Patients with cancer have a higher risk of severe coronavirus disease (COVID-19) and associated mortality than the general population. Owing to this increased risk, patients with cancer have been prioritized for COVID-19 vaccination globally, for both primary and booster vaccinations. However, given that these patients were not included in the pivotal clinical trials, considerable uncertainty remains regarding vaccine efficacy, and the extent of humoral and cellular immune responses in these patients, as well as the risks of vaccine-related adverse events. In this Review, we summarize the current knowledge generated in studies conducted since COVID-19 vaccines first became available. We also highlight critical points that might affect vaccine efficacy in patients with cancer in the future.
Vaccination against COVID-19 administered according to current prime–boost concepts is both safe and clinically effective in patients with cancer.
To date, no reliable correlate of protection that allows the definite deduction of clinical efficacy from immune responses has been established, either in patients with cancer or in the general population.
Patient-associated factors such as advanced age, haematological malignancy and/or treatment-associated factors such as B cell depletion might all lead to less proficient immune responses following vaccination.
Future research will determine the necessity of further booster regimens as well as therapeutic options for those who do not benefit from active COVID-19 vaccination.
Similar content being viewed by others
Shortly after the emergence of a novel coronavirus towards the end of 2019, the virus was named SARS-CoV-2 by the WHO, and the corresponding disease was termed coronavirus disease (COVID-19)1. COVID-19 has a mild or moderate course in most people without comorbidities, whereas patients with cancer have a much higher risk of severe COVID-19 and associated mortality2. The presence of risk factors that are also relevant to the general population, such as advanced age and/or other comorbidities, can contribute to this increased risk, although active malignancy is an independent risk factor in almost all reports3,4,5. The adverse effects of the malignancy itself on the risk of severe COVID-19 are particularly visible in younger patients with cancer (<65 years of age)3,5. Mortality rates were exceptionally high among patients with active cancer and COVID-19 during the first wave, with mortality rates commonly reported to be around 40%, decreasing to approximately 25% in the following waves in European countries in 2021 (refs3,4,5,6). However, mortality rates are usually reported from hospitalized cohorts; therefore, these rates might be an overestimate for patients with cancer. The incidence of long-term COVID-19 sequelae in patients with cancer is estimated to be 15–30%7,8. Besides the direct effects of the pandemic, cancer-specific mortality was also increased, for example, owing to the need for frequent treatment modifications and reduced screening7.
Prevention of infection and subsequent severe COVID-19 is crucial for patients with cancer, with vaccination being the most effective method of achieving this goal. Fortunately, owing to a concerted global effort, several highly effective vaccines have been developed at an unprecedented speed. In large parts of the world, mass vaccination campaigns have considerably reduced the incidence of severe COVID-19 in the general population after at least two vaccine doses. Owing to the high risk of developing severe COVID-19, patients with cancer were prioritized for vaccination in most countries9. However, these patients were also excluded from the pivotal clinical trials; therefore, important questions concerning the efficacy and safety of currently available vaccines as well as the durability of vaccine responses remain for this population. Owing to disease-associated and therapy-induced impairment of the immune system, these patients are more likely to develop a less proficient immune response upon vaccination.
In this Review, we provide an overview of current knowledge of the effectiveness of COVID-19 vaccines in patients with cancer, the risk factors for a reduced vaccine response, safety and measures that might increase protection. Reflecting the available data, we focus primarily on mRNA vaccines and adenovirus-vectored vaccines, although we also discuss the available data on inactivated virus and protein subunit vaccines. Wherever possible, we attempt to address clinically relevant questions based on the available evidence. However, studies investigating clinical efficacy in patients with cancer are few and are often hampered by a retrospective design and limited granularity of the data. By contrast, studies investigating immune responses are numerous, often prospective and provide high-quality data. From these data, conclusions can be drawn regarding the risks of reduced or absent responses to vaccination. However, how reliable and meaningful these laboratory values are in clinical terms is not entirely clear. This lack of clarity is particularly true for the expected changes in SARS-CoV-2 epidemiology owing to the emergence of novel variants of concern (VOCs).
Effectiveness in the general population
The most widely used vaccines against COVID-19 in high-income countries are mRNA vaccines (BNT162b2 and mRNA-1273) and adenovirus-vectored vaccines (ChAdOx1 nCoV19, Ad26.COV2-S and Gam-COVID-Vac), both of which induce endogenous expression of modified versions of the viral spike protein to elicit immune responses10,11,12,13,14,15,16. More conventional vaccines use inactivated virus (CoronaVac and BBIBP-CorV)17,18 or purified or recombinant viral proteins (NVX-CoV2373)19 plus an adjuvant to promote an effective immune response (Fig. 1). The immune response elicited by vaccines relies strongly on the production of neutralizing antibodies by B cells and ideally also on the induction of memory cells for longer (potentially lifelong) durability20,21. Furthermore, specific T cells can be induced by the available vaccines to varying degrees21; these might persist for >6 months and seem to be less affected by antigenic drift22,23,24. Vaccine-induced immune responses occurred in most participants (>90%) in the trials testing all of the available vaccines10,15,25,26. However, these measures are surrogate end points and should not be viewed as reliable correlates of protection. Importantly, clinical vaccine efficacy (VE) in these trials was defined as self-reported symptomatic laboratory-confirmed COVID-19. This end point clearly underestimates the incidence of asymptomatic infections; therefore the primary end point of these studies is usually prevention of COVID-19 as opposed to prevention of SARS-CoV-2 infection. Usually, VE is quantified as the reduction of the risk ratio for an event, here symptomatic COVID-19, expressed as a percentage compared to the control group11,12,15,18,27,28,29,30. Secondary end points include the reduction in the incidence of severe COVID-19 or COVID-19-associated mortality (Fig. 2; Supplementary information).
The VE of all COVID-19 vaccines appears to decrease within a few months after vaccination. In a large retrospective analysis of data from the UK, the initial VE for BNT162b2 of around 90% after the second dose dropped drastically to <60% after 25 weeks31. In the same study, the VE for ChAdOx1 nCoV19 dropped to around 40%31, and in another study to 42–63% after 20 weeks32. There are two main reasons for these decreases. Firstly, immunity wanes over time, which is most prominent in older individuals33. This effect is typically quantified using the amount of virus-specific antibodies as a surrogate. Secondly, newly emergent VOCs capable of evading immunity to existing SARS-CoV-2 variants can drastically reduce VE31,34. To improve VE, an additional, so-called ‘booster’, dose is given around 6 months after the priming doses, which is an established practice in vaccination against various other infectious diseases. Importantly, the different types of vaccine can be safely combined, and all vaccines appear to increase immunogenicity when administered as boosters35,36,37,38,39,40. However, mRNA vaccines appear to result in higher antibody levels than adenovirus-vectored vaccines when administered as boosters (Fig. 2a). Retrospective data suggest that VE returned to >90% following administration of a booster dose of an mRNA vaccine after approximately 6 months during the predominance of the Delta VOC31.
Variants of concern
Respiratory viruses are known to have high mutation rates, enabling their evolution to increase the extent of transmission between individuals. Adaptive immunity to viruses, induced by either vaccination or natural infection, can create selection pressures resulting in the selection of mutations that enable immune escape from antibodies and T cells. Despite the existence of proofreading mechanisms, SARS-CoV-2 is constantly acquiring mutations and can also diversify through recombination when an individual is simultaneously infected with more than one variant41. Depending on the location, most mutations in the viral genome will not, or will only minimally, affect the course of infection. Nonetheless, a minority of these alterations will provide the virus with a fitness advantage42. Most notably, mutations in the genome encoding the receptor-binding domain (RBD) or the amino terminal domain (NTD) of the spike protein (containing important antigen epitopes) can have implications for VE43,44. For example, one of the earliest identified spike mutations, D614G, increases both the transmissibility and infectivity of SARS-CoV-2. This variant emerged independently in China and Europe, providing evidence of convergent evolution. According to the WHO, SARS-CoV-2 variants are regarded as VOCs if they meet one of the following criteria: (1) increase in transmissibility, (2) increase in virulence, and/or (3) decreased effectiveness of therapeutic and public health measures. To date, five major VOCs have been identified: Alpha, Beta, Gamma, Delta and Omicron. Alpha, Beta and Gamma share the N501Y mutation, which is associated with increased transmissibility45. By contrast, the E484K mutation, identified in Beta and Gamma, is associated with antibody escape46. A number of mutations in Delta also confer immune escape47. The latest VOC, Omicron, originally identified in November 2021, carries several mutations resulting in robust immune escape48. Specifically, this variant harbours 37 amino acid substitutions in the spike protein, of which 15 are in the RBD, thus impairing the effectiveness of available vaccines and monoclonal antibody therapeutic agents, which mostly target this domain44,49,50,51. Not surprisingly, reports on VE in the general population when the Omicron variant is highly prevalent suggest a dramatic reduction in VE after prime vaccination with mRNA vaccines or adenovirus-vectored vaccines31,52.
In addition to immune escape, the mutations present in Omicron have also changed the infectivity of this variant. Omicron still binds ACE2 with similar (or even higher) affinity to other variants53,54, although this variant can no longer facilitate cellular entry via cell fusion, which is dependent on TMPRSS2 (ref.55). These findings might be reflected by a propensity for infection of upper airway cells relative to other variants56, as well as less severe lung pathology in animal models57. Importantly, retrospective clinical data as well as in vitro neutralization data uniformly support an increase in VE against the Omicron VOC following administration of an mRNA vaccine as a third vaccine dose24,31,50,53,58,59.
Correlates of protection
Serology and neutralizing antibodies
In most individuals, neutralizing antibodies develop rapidly after infection with SARS-CoV-2 (ref.60), and high levels of neutralizing activity are associated with rapid clearance of the virus61 and a lower risk of infection62. Most of the available COVID-19 vaccines are specifically directed against the spike protein, whereas infection is likely to induce a broad spectrum of functional and non-functional antibodies against other viral proteins (such as the nucleocapsid). Nonetheless, vaccine-induced antibodies against the spike RBD and NTD have potent SARS-CoV-2-neutralizing activity63,64. Thus far, the available vaccines were all developed to target the ancestral SARS-CoV-2 spike protein. Efficient cross-neutralization against VOCs has been described shortly after vaccination and after three vaccine doses, although a reduction in neutralizing activity specifically against the Beta, Delta and Omicron VOCs is generally observed31,50,52,59,65,66. Positive neutralization against VOCs is defined variably across studies with the lower limit of detection of the assay usually denoted, such measures are not a correlate of protection from either infection or severe COVID-19.
In clinical settings, the most common method of assessing an immune response after infection or vaccination is to measure the extent of antibody-mediated SARS-CoV-2 binding. To support the interpretation of results from different studies and enable international comparisons, binding antibody assays are often calibrated towards an international WHO serum standard, which recommends reporting the SARS-CoV-2 binding activity of antibody titres in SARS-CoV-2 binding-antibody units (BAU) per millilitre. Concentration in BAU per millilitre often serves as an end point in studies investigating vaccine immunogenicity. Up to now, BAU per millilitre against the wild-type spike antigen has correlated well with the extent of virus neutralization, even of VOCs. However, this correlation is less robust for the Omicron variant24, and a higher cut-off of for positivity might be needed to accurately predict neutralizing antibody responses from BAUs53. Furthermore, the correlation between binding antibodies and virus neutralization will be affected by the time of sampling, the extent of maturation of the B cell response, type of vaccine and the inter-assay variability of virus neutralization assays67.
In certain studies investigating breakthrough SARS-CoV-2 infections, including in patients with cancer, levels of virus-specific antibodies were either reduced or undetectable in those with infections68,69, and correlated negatively with viral load70. Moreover, in patients with comorbidities, a trend towards a more severe breakthrough infection with lower antibody levels was observed68. Despite these observations, a specific antibody level defining the correlate of protection is currently unavailable. Reports confirm a high correlation of (neutralizing) antibodies with clinical VE against both the original Wuhan variant and several VOCs, including Beta, Delta and Gamma71,72. However, as described above, a dramatic reduction in neutralization of Omicron by vaccine-induced antibodies has been observed compared to the wild-type strain24,50,53,58. This observation further reduces the reliability of BAU per millilitre as a correlate of protection. Another piece of evidence against the value of antibody binding as a correlate of protection is the consistent finding that men have lower immune responses (Box 1), despite data from a meta-analysis indicating that VE is higher in men than in women (OR 0.67, 95% CI 0.48–0.94)73.
