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ESMO Statements on vaccination against COVID-19 in people with cancer

COVID-19 vaccination in cancer patients: ESMO statements

ESMO has released twenty-three statements to address issues and concerns on immunising patients with cancer against COVID-19.

By reviewing the current knowledge available, a group of 18 ESMO representatives authored and reviewed answers to key questions on the efficacy and safety of vaccines targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The World Health Organization (WHO) currently counts >300 research projects for the development of a vaccine conferring protective immunity against the SARS-CoV-2 virus, among which >100 are in clinical development.1

New technologies, previous experience with vaccine projects against related viruses and the presence of a pandemic health hazard accelerated the usual development cycle from years to months. Presentation of SARS-CoV-2 antigens to the host, in the context of vaccine development, relied on technologies based on messenger RNA (mRNA), inactivated/attenuated or genetically modified viruses, synthetic long viral peptides and plasmid DNA vaccines.2

By November 23rd 2021, the WHO had eight vaccines approved against COVID-19, including two mRNA vaccines (mRNA-1273/Spikevax and BNT162b2/Comirnaty), three non-replicant viral vector-based [Ad26.COV2.S and two formulations of ChAdOx1 nCoV-13 (AZD1222/Vaxzevria and Covidshield)] and three inactivated viral vaccines (Sinopharm-BBB, CoronaVac and Bharat Biotech Covaxin).3

The European Medicines Agency (EMA) currently authorises four vaccines (Comirnaty, Spikevax, Vaxzevria and COVID-19 Vaccine Janssen) for use in the European Union, having another three under rolling review (Sputnik V, Vero Cell and Vidprevtyn).4

More vaccines are under clinical development and are being assessed for efficacy and safety.

For the overall population, mRNA-based vaccines have shown >90% protection from COVID-19 disease with good tolerance,5, 6 whereas non-replicating adenoviral vector-based vaccines have shown protection rates of 62-90% conferred by different dosing regimens.7, 8

The efficacy has been assessed by examining endpoints based on rates of infection, as well as on seroconversion, as evaluated most often by the development of serum anti-SARS-CoV-2 spike protein antibodies, or recently, more accurately of serum SARS-CoV-2 neutralising antibodies.

Some variants of concern have been emerging globally, with potential consequences on the  transmission, disease severity or resistance to vaccines. By the end of November 2021, the European Centre for Disease Prevention and Control identified Beta, Gamma, Delta and Omicron as variants of concern.9

Different studies have demonstrated that the vaccines remain effective against severe COVID-19 from the current variants of concern, after vaccination completion.10-12

A rational strategy for minimising the risk of emergence of additional virus variants is based on effective mass vaccination programmes for establishment of vaccine-induced immunity in order to prevent COVID-19, reduce the virus circulation in the community and therefore the risk of emergence of new variants. Additional questions related to long-term safety, duration of immunity (long-term efficacy), optimal timing of booster doses, protective immunity in the elderly and immunosuppressed, and contagious potential of vaccinated people, can render the generation of high-quality data an imperative need.

Storage requirements and number of doses differ between vaccines and operational practicalities related to transport, administration, recording and follow-up of vaccinated people has been important for the successful roll-out of vaccination programmes and their optimal impact on public health.

The use of all approved COVID-19 vaccines should be in accordance with official international and national recommendations as well as regulatory guidance.

Specifically, for patients with cancer or a history of cancer, strategies of continued generation of data within clinical trials as well in real world settings will provide more insights on vaccine efficacy, optimal dose and frequency, safety and potential for interaction with malignant disease, antineoplastic therapies and/or other medical comorbidities. Consequently, clinical trials and prospective observational studies are warranted, focusing on patients with active or recent cancer receiving cytotoxic chemotherapy, targeted therapy and/or immunotherapy, as well as patients in the chronic phase of disease or in the survivorship phase.

These recommendations should be used as guidance for prioritising the various aspects of cancer care in order to mitigate the negative effects of the COVID-19 pandemic on the management of people with cancer. The situation is rapidly evolving, and pragmatic actions are required to deal with the challenges of treating patients, while ensuring their rights, safety, access to vaccination and therapies, and overall wellbeing.

Statements:

  • The use of all approved COVID-19 vaccines should be in accordance with official international and national recommendations [V].
  • Effective and safe vaccines against COVID-19, authorised after thorough, independent and robust scientific review by regulatory authorities, should be administered in the context of operationally sound vaccination programmes [V]. A pharmacovigilance plan is mandatory in the context of every vaccination programme.
  • Effective mass vaccination programmes are key for preventing severe COVID-19 and emergence of variants, while safeguarding favourable vaccine risk/benefit profiles [V].
  • Ongoing scientific assessment by medical and regulatory authorities underpins the safe and effective use of COVID-19 vaccines. Use of the vaccine during vaccination campaigns takes into account the pandemic situation and vaccine availability at the international level [V].
  • Continued research in the context of clinical trials and registries as well as in-trial and post-trial follow-up is advised in order to generate more data on vaccine efficacy and safety in the general population as well as in special populations, including patients with active cancer or history of cancer [V].

Different research groups and international collaborative registries have demonstrated that patients with cancer are at variably higher risk of severe COVID-19 as opposed to the general population.13-15

Among people with cancer, including haematological and lung malignancies, older age, male sex, presence of (progressive) metastatic disease, poor performance status and/or medical comorbidities, particular laboratory parameters, as well as recent cytotoxic chemotherapy and/or B-cell depleting therapies are associated with a persistently increased risk for COVID-19 severity and mortality.15-18 Patients with solid tumours appear to suffer an increased risk, particularly in the first year after malignant diagnosis which drops to baseline if diagnosis occurred >5 years ago.19 For any malignancy, active disease confers a significantly increased risk of severe COVID-19 [IV].15, 20

Severity and mortality rates ranged from 5% to 61% in various studies, which is much higher than the overall population mortality rate (~2-3%).15, 16, 21 However, the caveats of additional confounders in the cancer population, such as older age, compromised organ function, immunosuppression or poor performance status, make safe conclusions on the relative contribution of COVID-19 in the high mortality relatively problematic [IV].

