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Could a good night's sleep improve COVID-19 vaccine efficacy?

2021; Elsevier BV; Volume: 9; Issue: 5 Linguagem: Inglês

10.1016/s2213-2600(21)00126-0

2213-2619

Christian Benedict, Jonathan Cedernaes,

Long-Term Effects of COVID-19

More than 2 million people have died from COVID-19, caused by SARS-CoV-2.1Wu A Peng Y Huang B et al.Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China.Cell Host Microbe. 2020; 27: 325-328Summary Full Text Full Text PDF PubMed Scopus (1636) Google Scholar In an unprecedented effort to develop vaccines to control the COVID-19 pandemic, mRNA, protein subunit, and viral vector-based vaccines have been developed within an extraordinarily swift timeframe. However, the efficacy of these vaccines (ie, their ability to reduce the incidence of severe disease and death from COVID-19) can vary considerably. For example, among 43 448 adults, the efficacy of the mRNA-based COVID-19 vaccine produced by Pfizer and BioNTech ranged between 29·5% and 68·4% against symptomatic COVID-19 after the first dose, and between 90·3 and 97·6% after the second dose.2Polack FP Thomas SJ Kitchin N et al.Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.N Engl J Med. 2020; 383: 2603-2615Crossref PubMed Scopus (9498) Google Scholar By comparison, in an interim analysis of ongoing clinical trials (involving 23 484 participants), the corresponding efficacy of two standard doses of the ChAdOx1 nCoV-19 adenovirus vector vaccine produced by AstraZeneca ranged between 41·0% and 75·2%.3Voysey M Clemens SAC Madhi SA et al.Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.Lancet. 2021; 397: 99-111Summary Full Text Full Text PDF PubMed Scopus (3260) Google Scholar Although data from phase 3 trials indicate that factors such as age and biological sex might not be as prominent in modulating the efficacy of certain COVID-19 vaccines (eg, in case of the mRNA-based COVID-19 vaccine produced by Pfizer and BioNTech),2Polack FP Thomas SJ Kitchin N et al.Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.N Engl J Med. 2020; 383: 2603-2615Crossref PubMed Scopus (9498) Google Scholar 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 (figure). For instance, 10 days after vaccination against the seasonal influenza virus (1996–97), IgG antibody titres in individuals who were immunised after four consecutive nights of sleep restricted to 4 h were less than half of those measured in individuals without such sleep deficits.4Spiegel K Sheridan JF Van Cauter E Effect of sleep deprivation on response to immunization.JAMA. 2002; 288: 1471-1472Crossref PubMed Scopus (426) Google Scholar Similarly, shorter actigraphy-based sleep duration was associated with a lower secondary antibody response to hepatitis B vaccination.5Prather AA Hall M Fury JM et al.Sleep and antibody response to hepatitis B vaccination.Sleep. 2012; 35: 1063-1069PubMed Google Scholar Sleep might also 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 helper cells, which are known to play a prominent role in host-protective immune responses.6Lange T Dimitrov S Bollinger T Diekelmann S Born J Sleep after vaccination boosts immunological memory.J Immunol. 2011; 187: 283-290Crossref PubMed Scopus (133) Google Scholar Interestingly, in individuals who slept the night after the first vaccination, the increase in the fraction of interferon-γ (IFN-γ)-positive immune cells at weeks 0–8 was significantly more pronounced than in those who had stayed awake on that night.6Lange T Dimitrov S Bollinger T Diekelmann S Born J Sleep after vaccination boosts immunological memory.J Immunol. 2011; 187: 283-290Crossref PubMed Scopus (133) Google Scholar IFN-γ directly inhibits viral replication and activates immune responses to eliminate viruses, thus protecting the host against virus-induced pathogenesis and lethality.7Presti RM Pollock JL Dal Canto AJ O'Guin AK Virgin 4th, HW Interferon gamma regulates acute and latent murine cytomegalovirus infection and chronic disease of the great vessels.J Exp Med. 1998; 188: 577-588Crossref PubMed Scopus (194) Google Scholar Further emphasising the importance of sleep in the fight against viral pandemics, 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.8Benedict C Brytting M Markström A Broman JE Schiöth HB Acute sleep deprivation has no lasting effects on the human antibody titer response following a novel influenza A H1N1 virus vaccination.BMC Immunol. 2012; 13: 1Crossref PubMed Scopus (67) Google Scholar Finally, nocturnal sleep has been shown to promote a cytokine milieu supporting adaptive cellular immune responses, such as decreased activity of the anti-inflammatory cytokine interleukin-10 and increased activity of the pro-inflammatory cytokine interleukin-12.9Lange T Dimitrov S Fehm HL Westermann J Born J Shift of monocyte function toward cellular immunity during sleep.Arch Intern Med. 2006; 166: 1695-1700Crossref PubMed Scopus (125) Google Scholar Although these data suggest that extending sleep duration at the time of vaccination can boost host immune responses, there is no evidence indicating that sleep quality and moderate-to-severe obstructive sleep apnoea are related to antibody responses to vaccination against viruses.5Prather AA Hall M Fury JM et al.Sleep and antibody response to hepatitis B vaccination.Sleep. 