Analgesia and COVID-19
William F Laughey, Imran Lodhi, Olutoba Sanni, Graham Pennick, Bruce Charlesworth
Dear editor,
In their comprehensive review of immunomodulatory effects of opioids and analgesics, Abdel Shaheed et al. report research indicating that some NSAIDs demonstrate in vitro and in vivo anti-viral activity against SARS-CoV-2, focussing particularly on indomethacin1. They point out that ibuprofen has not shown such activity, citing the work of Chen et al2. However, more recent in vitro research in Caco-2 cells indicates that ibuprofen does indeed suppress SARS-CoV-2 viral load3, albeit only at higher concentrations than those tested by Chen at al2. Flurbiprofen has similar anti-viral activity at higher concentrations3. The emerging evidence base for NSAIDs demonstrating in vitro anti-SARS-CoV-2 activity now includes indomethacin1, naproxen4, flurbiprofen3 and ibuprofen3.
The review also considers controversies surrounding immunisation and whether the use of analgesics to treat post-vaccination symptoms adversely affects immunogenicity. This is particularly relevant in the present context of COVID-19 and concerns over vaccine hesitancy.
For vaccinations in general, Saleh et al. note observational studies are reassuring and ‘that only few RCTS demonstrated blunted antibody response of unknown clinical significance.5 The authors suggest that timing of medication is paramount. In all studies reporting a negative effect on antibody response, medications were given prophylactically, before vaccination, rather than the more common practice of using medication after vaccination if required5.
The emerging evidence in COVID-19 immunisation is also reassuring. In trials of the Oxford/AZ vaccine, a protocol amendment meant two of the five sites allowed prophylactic paracetamol to be administered before vaccination6. This significantly reduced adverse effects of the vaccine without compromising immunogenicity based on antibody titres6. A recent review by Ooi et al. 7 considers data from the Pfizer/BioNTech and Jansen/J&J trials in which analgesics and antipyretics were permitted, if needed, post-vaccination. Whilst younger participants were more likely to need medication than older participants, vaccine efficacy remained stable across age groups7. Furthermore, the fact that up to one-fifth of patients required analgesia did not prevent these vaccines from demonstrating remarkable efficacy7.
Whilst further research, particularly into cell mediated mechanisms, is required, current evidence supports the short-term use of analgesics after COVID vaccination7. As Omicron is currently surging in several countries, vaccination will continue to play a key role in limiting morbidity and mortality. Measures which reduce vaccine hesitancy – including the availability of effective post-vaccination symptom relief – have significant implications for public health.