SARS-CoV-2 infection may also result in significant and devastating delays in cancer screening, diagnosis, treatment (standard and/or clinical trials) and monitoring/surveillance strategies in patients with cancer, which can ultimately cause an increased risk of cancer-related morbidity and mortality, more advanced cancer at diagnosis, as well as major economic burden and a very high number of patients needing care at the same time in the healthcare systems. Moreover, the impact on accrual in clinical trials evaluating innovative anticancer therapies has been detrimental,22, 23 the education of trainees has been significantly affected and the burnout of healthcare providers increased significantly [V].24-26

There is enough evidence to support anti-infective vaccination in general for patients with cancer (excluding live-attenuated vaccines and replication-competent vector vaccines), including those undergoing active antineoplastic therapy.27-29

Reduced protective effects may occur in patients treated with B cell-depleting agents (anti-CD19, anti-CD20 and anti-CD10 monoclonal antibodies, and CD19 CAR-T cells) in view of suboptimal immune response.30-34 The level of efficacy may be expected to be generally reduced in certain populations of people with cancer with intense immunosuppression, such as recipients of haematopoietic stem cell transplantation or those on chemotherapy [V].27-29 Beyond stem cell transplantation, the efficacy of COVID-19 vaccines can also vary in patients with distinct contexts of malignant disease (tumour type, cancer burden/extent, intrinsic and/or therapy-induced immunosuppression); however, the benefits of vaccination significantly and substantially outweigh potential risks, as these patients also have much higher risk of suffering from more severe COVID-19 disease and its sequelae, including death [V].

The timing of vaccination depends on individual therapy scenarios and may ideally occur before systemic therapy starts; however, if the patient has already started systemic therapy, vaccination during therapy may be implemented [V].

Additionally, COVID-19 vaccination should not affect clinical trial eligibility for people with cancer [V].35

Vaccinating healthcare staff against influenza has been shown to reduce nosocomial transmission of the infection in cancer care.36  Furthermore, certain immunocompromised people with cancer might not achieve sufficient immune response to vaccination depending on the individual scenario. This provides a strong rationale for vaccinating healthcare staff who work in a high-risk setting against COVID-19 [Level of Evidence III for influenza], as well as the patient`s close relatives, family and caregivers.

Statements:

  • People with cancer have increased risk of severe COVID-19 (i.e. patients with haematological malignancy requiring active therapy or with active, advanced solid tumours) and should be vaccinated against SARS-CoV-2 regardless of any other indication (i.e. age) and positioned at high prioritisation based on guidelines [IV]. Patients participating in clinical trials of novel anticancer therapeutics should not be deprived of COVID-19 vaccination; therefore, efforts should be made for clinical trial protocols to explicitly allow and/or not exclude concurrent COVID-19 vaccination, which should take place preferably before trial accrual or during treatment breaks, if that is feasible [V].
  • Healthcare workers and other caregivers (e.g. family, caring for people with cancer) should be prioritised in receiving vaccination to minimise nosocomial or ambulatory setting transmission [III].
  • Close surveillance and monitoring of people with cancer is required after COVID-19 vaccination in order to assess potential adverse events and measure clinical outcomes based on infection rates, severity and mortality from COVID-19, complications from cancer, drug interactions and duration of protection [V].
  • Physical distancing measures, masks, sanitisers, optimal air filtration and other hygiene measures should be considered according to national guidance and should accompany the optimisation of vaccination strategies [V].

Before the COVID-19 pandemic, data on humoral and cellular immune response to antiviral vaccination in cancer patients was scarce, and mostly addressed the issue of influenza vaccination.37, 38

In order to generate protective immunity following vaccination, intact host immunity is needed, particularly with respect to antigen presentation, B- and T-cell activation.

Despite a general exclusion from COVID-19 pivotal clinical trials, recent data consistently demonstrated the efficacy and safety from anti-SARS-CoV-2 vaccination in people with cancer.

Overall, people with cancer have clinically relevant seroconversion rates after full COVID-19 vaccination.39-43

The efficacy seems grossly similar between mRNA and adenoviral vector vaccines,41 however, there are limited comparative effectiveness data, especially in people with cancer.

Importantly, the rate of seroconversion is significantly lower when only one dose of an mRNA vaccine is administered, thus reinforcing the importance of vaccination completion and eventually booster for people with cancer.44, 45

In the VOICE study, the antibody response after only one dose of the mRNA-1273 vaccine was significantly inferior in the three cohorts of cancer patients (32-37%), compared with the non-cancer cohort (66%). However, after full vaccination the rate of participants with neutralising capacity was >99% in the control arm, 93% in the immunotherapy-, 84% in the chemotherapy- and 89% in the immunochemotherapy-treated patient cohorts, respectively.39

In the CAPTURE study, after the first dose only 39% of patients developed SARS-CoV-2 neutralising antibodies and 44% had detectable specific T cells, while after full vaccination 83% of patients with cancer developed neutralising antibodies and 79% T-cell responses. Importantly, only 53% of patients developed specific neutralising antibodies against the delta variant, suggesting a lower efficacy towards this variant of concern.40

In a real-world study enrolling 232 patients with cancer and 261 controls, only 29% of patients with cancer had an antibody response after the first vaccine dose, compared with 84% of controls (P < 0.001). However, after the second dose a 86% seroconversion rate was established in patients with cancer.46

Despite the global satisfactory results for patients with cancer, there exist subgroups with impaired immune responses following anti-SARS-CoV-2 vaccination.

