An interesting commentary published in The Lancet March 12th by Benedict and Cedernaes discusses this issue.  

Within an extraordinarily swift timeframe vaccines to control the COVID-19 pandemic have been developed using either an mRNA protein subunit or viral vector-based vaccine.  

However, the efficacy of these vaccines varies considerably; For example, among 43,448 adults, the efficacy of the mRNA based COVID-19 vaccine produced by Pfizer ranged between 29.5 to 68.4% against symptomatic COVID-19 after the first dose and between 90.3 and 97.6% after the second dose.  

By comparison, the corresponding efficacy of two standard doses of the AstraZeneca vaccine range between 41 and 75.2%.

Although data from phase 3 trials indicate the factors such as age and biological sex might not be as prominent in modulating the efficacy of certain COVID-19 vaccines, the role of sleep in this context is unclear.  

As suggested by previous studies, sleep duration at the time of vaccination against viral infections can affect the immune response.  

For instance. 10 days after vaccination against the seasonal influenza virus in 1996 to 1997, IgG antibody titres in individuals who were immunised after four consecutive nights of sleep restricted to four hours were less than half of those measured in individuals without such sleep deficits.  

Similarly, shorter based sleep duration was associated with a lower secondary antibody response to hepatitis B vaccination.  

Sleep is also thought to boost aspects of virus specific adaptive cellular immunity.  

Compared to wakefulness, sleep in the night following vaccination against hepatitis A doubled the relative proportion of virus specific T healthy cells, which are known to play a prominent role in host protective immune responses.

Interestingly, in individuals who slept the night after the first vaccination, the increase in the fraction of interferon-γ positive immune cells at weeks 0 to 8 were significantly more pronounced than in those who had stayed awake on that night. 

IFN-γ is known to directly inhibit viral replication and activates immune responses to eliminate viruses, this therefore protects the host against virus induced pathogenesis and lethality.  

Further evidence was found that a lack of sleep in the night after vaccination against the 2009 H1N1 influenza virus was found to reduce the early phase production of H1N1 specific antibodies in men but not women.

It is thought that nocturnal sleep has been shown to promote a cytokine milieu supporting adaptive cellular immune responses.  This encourages an increased activity with the pro inflammatory cytokine interleukin 12 with a decreased activity of the anti-inflammatory cytokine interleukin 10.  

This data suggests that extending sleep duration at the time of vaccination can boost host immune responses.  However, there is no evidence indicating that sleep quality and moderate to severe obstructive sleep apnoea are related to antibody responses to vaccination against viruses.  

Whether reduced antibody production due to sleep loss can impact vaccine efficacy remains largely undetermined. 

One study investigating the impact of acute sleep loss in the night following vaccination against hepatitis A in healthy young adults showed a small sub sample of individuals failed to reach the clinically significant antibody level at week 20.  This was the threshold for an additional vaccination.  

Clearly, for most healthy people, sleep loss in the night after vaccination might be a minor concern with respect to vaccines’ efficacy. 

However, amongst those whose immune systems ability to fight infectious disease is compromised or absent extending sleep duration during the night after the vaccination might help ensure an adequate response to vaccines and potentially contribute to reducing the incidence of severe disease.  

With the emergence of new variants, the difference in antibody levels due to differences in sleep duration in the night after vaccination might become more clinically relevant. 

Encouragingly, for some individuals, sleep duration appears to have increased during the COVID-19 pandemic as a result of greater work flexibility and this has enabled improved daily activities with individuals sleep wake preferences. 

The immune system is known to exhibit marked circadian rhythmicity, and the timing of vaccination might also affect the immune response to COVID-19 vaccines.  

One study found that administering hepatitis A and influenza vaccine in the morning instead of the afternoon resulted in an almost twofold higher antibody titre at four weeks later, but this effect was only seen in men.  

The authors suggest that it is possible that administering COVID-19 vaccines in the morning might result in higher antibody titres.  

However, several uncertainties remain. 

How does one determine the appropriate time for vaccination in nightshift workers?  This group often has chronic circadian disruption and exhibits a markedly greater risk of COVID-19 diagnosis.  

This is clearly an area which needs more research but if possible, it is probable that one should try and have vaccination in the morning rather than in the afternoon and have a good night’s sleep following.  

The London general practice commends the government on achieving a remarkable vaccination rollout and looks forward to the whole of the world’s population being immunised against COVID-19.

Dr Paul Ettlinger

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