British Journal of Cancer www.nature.

com/bjc

ARTICLE OPEN

Clinical Studies

Natural immunity to SARS-CoV-2 and breakthrough infections

in vaccinated and unvaccinated patients with cancer
✉
Alessio Cortellini 1,2 , Juan Aguilar-Company3,4, Ramon Salazar5, Mark Bower6, Ailsa Sita-Lumsden7, Andrea Plaja8, Alvin J. X. Lee9,
Alexia Bertuzzi , Carlo Tondini11, Nikolaos Diamantis12, Clara Martinez-Vila13, Aleix Prat 14, Eleanor Apthorp15,
10

Alessandra Gennari16 and David J. Pinato 1,16

© The Author(s) 2022

BACKGROUND: Consolidated evidence suggests spontaneous immunity from SARS-CoV-2 is not durable, leading to the risk of
reinfection, especially in the context of newly emerging viral strains. In patients with cancer who survive COVID-19 prevalence and
severity of SARS-CoV-2 reinfections are unknown.
METHODS: We aimed to document natural history and outcome from SARS-CoV-2 reinfection in patients recruited to OnCovid
1234567890();,:

(NCT04393974), an active European registry enrolling consecutive patients with a history of solid or haematologic malignancy
diagnosed with COVID-19.
RESULTS: As of December 2021, out of 3108 eligible participants, 1806 COVID-19 survivors were subsequently followed at
participating institutions. Among them, 34 reinfections (1.9%) were reported after a median time of 152 days (range: 40–620) from
the first COVID-19 diagnosis, and with a median observation period from the second infection of 115 days (95% CI: 27–196). Most of
the first infections were diagnosed in 2020 (27, 79.4%), while most of reinfections in 2021 (25, 73.5%). Haematological malignancies
were the most frequent primary tumour (12, 35%). Compared to first infections, second infections had lower prevalence of COVID-
19 symptoms (52.9% vs 91.2%, P = 0.0008) and required less COVID-19-specific therapy (11.8% vs 50%, P = 0.0013). Overall, 11
patients (32.4%) and 3 (8.8%) were fully and partially vaccinated against SARS-CoV-2 before the second infection, respectively. The
14-day case fatality rate was 11.8%, with four death events, none of which among fully vaccinated patients.
CONCLUSION: This study shows that reinfections in COVID-19 survivors with cancer are possible and more common in patients
with haematological malignancies. Reinfections carry a 11% risk of mortality, which rises to 15% among unvaccinated patients,
highlighting the importance of universal vaccination of patients with cancer.
British Journal of Cancer (2022) 127:1787–1792; https://doi.org/10.1038/s41416-022-01952-x

INTRODUCTION protective capacity over time [5]. Waning immunity from SARS-
In the general population the seroconversion rate following CoV-2 and the emergence of new viral strains with varying
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) capacity to escape immunity [6] are key immunologic mechanisms
infection exceeds 95%, with clear evidence of neutralising explaining mounting cases of SARS-Cov-2 reinfections [7, 8]. Whilst
antibody response leading to protective immunity [1]. Whilst mechanisms underlying natural and vaccinal immunity are
anti-SARS-CoV-2 antibodies may not be an optimal predictive different [9], the question of durability of protection is central to
correlate of protection from SARS-CoV-2, several studies have vaccinal efficacy, having led to the recommendation to offer
shown a decline in neutralising antibody titres over time [2, 3]. In “booster” doses in an attempt to prevent reinfection and adverse
addition, even though SARS-CoV-2 infection can elicit a potent, consequences from it [10].
antigen-specific memory T-cell response in the host [4], evidence Patients with cancer are especially vulnerable from coronavirus
suggests that virus-specific CD4 + and CD8 + T cells may lose disease 2019 (COVID-19) [11], but similar degree of seroconversion