Several studies demonstrated consistently lower seroconversion rates for patients with haematological malignancies compared with patients with solid tumours.40, 41, 47, 48

Specifically, Ehmsen et al. reported a seroconversion rate of 66% (215/323) after full mRNA vaccination in patients with haematological malignancies versus 93% (197/210) in those with solid tumours.48

In the haematology cohort, the seropositivity also varied according to the disease subtype: 11% (1/9) for patients with mantle cell lymphoma, 55% (66/121) with chronic lymphocytic leukaemia (CLL)/small lymphocytic leukaemia (SLL), 62% (24/39) with follicular lymphoma, 72% (13/18) for marginal zone lymphoma, 80% (82/103) for multiple myeloma and 85% (29/34) for diffuse large B-cell lymphoma. Additionally, patients with progressive disease had lower seroconversion rates.48

These findings were confirmed by Thakkar et al,41 who observed that certain classes of therapeutics such as anti-CD20 therapies, Bruton tyrosine kinase inhibitors (BTKis), CAR-T cells and stem cell transplants have been associated with lower seroconversion and vaccination effectiveness.44, 47-49

A lower seropositivity rate post vaccination was reported for patients treated with cytotoxic chemotherapy (92%) compared with other patients with cancer (99%; P = 0.04), 73% for stem cell transplant receipts (19/26; P = 0.0002), 70% for patients on anti-CD20 therapies (16/23, P = 0.0001), and no seroconversion for those very few treated with CAR-T cells (0/3; P = 0.0002178).41

Immunological variables fully capturing cellular and humoral responses are lacking or are difficult to study. It is important to assess clinical vaccination effectiveness based on hard outcomes, such as rates of infection, COVID-19 disease severity and mortality. Embi et al., assessing data from 187 USA hospitals, found that mRNA vaccine effectiveness against COVID-19–associated hospitalisation was clinically significant among immunocompromised patients [77%; 95% confidence interval (CI) 74-80%] but lower than immunocompetent patients (90%; 95% CI 89-91%).50

In a subgroup analysis of 3813 patients with history of cancer from a global phase III randomised trial of Comirnaty/BNT162b2, the clinical vaccination effectiveness was 94.4%, comparable with the general population. However, patients on active anti-cancer therapy were excluded from this trial.42

A retrospective cohort study in 29,152 vaccinated patients with cancer suggested a clinical effectiveness of 57% (95% CI 23-90%) for patients on chemotherapy, 76% (95% CI 50-91%) for those on endocrine therapy and 85% (95% CI 29-100%) for those not receiving systemic therapy.49

Statements:

  • COVID-19 vaccines are both safe and effective for people with cancer. Currently there is no strong evidence to recommend one vaccine option over others [II].
  • Despite a lower efficacy for certain subgroups of patients with cancer, the protection is still clinically relevant, thus vaccination is strongly recommended. These subgroups include patients with haematological malignancies, especially those undergoing cytotoxic chemotherapy, anti-CD20, CAR-T cell or stem cell transplant -based therapies [IV].

It has been hypothesised that a vaccination booster dose could enhance protection in the presence of initial incomplete or waning immunity, and some studies have suggested presence of such benefits for the overall population.51-53

Moreover, there is a gradual increase in the risk of infection for the general population after at least 90 days from the second Comirnaty mRNA vaccine dose.54

In a randomised controlled trial enrolling 120 immunocompromised patients with solid organ transplant, a third dose of the mRNA-1273 vaccine provided a significant increase in specific anti-SARS-COV-2 antibodies and T cells compared with the placebo.55 Importantly, no severe side effects were reported after the boost in this study.55

For people with cancer, different studies have shown that SARS-CoV-2 infection followed by vaccination leads to increased antibody responses compared with vaccination alone.40, 41, 44, 56

In the CAPTURE study, patients who previously had SARS-CoV-2 infection obtained higher levels of neutralising antibody responses (including against the Delta variant) after vaccination when compared with the non-infected, vaccinated population.40

In the CoVigi study, patients with cancer who recovered from COVID-19 and completed vaccination had comparable levels of anti-S antibody (anti-S Ab) as healthy volunteers (P = 0.456), while SARS-CoV-2-naive patients had substantially lower levels of anti-S Ab after the second dose compared with healthy volunteers (P < 0.001).56

In a phase I study enrolling 20 patients with cancer, after a third immunisation with anti-COVID-19 mRNA vaccine, no serious adverse events were reported, while there was a modest increase in neutralising antibodies, without impact on spike-specific T cells.57

In an observational study, 55% (21/38) of patients with B-cell malignancies seroconverted following a COVID-19 vaccination boost, despite insufficient anti-S Ab titres after previous vaccination.58

Similar results were found in another study with 56% (18/32) of fully vaccinated patients with cancer who had seronegative anti-S IgG titres seroconverting after the boost dose.59 Importantly, prior therapy with BTKis and/or anti-CD20 were associated with lower antibody seroconversion (P = 0.01333) and titres (P = 0.0000575), before and after the booster.59

In another study enrolling 37 patients with cancer receiving active systemic therapy, humoral response after a third dose of mRNA vaccine was demonstrated.60

Overall, the current available evidence suggests a potential benefit from a booster dose in fully vaccinated patients with cancer.

Most countries administer the booster dose three to six months after completion of the initial mRNA vaccination (or sooner after the monodosic vaccines).61-63 For people with severely weakened immune systems, the EMA’s Committee for Medicinal Products for Human Use (CHMP) approved an extra dose of the COVID-19 mRNA vaccines at least 28 days after their second dose.61

The identification of patients with cancer with insufficient or waning immunity post-vaccination is scientifically and logistically complex and warrants further study.

Until higher quality evidence becomes available on booster dose benefit, (inter)national guidance that takes into consideration the risk of poor COVID-19 outcomes in people with cancer, vaccine availability/access, vaccination progress and pandemic burden should be followed.

Statement:

  • Given the scientific and logistical complexity in the identification of people with cancer with insufficient or waning immunity, a ‘global’ strategy of a vaccine booster dose should be considered for people with cancer. Until higher quality evidence becomes available on booster dose benefit, (inter)national guidance that takes into consideration the risk of poor COVID-19 outcomes in people with cancer, vaccine availability/access, vaccination progress and the pandemic burden should be followed [IV].

Few SARS-CoV-2 vaccine trials enrolled patients receiving active antineoplastic therapy.

Currently SARS-CoV-2 vaccines approved and in development are non-replicating vaccines, mRNA-based vaccines or more conventional protein subunit vaccines.64

Live-attenuated vaccines are, in general, contraindicated in patients under immunosuppressive therapy [V].38, 65 Indeed, serious adverse events are possible, as was shown with BCG (Bacillus Calmette–Guérin).65 However, it is important to distinguish the risks of attenuated-virus vaccines from replication-incompetent vaccines.66

Two of the anti-SARS-CoV-2 vaccines utilised replication-deficient adenoviral vectors (ChAdOx1, Ad26.COV2-S). Overall, these vaccines are well tolerated, without reactivation risks,67 thus safer for immunocompromised patients.

