutralizing antibody. J Exp Med 1977; 146(1): 201-17.
  39. Halstead SB. Immune enhancement of viral infection. Prog Allergy 1982; 31: 301-64.
  40. Halstead SB. Observations related to pathogensis of dengue hemorrhagic fever. VI. Hypotheses and discussion. Yale J Biol Med 1970; 42(5): 350-62.
  41. Rothman AL. Immunity to dengue virus: a tale of original antigenic sin and tropical cytokine storms. Nat Rev Immunol 2011; 11(8): 532-43.
  42. Sanyaolu A, Okorie C, Badaru O, et al. Global epidemiology of dengue hemorrhagic fever: An update. Journal of Human Virology & Retrovirology 2017; 5(6): 00179.
  43. Halstead SB, Nimmannitya S, Cohen SN. Observations related to pathogenesis of dengue hemorrhagic fever. IV. Relation of disease severity to antibody response and virus recovered. Yale J Biol Med 1970; 42(5): 311-28.
  44. Hartmann K. Feline infectious peritonitis. Vet Clin North Am Small Anim Pract 2005; 35(1): 39-79, vi.
  45. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020; 395(10223): 507-13.
  46. Kim D, Quinn J, Pinsky B, Shah NH, Brown I. Rates of Co-infection Between SARS-CoV-2 and Other Respiratory Pathogens. JAMA 2020.
  47. Donovan J. Social-media companies must flatten the curve of misinformation. Nature 2020.
  48. Broad WJ. Putin’s Long War Against American Science. New York Times. 2020 April 13, 2020.


This entry was posted in Uncategorized and tagged , , , , , by Nick Wilson. Bookmark the permalink.

Leave a Reply

Your email address will not be published. Required fields are marked *

* *