The use of serology as the sole measure of protection might lead to an underestimation of the proportion of protected individuals, specifically when looking into protection against severe disease. For example, studies in the context of influenza infection indicate the importance of T cell-mediated immunity as a correlate of protection in vulnerable populations, such as those >60 years of age74. In addition, T cells recognizing influenza or SARS-CoV-2 antigens are both cross-reactive and are thus less susceptible to waning immunity owing to emerging VOCs43.
In a prospective study, seronegative individuals had a lower burden of H1N1 disease (following infection with the 2009 H1N1 or ‘swine flu’ strain of influenza) if they had pre-existing cross-reactive T cells75. Similarly in experimental influenza, seronegative individuals showed a shorter duration of symptoms and lower disease severity if virus-specific T cells were pre-existing76,77. This observation remains true for T cells specific for another virus strain76. Initial observations regarding COVID-19 suggest a similar phenomenon: patients with X-linked agammaglobulinaemia (who are genetically incapable of producing B cells) can nonetheless clear SARS-CoV-2 infections78. Furthermore, a large retrospective UK cohort study analysing the likelihood of SARS-CoV-2 infection during the second wave showed that those with a prior SARS-CoV-2 infection had a probability of a second infection of 0.9%, while the probability was 4.3% in those without prior SARS-CoV-2 infection. This protective effect was independent of the presence of binding antibodies79.
Currently approved COVID-19 vaccines elicit robust CD4+ and CD8+ T cell responses in trial participants21,22,23. This effect occurs to a similar extent in patients with cancer65,66. However, data correlating vaccine-induced specific T cells with clinical efficacy against COVID-19 remain limited. In one large UK keyworker cohort, T cell response was associated with protection from COVID-19 in participants with moderate serological responses80, and cross-reactive T cells against the SARS-CoV-2 polymerase were protective against SARS-CoV-2 infection in a large cohort of health-care workers81. T cells can be induced by a broad range of epitopes, and are more likely to retain activity against VOCs compared with neutralizing antibody responses. In turn, vaccine-induced T cell responses against VOCs, including Omicron, are largely preserved24,82,83,84.
Vaccination in patients with cancer
Previous clinical experience
Prior to the SARS-CoV-2 pandemic, most vaccination studies in patients with cancer involved vaccines against influenza, pneumococcal infection, hepatitis B or zoster reactivation. For most infections, the clinical benefit of the vaccination had already been established85,86,87,88. Of note, previous experience revealed that patients with cancer benefit from one or more additional vaccine doses. For example, in patients with cancer, two doses of vaccine against seasonal influenza leads to higher immunogenicity than a single dose89,90. Similarly, two doses of vaccine against hepatitis B or herpes zoster91, three doses of vaccine against pneumococcal infection92, three doses of a recombinant subunit zoster vaccine93 and four doses of an inactivated herpes zoster vaccine85,94,95 lead to high seropositivity rates and acceptable levels of protection. This experience supports the idea that patients who are either immunocompromised or immunosuppressed might require more vaccine doses than those who are immunocompetent. Vaccination strategies involving several doses have the additional advantage of being effective regardless of the timing of chemotherapy. Data from one study indicate a reduced response to single-dose influenza vaccination when administered close to chemotherapy, albeit with no reduction in immune response when two vaccine doses were administered89. Similarly, a study testing a recombinant zoster vaccine in patients with cancer demonstrated a better immune response after the first dose of the vaccine if it was administered 1 week prior to the start of the chemotherapy96. However, the overall immune responses after two doses of this vaccine were comparable in the group that received the first dose before chemotherapy and the group that received the first dose during chemotherapy96. In contrast to chemotherapy, most targeted cancer therapies do not seem to interfere with the immune response89,97.
Of note, the above-mentioned studies focused on the antibody responses elicited by vaccines. Fewer studies have also investigated cellular responses to vaccination, but these have often found the cellular response to be more robust than the humoral response93 even in patients who also received B cell-depleting agents95. In terms of clinical efficacy, the cellular response might also be more relevant. For example, one study investigating a recombinant subunit zoster vaccine in patients with haematological malignancies attributed the clinical efficacy of this vaccine (>60%) in patients with B cell non-Hodgkin lymphoma (B-NHL) to a robust T cell response that could be detected in all patients with B-NHL, whereas only 15% had a detectable serological response88. Not surprisingly, targeted therapies seem to have little effect on the cellular response to vaccination97. Regarding safety, no evidence exists that vaccines generally have a different toxicity profile in patients with cancer than in the general population, and even patients receiving immune checkpoint inhibitors at the time of influenza vaccination do not have an increased risk of immune-related adverse events (irAEs)98.
Response to COVID-19 vaccination
Most studies investigating COVID-19 vaccination in patients with cancer only assessed the presence of spike-reactive or RBD-reactive antibodies, although some have additionally performed neutralizing assays, including against VOCs65,66,99,100,101,102. T cell responses have been addressed in fewer studies and often in smaller subsets, and therefore additional research is needed to validate the observed effects. A summary of all studies investigating the immunogenicity of COVID-19 vaccines included in this Review, including end points analysed and number of participants is provided in the Supplementary information.
In general, patients with cancer seem more likely to develop a less proficient immune response following vaccination against COVID-19 than individuals without cancer103,104,105,106,107,108,109,110 (Fig. 2b). The VE of mRNA vaccines against COVID-19 hospitalization in patients with cancer prior to the predominance of the Omicron variant was estimated to be ~75% and thus lower than the 90% in immunocompetent individuals, as described in a real-world study including >89,000 people, of whom >10,000 had cancer111. VE in this study was further reduced with advancing age. In a large US Veterans study including only patients with cancer who received mRNA vaccines, VE was about 60%112. Of note, no further reduction in VE was observed following a high prevalence of the Delta variant (VE pre-Delta 76%, during Delta 79%)111. VE was affected by the timing of cancer therapy and ranged from 54% in patients receiving any therapy (including endocrine therapies, targeted therapies and/or chemotherapy) to 85% in those not treated within the past 6 months. Unfortunately, separate estimates of these effects were not provided for solid and haematological malignancies. A prospective cohort study involving almost seven million vaccinated participants in the UK identified the following as risk factors for COVID-19-related death despite vaccination with two doses: receiving moderate-to-high intensity chemotherapy (HR 3.63–4.3), stem cell transplantation within the past 6 months (HR 2.5), haematological cancer (HR 1.86), and respiratory tract cancer (HR 1.35)113. Two of these studies112,113 included data from patients up to late spring 2021. Therefore, these data include virtually no patients infected with the Delta VOC and are not well placed to consider the effects of waning immunity, both of which are important contributors to declining VE in the general population. Neutralizing responses to VOCs also decrease progressively in patients with cancer65. This observation is in line with reports from individuals without cancer114, although the combined reductions in neutralizing responses owing to VOCs and malignancy can result in substantially reduced VE72. Patients with haematological malignancies are most likely to be affected by this effect. For example, 56% of these patients had detectable antibody titres with neutralizing activity against the ancestral Wuhan strain, whereas only 31% had detectable titres with activity against the Delta variant after two vaccine doses65. Importantly, the percentage of patients with detectable neutralizing responses to VOCs is broadened following booster vaccination115. Initial data on Omicron neutralization in patients with cancer confirm the expected findings deduced from the general population116: the percentage of patients with solid tumours with neutralizing responses against Omicron increased from 47.8% to 88.9% following a third vaccine dose117. In particular, patients with non-small-cell lung cancer have a 79-fold lower neutralizing response to Omicron compared with individuals without cancer after two doses of an mRNA vaccine118. In patients with haematological malignancies, neutralizing antibodies against Omicron are rarely detected after two vaccine doses, although approximately 50% have detectable neutralizing antibodies after a third dose119.
Risk factors affecting vaccine responses in patients with solid tumours
A substantial majority (90–100%) of patients with solid tumours seroconvert after two vaccine doses, and data from several studies suggest that antibody titres are either comparable to those in individuals without cancer65,66,120 or reduced107,110,121. A meta-analysis of data from four studies including fully vaccinated patients with solid tumours108 found a reduced seroconversion rate relative to those without cancer (risk ratio 0.95, 95% CI 0.92–0.99). Differences in seroconversion between patients with solid tumours and those without cancer are probably moderate and/or restricted to specific subgroups. Therefore, such differences might not be detected in individual studies, highlighting the need for ongoing systematic meta-analyses to precisely define the at-risk groups among patients with solid tumours. Moreover, risk factors for reduced seroconversion in patients with solid tumours at least partially overlap with those of the general population, including older age65, male sex99 and vaccine type65,120 (Box 1). Differences in antibody response depending on the vaccine administered largely resemble the differences seen in the general population (that is, mRNA vaccines are more effective than adenovirus-vectored vaccines65,120, and within the mRNA vaccines, mRNA-1273 is more effective than BNT162b2 (refs111,122)). No data are available on the performance of other types of vaccine compared with mRNA or adenovirus-vectored vaccines.
Several cancer therapies are known to impair vaccine-induced immune responses (Box 2). Recent chemotherapy (defined variably as receiving chemotherapy from within 28 days to within 6 months of vaccination) has been repeatedly identified as a risk factor for lower seroconversion and neutralizing responses, although not in all studies65, which is in line with the reported reduction in VE in this population112. Importantly, the timing of the vaccination with regard to the schedule of ongoing chemotherapy does not seem to affect seroconversion100,120, which is consistent with prior experience with double-dose influenza vaccination89. Many centres therefore avoid administering vaccines and chemotherapy on the same day to minimize the risks of overlapping acute adverse effects, but do not reschedule cancer therapies. While the extent of seroconversion is generally high among patients receiving immune checkpoint inhibitors, 7% of these patients have a suboptimal response66. No indications exist that endocrine therapy or small molecules generally are associated with reduced seroconversion. Poly(ADP-ribose) polymerase inhibitors have been associated with reduced seroconversion in women with ovarian cancer123, and CDK4/6 inhibitors with reduced but not absent antibody responses120. Besides cancer-specific therapies, chronic steroid use is also a risk factor for reduced seroconversion124. No specific solid tumour type has been associated with a reduced antibody response. Neutralizing responses have mainly been evaluated for wild-type SARS-CoV-2 (the Wuhan or D614G variant)100,102. However, when considering neutralizing activities against VOCs, a progressive reduction in neutralizing titres is observed, especially against the Beta, Delta and Omicron VOCs65,119.
T cell responses to vaccination against COVID-19, defined as IFNγ release65,66,125, combined IFNγ and IL-2 release102,110, or flow cytometric analysis of cellular activation-induced markers126, are detectable in 46–79% of patients with solid tumours. In contrast to individuals without cancer, these patients often have discordant antibody and cellular responses65,102,110,126. Overall, establishing risk factors for poor T cell responses to vaccination is more challenging than for antibody responses. This observation can be attributed to several factors: firstly, differences between the assays can influence the observed responses, and no unified cut-off for T cell positivity exists. For example, some studies have measured T cell reactivity by broadly quantifying cellular cytokine secretion whereas others have used the presence of certain activation markers on virus-specific T cells for this purpose. Secondly, T cell responses have often been assessed in subsets of patients, such as those with no seroconversion, thereby limiting the ability to detect less overt risk factors. Nevertheless, receiving treatment for cancer110,126, chemotherapy102 or steroids within 15 days of vaccination102 has been associated with reduced T cell responses to vaccination. Although reduced in patients receiving chemotherapy, T cells are detectable in the absence of antibody responses in patients receiving chemotherapy or immune checkpoint inhibitors66. T cell responses to spike peptide pools specific for VOCs have also been detected65. This observation confirms that T cell epitopes are more broadly conserved82 and less overtly affected by mutations in viral peptides than antibody responses.
The data summarized above originate from studies investigating mRNA or adenovirus-vectored vaccines. Limited information exists on the performance of other COVID-19 vaccines in patients with cancer. In a study from Turkey, investigators analysed the immunogenicity of the inactivated virus vaccine CoronaVac in 47 patients with solid tumours who were mostly receiving chemotherapy. Here, 64% of patients had detectable seroconversion, including both patients receiving immune checkpoint inhibitors. Consistent with data from other studies, age was an independent risk factor for a reduced antibody response127. In another study, investigators in Iran assessed the effects of BBIBP-CorV. Serological responses after a full vaccination regimen comprising two doses of BBIBP-CorV were analysed in 364 patients with cancer. Most patients (87%) had a serological response, with older age and the presence of haematological malignancies emerging as the most important risk factors for a reduced response. The vaccine was overall well tolerated128.