2012; 35: 1063-1069PubMed Google Scholar, 10Dopp JM Wiegert NA Moran JJ Muller D Weber S Hayney MS Humoral immune responses to influenza vaccination in patients with obstructive sleep apnea.Pharmacotherapy. 2007; 27: 1483-1489Crossref PubMed Scopus (19) Google Scholar, 11Prather AA Pressman SD Miller GE Cohen S Temporal links between self-reported sleep and antibody responses to the influenza vaccine.Int J Behav Med. 2021; 28: 151-158Crossref PubMed Scopus (39) Google Scholar Whether reduced antibody production due to sleep loss can impact vaccine efficacy remains largely undetermined. In one study investigating the impact of acute sleep loss in the night following vaccination against hepatitis A in healthy young adults, a small subsample of individuals failed to reach the clinically significant antibody level at week 20—the threshold for an additional vaccination.6Lange T Dimitrov S Bollinger T Diekelmann S Born J Sleep after vaccination boosts immunological memory.J Immunol. 2011; 187: 283-290Crossref PubMed Scopus (133) Google Scholar For most healthy people, sleep loss in the night after vaccination might be of minor concern with respect to the vaccine's efficacy. However, among those whose immune systems' ability to fight infectious diseases is compromised or absent (eg, immunosuppressed individuals), 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. Furthermore, emerging variants of SARS-CoV-2 might modulate vaccine efficacy against COVID-19. In particular, mutations found in the variant B.1.351 might reduce vaccine-derived neutralisation of SARS-CoV-2 by the mRNA vaccines by about threefold to sixfold.12Liu Y Liu J Xia H et al.Neutralizing activity of BNT162b2-elicited serum—preliminary report.N Engl J Med. 2021; (published online Feb 17.)https://doi.org/10.1056/nejmc2102017Crossref Scopus (390) Google Scholar In this context, the difference in antibody levels, due to differences in sleep duration in the night after vaccination, might become clinically more significant. Encouragingly, for some individuals, sleep duration might even have increased during the COVID-19 pandemic, possibly as a result of greater work flexibility that enables improved daily activities with individual sleep–wake preferences.13Blume C Schmidt MH Cajochen C Effects of the COVID-19 lockdown on human sleep and rest-activity rhythms.Curr Biol. 2020; 30: R795-R797Summary Full Text Full Text PDF PubMed Scopus (216) Google Scholar Since the immune system exhibits marked circadian rhythmicity,14Druzd D Matveeva O Ince L et al.Lymphocyte circadian clocks control lymph node trafficking and adaptive immune responses.Immunity. 2017; 46: 120-132Summary Full Text Full Text PDF PubMed Scopus (289) Google Scholar the timing of vaccination might also affect the immune response to COVID-19 vaccines. For instance, one study found that administering hepatitis A and influenza vaccines in the morning instead of the afternoon results in an almost twofold higher antibody titre 4 weeks later, an effect only seen in men.15Phillips AC Gallagher S Carroll D Drayson M Preliminary evidence that morning vaccination is associated with an enhanced antibody response in men.Psychophysiology. 2008; 45: 663-666Crossref PubMed Scopus (62) Google Scholar Thus, it is possible that administering COVID-19 vaccines in the morning might result in higher antibody titres. However, several uncertainties remain, such as how to determine the appropriate time of vaccination for night-shift workers. This group often has chronic circadian disruption and exhibits a markedly greater risk of COVID-19 diagnosis.16Rizza S Coppeta L Grelli S et al.High body mass index and night shift work are associated with COVID-19 in health care workers.J Endocrinol Invest. 2020; (published online Aug 27.)https://doi.org/10.1007/s40618-020-01397-0Crossref Scopus (43) Google Scholar Given the urgency of achieving effective global COVID-19 vaccination, we strongly advocate gathering information about individuals' sleep patterns preceding and following vaccination, as well as information about vaccination timing. Combined with data such as baseline serostatus, possible re-infections, work schedules, and comorbidities, monitoring of sleep and the timing of vaccination could provide more conclusive information for public health agencies, health-care providers, patients, and vaccine developers about the importance of these factors for optimising vaccine efficacy. We declare no competing interests.