1
Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London, UK. 2Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico,
Rome, Italy. 3Medical Oncology, Vall d’Hebron University Hospital and Institute of Oncology (VHIO), Barcelona, Spain. 4Infectious Diseases, Vall d’Hebron University Hospital,
Barcelona, Spain. 5Department of Medical Oncology, ICO L’Hospitalet, Oncobell Program (IDIBELL), CIBERONC, Hospitalet de Llobregat, Spain. 6Department of Oncology and
National Centre for HIV Malignancy, Chelsea and Westminster Hospital, London, UK. 7Medical Oncology, Guy’s and St Thomas’ NHS Foundation Trust (GSTT), London, UK.
8
Medical Oncology Department, B-ARGO Group, IGTP, Catalan Institute of Oncology-Badalona, Badalona, Spain. 9Cancer Division, University College London Hospitals, London,
UK. 10Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. 11Oncology Unit, ASST Papa Giovanni XXIII,
Bergamo, Italy. 12Medical Oncology, Barts Health NHS Trust, London, UK. 13Fundació Althaia Manresa, Manresa, Spain. 14Translational Genomics and Targeted Therapies in Solid
Tumors, IDIBAPS, Barcelona, Spain. 15Medical School, King’s College London, London, UK. 16Division of Oncology, Department of Translational Medicine, University of Piemonte
Orientale, Novara, Italy. ✉email: [email protected]

Received: 4 May 2022 Revised: 3 August 2022 Accepted: 5 August 2022

Published online: 22 August 2022

Published on Behalf of CRUK

 A. Cortellini et al.
1788
Data lock 22/12/2021
3237 patients entered

Missing information about date of COVID-19 diagnosis

66 patients
Missing mortality outcome
63 patients

Study population: 3108 patients

(diagnosed between the 27/02/2020 and the 30/11/2021)

Died within 28 days after COVID-19 diagnosis

812 patients
Missing post-COVID-19 reassessment (mortality outcome available)
490 patients

1806 post COVID-19 reassessed

Median post-COVID-19 observation period: 158 days (IQR: 28–321)

34 patients with documented SARS-CoV-2 reinfections

Median interval between infections: 152 days (range: 40–620).

Fig. 1 Study flowchart. IQR interquartile range.

after recovery compared to the general population has been COVID-19-related mortality, in an attempt of differentiating early (COVID-
reported from large real-world case series [12]. However, weaker 19 related) from late (cancer-related) mortality as already done in with our
immune responses to the infection, with possible implications for registry [17].
the risk of reinfection, are reported [13]. No reliable evidence SARS-CoV-2 vaccination status prior to both infections were also
reported. Patients were categorised as fully vaccinated if they had
exists as to the prevalence and severity of SARS-CoV-2 reinfections
received two doses for the BNT162b2, mRNA-1273 and ChAdOx1-S
in patients with cancer. To address this gap in knowledge, we vaccines at least 14 days prior to COVID-19 diagnosis or in case of
interrogated the OnCovid study and described the natural course infection diagnosed at least 28 days after a single dose of the Ad.26.COV2.S
and clinical outcome of SARS-CoV-2 breakthrough infections after vaccine. Patients who received at least one vaccination, without meeting
prior COVID-19 in our study population. the above-mentioned criteria, were considered partially vaccinated. A
detailed description of study methodology is provided in Supplementary
Methods.
METHODS
OnCovid (NCT04393974) is an active European registry study that, since
the beginning of the pandemic, has collected data from consecutive RESULTS
patients with a history of solid or haematologic malignancy diagnosed After the exclusion of 129 patients (66 due to missing date of
with COVID-19. Patients’ observation time started from the date of first COVID-19 diagnosis, 63 due to missing mortality outcome), out of
SARS-CoV-2 infection confirmation until patient’ death or loss to follow-up. 3108 eligible participants, 1806 COVID-19 survivors were subse-
Clinical information of patients who survived COVID-19 and were
subsequently followed at the participating institutions according to local quently followed at participating institutions, with a median post-
practice are regularly entered the registry in the context of the post- COVID-19 observation period of 158 days (interquartile range:
COVID-19 follow-up analysis [14–16]. 28–321 days). Among the 1302 excluded patients, 812 (62.4%)
In the present analysis, we evaluated the prevalence and clinical died within 28 days of COVID-19 diagnosis whilst post-COVID-19
characteristics of SARS-CoV-2 breakthrough infections among COVID-19 information was not available for 490 (37.6%) patients. Overall, 34
survivors who underwent a formal clinical post-COVID-19 follow-up in the reinfections (1.9%) were reported after a median time of 152 days
study population. (range: 40–620) from the first COVID-19 diagnosis (Fig. 1). Baseline
By the data lock of 22nd of December 2021, the registry included 3237 demographics and oncological characteristics are reported in
consecutive patients from 37 institutions across six countries (UK, Italy, Supplementary Table 2. The majority of patients were female
Spain, France, Belgium and Germany), and included patients diagnosed
with COVID-19 between February 27, 2020 and November 30, 2021. A list (18, 52.9%), aged ≥65 years old (20, 58.8%) and presented at least
of the participating centres with eligible patients for this analysis is one comorbidity (26, 76.5%). The most frequent primary tumour
provided in Supplementary Table 1. were haematological malignancies (12, 35%), of which 4 lym-
We first described baseline demographics and oncological character- phoma (4, 33.3%), 1 Hodgkin’s disease (8.3%), 2 (16.7%) multiple
istics of patients who experienced a second SARS-CoV-2 infection among myeloma, 2 (16.7%) myeloid leukaemia.
the study population. The vaccination status prior the first and the second No reinfected patient was fully vaccinated against SARS-CoV-2
infection was also reported. COVID-19 sequelae stemming from the first prior to the first infection. Overall, 11 (32.4%) patients were
SARS-CoV-2 infection were also described in patients who underwent a receiving systemic anticancer therapy (SACT) at first COVID-19, in
clinical assessment between the two infections. We compared COVID-19 detail: 4 (36.4%) chemotherapy (either alone or in combination
symptoms and COVID-19 severity between the first and the second
infections. As measures of severity, we described proportions of COVID-19 with other agents), 1 (9.1%) immune checkpoint inhibitors,
complications, receipt of COVID-19-specific therapy, hospitalisation rates 5 (45.4%) monoclonal antibodies/tyrosine kinase inhibitors, and
and requirement for oxygen therapy. We established the all-cause case 1 (9.1%) endocrine therapy. Of note, among patients on SACT at
fatality rate (CFR) at 14 days following the second infection as a measure of the moment of the first infection (within 4 weeks prior to