The mRNA vaccines (mRNA-1273 and BNT162b2) are encapsulated in small liposomes, vectors that are expected to accumulate in tumour tissues. An increased uptake of these liposomes in tumour tissues might impact the immunogenicity of such vaccines, however clinical data on the efficacy of full vaccination in patients with cancer did not substantiate these theoretical concerns [V].68  Importantly, mRNA-based vaccines against non-communicable diseases (e.g. melanoma) have been tested in patients with cancer for the past decade, without raising specific safety concerns.69 Retrospective datasets suggest good tolerability and safety of influenza vaccination (inactivated virus) in patients with cancer receiving immune checkpoint inhibitors,70-72 as well as in patients on cytotoxic therapy or targeted agents.73, 74

Currently, there is no evidence that COVID-19 vaccines impact on the efficacy of chemotherapy, immune checkpoint inhibitors, tyrosine kinase inhibitors or antibodies in a clinically significant way [V].

Whenever possible, the administration of the vaccine should be performed ideally before initiation of chemotherapy and/or other anti-cancer therapies [V].38 In patients who have already initiated therapy, the existing data do not support a specific timing of administration with respect to chemotherapy or other therapeutics, including immune checkpoint inhibitors or targeted therapies [III].38, 74

If an anti-cancer therapy is urgently needed for disease control, it is recommended to proceed with it, followed by COVID-19 vaccine administration as soon as possible when the patient is clinically stable and major symptoms or side-effects are relatively controlled [V].

Statements:

  • There is no evidence to suggest that COVID-19 vaccines significantly impact the efficacy or safety profile of anti-cancer therapies, including cytotoxic chemotherapy, immune checkpoint inhibitors or targeted therapies; therefore, COVID-19 vaccination is strongly recommended [V].
  • It is important to generate more data on the preference for a specific vaccine technology and on potential rare interactions of SARS-CoV-2 vaccines with antineoplastic therapies, via in-trial, post-trial and registry monitoring [V].
  • If an anti-cancer therapeutic is urgently needed for disease control, it is recommended to implement appropriate therapy, followed by COVID-19 vaccination as soon as possible when the patient is clinically stable and major symptoms are relatively controlled. Providers may consider giving anti-cancer therapy and COVID-19 vaccines on different days to avoid misattribution of potential short-term reactions/side-effects [V].

Overall, pharmacovigilance systems worldwide confirmed the excellent safety profile of the various COVID-19 vaccines in the general population, while identifying very rare cases of more severe side-effects (Table 1).

Table 1. Summary of rare/very rare/extremely rare side-effects from the several COVID-19 vaccines approved by the European Medicines Agency (EMA)*

Vaccine

Rare/very rare** side effects

Extremely rare, not known incidence**

Comirnaty

Acute peripheral facial paralysis

Anaphylaxis, myocarditis, pericarditis, extensive swelling of vaccinated limb, facial swelling

Spikevax

Acute peripheral facial paralysis, hypoaesthesia

Myocarditis, pericarditis, facial swelling

Vaxzevria

Facial paralysis, Guillain-Barré syndrome, thrombosis with thrombocytopaenia syndrome

Capillary leak syndrome, angioedema

Ad26.COV2-S

Lymphadenopathy, hypersensitivity, urticaria, hypoaesthesia, tinnitus, venous thromboembolism, vomiting, Guillain-Barré syndrome, thrombosis in combination with thrombocytopaenia

Immune thrombocytopaenia, anaphylaxis, capillary leak syndrome

*Information extracted from EMA Summary of Products Characteristics (SmPC), available 28 October 2021.

**Rare (≥1/10,000 to <1/1000); very rare (<1/10,000); not known incidence (cannot be estimated from available data).

 

The safety of various vaccines is continuously monitored, with regular updates provided by the EMA and other global or national regulatory authorities.

Different studies showed a similar safety profile of COVID-19 vaccines in patients with cancer in comparison with the general population.42, 43, 45, 75-77

Additionally, the safety profile of COVID-19 mRNA vaccines in patients with haematological malignancies were found to be similar compared to age-matched healthy individuals.78

In a subgroup analysis of 3813 patients with history of cancer from a phase III randomised trial of the mRNA vaccine Comirnaty, only two cases of severe related adverse events (one ventricular arrhythmia and one lymphadenopathy) were reported, and both were resolved. The common and mild adverse events were similar to the non-cancer population, mainly injection-site pain, fatigue, pyrexia, chills, headache and myalgia.42

Similar results were reported from a prospective cohort study including 232 patients with solid tumours on active treatment and 261 age-matched health care workers vaccinated against COVID-19.75 Moreover, in the VOICE cohort no new safety signs were found after mRNA-1273 (Spikevax) vaccination in 791 patients with cancer.76

A survey on 1069 patients with cancer reported that 82.3% had none or mild adverse events, and only 2% reported severe events after vaccination against COVID-19. Importantly, in 96% of the patients, their ongoing anticancer therapy did not need to be delayed, interrupted or stopped.79

Statement:

  • COVID-19 vaccines are safe and very well tolerated by patients with cancer, exhibiting excellent tolerability profiles, similar to the general population. Pharmacovigilance systems should continue to monitor the benefit/risk ratio of the different COVID-19 vaccines in patients with cancer [V].

Availability and equitable access of COVID-19 vaccination is the most important driver for protection of public health, with compliance to international guidelines to be promoted and supported.

Vaccination strategies have been published worldwide, in order to prioritise vaccine administration in the different populations, including for people with cancer. However, patients with cancer do not represent a homogeneous population.

In general, cancer disease reveals three aspects of pathways: patients with active disease on treatment, those with chronic disease after specific treatment and patients in the survivorship phase. Vaccination is absolutely essential to protect all these groups of patients.

The rate of COVID-19 vaccination acceptance amongst patients with cancer has been very positive across Europe, as assessed through different surveys, for instance with 84% acceptance in Portugal,80 85% in Italy81 and 81-90% in Ireland.82, 83

Despite the encouraging compliance rates, 10-20% of patients are still hesitant about COVID-19 vaccination, despite the available evidence/data. These patients are faced with a higher risk of severe COVID-19 disease, while they represent a higher potential source of transmission of SARS-CoV-2 to other, vulnerable patients with cancer.