Risk factors affecting vaccine responses in patients with haematological malignancies
Patients with haematological malignancies have a higher risk of developing reduced immune responses to COVID-19 vaccination65,100,109,110,120,125,129 and, as found in a large-cohort study in the USA, also show a lower VE (VE 74% versus 90% in non-immunocompromised individuals)111. Encouragingly, however, long-term survivors of haematological malignancies, including stem cell transplant recipients, have a response to vaccination similar to that in the general population, even if prior therapy was very immunosuppressive112,130. Regarding the type of vaccine, mRNA vaccines seem to elicit better immune responses in this population than adenovirus-vectored vaccines65,120 and this seems to be particularly the case for mRNA-1273 (refs111,120,122). Most studies to date have analysed the antibody-mediated immune response only. A number of individual risk factors have been associated with a reduced humoral immune response, including advanced age, active malignancy and/or lymphoproliferative disorders (Box 1). Treatment with certain anticancer therapies has been consistently associated with a drastically reduced humoral immune response to vaccination (Box 2). These suppressive effects are most evident for all B cell-depleting treatments (including CD20, BCMA and CD38 targeted therapies; Box 2). The magnitude of a patient’s spike protein-reactive IgG response correlates with the absolute number of B cells131 and the suppressive effects of B cell-depleting therapies probably last for ≥1 year after treatment cessation120,132, putting these patients at an increased risk of breakthrough infections.
A few studies also investigated the cellular immune response, and perhaps unsurprisingly, T cell responses are consistently more robust, with 30–75% of seronegative patients having specific T cell responses to vaccination independent of disease subtype65,125,133,134. Patients with haematological malignancies often have discordant humoral and cellular responses to vaccination, a situation that is rarely observed in other populations126. T cell responses to vaccination appear to be less affected by ongoing treatment with B cell-depleting therapies65,131, highlighting that the ability of these patients to develop adaptive immunity is not completely disrupted. Furthermore, T cell responses, most importantly CD8+ responses, have been detected in patients with cancer receiving B cell-depleting therapies who subsequently developed COVID-19, even in the absence of humoral responses135,136, indicating that T cell responses alone can provide protection from severe outcomes. Ongoing graft-versus-host disease prophylaxis after allogeneic stem cell transplantation is the only scenario that predisposes to a reduced T cell response despite adequate virus-specific antibody levels. In this setting the vast majority of patients have a detectable serological response, although T cell responses seem to occur in only 20–30% of patients137,138.
Data from initial studies suggest that the waning of the immune response seen in the months following vaccination against COVID-19 is comparable among patients with cancer and in the general population139, possibly with more pronounced waning in patients with cancer140. In the light of these waning antibody responses and a greater proportion of patients with cancer already being at risk of inferior immune responses to vaccination, these patients have been globally prioritized to receive booster vaccination. All studies to date confirm that booster vaccination in these patients is well tolerated101. The use of booster vaccines in patients with cancer is further supported by the observation that titres after vaccination are higher in those previously infected with SARS-CoV-2 than in infection-naive patients65,141. The available evidence suggests that heterologous vaccination is superior to homologous vaccination, at least in those originally vaccinated with adenovirus-vectored vaccines142. Interestingly, vaccination with an adenovirus-vectored vaccine followed by an mRNA vaccine seems to be more effective than a homologous adenovirus-vectored vaccination regimen, in contrast to the experience with mRNA vaccines followed by an adenovirus-vectored vaccine37 (Fig. 2b). However, the heterogeneity of booster vaccination approaches used in patients with cancer presented thus far precludes any meaningful conclusions on the most effective vaccine combination. Data on immune responses after booster vaccination to date are mainly provided by small observational studies focused on measuring binding antibodies only.
Booster vaccination increases the antibody responses of patients with solid tumours101,143 even in those vaccinated while also receiving treatment140. The level of benefit in these patients appears to be high even in those who were seronegative after the second vaccine dose144.
Patients with haematological malignancies have a higher risk of not seroconverting following vaccination against COVID-19. This effect is most pronounced in patients with B cell malignancies receiving B cell-depleting therapies (CD20 targeted therapies or BTK inhibitors)144,145,146. Neutralizing antibody responses, which have been investigated only in limited numbers of patients with cancer, can also be boosted using the same vaccine that was initially administered, even in patients lacking a detectable response after the second dose101,147. Booster vaccination is also associated with an increased ability to neutralize VOCs115. T cell responses to booster vaccination have also only rarely been analysed, and the available data indicate no significant increase101, a relevant increase only after booster vaccination with an mRNA vaccine142 and discordant effects in patients who remain seronegative after booster vaccination144.
In summary, many health-care systems have adopted the practice of routinely offering patients with cancer a total of three doses of a COVID-19 vaccine to provide a level of protection comparable to that in individuals without cancer. In the future, regular booster doses, possibly with novel vaccines, are likely to be required to maintain protection.
Data from prospective studies involving patients with cancer so far indicate that the rate of vaccine-induced adverse events is very similar to that demonstrated in the registration studies with the various vaccine platforms. As an example, the most common adverse events reported in an early study involving patients with cancer were soreness or pain at or around the injection site (63% of vaccinees), local swelling (9%) and systemic reactions including muscle pain (34%), fatigue (34%), headache (16%), fever (10%), chills (10%) and gastrointestinal events (10%)148. In the VOICE study, grade 3–4 local and/or systemic adverse events occurring in the first week following each vaccination were seen in 1–2% of patients, but only a quarter of these were deemed vaccine-related. By contrast, lower-grade events were more common following the second vaccination. For example, grade 1–2 fatigue, muscle ache, chills and/or joint ache occurred in up to 44% of patients whereas fever occurred in about 25%66. Another study involving both patients with solid tumours and patients with haematological malignancies also failed to reveal any new safety signals110. The incidences of both local and systemic vaccine-mediated reactions did not differ between the two patient populations included in this study. Very little knowledge of longer-term adverse effects of COVID-19 vaccines in individuals with and without cancer currently exists, owing to the short observation time.
Initially, receiving immune checkpoint inhibitors was considered a potential risk factor that might increase the risk of developing exacerbated irAEs after COVID-19 vaccination. However, in the VOICE trial, the incidence of grade ≥3 irAEs measured within 28 days of vaccination with mRNA-1273 was ~4% in the cohorts receiving immune checkpoint inhibitors either without or with chemotherapy66. Similarly, data from two other studies reveal no significant increase in the incidence of irAEs in patients vaccinated with mRNA vaccines while also receiving immune checkpoint inhibitors148,149. Examples of possible vaccine-related irAEs include a case report describing grade 3–4 exacerbations of psoriasis shortly after COVID-19 vaccination. This patient had stopped receiving an anti-PD-1 antibody 3 months earlier150. In another case report, a patient developing multiple irAEs on nivolumab plus ipilimumab, developed a cotrimoxazole-attributed skin rash while receiving steroids and prophylactic cotrimoxazole. The rash disappeared after withdrawal of the systemic medication and topical steroids; however, a new flare occurred shortly after vaccination with a second dose of BNT162b2 (ref.151). Also, one patient with colorectal cancer receiving anti-PD-1 antibody monotherapy developed cytokine-release syndrome 5 days after vaccination with BNT162b2 (ref.152).
Local lymphadenopathy commonly occurs after COVID-19 vaccination. Vaccine-induced lymphadenopathy found on CT or PET could be mistaken for lymph node metastases in certain patients, such as those with breast cancer or melanoma153,154,155,156, although unlike cancer, the lymph node enlargement usually completely resolves spontaneously139. A literature review of data from 15 studies involving >2,000 patients with breast cancer showed that the incidence of vaccine-induced lymphadenopathy ranges from 14.5% to 53%. This lymphadenopathy persisted for >6 weeks in 29% of patients153. Radiation recall phenomena, such as pneumonitis or dermatitis, have been described following COVID-19 vaccination157,158,159. These phenomena are rare, although an awareness of this complication is important in order to avoid accidental mis-attribution as an adverse effect of cancer therapy.
Patients who have undergone allogeneic peripheral stem cell transplantation are at risk of cytopenias and worsening of graft-versus-host disease following vaccination, even several years after transplantation. Furthermore, newly emergent graft-versus-host disease complications have been reported after vaccination with BNT162b2 or mRNA-1273 in up to 10% of patients138,160,161.
In summary, the safety of COVID-19 vaccines in patients with cancer, including the incidence of severe adverse events such as vaccine-induced immune thrombotic thrombocytopenia, is comparable to that in the general population. Certain well-defined toxicity profiles have been reported in specific patient populations. Overall, similar to the general population, the benefits of vaccination against COVID-19 clearly outweigh the risks in all patients with cancer.
Data from large prospective studies demonstrate that vaccination is highly effective at preventing COVID-19-related morbidity and mortality (Fig. 2), although sterilizing immunity will not be achieved and the probability of breakthrough infections increases over time owing to waning immunity70,162. Breakthrough infections have also been reported in several follow-up studies monitoring vaccinated patients with cancer69,100,122,163,164,165,166,167. Infection risk is clearly lower in patients with cancer after vaccination168, although breakthrough infections can have a more severe course and a higher risk of mortality than in those without cancer69,100,163,166.
Data from several studies indicate either reduced or absent antibody responses in those with breakthrough infections69,100,122,163,165, while others suggest that antibody levels are comparable to those in patients without such infections169. Of note, these conclusions are based on limited numbers of patients with breakthrough infections (fewer than ten patients per study), highlighting an ongoing need to associate the immune responses seen in patients with cancer with patterns of infection in larger cohorts. Finally, all data on breakthrough infections were based on measurements of binding antibodies, although levels of neutralizing antibodies against VOCs might be reduced even in the presence of binding antibodies against the wild-type spike protein65,69.
Increasing protection from COVID-19
Cancer, and related symptoms such as treatment-associated immunodeficiencies, cannot be easily overcome. However, patients with cancer might be particularly prone to vitamin and nutrient deficiencies for several reasons and some of these, such as iron deficiency, have been associated with an impaired immune response to vaccination170. So far, no data are available on the benefits of interventional dietary supplementation around the time of vaccination despite increasing evidence that vitamin D or vitamin A might be protective against severe respiratory infections171,172,173,174. In conclusion, nutrient or vitamin deficiencies in patients with cancer deserve attention, although no evidence exists that dietary supplementation with additional nutrients or vitamins will improve vaccine response.
Role of antipyretic agents
To prevent COVID-19 vaccine-induced adverse effects, some doctors might be tempted to prescribe prophylactic antipyretic medications. However, prophylactic administration of antipyretics has been shown to suppress the immune response to several other vaccines administered during childhood175,176,177,178. By contrast, this effect is not evident when antipyretic agents are administered therapeutically upon the development of systemic adverse effects; therefore, this seems to be the favoured approach175. Despite this general recommendation, data from a subgroup of patients who received prophylactic paracetamol before vaccination with ChAdOx-1 in an early trial reveal no evidence of a reduced immune response179.
Another way to protect patients with a deficient immune system and therefore an impaired response to COVID-19 vaccination is to adequately vaccinate all close contacts, such as family members, spouses and carers. Evidence supporting this strategy is provided by previous experience with respiratory virus infections such as influenza. Data from a cluster-randomized trial involving nursing home residents showed a 20% reduction in all-cause mortality when influenza vaccine uptake among staff increased from 31.8% to 69.9%180. Similarly, a decrease in nosocomial influenza infections has been reported in an oncology department following the introduction of mandatory influenza vaccination for health-care workers181. A high level of population immunity to COVID-19 is expected to develop and this effect is likely to benefit patients with cancer during the later stages of the pandemic (if and when a high level of vaccination is achieved in both the general population and among health-care workers in particular). Initial data from Sweden demonstrate that COVID-19 vaccination of family members reduces the risk of COVID-19 by up to 97% in those who cannot be immunized182.
Addressing vaccine hesitancy
Vaccine hesitancy is a global phenomenon that poses a major threat to the successful management of the pandemic. Attitudes to vaccination vary considerably across countries ranging from an acceptance rate of >90% to <50%183,184. Vaccine hesitancy is probably lower in patients with cancer, but still seems to occur in ~10% of patients185,186,187,188. High levels of vaccine hesitancy might also suppress population immunity, thus reducing the extent of protection for patients with cancer who cannot mount an adequate immune response themselves. Female and younger individuals, and those who do not believe that the disease itself poses a relevant risk to them, are more likely to have a critical attitude to vaccination. Common reasons for vaccine hesitancy include concerns regarding vaccine safety, misperception of the risks associated with the disease and/or persistent beliefs in misinformation. Importantly, certain examples of misinformation, such as the potential to increase the rate of miscarriage, regardless of a lack of any evidential basis when originally suggested, have been specifically disproven189,190. For patients with cancer, there is both no evidence and no rationale whatsoever supporting the suggestion that vaccination against COVID-19 leads to cancer recurrence.
