Intended for healthcare professionals

Rapid response to:


Covid-19: risk factors for severe disease and death

BMJ 2020; 368 doi: (Published 26 March 2020) Cite this as: BMJ 2020;368:m1198

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Rapid Response:

Is opioid use also a risk factor for Covid-19 disease severity?

Dear Editor,

The pathogenicity of the SARS-Cov 2 virus and the risk factors for disease severity of Covid-19 are still being elucidated amongst different population groups(1). Meanwhile, the Opioid crisis is estimated to cause the deaths of 130 people in the USA per day(2), and opioid prescribing has been rising in many other countries(3). The use of opioids for chronic non-cancer pain is controversial and this has led to the World Health Organization withdrawing its opioid guidelines in 2019(4). As Stannard states, the “US opioid crisis is a story that keeps on giving”(5), and we wonder what effect Covid-19 will have on those members of the population who are using high-dose opioids, especially when the benefits are questionable.

Whilst the benefits may be questionable, the harms are not. The chronic use of high dose of opioids is associated with side effects which may increase disease severity of Covid-19. Opioids definitely interact with the immune system(6) and may decrease immune responses(7). Sleep-disordered breathing is exacerbated by opioids(8) and opioid induced ventilatory impairment is well described in both the post-operative(9) and obese(10) population groups. These opioid effects may point to pathophysiological causes for the increased the risk of pneumonia(7) seen in patients on opioids. Our own anecdotal (non-Covid-19) experience is that patients on high dose opioids are commonly only a severe infection away from opioid toxicity. In addition, opioids and other sedating agents are often weaned and ceased during their intensive care stays.

We acknowledge the importance of patients remaining on opioid agonist treatment in a harm minimisation paradigm(11). However, in some situations (where the patients and their treating clinicians are willing and able) the Covid-19 pandemic may provide further motivation, incentive and opportunity to reflect on opioid prescribing practices given the risks might outweigh the benefits. Opioid use, in our opinion, is modifiable, and by extension a modifiable potential risk factor during the Covid-19 pandemic.

At this point, we must stress that this link between Covid-19 and opioid use is purely speculative, as we were unable to find any published data looking specifically at associations between Covid-19 and opioid use. Given that most early data emerged from China, and given China’s history with opioids, it is unlikely that opioids played a role in disease severity there. However, now that Covid-19 is spreading quickly in Western countries where opioid use is problematic, we feel that collecting this data should be a matter of some urgency. This data may be difficult to collect but it is certainly not impossible in the age of electronic medical records. We therefore call for formal epidemiological studies analysing the relationship between Covid-19 disease severity and opioid use so that we might better stratify patient population risk to guide treatment decisions.

1. Jordan RE, Adab P, Cheng KK. Covid-19: risk factors for severe disease and death. BMJ [Internet]. 2020 Mar 26 [cited 2020 Apr 3];368. Available from:
2. NIDA, National Institute on Drug Abuse. Opioid Overdose Crisis [Internet]. 2019 [cited 2019 May 12]. Available from:
3. Smith BH, Fletcher EH, Colvin LA. Opioid prescribing is rising in many countries. BMJ [Internet]. 2019 Oct 17 [cited 2020 Apr 4];367. Available from:
4. Dyer O. WHO retracts opioid guidelines after accepting that industry had an influence. BMJ [Internet]. 2020 Jan 10 [cited 2020 Apr 3];368. Available from:
5. Stannard C. Tramadol is not ‘opioid-lite’. BMJ [Internet]. 2019 May 14 [cited 2020 Apr 3];365. Available from:
6. Sacerdote P. Opioids and the immune system. Palliat Med. 2006 Jan 1;20(8_suppl):9–15.
7. Plein LM, Rittner HL. Opioids and the immune system – friend or foe. Br J Pharmacol. 2018 Jul 1;175(14):2717–25.
8. Grote L. Drug-Induced Sleep-Disordered Breathing and Ventilatory Impairment. Sleep Med Clin. 2018 Jun;13(2):161–8.
9. Gupta K, Prasad A, Nagappa M, Wong J, Abrahamyan L, Chung FF. Risk factors for opioid-induced respiratory depression and failure to rescue: a review. Curr Opin Anaesthesiol. 2018 Feb;31(1):110–9.
10. Raveendran R, Wong J, Chung F. Morbid obesity, sleep apnea, obesity hypoventilation syndrome: Are we sleepwalking into disaster? Perioper Care Oper Room Manag. 2017 Dec 1;9:24–32.
11. Pearce LA, Min JE, Piske M, Zhou H, Homayra F, Slaunwhite A, et al. Opioid agonist treatment and risk of mortality during opioid overdose public health emergency: population based retrospective cohort study. BMJ [Internet]. 2020 Mar 31 [cited 2020 Apr 3];368. Available from:

Competing interests: No competing interests

05 April 2020
Ferghal Armstrong
General practitioner, and Addiction Medicine Registrar
Andrew Y Huang (Anaesthetist and Specialist Pain Medicine Physician | Austin Health | Eastern Health | Dept of Medical Education, University of Melbourne)
Turning Point, Eastern Health
Arnold St, Box Hill