It is important to reinforce trust, education and easy, transparent communication with those patients and their relatives based on establishing a better understanding of their concerns; communicating mature data on vaccines’ established safety and efficacy, including people with cancer; reassuring them on the non-interference of COVID-19 vaccines with their cancer treatment.

Informed consent and shared decision making should be the rule to discuss benefits and risks of the COVID-19 vaccination to prevent patients from a “double jeopardy”: cancer progression and SARS-CoV-2 infection.

Most European countries are successfully implementing their vaccination campaigns for patients with cancer. However, vast populations worldwide have no access to anti-SARS-CoV-2 vaccines, including patients with cancer. Solidarity mechanisms focused on accessibility, equity and sustainability should be reinforced to vaccinate and protect the global population of vulnerable patients worldwide.

Statements:

  • Vaccination is absolutely essential to protect all patients with cancer.
  • In order to better refine the risk/benefit profile and implement shared decision making with cancer patients, we propose a four-step process [V]:
    • Step 1: Consider the phase of malignant disease and therapy: active cancer on treatment, chronic disease after treatment or survivorship.
    • Step 2: Consider age, fitness/performance status and medical comorbidities as general risk factors; specifically, anaphylactic history, obesity, diabetes mellitus, hypertension, respiratory, cardiac and renal disorders, hypercoagulability.
    • Step 3: Consider vaccine-related interactions on treatment efficacy and safety.
    • Step 4: Secure informed consent and implement shared decision making enabling and facilitating broader vaccination against COVID-19.
  • It is important to encourage open communication with patients and relatives hesitant toward vaccination based on understanding of their concerns, establishing trust and communicating data on the safety, efficacy and non-interference of COVID-19 vaccines with their cancer treatment [V].
  • Solidarity mechanisms should be reinforced in order to secure immediate and equitable access to COVID-19 vaccines for all vulnerable patients worldwide [V].

Vaccination has been key to protect the overall population, but some people with immune-deficient conditions may still suffer from COVID-19. Beyond vaccination, other treatments may provide benefit after a close contact or developing COVID-19 infection (see Appendix).

In November 2021, the EMA approved two monoclonal antibodies targeting the spike protein of SARS-CoV-2, for patients at risk of severe COVID-19,84 while several others are being tested.85

Monoclonal antibodies can be an additional option to reduce disease progression, viral load and the duration of viral shedding.

The use of monoclonal antibodies in the outpatient setting for preventing severe COVID-19 disease suggests that passive antibody prophylaxis may be another approach for immunosuppressed patients who do not mount an adequate immune response to vaccination.86

Monoclonal antibodies with modifications in the Fc portion of the formulation that extend the half-life and the likely effective concentration for several months or enhance the immune clearance of SARS-CoV-2 may be considered for immunocompromised patients who may not have a response to a vaccine.87

Antiviral agents that inhibit SARS-CoV-2 replication offer an alternative mechanism of protection that should be unaffected by viral mutations that compromise the efficacy of monoclonal antibodies.

Molnupiravir was reported to suppress replication of SARS-CoV-2 in patients with early infection, and two larger clinical trials are in progress (NCT04575584 and NCT04575597).88

Paxlovid, another antiviral drug, was shown in a clinical trial to reduce hospitalisation or death among people with COVID-19 at high risk of severe illness.89

Stopping the replication of SARS-CoV-2 in a compromised host by means of vaccination or an effective monoclonal antibody or small molecule may halt the development of mutations/variants and the spread of SARS-CoV-2 to close contacts.

Statements:

  • Passive monoclonal antibodies could be used as post-exposure prophylaxis or early treatment in order to increase protection of immunosuppressed patients against severe COVID-19 [II].
  • Antiviral agents that inhibit SARS-CoV-2 replication offer an alternative mechanism of protection that may be unaffected by mutations that compromise monoclonal antibodies. More data are needed to better study this new class of agents [V].
  • Approved monoclonal antibodies and antiviral agents should not substitute COVID-19 vaccination and could be used as supplementary therapies preventing severe COVID-19, according to the formal indications [V].

I - Evidence from at least one large randomised, controlled trial of good methodological quality (low potential for bias) or meta-analyses of well-conducted randomised trials without heterogeneity

II - Small randomised trials or large randomised trials with a suspicion of bias (lower methodological quality) or meta-analyses of such trials or of trials with demonstrated heterogeneity

III - Prospective cohort studies

IV - Retrospective cohort studies or case–control studies

V - Studies without control group, case reports, expert opinions

Medicines approved by the WHO and/or the EMA against COVID-19.

Treatments against SARS-CoV-2
Drugs
Marketing authorisation holder
Prevention

mRNA vaccines

Comirnaty

mRNA1273

Pfizer

Moderna

Non-replicating viral vector vaccines

Ad26.COV2.S

AZD1222/ Vaxzevria

Covishield*

Janssen,

Oxford/AstraZeneca

Oxford/AstraZeneca

Inactivated viral vaccines

Covaxin*

BBIBP-CorV*

CoronaVac*

Bharat Biotech

Sinopharm

Sinovac

Close Contacts and/or COVID-19 infection

Monoclonal antibodies

Regdanvimab (Regkirona)

Ronapreve (casirivimab + imdevimab)

Celltrion

Regeneron/Roche

Anti-virals

Remdesivir (Veklury)

(RNA polymerase inhibitor)

Gilead

Only severe COVID-19

IL-receptor blockers

Tocilizumab

Sarilumab*

Roche

Regeneron/Sanofi

Steroids

-

-

Notes:

Information retrieved by 10th of December 2021.

The list of vaccine/drugs approved is not exhaustive, as all regulators are not covered

*WHO approval; NOT EMA approval

EMA, European Medicines Agency; IL, interleukin; mRNA, messenger RNA; WHO, World Health Organization.