A common method of addressing vaccine hesitancy uses the 5C model: build up confidence in the vaccine, tackle complacency regarding the risks of infection, increase convenience by providing easy access to vaccines, and promote accurate risk calculation and collective responsibility191. These 5Cs were derived from the populations of high-income countries. These measures might have to be adapted for lower-income countries, for example, by replacing the last two Cs with communication and context192. The last part might be particularly vital for a successful campaign and includes the prudent selection of the communication messenger by choosing individuals who are particularly respected within specific communities192,193, which might well be the treating oncologist in certain scenarios. Providing valuable training regarding the content of the information194 and in-depth knowledge on how to approach misinformation can support this195. Context-adapted ‘nudging’ approaches might be particularly helpful193,196, especially if such measures are designed to counteract negative emotions197. Finally, allowing each individual to choose the type of vaccine they receive might increase acceptance198. In summary, vaccine hesitancy is largely underestimated and often addressed unprofessionally. A multidisciplinary, professional and context-specific approach is required to address vaccine hesitancy and thus increase vaccination coverage.
Alternatives to vaccination
Monoclonal antibodies against SARS-CoV-2 would be the logical candidate for those who are unable to mount an immune response and thus require passive immunization. Such approaches are best studied early in the course of COVID-19 and are particularly effective in patients with multiple comorbidities. For example, in a retrospective study the number needed to treat (NNT) with the monoclonal antibodies bamlanivimab, bamlanivimab–etesevimab or casirivimab–imdevimab to prevent one COVID-19 hospitalization among the lowest risk group was 225, compared with an NNT of 4 among those deemed to have the highest risk, determined by number of medical comorbidities199. These monoclonal antibodies have shown promising activity in preventing COVID-19 in non-immunized patients. A randomized trial testing a post-exposure prophylaxis approach using casirivimab– imdevimab demonstrated a reduction in the incidence of symptomatic COVID-19 of 81% relative to placebo (in 1.5% versus 7.8% of patients; P < 0.001)200 in people without comorbidities and at least one household contact with a detectable SARS-CoV-2 infection. Regarding pre-exposure prophylaxis, which would be the equivalent of passive immunization, a monthly dose of casirivimab–imdevimab for 6 months was >90% effective in preventing COVID-19 relative to placebo (clinically defined COVID-19 in 0.4% versus 5.4% of patients)201. Nonetheless, these studies were conducted prior to the emergence of the Omicron variant, against which there is a high probability that these agents will not be effective202,203. Another passive immunization approach involves a cocktail containing the two long-acting antibodies tixagevimab and cilgavimab, which has been tested as a single intramuscular 300 mg administration in >5,000 unvaccinated adults. According to media reports, the risk of developing symptomatic COVID-19 over 6 months was reduced by 83% in the group that received the antibody cocktail, despite >75% of study participants having comorbidities204. Given the long-lasting passive immunity and relative ease of administration, this alternative might be very attractive for those who cannot mount an adequate immune response to active vaccination. However, the same caveat regarding VOCs also applies here. The novel monoclonal antibody sotrovimab has been granted emergency use authorization in patients with laboratory-confirmed COVID-19 and at least one risk factor for severe disease205. This decision is based on data from a positive study in which 1% of outpatients with symptomatic COVID-19 in the sotrovimab group versus 7% in the placebo group required hospitalization (relative risk reduction 85%, 97.24% CI 44–96%; P = 0.002)206 despite the fact that no significant improvement in clinical outcomes was observed among adults treated while hospitalized with COVID-19 (ref.207). Sotrovimab has in vitro activity against a broad range of VOCs including Omicron; therefore, this agent might be of clinical value in prophylaxis (pre-exposure and post-exposure) and as an early intervention in patients with cancer116,203,208,209. In summary, passive immunization is feasible although many of the agents are hampered by a rapid loss of efficacy owing to mutations in VOCs that reduce the affinity of the antibodies. Furthermore, passive immunization strategies, unlike active vaccination, currently do not include a cellular immunity component.
Antiviral prophylaxis, frequently used to prevent zoster reactivation in patients with cancer, provides another method of reducing the risk of severe COVID-19 (refs210,211). The first trials aiming for COVID-19 prophylaxis clearly demonstrated that hydroxychloroquine is ineffective for this purpose212. More recently, molnupiravir, an oral prodrug form of a synthetic nucleoside analogue, which provides a 30% reduction in risk of hospitalization or death if taken within 5 days of COVID-19 symptom onset (COVID-19 hospitalization or mortality in 6.8% versus 9.7% of patients (difference 3%, 95% CI −5.9% to −0.1%)) received an FDA emergency use authorization in December 2021 (ref.213). Similarly, paxlovid, a combination of two protease inhibitors (PF-07321332 (ref.214) and ritonavir) administered orally within 3 days of COVID-19 infection reduces the incidence of hospitalization and death by 88.9% relative to placebo (COVID-19 hospitalization or mortality in 0.72% versus 6.53%, difference -5.81%, 95% CI, −7.78 to −3.84; P < 0.001 in the final analysis)215,216. Paxlovid has already received preliminary authorization for use from several regulatory authorities. However, interactions via CYP3A4 and p-glycoprotein have to be considered, especially in patients with cancer receiving ongoing therapy. Provided the safety profiles of these agents are deemed favourable and clinical activity against VOCs is retained, both drugs could provide effective pre-exposure or post-exposure prophylaxis for vulnerable patient populations.
Given the emergence of VOCs as well as the less-proficient immune responses of patients with cancer who receive vaccines against antigens derived from the spike protein, development of novel vaccination strategies is both necessary and ongoing. Various pharmaceutical companies, including BioNTech, Moderna and AstraZeneca, have initiated clinical trials assessing vaccines that have been modified for improved activity against specific VOCs. Booster vaccination with Beta-specific vaccines has already been shown to induce neutralizing responses against this VOC217,218. Studies on Omicron-specific vaccines are also currently ongoing.
Beyond variant-specific versions of current vaccines, other strategies might render vaccines more effective against VOCs. For example, a peptide vaccine composed of various SARS-CoV-2 derived epitopes combined with an adjuvant TLR agonist (CoVac-1) resulted in a very robust T cell immune response in addition to a mild antibody response, with only mild toxicities in a phase I/II trial219. Of note, the T cell response was largely unaffected by mutations in the VOC. With this mechanism of action and activity, the CoVac-1 vaccine could be ideal for patients who are likely to have an impaired serological response. Preclinical data indicate that vaccines targeting the highly conserved S2 subunit of the spike protein might induce broad responses against VOCs and, even against other coronaviruses220.
Global vaccine disparities
Many aspects discussed in this Review are largely of relevance to residents of economically developed countries only. Everything said regarding differential responses to vaccines, toxicities and improvements in vaccine responses only applies if vaccines are available and accessible. Unfortunately, this is not the case for many countries that, owing to inequalities in vaccine distribution, can only achieve a 10% vaccine coverage of the population221. In addition to leaving patients in low-income countries potentially unprotected, this disparity contributes to the development of novel VOCs, thus prolonging the pandemic worldwide. Therefore, distributing the available vaccine doses fairly worldwide is of the utmost importance. In this context, from a global perspective in patients with cancer as much as in all other populations, providing primary vaccination is more effective than administering boosters to those who are already vaccinated221,222.
In response to the pandemic, an unprecedented number of studies have addressed the efficacy and immunogenicity of COVID-19 vaccines in patients with cancer. However, several open questions remain and will require additional research. Firstly, most studies have addressed immune responses, although granular data on VE are still needed for specific cancer subtypes and therapies. These data need to be defined for all available vaccines and are research end points that can only be completely addressed in large prospective trials. Secondly, the available data reported thus far mostly originated from heterogeneous patient cohorts, which makes drawing robust conclusions on the optimal approach to COVID-19 vaccination in patients with cancer challenging. Such conclusions include the number of vaccine doses needed, the optimal time between doses, the identification of at-risk patients after vaccination and strategies for additional protection of at-risk patients beyond vaccination — aspects that are especially relevant for patients with haematological malignancies. From these studies, recommendations regarding the management of vaccination in patients with cancer can be deduced9,223 but many open questions remain. Vaccine responses in paediatric patients with cancer have not been investigated and should be the focus of future studies. Finally, the identification of a reliable correlate of protection is urgently needed for patients with cancer as well as for the general population.
The development of COVID-19 vaccines has been a massive global effort, leading to a marked reduction in the risk of severe COVID-19 and death. Encouragingly, the available vaccines are safe and effective in patients with cancer, although lower VE has been observed than in those without cancer. A high proportion of patients with solid tumours will develop both humoral and T cell responses following vaccination, although cancer therapies such as chemotherapy can suppress these responses. Patients with haematological malignancies are more vulnerable to breakthrough infections given the reduced VE and often limited immune responses in many of these patients, especially those with B cell malignancies receiving B cell-depleting therapies. Booster vaccines can result in seroconversion in those who were previously seronegative following two vaccine doses. This observation indicates that regular booster vaccines might be effective for immunocompromised patients with cancer. Additionally, high vaccination rates in the community, especially among the families of vulnerable patients and in clinical care settings, will help protect those with impaired vaccine responses.
Coronaviridae Study Group of the International Committee on Taxonomy of Viruses The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat. Microbiol. 5, 536–544 (2020).
Williamson, E. J. et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature 584, 430–436 (2020).
Venkatesulu, B. P. et al. A systematic review and meta-analysis of cancer patients affected by a novel coronavirus. JNCI Cancer Spectr. 5, pkaa102 (2021).
Pagano, L. et al. COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA). J. Hematol. Oncol. 14, 168 (2021).
Rüthrich, M. M. et al. COVID-19 in cancer patients: clinical characteristics and outcome –an analysis of the LEOSS registry. Ann. Hematol. https://doi.org/10.1007/s00277-020-04328-4 (2020).
Pinato, D. J. et al. Time-dependent COVID-19 portality in patients with cancer: an updated analysis of the OnCovid registry. JAMA Oncol. https://doi.org/10.1001/jamaoncol.2021.6199 (2021).
Pinato, D. J. et al. Prevalence and impact of COVID-19 sequelae on treatment and survival of patients with cancer who recovered from SARS-CoV-2 infection: evidence from the OnCovid retrospective, multicentre registry study. Lancet Oncol. 22, 1669–1680 (2021).
Barbui, T. et al. Long-term follow-up of recovered MPN patients with COVID-19. Blood Cancer J. 11, 115 (2021).
Giesen, N. et al. 2021 update of the AGIHO guideline on evidence-based management of COVID-19 in patients with cancer regarding diagnostics, viral shedding, vaccination and therapy. Eur. J. Cancer 147, 154–160 (2021).
Walsh, E. E. et al. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. N. Engl. J. Med. 383, 2439–2450 (2020).
Baden, L. R. et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 384, 403–416 (2021).
Polack, F. P. et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N. Engl. J. Med. 383, 2603–2615 (2020).
Voysey, M. et al. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials. Lancet 397, 881–891 (2021).
Bos, R. et al. Ad26 vector-based COVID-19 vaccine encoding a prefusion-stabilized SARS-CoV-2 Spike immunogen induces potent humoral and cellular immune responses. NPJ Vaccines 5, 91 (2020).
Logunov, D. Y. et al. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia. Lancet 397, 671–681 (2021).
González, S. et al. Effectiveness of the first component of Gam-COVID-Vac (Sputnik V) on reduction of SARS-CoV-2 confirmed infections, hospitalisations and mortality in patients aged 60-79: a retrospective cohort study in Argentina. EClinicalMedicine https://doi.org/10.1016/j.eclinm.2021.101126 (2021).
Wu, Z. et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect. Dis. 21, 803–812 (2021).
Al Kaabi, N. et al. Effect of 2 inactivated SARS-CoV-2 vaccines on symptomatic COVID-19 infection in adults: a randomized clinical trial. JAMA 326, 35–45 (2021).
van Riel, D. & de Wit, E. Next-generation vaccine platforms for COVID-19. Nat. Mater. 19, 810–812 (2020).
Yu, X. et al. Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors. Nature 455, 532–536 (2008).
Sahin, U. et al. COVID-19 vaccine BNT162b1 elicits human antibody and T(H)1T cell responses. Nature 586, 594–599 (2020).
Mudd, P. A. et al. SARS-CoV-2 mRNA vaccination elicits a robust and persistent T follicular helper cell response in humans. Cell https://doi.org/10.1016/j.cell.2021.12.026 (2021).
Guerrera, G. et al. BNT162b2 vaccination induces durable SARS-CoV-2-specific T cells with a stem cell memory phenotype. Sci. Immunol. 6, eabl5344 (2021).
GeurtsvanKessel, C. H. et al. Divergent SARS CoV-2 Omicron-reactive T- and B cell responses in COVID-19 vaccine recipients. Sci. Immunol. https://doi.org/10.1126/sciimmunol.abo2202 (2022).
Tanriover, M. D. et al. Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey. Lancet 398, 213–222 (2021).
Formica, N. et al. Different dose regimens of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373) in younger and older adults: a phase 2 randomized placebo-controlled trial. PLoS Med. 18, e1003769 (2021).
Falsey, A. R. et al. Phase 3 safety and efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 vaccine. N. Engl. J. Med. 385, 2348–2360 (2021).
Sadoff, J. et al. Safety and efficacy of single-dose Ad26.COV2.S vaccine against Covid-19. N. Engl. J. Med. 384, 2187–2201 (2021).
Heath, P. T. et al. Safety and efficacy of NVX-CoV2373 Covid-19 vaccine. N. Engl. J. Med. 385, 1172–1183 (2021).
Shinde, V. et al. Efficacy of NVX-CoV2373 Covid-19 vaccine against the B.1.351 variant. N. Engl. J. Med. 384, 1899–1909 (2021).
Andrews, N. et al. Effectiveness of BNT162b2 (Comirnaty, Pfizer-BioNTech) COVID-19 booster vaccine against Covid-19 related symptoms in England: test negative case-control study. Preprint at medRxiv https://doi.org/10.1101/2021.11.15.21266341 (2021).
Katikireddi, S. V. et al. Two-dose ChAdOx1 nCoV-19 vaccine protection against COVID-19 hospital admissions and deaths over time: a retrospective, population-based cohort study in Scotland and Brazil. Lancet https://doi.org/10.1016/s0140-6736(21)02754-9 (2021).
Brockman, M. A. et al. Reduced magnitude and durability of humoral immune responses to COVID-19 mRNA vaccines among older adults. J. Infect. Dis. https://doi.org/10.1093/infdis/jiab592 (2021).
Andrews, N. et al. Effectiveness of COVID-19 vaccines against the Omicron (B.1.1.529) variant of concern. Preprint at medRxiv https://doi.org/10.1101/2021.12.14.21267615 (2021).
Munro, A. P. S. et al. Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial. Lancet 398, 2258–2276 (2021).
Stuart, A. S. V. et al. Immunogenicity, safety, and reactogenicity of heterologous COVID-19 primary vaccination incorporating mRNA, viral-vector, and protein-adjuvant vaccines in the UK (Com-COV2): a single-blind, randomised, phase 2, non-inferiority trial. Lancet https://doi.org/10.1016/s0140-6736(21)02718-5 (2021).
Liu, X. et al. Safety and immunogenicity of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine (Com-COV): a single-blind, randomised, non-inferiority trial. Lancet 398, 856–869 (2021).
Sablerolles, R. S. G. et al. Immunogenicity and reactogenicity of vaccine boosters after Ad26.COV2.S priming. N. Engl. J. Med., https://doi.org/10.1056/NEJMoa2116747 (2022).
Moghnieh, R. et al. Immunogenicity and reactogenicity of BNT162b2 booster in BBIBP-CorV-vaccinated individuals compared with homologous BNT162b2 vaccination: results of a pilot prospective cohort study from Lebanon. Vaccine 39, 6713–6719 (2021).
Ai, J. et al. Safety and immunogenicity of a third-dose homologous BBIBP-CorV boosting vaccination: interim results from a prospective open-label study. Emerg. Microbes Infect. https://doi.org/10.1080/22221751.2022.2025746 (2022).
Gribble, J. et al. The coronavirus proofreading exoribonuclease mediates extensive viral recombination. PLoS Pathog. 17, e1009226 (2021).
Frost, S. D. W., Magalis, B. R. & Kosakovsky Pond, S. L. Neutral theory and rapidly evolving viral pathogens. Mol. Biol. Evol. 35, 1348–1354 (2018).
Geers, D. et al. SARS-CoV-2 variants of concern partially escape humoral but not T-cell responses in COVID-19 convalescent donors and vaccinees. Sci. Immunol. https://doi.org/10.1126/sciimmunol.abj1750 (2021).
Liu, L. et al. Striking antibody evasion manifested by the omicron variant of SARS-CoV-2. Nature https://doi.org/10.1038/s41586-021-04388-0 (2021).
Wang, P. et al. Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature 593, 130–135 (2021).
Corey, L. et al. SARS-CoV-2 variants in patients with immunosuppression. N. Engl. J. Med. 385, 562–566 (2021).
Mlcochova, P. et al. SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion. Nature 599, 114–119 (2021).
Cele, S. et al. SARS-CoV-2 Omicron has extensive but incomplete escape of Pfizer BNT162b2 elicited neutralization and requires ACE2 for infection. Preprint at medRxiv https://doi.org/10.1101/2021.12.08.21267417 (2021).
Rössler, A., Riepler, L., Bante, D., von Laer, D. & Kimpel, J. SARS-CoV-2 Omicon variant neutralization in serum from vaccinated and convalescent persons. N. Engl. J. Med. 386, 698–700 (2022).
Nemet, I. et al. Third BNT162b2 vaccination neutralization of SARS-CoV-2 Omicron infection. N. Engl. J. Med. https://doi.org/10.1056/NEJMc2119358 (2021).
Hoffmann, M. et al. The Omicron variant is highly resistant against antibody-mediated neutralization: implications for control of the COVID-19 pandemic. Cell https://doi.org/10.1016/j.cell.2021.12.032 (2022).
Collie, S., Champion, J., Moultrie, H., Bekker, L. G. & Gray, G. Effectiveness of BNT162b2 vaccine against Omicron variant in South Africa. N. Engl. J. Med. https://doi.org/10.1056/NEJMc2119270 (2021).
Garcia-Beltran, W. F. et al. mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant. Cell https://doi.org/10.1016/j.cell.2021.12.033 (2022).
Han, P. et al. Receptor binding and complex structures of human ACE2 to spike RBD from Omicron and Delta SARS-CoV-2. Cell https://doi.org/10.1016/j.cell.2022.01.001 (2022).
Meng, B. et al. Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts tropism and fusogenicity. Nature, https://doi.org/10.1038/s41586-022-04474-x (2022).
Hui, K. P. Y. et al. SARS-CoV-2 Omicron variant replication in human bronchus and lung ex vivo. Nature https://doi.org/10.1038/s41586-022-04479-6 (2022).
McMahan, K. et al. Reduced pathogenicity of the SARS-CoV-2 omicron variant in hamsters. Preprint at bioRxiv https://doi.org/10.1101/2022.01.02.474743 (2022).
Basile, K. et al. Improved neutralization of the SARS-CoV-2 Omicron variant after Pfizer-BioNTech BNT162b2 COVID-19 vaccine boosting. Preprint at bioRxiv https://doi.org/10.1101/2021.12.12.472252 (2021).
Schmidt, F. et al. Plasma neutralization of the SARS-CoV-2 omicron variant. N. Engl. J. Med. https://doi.org/10.1056/NEJMc2119641 (2021).
Wölfel, R. et al. Virological assessment of hospitalized patients with COVID-2019. Nature 581, 465–469 (2020).
van Kampen, J. J. A. et al. Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19). Nat. Commun. 12, 267 (2021).
Gilbert, P. B. et al. Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial. Science https://doi.org/10.1101/2021.08.09.21261290 (2021).
Zost, S. J. et al. Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein. Nat. Med. 26, 1422–1427 (2020).
Robbiani, D. F. et al. Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature 584, 437–442 (2020).
Fendler, A. et al. Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: the CAPTURE study. Nat. Cancer https://doi.org/10.1038/s43018-021-00274-w (2021).
Oosting, S. F. et al. mRNA-1273 COVID-19 vaccination in patients receiving chemotherapy, immunotherapy, or chemoimmunotherapy for solid tumours: a prospective, multicentre, non-inferiority trial. Lancet Oncol. https://doi.org/10.1016/s1470-2045(21)00574-x (2021).
GeurtsvanKessel, C. H. et al. An evaluation of COVID-19 serological assays informs future diagnostics and exposure assessment. Nat. Commun. 11, 3436 (2020).
Brosh-Nissimov, T. et al. BNT162b2 vaccine breakthrough: clinical characteristics of 152 fully vaccinated hospitalized COVID-19 patients in Israel. Clin. Microbiol. Infect. 27, 1652–1657 (2021).
Maneikis, K. et al. Immunogenicity of the BNT162b2 COVID-19 mRNA vaccine and early clinical outcomes in patients with haematological malignancies in Lithuania: a national prospective cohort study. Lancet Haematol. 8, e583–e592 (2021).
Bergwerk, M. et al. Covid-19 breakthrough infections in vaccinated health care workers. N. Engl. J. Med. 385, 1474–1484 (2021).
Cromer, D. et al. Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting: a meta-analysis. Lancet Microbe https://doi.org/10.1016/s2666-5247(21)00267-6 (2021).
Khoury, D. S. et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat. Med. 27, 1205–1211 (2021).
Bignucolo, A. et al. Sex disparities in efficacy in COVID-19 vaccines: a systematic review and meta-analysis. Vaccines https://doi.org/10.3390/vaccines9080825 (2021).
McElhaney, J. E. et al. T cell responses are better correlates of vaccine protection in the elderly. J. Immunol. 176, 6333–6339 (2006).
Sridhar, S. et al. Cellular immune correlates of protection against symptomatic pandemic influenza. Nat. Med. 19, 1305–1312 (2013).
McMichael, A. J., Gotch, F. M., Noble, G. R. & Beare, P. A. Cytotoxic T-cell immunity to influenza. N. Engl. J. Med. 309, 13–17 (1983).
Wilkinson, T. M. et al. Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans. Nat. Med. 18, 274–280 (2012).
Soresina, A. et al. Two X-linked agammaglobulinemia patients develop pneumonia as COVID-19 manifestation but recover. Pediatr. Allergy Immunol. 31, 565–569 (2020).
Breathnach, A. S. et al. Prior COVID-19 protects against reinfection, even in the absence of detectable antibodies. J. Infect. 83, 237–279 (2021).
Wyllie, D. et al. SARS-CoV-2 responsive T cell numbers are associated with protection from COVID-19: a prospective cohort study in keyworkers. Preprint at medRxiv https://doi.org/10.1101/2020.11.02.20222778 (2020).
Swadling, L. et al. Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2. Nature https://doi.org/10.1038/s41586-021-04186-8 (2021).
Tarke, A. et al. Impact of SARS-CoV-2 variants on the total CD4(+) and CD8(+) T cell reactivity in infected or vaccinated individuals. Cell Rep. Med. 2, 100355 (2021).
Keeton, R. et al. T cell responses to SARS-CoV-2 spike cross-recognize Omicron. Nature, https://doi.org/10.1038/s41586-022-04460-3 (2022).
Tarke, A. et al. SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron. Cell https://doi.org/10.1016/j.cell.2022.01.015 (2021).
Winston, D. J. et al. Inactivated varicella zoster vaccine in autologous haemopoietic stem-cell transplant recipients: an international, multicentre, randomised, double-blind, placebo-controlled trial. Lancet 391, 2116–2127 (2018).
Beck, C. R. et al. Influenza vaccination for immunocompromised patients: summary of a systematic review and meta-analysis. Influenza Other Respir. Viruses 7(Suppl 2), 72–75 (2013).
Bitterman, R. et al. Influenza vaccines in immunosuppressed adults with cancer. Cochrane Database Syst. Rev. 2, Cd008983 (2018).
Stadtmauer, E. A. et al. Adjuvanted recombinant zoster vaccine in adult autologous stem cell transplant recipients: polyfunctional immune responses and lessons for clinical practice. Hum. Vaccin. Immunother. 17, 4144–4154 (2021).
Rousseau, B. et al. Immunogenicity and safety of the influenza A H1N1v 2009 vaccine in cancer patients treated with cytotoxic chemotherapy and/or targeted therapy: the VACANCE study. Ann. Oncol. 23, 450–457 (2012).
de Lavallade, H. et al. Repeated vaccination is required to optimize seroprotection against H1N1 in the immunocompromised host. Haematologica 96, 307–314 (2011).