  1. COVID-19 vaccine tracker and landscape. World Health Organization, 2021. https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines (8 November 2021, date last accessed).
  2. Dong Y, Dai T, Wei Y et al. A systematic review of SARS-CoV-2 vaccine candidates. Signal Transduction and Targeted Therapy 2020; 5 (1): 237.
  3. COVID-19 vaccines. World Health Organization, 2021. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/covid-19-vaccines (8 November 2021, date last accessed).
  4. COVID-19 vaccines. European Medicines Agency, 2021. https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/treatments-vaccines/covid-19-vaccines (3 December 2021, date last accessed).
  5. Polack FP, Thomas SJ, Kitchin N et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. New England Journal of Medicine 2020; 383 (27): 2603-2615.
  6. Baden LR, El Sahly HM, Essink B et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. New England Journal of Medicine 2020; 384 (5): 403-416.
  7. Voysey M, Clemens SAC, Madhi SA et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. The Lancet 2021; 397 (10269): 99-111.
  8. Sadoff J, Gray G, Vandebosch A et al. Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19. New England Journal of Medicine 2021; 384 (23): 2187-2201.
  9. SARS-CoV-2 variants of concern as of 3 December 2021. European Centre for Disease Prevention and Control, 2021. https://www.ecdc.europa.eu/en/covid-19/variants-concern (3 December 2021, date last accessed).
  10. Lopez Bernal J, Andrews N, Gower C et al. Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant. New England Journal of Medicine 2021; 385 (7): 585-594.
  11. Nasreen S, Chung H, He S et al. Effectiveness of COVID-19 vaccines against variants of concern in Ontario, Canada. medRxiv 2021: 2021.2006.2028.21259420.
  12. Pouwels KB, Pritchard E, Matthews PC et al. Impact of Delta on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK. medRxiv 2021: 2021.2008.2018.21262237.
  13. Ruthrich MM, Giessen-Jung C, Borgmann S et al. COVID-19 in cancer patients: clinical characteristics and outcome-an analysis of the LEOSS registry. Ann Hematol 2021; 100 (2): 383-393.
  14. Chavez-MacGregor M, Lei X, Zhao H et al. Evaluation of COVID-19 Mortality and Adverse Outcomes in US Patients With or Without Cancer. JAMA Oncology 2021.
  15. Kuderer NM, Choueiri TK, Shah DP et al. Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study. The Lancet 2020; 395 (10241): 1907-1918.
  16. Romano E, Gennatas S, Rogado J et al. 1567MO COVID-19 and cancer: First report of the ESMO international, registry-based, cohort study (ESMO CoCARE). Annals of Oncology 2021; 32: S1133.
  17. Grivas P, Khaki AR, Wise-Draper TM et al. Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: a report from the COVID-19 and Cancer Consortium. Ann Oncol 2021; 32 (6): 787-800.
  18. Lee LY, Cazier JB, Angelis V et al. COVID-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: a prospective cohort study. Lancet 2020; 395 (10241): 1919-1926.
  19. Williamson EJ, Walker AJ, Bhaskaran K et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature 2020; 584 (7821): 430-436.
  20. Martin-Moro F, Marquet J, Piris M et al. Survival study of hospitalised patients with concurrent COVID-19 and haematological malignancies. Br J Haematol 2020; 190 (1): e16-e20.
  21. Palmieri C, Turtle L, Docherty A et al. 1670O Prospective data of first 1,797 hospitalised patients with cancer and COVID-19 derived from the COVID-19 Clinical Information Network and international Severe Acute Respiratory and emerging Infections Consortium, WHO Coronavirus Clinical Characterisation Consortium. Annals of Oncology 2020; 31: S992.
  22. Boughey JC, Snyder RA, Kantor O et al. Impact of the COVID-19 Pandemic on Cancer Clinical Trials. Ann Surg Oncol 2021; 28 (12): 7311-7316.
  23. Castelo-Branco L, Awada A, Pentheroudakis G et al. Beyond the lessons learned from the COVID-19 pandemic: opportunities to optimize clinical trial implementation in oncology. ESMO Open 2021; 6 (5).
  24. Papapanou M, Routsi E, Tsamakis K et al. Medical education challenges and innovations during COVID-19 pandemic. Postgrad Med J 2021.
  25. Banerjee S, Lim KHJ, Murali K et al. The impact of COVID-19 on oncology professionals: results of the ESMO Resilience Task Force survey collaboration. ESMO Open 2021; 6 (2): 100058.
  26. Prasad K, McLoughlin C, Stillman M et al. Prevalence and correlates of stress and burnout among U.S. healthcare workers during the COVID-19 pandemic: A national cross-sectional survey study. EClinicalMedicine 2021; 35: 100879.
  27. Cordonnier C, Einarsdottir S, Cesaro S et al. Vaccination of haemopoietic stem cell transplant recipients: guidelines of the 2017 European Conference on Infections in Leukaemia (ECIL 7). Lancet Infect Dis 2019; 19 (6): e200-e212.
  28. Mikulska M, Cesaro S, de Lavallade H et al. Vaccination of patients with haematological malignancies who did not have transplantations: guidelines from the 2017 European Conference on Infections in Leukaemia (ECIL 7). Lancet Infect Dis 2019; 19 (6): e188-e199.
  29. Rieger CT, Liss B, Mellinghoff S et al. Anti-infective vaccination strategies in patients with hematologic malignancies or solid tumors-Guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO). Ann Oncol 2018; 29 (6): 1354-1365.
  30. Bedognetti D, Ansaldi F, Zanardi E et al. Seasonal and pandemic (A/H1N1 2009) MF-59-adjuvanted influenza vaccines in complete remission non-Hodgkin lymphoma patients previously treated with rituximab containing regimens. Blood 2012; 120 (9): 1954-1957.