Pleyer, C. et al. Effect of Bruton tyrosine kinase inhibitor on efficacy of adjuvanted recombinant hepatitis B and zoster vaccines. Blood 137, 185–189 (2021).
Meisel, R. et al. Pneumococcal conjugate vaccine provides early protective antibody responses in children after related and unrelated allogeneic hematopoietic stem cell transplantation. Blood 109, 2322–2326 (2007).
Stadtmauer, E. A. et al. A phase 1/2 study of an adjuvanted varicella-zoster virus subunit vaccine in autologous hematopoietic cell transplant recipients. Blood 124, 2921–2929 (2014).
Mullane, K. M. et al. Safety and efficacy of inactivated varicella zoster virus vaccine in immunocompromised patients with malignancies: a two-arm, randomised, double-blind, phase 3 trial. Lancet Infect. Dis. 19, 1001–1012 (2019).
Parrino, J. et al. Safety and immunogenicity of inactivated varicella-zoster virus vaccine in adults with hematologic malignancies receiving treatment with anti-CD20 monoclonal antibodies. Vaccine 35, 1764–1769 (2017).
Vink, P. et al. Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in patients with solid tumors, vaccinated before or during chemotherapy: a randomized trial. Cancer 125, 1301–1312 (2019).
Mulder, S. F. et al. Cancer patients treated with sunitinib or sorafenib have sufficient antibody and cellular immune responses to warrant influenza vaccination. Clin. Cancer Res. 17, 4541–4549 (2011).
Wijn, D. H. et al. Influenza vaccination in patients with lung cancer receiving anti-programmed death receptor 1 immunotherapy does not induce immune-related adverse events. Eur. J. Cancer 104, 182–187 (2018).
Cavanna, L. et al. COVID-19 vaccines in adult cancer patients with solid tumours undergoing active treatment: seropositivity and safety. A prospective observational study in Italy. Eur. J. Cancer 157, 441–449 (2021).
Peeters, M. et al. Reduced humoral immune response after BNT162b2 coronavirus disease 2019 messenger RNA vaccination in cancer patients under antineoplastic treatment. ESMO Open 6, 100274 (2021).
Shroff, R. T. et al. Immune responses to two and three doses of the BNT162b2 mRNA vaccine in adults with solid tumors. Nat. Med. 27, 2002–2011 (2021).
McKenzie, D. R. et al. Humoral and cellular immunity to delayed second dose of SARS-CoV-2 BNT162b2 mRNA vaccination in patients with cancer. Cancer Cell 39, 1445–1447 (2021).
Linardou, H. et al. Responses to SARS-CoV-2 vaccination in patients with cancer (ReCOVer study): a prospective cohort study of the Hellenic Cooperative Oncology Group. Cancers https://doi.org/10.3390/cancers13184621 (2021).
Shmueli, E. S. et al. Efficacy and safety of BNT162b2 vaccination in patients with solid cancer receiving anticancer therapy – a single centre prospective study. Eur. J. Cancer 157, 124–131 (2021).
Agbarya, A. et al. Efficacy of the mRNA-based BNT162b2 COVID-19 vaccine in patients with solid malignancies treated with anti-neoplastic drugs. Cancers https://doi.org/10.3390/cancers13164191 (2021).
Ligumsky, H. et al. Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine among actively treated cancer patients. J. Natl Cancer Inst. https://doi.org/10.1093/jnci/djab174 (2021).
Barrière, J. et al. Impaired immunogenicity of BNT162b2 anti-SARS-CoV-2 vaccine in patients treated for solid tumors. Ann. Oncol. 32, 1053–1055 (2021).
Becerril-Gaitan, A. et al. Immunogenicity and risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection after coronavirus disease 2019 (COVID-19) vaccination in patients with cancer: a systematic review and meta-analysis. Eur. J. Cancer https://doi.org/10.1016/j.ejca.2021.10.014 (2021).
Mair, M. J. et al. Humoral immune response in hematooncological patients and health care workers who received SARS-CoV-2 vaccinations. JAMA Oncol. https://doi.org/10.1001/jamaoncol.2021.5437 (2021).
Monin, L. et al. Safety and immunogenicity of one versus two doses of the COVID-19 vaccine BNT162b2 for patients with cancer: interim analysis of a prospective observational study. Lancet Oncol. 22, 765–778 (2021).
Embi, P. J. et al. Effectiveness of 2-dose vaccination with mRNA COVID-19 vaccines against COVID-19-associated hospitalizations among immunocompromised adults – nine states, January-September 2021. MMWR 70, 1553–1559 (2021).
Wu, J. T. et al. Association of COVID-19 vaccination with SARS-CoV-2 infection in patients with cancer: a US nationwide Veterans Affairs study. JAMA Oncol. https://doi.org/10.1001/jamaoncol.2021.5771 (2021).
Hippisley-Cox, J. et al. Risk prediction of covid-19 related death and hospital admission in adults after covid-19 vaccination: national prospective cohort study. BMJ 374, n2244 (2021).
Wall, E. C. et al. AZD1222-induced neutralising antibody activity against SARS-CoV-2 Delta VOC. Lancet 398, 207–209 (2021).
Naranbhai, V. et al. Neutralization breadth of SARS-CoV-2 viral variants following primary series and booster SARS-CoV-2 vaccines in patients with cancer. Cancer Cell https://doi.org/10.1016/j.ccell.2021.12.002 (2022).
Wu, M. et al. Three-dose vaccination elicits neutralising antibodies against omicron. Lancet https://doi.org/10.1016/S0140-6736(22)00092-7 (2022).
Zeng, C. et al. COVID-19 mRNA booster vaccines elicit strong protection against SARS-CoV-2 Omicron variant in patients with cancer. Cancer Cell https://doi.org/10.1016/j.ccell.2021.12.014 (2021).
Valanparambil, R. et al. Antibody response to SARS-CoV-2 mRNA vaccine in lung cancer patients: reactivity to vaccine antigen and variants of concern. Preprint at medRxiv https://doi.org/10.1101/2022.01.03.22268599 (2022).
Fendler, A. et al. Omicron neutralising antibodies after third COVID-19 vaccine dose in patients with cancer. Lancet https://doi.org/10.1016/S0140-6736(22)00147-7 (2022).
Thakkar, A. et al. Seroconversion rates following COVID-19 vaccination among patients with cancer. Cancer Cell 39, 1081–1090.e2 (2021).
Massarweh, A. et al. Evaluation of seropositivity following BNT162b2 messenger RNA vaccination for SARS-CoV-2 in patients undergoing treatment for cancer. JAMA Oncol. 7, 1133–1140 (2021).
Stampfer, S. D. et al. Response to mRNA vaccination for COVID-19 among patients with multiple myeloma. Leukemia 35, 3534–3541 (2021).
Liontos, M. et al. Immunological response to COVID-19 vaccination in ovarian cancer patients receiving PARP inhibitors. Vaccines https://doi.org/10.3390/vaccines9101148 (2021).
Di Noia, V. et al. Immunogenicity and safety of COVID-19 vaccine BNT162b2 for patients with solid cancer: a large cohort prospective study from a single institution. Clin. Cancer Res. https://doi.org/10.1158/1078-0432.Ccr-21-2439 (2021).
Ehmsen, S. et al. Antibody and T cell immune responses following mRNA COVID-19 vaccination in patients with cancer. Cancer Cell 39, 1034–1036 (2021).
Mairhofer, M. et al. Humoral and cellular immune responses in SARS-CoV-2 mRNA-vaccinated patients with cancer. Cancer Cell 39, 1171–1172 (2021).
Karacin, C. et al. Immunogenicity and safety of the CoronaVac vaccine in patients with cancer receiving active systemic therapy. Future Oncol. 17, 4447–4456 (2021).
Ariamanesh, M. et al. Immunogenicity and safety of the inactivated SARS-CoV-2 vaccine (BBIBP-CorV) in patients with malignancy. Cancer Invest. 40, 26–34 (2022).
Addeo, A. et al. Immunogenicity of SARS-CoV-2 messenger RNA vaccines in patients with cancer. Cancer Cell 39, 1091–1098.e2 (2021).
Matkowska-Kocjan, A. et al. The COVID-19 mRNA BNT163b2 vaccine was well tolerated and highly immunogenic in young adults in long follow-up after haematopoietic stem cell transplantation. Vaccines https://doi.org/10.3390/vaccines9101209 (2021).
Malard, F. et al. Weak immunogenicity of SARS-CoV-2 vaccine in patients with hematologic malignancies. Blood Cancer J. 11, 142 (2021).
Liebers, N. et al. Humoral and cellular responses after COVID-19 vaccination in anti-CD20-treated lymphoma patients. Blood 139, 142–147 (2022).
Aleman, A. et al. Variable cellular responses to SARS-CoV-2 in fully vaccinated patients with multiple myeloma. Cancer Cell 39, 1442–1444 (2021).
Marasco, V. et al. T-cell immune response after mRNA SARS-CoV-2 vaccines is frequently detected also in the absence of seroconversion in patients with lymphoid malignancies. Br. J. Haematol. https://doi.org/10.1111/bjh.17877 (2021).
Bange, E. M. et al. CD8(+) T cells contribute to survival in patients with COVID-19 and hematologic cancer. Nat. Med. 27, 1280–1289 (2021).
Fendler, A. et al. Functional antibody and T-cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study. Nat. Cancer 2, 1321–1337 (2021).
Lindemann, M. et al. Humoral and cellular vaccination responses against SARS-CoV-2 in hematopoietic stem cell transplant recipients. Vaccines https://doi.org/10.3390/vaccines9101075 (2021).
Ram, R. et al. Safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in patients after allogeneic HCT or CD19-based CART therapy–a single-center prospective cohort study. Transpl. Cell Ther. 27, 788–794 (2021).
Waldhorn, I. et al. Six-month efficacy and toxicity profile of BNT162b2 vaccine in cancer patients with solid tumors. Cancer Discov. 11, 2430–2435 (2021).
Ligumsky, H. et al. Immunogenicity and safety of BNT162b2 mRNA vaccine booster in actively treated patients with cancer. Lancet Oncol. https://doi.org/10.1016/S1470-2045(21)00715-4 (2021).
Fong, D., Mair, M. J. & Mitterer, M. High levels of anti-SARS-CoV-2 IgG antibodies in previously infected patients with cancer after a single dose of BNT 162b2 vaccine. Eur. J. Cancer 154, 4–6 (2021).
Sablerolles, R. S. G. et al. Immunogenicity and reactogenicity of vaccine boosters after Ad26.COV2.S priming. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa2116747 (2022).
Rottenberg, Y. et al. Assessment of response to a third dose of the SARS-CoV-2 BNT162b2 mRNA vaccine in patients with solid tumors undergoing active treatment. JAMA Oncol. https://doi.org/10.1001/jamaoncol.2021.6764 (2021).
Shapiro, L. C. et al. Efficacy of booster doses in augmenting waning immune responses to COVID-19 vaccine in patients with cancer. Cancer Cell https://doi.org/10.1016/j.ccell.2021.11.006 (2021).
Greenberger, L. M. et al. Antibody response to SARS-CoV-2 vaccines in patients with hematologic malignancies. Cancer Cell 39, 1031–1033 (2021).
Reimann, P. et al. Efficacy and safety of heterologous booster vaccination with Ad26.COV2.S after BNT162b2 mRNA COVID-19 vaccine in haemato-oncological patients with no antibody response. Br. J. Haematol. https://doi.org/10.1111/bjh.17982 (2021).
Fendler, A. et al. Immune responses following third COVID-19 vaccination are reduced in patients with hematologic malignancies compared to patients with solid cancer. Cancer Cell 40, 114–116 (2022).
Waissengrin, B., Agbarya, A., Safadi, E., Padova, H. & Wolf, I. Short-term safety of the BNT162b2 mRNA COVID-19 vaccine in patients with cancer treated with immune checkpoint inhibitors. Lancet Oncol. 22, 581–583 (2021).
Chen, Y. W. et al. COVID-19 mRNA vaccines and immune-related adverse events in cancer patients treated with immune checkpoint inhibitors. Eur. J. Cancer 155, 291–293 (2021).
Mieczkowska, K., Kaubisch, A. & McLellan, B. N. Exacerbation of psoriasis following COVID-19 vaccination in a patient previously treated with PD-1 inhibitor. Dermatol. Ther. 34, e15055 (2021).
Hussain, K. et al. Severe cutaneous adverse reaction following COVID-19 vaccination and immunotherapy: a second hit? Clin. Exp. Dermatol. https://doi.org/10.1111/ced.14852 (2021).
Au, L. et al. Cytokine release syndrome in a patient with colorectal cancer after vaccination with BNT162b2. Nat. Med. 27, 1362–1366 (2021).
Garreffa, E. et al. Regional lymphadenopathy following COVID-19 vaccination: literature review and considerations for patient management in breast cancer care. Eur. J. Cancer 159, 38–51 (2021).
Goshen-Lago, T. et al. Serologic status and toxic effects of the SARS-CoV-2 BNT162b2 vaccine in patients undergoing treatment for cancer. JAMA Oncol. 7, 1507–1513 (2021).
Özütemiz, C. et al. Lymphadenopathy in COVID-19 vaccine recipients: diagnostic dilemma in oncologic patients. Radiology 300, E296–E300 (2021).
Özütemiz, C., Potter, D. A., Özütemiz, A. & Steinberger, D. Lymphadenopathy after the third Covid-19 vaccine. Curr. Probl. Cancer Case Rep. 4, 100127 (2021).
Soyfer, V., Gutfeld, O., Shamai, S., Schlocker, A. & Merimsky, O. COVID-19 vaccine-induced radiation recall phenomenon. Int. J. Radiat. Oncol. Biol. Phys. 110, 957–961 (2021).
Steber, C. R., Ponnatapura, J., Hughes, R. T. & Farris, M. K. Rapid development of clinically symptomatic radiation recall pneumonitis immediately following COVID-19 vaccination. Cureus 13, e14303 (2021).
Stewart, R. & McDowell, L. Radiation recall phenomenon following COVID-19 vaccination. Int. J. Radiat. Oncol. Biol. Phys. 111, 835–836 (2021).
Piñana, J. L. et al. SARS-CoV-2-reactive antibody detection after SARS-CoV-2 vaccination in hematopoietic stem cell transplant recipients: prospective survey from the spanish hematopoietic stem cell transplantation and cell therapy group (GETH-TC). Am. J. Hematol. https://doi.org/10.1002/ajh.26385 (2021).
Ali, H. et al. Safety and tolerability of SARS-CoV2 emergency-use authorized vaccines for allogeneic hematopoietic stem cell transplant recipients. Transpl. Cell Ther. 27, 938.e1–938.e6 (2021).
Mizrahi, B. et al. Correlation of SARS-CoV-2-breakthrough infections to time-from-vaccine. Nat. Commun. 12, 6379 (2021).
Van Oekelen, O. et al. Highly variable SARS-CoV-2 spike antibody responses to two doses of COVID-19 RNA vaccination in patients with multiple myeloma. Cancer Cell 39, 1028–1030 (2021).
Choi, B. et al. Persistence and evolution of SARS-CoV-2 in an immunocompromised host. N. Engl. J. Med. 383, 2291–2293 (2020).
Stampfer, S. et al. Severe breakthrough COVID-19 with a heavily mutated variant in a multiple myeloma patient 10 weeks after vaccination. Clin. Infect. Pract. 13, 100130 (2021).
Wang, L., Berger, N. A. & Xu, R. Risks of SARS-CoV-2 breakthrough infection and hospitalization in fully vaccinated patients with multiple myeloma. JAMA Netw. Open 4, e2137575 (2021).
Figueiredo, J. C. et al. Longitudinal SARS-CoV-2 mRNA vaccine-induced humoral immune responses in patients with cancer. Cancer Res. 81, 6273–6280 (2021).
Alhazzani, W. et al. Surviving sepsis campaign guidelines on the management of adults with coronavirus disease 2019 (COVID-19) in the ICU: first update. Crit. Care Med. 49, e219–e234 (2021).
Konishi, Y. et al. Attenuated response to SARS-CoV-2 vaccine in patients with asymptomatic precursor stages of multiple myeloma and Waldenstrom macroglobulinemia. Cancer Cell https://doi.org/10.1016/j.ccell.2021.12.003 (2022).
Drakesmith, H. et al. Vaccine efficacy and iron deficiency: an intertwined pair? Lancet Haematol. 8, e666–e669 (2021).
Kashi, D. S. et al. Vitamin D and the hepatitis B vaccine response: a prospective cohort study and a randomized, placebo-controlled oral vitamin D(3) and simulated sunlight supplementation trial in healthy adults. Eur. J. Nutr. 60, 475–491 (2021).
Lee, M. D. et al. Does vitamin D deficiency affect the immunogenic responses to influenza vaccination? A systematic review and meta-analysis. Nutrients https://doi.org/10.3390/nu10040409 (2018).
Martineau, A. R. et al. Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis. Health Technol. Assess. 23, 1–44 (2019).
Penkert, R. R. et al. Influences of vitamin A on vaccine immunogenicity and efficacy. Front. Immunol. 10, 1576 (2019).
Doedée, A. M. et al. Effects of prophylactic and therapeutic paracetamol treatment during vaccination on hepatitis B antibody levels in adults: two open-label, randomized controlled trials. PLoS ONE 9, e98175 (2014).
Jackson, L. A. et al. A randomized placebo-controlled trial of acetaminophen for prevention of post-vaccination fever in infants. PLoS ONE 6, e20102 (2011).
Prymula, R. et al. Effect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: two open-label, randomised controlled trials. Lancet 374, 1339–1350 (2009).
Rose, M. A. et al. An open-label randomized clinical trial of prophylactic paracetamol coadministered with 7-valent pneumococcal conjugate vaccine and hexavalent diphtheria toxoid, tetanus toxoid, 3-component acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b vaccine. BMC Pediatr. 13, 98 (2013).
Folegatti, P. M. et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet 396, 467–478 (2020).
Lemaitre, M. et al. Effect of influenza vaccination of nursing home staff on mortality of residents: a cluster-randomized trial. J. Am. Geriatrics Soc. 57, 1580–1586 (2009).
Frenzel, E. et al. Association of increased influenza vaccination in health care workers with a reduction in nosocomial influenza infections in cancer patients. Am. J. Infect. Control. 44, 1016–1021 (2016).
Nordström, P., Ballin, M. & Nordström, A. Association between risk of COVID-19 infection in nonimmune individuals and COVID-19 immunity in their family members. JAMA Intern. Med. 181, 1589–1595 (2021).
Solís Arce, J. S. et al. COVID-19 vaccine acceptance and hesitancy in low- and middle-income countries. Nat. Med. 27, 1385–1394 (2021).
Wong, L. P. et al. COVID-19 vaccination intention and vaccine characteristics influencing vaccination acceptance: a global survey of 17 countries. Infect. Dis. Poverty 10, 122 (2021).
Di Noia, V. et al. The first report on coronavirus disease 2019 (COVID-19) vaccine refusal by patients with solid cancer in Italy: early data from a single-institute survey. Eur. J. Cancer 153, 260–264 (2021).
Cavanna, L., Citterio, C., Cattadori, E., Bosi, C. & Caprioli, S. Re: The first report on coronavirus disease 2019 vaccine refusal by patients with cancer in Italy: early data from a single-institute survey: consideration of recent findings on COVID-19 vaccine adherence in cancer patients. Eur. J. Cancer https://doi.org/10.1016/j.ejca.2021.07.048 (2021).
Barrière, J. et al. Acceptance of SARS-CoV-2 vaccination among French patients with cancer: a cross-sectional survey. Ann. Oncol. 32, 673–674 (2021).
Mejri, N. et al. Understanding COVID-19 vaccine hesitancy and resistance: another challenge in cancer patients. Support. Care Cancer 30, 289–293 (2022).
Magnus, M. C. et al. Covid-19 vaccination during pregnancy and first-trimester miscarriage. N. Engl. J. Med. https://doi.org/10.1056/NEJMc2114466 (2021).
Chen, F. et al. Effects of COVID-19 and mRNA vaccines on human fertility. Hum. Reprod. https://doi.org/10.1093/humrep/deab238 (2021).
Machingaidze, S. & Wiysonge, C. S. Understanding COVID-19 vaccine hesitancy. Nat. Med. 27, 1338–1339 (2021).
Razai, M. S. et al. COVID-19 vaccine hesitancy: the five Cs to tackle behavioural and sociodemographic factors. J. R. Soc. Med. 114, 295–298 (2021).
Carson, S. L. et al. COVID-19 vaccine decision-making factors in racial and ethnic minority communities in Los Angeles, California. JAMA Netw. Open 4, e2127582 (2021).
Quinn, S. C. & Andrasik, M. P. Addressing vaccine hesitancy in BIPOC communities – toward trustworthiness, partnership, and reciprocity. N. Engl. J. Med. 385, 97 (2021).
Lewandowsky, S., Ecker, U. K., Seifert, C. M., Schwarz, N. & Cook, J. Misinformation and its correction: continued influence and successful debiasing. Psychol. Sci. Public Interest. 13, 106–131 (2012).
Reñosa, M. D. C. et al. Nudging toward vaccination: a systematic review. BMJ Glob. Health https://doi.org/10.1136/bmjgh-2021-006237 (2021).
Chou, W. S. & Budenz, A. Considering emotion in COVID-19 vaccine communication: addressing vaccine hesitancy and fostering vaccine confidence. Health Commun. 35, 1718–1722 (2020).
Hughes, M. T. et al. Opinion: The importance of offering vaccine choice in the fight against COVID-19. Proc. Natl Acad. Sci. USA https://doi.org/10.1073/pnas.2117185118 (2021).
Bierle, D. M. et al. Monoclonal antibody treatment of breakthrough COVID-19 in fully vaccinated individuals with high-risk comorbidities. J. Infect. Dis. https://doi.org/10.1093/infdis/jiab570 (2021).
O’Brien, M. P. et al. Subcutaneous REGEN-COV antibody combination to prevent Covid-19. N. Engl. J. Med. 385, 1184–1195 (2021).
Isa, F. et al. Repeat subcutaneous administration of REGEN-COV® in adults is well-tolerated and prevents the occurrence of COVID-19. Preprint at medRxiv https://doi.org/10.1101/2021.11.10.21265889 (2021).
Wilhelm, A. et al. Reduced neutralization of SARS-CoV-2 omicron variant by vaccine sera and monoclonal antibodies. Preprint at medRxiv https://doi.org/10.1101/2021.12.07.21267432 (2021).
Henning, G. et al. mRNA booster immunization elicits potent neutralizing serum activity against the SARS-CoV-2 Omicron variant. Nat. Portf. https://doi.org/10.21203/rs.3.rs-1168453/v1 (2021).
Mahase, E. Covid-19: AstraZeneca says its antibody drug AZD7442 is effective for preventing and reducing severe illness. BMJ 375, n2860 (2021).
Mahase, E. Covid-19: UK approves monoclonal antibody sotrovimab for over 12s at high risk. BMJ 375, n2990 (2021).
Gupta, A. et al. Early treatment for Covid-19 with SARS-CoV-2 neutralizing antibody sotrovimab. N. Engl. J. Med. 385, 1941–1950 (2021).
ACTIV-3/Therapeutics for Inpatients with COVID-19 (TICO) Study Group. Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial. Lancet Infect. Dis. https://doi.org/10.1016/s1473-3099(21)00751-9 (2021).
VanBlargan, L. A. et al. An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies. Nat. Med. https://doi.org/10.1038/s41591-021-01678-y (2022).
Cameroni, E. et al. Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift. Nature https://doi.org/10.1038/s41586-021-04386-2 (2021).
Henze, L. et al. Management of herpesvirus reactivations in patients with solid tumours and hematologic malignancies: update of the Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) on herpes simplex virus type 1, herpes simplex virus type 2, and varicella zoster virus. Ann. Hematol. https://doi.org/10.1007/s00277-021-04746-y (2022).
Taplitz, R. A. et al. Antimicrobial prophylaxis for adult patients with cancer-related immunosuppression: ASCO and IDSA clinical practice guideline update. J. Clin. Oncol. 36, 3043–3054 (2018).
Boulware, D. R. et al. A randomized trial of hydroxychloroquine as postexposure prophylaxis for Covid-19. N. Engl. J. Med. 383, 517–525 (2020).
Jayk Bernal, A. et al. Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa2116044 (2021).
Owen, D. R. et al. An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19. Science 374, 1586–1593 (2021).
Couzin-Frankel, J. Antiviral pills could change pandemic’s course. Science 374, 799–800 (2021).
Mahase, E. Covid-19: Pfizer’s paxlovid is 89% effective in patients at risk of serious illness, company reports. BMJ 375, n2713 (2021).