  31. Bedognetti D, Zoppoli G, Massucco C et al. Impaired response to influenza vaccine associated with persistent memory B cell depletion in non-Hodgkin's lymphoma patients treated with rituximab-containing regimens. J Immunol 2011; 186 (10): 6044-6055.
  32. Berglund A, Willen L, Grodeberg L et al. The response to vaccination against influenza A(H1N1) 2009, seasonal influenza and Streptococcus pneumoniae in adult outpatients with ongoing treatment for cancer with and without rituximab. Acta Oncol 2014; 53 (9): 1212-1220.
  33. van Assen S, Holvast A, Benne CA et al. Humoral responses after influenza vaccination are severely reduced in patients with rheumatoid arthritis treated with rituximab. Arthritis Rheum 2010; 62 (1): 75-81.
  34. Yri OE, Torfoss D, Hungnes O et al. Rituximab blocks protective serologic response to influenza A (H1N1) 2009 vaccination in lymphoma patients during or within 6 months after treatment. Blood 2011; 118 (26): 6769-6771.
  35. Desai A, Gainor JF, Hegde A et al. COVID-19 vaccine guidance for patients with cancer participating in oncology clinical trials. Nat Rev Clin Oncol 2021; 18 (5): 313-319.
  36. Frenzel E, Chemaly RF, Ariza-Heredia 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 2016; 44 (9): 1016-1021.
  37. Ward EM, Flowers CR, Gansler T et al. The importance of immunization in cancer prevention, treatment, and survivorship. CA Cancer J Clin 2017; 67 (5): 398-410.
  38. Rubin LG, Levin MJ, Ljungman P et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014; 58 (3): 309-318.
  39. Oosting SF, van der Veldt AAM, GeurtsvanKessel CH 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 2021; 22 (12): 1681-1691.
  40. Shepherd STC, Fendler A, Au L et al. 1557O Adaptive immunity to SARS-CoV-2 infection and vaccination in cancer patients: The CAPTURE study. Annals of Oncology 2021; 32: S1129.
  41. Thakkar A, Gonzalez-Lugo JD, Goradia N et al. Seroconversion rates following COVID-19 vaccination among patients with cancer. Cancer Cell 2021; 39 (8): 1081-1090.e1082.
  42. Thomas SJ, Perez JL, Lockhart SP et al. 1558O COVID-19 vaccine in participants (ptcpts) with cancer: Subgroup analysis of efficacy/safety from a global phase III randomized trial of the BNT162b2 (tozinameran) mRNA vaccine. Annals of Oncology 2021; 32: S1129.
  43. Subbiah IM, Williams LA, Peek A et al. Real-world patient-reported and clinical outcomes of BNT162b2 mRNA COVID-19 vaccine in patients with cancer. Journal of Clinical Oncology 2021; 39 (15_suppl): 6510-6510.
  44. Mair MJ, Berger JM, Berghoff AS et al. Humoral Immune Response in Hematooncological Patients and Health Care Workers Who Received SARS-CoV-2 Vaccinations. JAMA Oncology 2021: 1-8.
  45. Monin L, Laing AG, Muñoz-Ruiz M 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. The Lancet Oncology 2021; 22 (6): 765-778.
  46. Ben-Aharon I, Waldhorn I, Holland R et al. 1559O Efficacy and toxicity of BNT162b2 vaccine in cancer patients. Annals of Oncology 2021; 32: S1130.
  47. Addeo A, Shah PK, Bordry N et al. Immunogenicity of SARS-CoV-2 messenger RNA vaccines in patients with cancer. Cancer Cell 2021; 39 (8): 1091-1098.e1092.
  48. Ehmsen S, Asmussen A, Jeppesen SS et al. Antibody and T cell immune responses following mRNA COVID-19 vaccination in patients with cancer. Cancer Cell 2021; 39 (8): 1034-1036.
  49. Wu JTY, La J, Branch-Elliman W et al. 1562MO Effectiveness of COVID-19 vaccination in cancer patients: A nationwide Veterans Affairs study. Annals of Oncology 2021; 32: S1131.
  50. Embi PJ, Levy ME, Naleway AL 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 Morb Mortal Wkly Rep 2021; 70 (44): 1553-1559.
  51. Barda N, Dagan N, Cohen C et al. Effectiveness of a third dose of the BNT162b2 mRNA COVID-19 vaccine for preventing severe outcomes in Israel: an observational study. Lancet 2021.
  52. Falsey AR, Frenck RW, Jr., Walsh EE et al. SARS-CoV-2 Neutralization with BNT162b2 Vaccine Dose 3. N Engl J Med 2021; 385 (17): 1627-1629.
  53. Krause PR, Fleming TR, Peto R et al. Considerations in boosting COVID-19 vaccine immune responses. Lancet 2021; 398 (10308): 1377-1380.
  54. Israel A, Merzon E, Schaffer AA et al. Elapsed time since BNT162b2 vaccine and risk of SARS-CoV-2 infection: test negative design study. BMJ 2021; 375: e067873.
  55. Hall VG, Ferreira VH, Ku T et al. Randomized Trial of a Third Dose of mRNA-1273 Vaccine in Transplant Recipients. N Engl J Med 2021; 385 (13): 1244-1246.
  56. Obermannova R, Demlova R, Selingerova I et al. 1563MO CoVigi phase IV multicentric trial evaluating COVID-19 vaccination adverse events and immune response dynamics in cancer patients: First results on antibody and cellular immunity. Annals of Oncology 2021; 32: S1131.
  57. Shroff RT, Chalasani P, Wei R et al. Immune responses to two and three doses of the BNT162b2 mRNA vaccine in adults with solid tumors. Nat Med 2021; 27 (11): 2002-2011.
  58. Greenberger LM, Saltzman LA, Senefeld JW et al. Anti-spike antibody response to SARS-CoV-2 booster vaccination in patients with B cell-derived hematologic malignancies. Cancer Cell 2021; 39 (10): 1297-1299.
  59. Shapiro LC, Thakkar A, Campbell ST et al. Efficacy of booster doses in augmenting waning immune responses to COVID-19 vaccine in patients with cancer. Cancer Cell 2021.
  60. Rottenberg Y, Grinshpun A, Ben-Dov IZ 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 2021.
  61. Comirnaty and Spikevax: EMA recommendations on extra doses and boosters. European Medicines Agency, 2021. https://www.ema.europa.eu/en/news/comirnaty-spikevax-ema-recommendations-extra-doses-boosters (3 December 2021, date last accessed).