Choi, A. et al. Safety and immunogenicity of SARS-CoV-2 variant mRNA vaccine boosters in healthy adults: an interim analysis. Nat. Med. 27, 2025–2031 (2021).
Spencer, A. J. et al. The ChAdOx1 vectored vaccine, AZD2816, induces strong immunogenicity against SARS-CoV-2 beta (B.1.351) and other variants of concern in preclinical studies. eBioMed. 77, 103902 (2022).
Heitmann, J. S. et al. A COVID-19 peptide vaccine for the induction of SARS-CoV-2 T cell immunity. Nature https://doi.org/10.1038/s41586-021-04232-5 (2021).
Ng, K. W. et al. Broad human and animal coronavirus neutralisation by SARS-CoV-2 S2-targeted vaccination. Preprint at bioRxiv https://doi.org/10.1101/2021.11.30.470568 (2021).
Oehler, R. L. & Vega, V. R. Conquering COVID: how global vaccine inequality risks prolonging the pandemic. Open Forum Infect. Dis. 8, ofab443 (2021).
Krause, P. R. et al. Considerations in boosting COVID-19 vaccine immune responses. Lancet 398, 1377–1380 (2021).
Ribas, A. et al. How to provide the needed protection from COVID-19 to patients with hematologic malignancies. Blood Cancer Discov. 2, 562–567 (2021).
Buttiron Webber, T. et al. Predictors of poor seroconversion and adverse events to SARS-CoV-2 mRNA BNT162b2 vaccine in cancer patients on active treatment. Eur. J. Cancer 159, 105–112 (2021).
Bird, S. et al. Response to first vaccination against SARS-CoV-2 in patients with multiple myeloma. Lancet Haematol. 8, e389–e392 (2021).
Herishanu, Y. et al. Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with chronic lymphocytic leukemia. Blood https://doi.org/10.1182/blood.2021011568 (2021).
Roeker, L. E. et al. COVID-19 vaccine efficacy in patients with chronic lymphocytic leukemia. Leukemia 35, 2703–2705 (2021).
Chan, W. Y. et al. Serological response to the BNT162b2 mRNA or ChAdOx1 nCoV-19 COVID-19 vaccine after first and second doses in patients with plasma cell disorders: influence of host and disease factors. Br. J. Haematol. https://doi.org/10.1111/bjh.17864 (2021).
Parry, H. et al. Antibody responses after first and second Covid-19 vaccination in patients with chronic lymphocytic leukaemia. Blood Cancer J. 11, 136 (2021).
Terpos, E. et al. The neutralizing antibody response post COVID-19 vaccination in patients with myeloma is highly dependent on the type of anti-myeloma treatment. Blood Cancer J. 11, 138 (2021).
Herzog Tzarfati, K. et al. BNT162b2 COVID-19 vaccine is significantly less effective in patients with hematologic malignancies. Am. J. Hematol. 96, 1195–1203 (2021).
Canti, L. et al. Predictors of neutralizing antibody response to BNT162b2 vaccination in allogeneic hematopoietic stem cell transplant recipients. J. Hematol. Oncol. 14, 174 (2021).
Mamez, A. C. et al. Antibody responses to SARS-CoV2 vaccination in allogeneic hematopoietic stem cell transplant recipients. Bone Marrow Transplant. https://doi.org/10.1038/s41409-021-01466-9 (2021).
Yeshurun, M. et al. Humoral serologic response to the BNT162b2 vaccine after allogeneic haematopoietic cell transplantation. Clin. Microbiol. Infect. https://doi.org/10.1016/j.cmi.2021.10.007 (2021).
Shem-Tov, N. et al. Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in haematopoietic stem cell transplantation recipients. Br. J. Haematol. https://doi.org/10.1111/bjh.17918 (2021).
Chiarucci, M. et al. Immunological response against SARS-COV-2 after BNT162b2 vaccine administration is impaired in allogeneic but not in autologous stem cell transplant recipients. Front. Oncol. 11, 737300 (2021).
Le Bourgeois, A. et al. Safety and antibody response after 1 and 2 doses of BNT162b2 mRNA vaccine in recipients of allogeneic hematopoietic stem cell transplant. JAMA Netw. Open 4, e2126344 (2021).
Redjoul, R., Le Bouter, A., Parinet, V., Fourati, S. & Maury, S. Antibody response after third BNT162b2 dose in recipients of allogeneic HSCT. Lancet Haematol. 8, e681–e683 (2021).
Chung, D. J. et al. Disease- and therapy-specific impact on humoral immune responses to COVID-19 vaccination in hematologic malignancies. Blood Cancer Discov. 2, 568–576 (2021).
Crombie, J. L. et al. Activity of mRNA COVID-19 vaccines in patients with lymphoid malignancies. Blood Adv. 5, 3062–3065 (2021).
Ghione, P. et al. Impaired humoral responses to COVID-19 vaccination in patients with lymphoma receiving B-cell-directed therapies. Blood 138, 811–814 (2021).
Benjamini, O. et al. Safety and efficacy of BNT162b mRNA Covid19 vaccine in patients with chronic lymphocytic leukemia. Haematologica https://doi.org/10.3324/haematol.2021.279196 (2021).
Mellinghoff, S. C. et al. SARS-CoV-2 specific cellular response following COVID-19 vaccination in patients with chronic lymphocytic leukemia. Leukemia https://doi.org/10.1038/s41375-021-01500-1 (2021).
Marchesi, F. et al. The 12-week kinetics of anti-SARS-CoV-2 antibodies in different haematological cancers after vaccination with BNT162b2. Br. J. Haematol. 196, 362–367 (2022).
Terpos, E. et al. Low neutralizing antibody responses against SARS-CoV-2 in older patients with myeloma after the first BNT162b2 vaccine dose. Blood 137, 3674–3676 (2021).
Grinshpun, A. et al. Serologic response to COVID-19 infection and/or vaccine in cancer patients on active treatment. ESMO Open 6, 100283 (2021).
Zagouri, F. et al. SARS-CoV-2 neutralizing antibodies after first vaccination dose in breast cancer patients receiving CDK4/6 inhibitors. Breast 60, 58–61 (2021).
Liontos, M. et al. Treatment with abiraterone or enzalutamide does not impair immunological response to COVID-19 vaccination in prostate cancer patients. Prostate Cancer Prostatic Dis. https://doi.org/10.1038/s41391-021-00455-9 (2021).
Lasagna, A. et al. A snapshot of the immunogenicity, efficacy and safety of a full course of BNT162b2 anti-SARS-CoV-2 vaccine in cancer patients treated with PD-1/PD-L1 inhibitors: a longitudinal cohort study. ESMO Open 6, 100272 (2021).
Fischer, L. et al. Pneumococcal polysaccharide vaccination in adults undergoing immunosuppressive treatment for inflammatory diseases – a longitudinal study. Arthritis Res. Ther. 17, 151 (2015).
Andrews, N. et al. Effectiveness of COVID-19 booster vaccines against covid-19 related symptoms, hospitalisation and death in England. Nat. Med. https://doi.org/10.1038/s41591-022-01699-1 (2022).
The authors thank S. Oosting of the University of Groningen for support in data research. The work of E.G.E.de V. and J.B.H. is supported within the VOICE study by project grant 10430072010005 ZonMw, The Netherlands Organisation for Health Research and Development. The work of M.v.L.-T. is supported by the German Research Foundation within the Collaborative Research Centre/Transregio 124 FungiNet, DFG project no. 210879364 (project A1) as well as the Deutsche Krebshilfe OncoReVir Registry (no. 70113851). The work of A.F. is supported by funding from the European Union’s Horizon 2020 Research and Innovation program under Marie Skłodowska-Curie grant no. 892360. The work of S.T. is supported by Cancer Research UK (grant no. C50947/A18176). This work was also supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (CRUK) (FC001988, FC001218, FC001099, FC001002, FC001078, FC001169 and FC001030), the UK Medical Research Council (FC001988, FC001218, FC001099, FC001002, FC001078, FC001169 and FC001030) and the Wellcome Trust (FC001988, FC001218, FC001099, FC001002, FC001078, FC001169 and FC001030).
E.G.E. de V has acted as an advisor and/or consultant to Crescendo Biologics, Daiichi Sankyo and NSABP, declares financial support for clinical trials and/or contract research from Amgen, Bayer, Crescendo Biologics, G1 Therapeutics, Genentech, Regeneron, Roche, Servier and Synthon, and declares unpaid roles as a co-chair of the RECIST committee, as a chair of the ESMO Cancer Medicines Committee, as a member of the ESMO-MCBS working party, as a member of the expert panel for the selection of Essential Medicines List WHO, as a member of the Royal Netherlands Academy of Arts & Sciences and as a member of the supervisory board of the Netherlands Comprehensive Cancer Organization, and is a Project leader of the ZOnMw-funded Vaccination against cOvid In CancEr (VOICE) study. J.B.H. has acted as an advisor to Achilles Therapeutics, AstraZeneca, Bristol Myers Squibb, BioNTech, Immunocore, Ipsen, Instil Bio, Iovance Bio, MSD, Merck Serono, Molecular Partners, Novartis, Neogene Therapeutics, Pfizer, Roche/Genentech, Sanofi and T-Knife, has received research funding from Asher Bio, Amgen, Bristol Myers Squibb, MSD, BioNTech, Neogene Therapeutics and Novartis, has stock options in Neogene therapeutics, and is the current Editor-in-Chief of ESMO Immuno-Oncology and Technology. S.T. has received speaker’s fees from AstraZeneca, Ipsen, Novartis and Roche, and is listed on the following patents: Indel mutations as a therapeutic target and predictive biomarker (PCTGB2018/051892 and PCTGB2018/051893, as inventor) and Clear Cell Renal Cell Carcinoma Biomarkers (P113326GB, as co-inventor). M.v.L.T. has received speaker’s fees from Abbvie, Amgen, AstraZeneca, BMS, CDDF, Celgene, Chugai, GSK, Gilead, Janssen, Medac, Merck, Novartis, Oncopeptides, Pfizer, Shionogi, Takeda and Thermofisher, and research funding from BMBF, Celgene, Deutsche Jose Carreras Leukämie-Stiftung, Deutsche Krebshilfe, DFG, Gilead, IZKF Jena, Novartis and Oncopeptides. A.F., C.H.G., and B.W. declare no competing interests.
Peer review information
Nature Reviews Clinical Oncology thanks A. Verma, G. Curigliano and the other, anonymous reviewer(s) for their contribution to the peer review of this work.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
ASCO Coronavirus Resources: https://www.asco.org/covid-resources
COVID-19 data portal: https://www.covid19dataportal.org/
ESMO: COVID-19 and cancer: https://www.esmo.org/covid-19-and-cancer
Johns Hopkins Coronavirus Resource Centre: https://coronavirus.jhu.edu/map.html
Our world in data: Coronavirus (COVID-19) Vaccinations: https://ourworldindata.org/covid-vaccinations
The International Severe Acute Respiratory Infection Consortium Clinical Characterization Protocol: https://isaric4c.net/
The National Comprehensive Cancer Network (NCCN) COVID-19 resources: https://www.nccn.org/covid-19
The New York Times: tracking coronavirus vaccinations around the world: https://www.nytimes.com/interactive/2021/world/covid-vaccinations-tracker.html
The UK Coronavirus Cancer Monitoring Project: https://ukcoronaviruscancermonitoring.com/
The UK National Institute for Biological Standards and Control: https://www.nibsc.org/standardisation/international_standards.aspx
The WHO: Tracking SARS-CoV-2 variants: https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/
WHO Coronavirus (COVID 19) dashboard: https://covid19.who.int/
About this article
Cite this article
Fendler, A., de Vries, E.G.E., GeurtsvanKessel, C.H. et al. COVID-19 vaccines in patients with cancer: immunogenicity, efficacy and safety. Nat Rev Clin Oncol 19, 385–401 (2022). https://doi.org/10.1038/s41571-022-00610-8
This article is cited by
Limited induction of polyfunctional lung-resident memory T cells against SARS-CoV-2 by mRNA vaccination compared to infection
Nature Communications (2023)
Attitude towards and perception of individual safety after SARS-CoV-2 vaccination among German cancer patients
Journal of Cancer Research and Clinical Oncology (2023)
memo - Magazine of European Medical Oncology (2023)
Racial and Ethnic Variation in COVID-19 Vaccination Uptake Among Medicare Beneficiaries with Cancer History
Journal of Racial and Ethnic Health Disparities (2023)