  62. EMA evaluating data on booster dose of COVID-19 Vaccine Janssen. European Medicines Agency, 2021. https://www.ema.europa.eu/en/news/ema-evaluating-data-booster-dose-covid-19-vaccine-janssen (3 December 2021, date last accessed).
  63. Coronavirus (COVID-19) Update: FDA Takes Additional Actions on the Use of a Booster Dose for COVID-19 Vaccines. U.S. Food & Drug Administration, 2021. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-takes-additional-actions-use-booster-dose-covid-19-vaccines (3 December 2021, date last accessed).
  64. Brisse M, Vrba SM, Kirk N et al. Emerging Concepts and Technologies in Vaccine Development. Front Immunol 2020; 11: 583077.
  65. Lopez A, Mariette X, Bachelez H et al. Vaccination recommendations for the adult immunosuppressed patient: A systematic review and comprehensive field synopsis. J Autoimmun 2017; 80: 10-27.
  66. Robert-Guroff M. Replicating and non-replicating viral vectors for vaccine development. Curr Opin Biotechnol 2007; 18 (6): 546-556.
  67. Custers J, Kim D, Leyssen M et al. Vaccines based on replication incompetent Ad26 viral vectors: Standardized template with key considerations for a risk/benefit assessment. Vaccine 2021; 39 (22): 3081-3101.
  68. Fanciullino R, Ciccolini J, Milano G. COVID-19 vaccine race: watch your step for cancer patients. Br J Cancer 2021; 124 (5): 860-861.
  69. Weide B, Carralot JP, Reese A et al. Results of the first phase I/II clinical vaccination trial with direct injection of mRNA. J Immunother 2008; 31 (2): 180-188.
  70. Failing JJ, Ho TP, Yadav S et al. Safety of Influenza Vaccine in Patients With Cancer Receiving Pembrolizumab. JCO Oncol Pract 2020; 16 (7): e573-e580.
  71. Chong CR, Park VJ, Cohen B et al. Safety of Inactivated Influenza Vaccine in Cancer Patients Receiving Immune Checkpoint Inhibitors. Clin Infect Dis 2020; 70 (2): 193-199.
  72. Wijn DH, Groeneveld GH, Vollaard AM 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 2018; 104: 182-187.
  73. Bayle A, Khettab M, Lucibello F et al. Immunogenicity and safety of influenza vaccination in cancer patients receiving checkpoint inhibitors targeting PD-1 or PD-L1. Ann Oncol 2020; 31 (7): 959-961.
  74. Rousseau B, Loulergue P, Mir O 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 2012; 23 (2): 450-457.
  75. Goshen-Lago T, Waldhorn I, Holland R et al. Serologic Status and Toxic Effects of the SARS-CoV-2 BNT162b2 Vaccine in Patients Undergoing Treatment for Cancer. JAMA Oncology 2021.
  76. Oosting S, Van der Veldt AAM, GeurtsvanKessel CH et al. LBA8 Vaccination against SARS-CoV-2 in patients receiving chemotherapy, immunotherapy, or chemo-immunotherapy for solid tumors. Annals of Oncology 2021; 32: S1337.
  77. Cavanna L, Citterio C, Biasini C et al. COVID-19 vaccines in adult cancer patients with solid tumours undergoing active treatment: Seropositivity and safety. A prospective observational study in Italy. European Journal of Cancer 2021; 157: 441-449.
  78. Greenberger LM, Saltzman LA, Senefeld JW et al. Antibody response to SARS-CoV-2 vaccines in patients with hematologic malignancies. Cancer Cell 2021; 39 (8): 1031-1033.
  79. Sapir E, Moisa N, Litvin A et al. 1594P SARS-CoV-2 vaccines in cancer patients (pts), real-world data (RWD) from 1069 Belong.life users. Annals of Oncology 2021; 32: S1144.
  80. de Sousa MJP, Caramujo C, Julio N et al. 1598P Acceptance of SARS-CoV-2 vaccination among patients with cancer undergoing immunosuppressive therapy: Portuguese study. Ann Oncol 2021; 32: S1145-S1146.
  81. Della Torre S, Curcio R, Galeassi A et al. 1644P What is the attitude to new vaccines against COVID-19 in cancer patients? Annals of Oncology 2021; 32: S1161.
  82. Mullally WJ, Flynn C, Carr P et al. 1595P Acceptance of COVID-19 vaccination among cancer patients in an Irish cancer centre. Annals of Oncology 2021; 32: S1144-S1145.
  83. Horan S, Murphy C, Keogh R et al. 1599P Vaccination in the COVID-19 era: Attitudes amongst oncology patients. Ann Oncol 2021; 32: S1146.
  84. COVID-19: EMA recommends authorisation of two monoclonal antibody medicines. European Medicines Agency, 2021. https://www.ema.europa.eu/en/news/covid-19-ema-recommends-authorisation-two-monoclonal-antibody-medicines (3 December 2021, date last accessed).
  85. Taylor PC, Adams AC, Hufford MM et al. Neutralizing monoclonal antibodies for treatment of COVID-19. Nat Rev Immunol 2021; 21 (6): 382-393.
  86. MS Cohen AN, M Mulligan, R Novak, M Marovich, A Stemer, AC  Adams, AE Schade, J Knorr, JL Tuttle, J Sabo, P Klekotka, L Shen, DM Skovronsky. Bamlanivimab prevents Covid-19 morbidity and mortality in nursing-home setting. Presented at the virtual Conference on Retroviruses and Opportunistic Infections, March 9, 2021:121-121. abstract. . https://www.croiconference.org/abstract/bamlanivimab-prevents-covid-19-morbidity-and-mortality-in-nursing-home-setting/ (3 December 2021, date last accessed).
  87. Ko SY, Pegu A, Rudicell RS et al. Enhanced neonatal Fc receptor function improves protection against primate SHIV infection. Nature 2014; 514 (7524): 642-645.
  88. Service RF. A call to arms. Researchers are testing an arsenal of weapons against the pandemic coronavirus. Science, 2021. https://www.science.org/content/article/researchers-race-develop-antiviral-weapons-fight-pandemic-coronavirus (3 December 2021, date last accessed).
  89. Mahase E. Covid-19: Pfizer's paxlovid is 89% effective in patients at risk of serious illness, company reports. BMJ 2021; 375: n2713.

Latest update 16 December 2021; first publication 22 December 2020 (previous update 27 April 2021).

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