British Journal of Cancer (2022) 127:1787 – 1792

 A. Cortellini et al.
1789
Table 1. Comparison of COVID-19 symptoms and surrogates of COVID-19 severity between the first and the second infections.
First infection Second infection
N = 34 (%) N = 34 (%)
Presenting COVID-19 symptoms
No 3 (8.8) 16 (47.1) 0.0008
Yes 31 (91.2) 18 (52.9)
Fever 19 (61.3) 7 (38.9)
Fatigue 9 (29) 5 (27.8)
Cough 13 (41.9) 6 (33.3)
Dyspnoea 13 (41.9) 3 (16.7)
Coryzal symptoms 1 (3.2) 1 (5.6)
Dysgeusia 2 (6.4) –
Anosmia 2 (6.4) –
Myalgia 1 (3.2) –
Headache 2 (6.4) –
Diarrhoea 3 (9.7) –
Nausea/vomiting 2 (6.4) 2 (11.1)
Others 6 (19.3) 6 (33.3)
≥2 symptoms 23 (67.6) 10 (29.4) 0.0003
Need of COVID-19 oriented therapy
No 17 (50) 30 (88.2) 0.0013
Yes 17 (50) 4 (11.8)
Chloroquine/hydroxicholoroquine 7 (41.2) –
Corticosteroids 8 (47.2) 3 (75)
Antivirals 4 (23.6) 2 (50)
Interleukin-6 inhibitors 1 (3.2) 2 (50)
Others 2 (6.4) 2 (50)
Complicated COVID-19
No 26 (76.5) 28 (82.4) 0.5516
Yes 8 (23.5) 6 (17.6)
Acute cardiac injury 1 (12.5) 1 (16.6)
Acute kidney injury 1 (12.5) 2 (33.3)
ARDS/acute respiratory failure 6 (75) 2 (33.3)
Secondary infection 2 (25) 2 (33.3)
Others 1 (12.5) 2 (33.3)
Hospitalisation
Not required 10 (29.4) 15 (44.1) 0.2636
Required due to COVID-19 10 (29.4) 5 (14.7)
Pre-existing 14 (41.2) 14 (41.2)
Oxygen therapy requirement
No 21 (64.7) 27 (79.4) 0.1552
Yes 12 (35.3) 7 (20.6)
Intensive care unit admission
No 32 (94.1) 32 (94.1) 1.0000
Yes 2 (5.9) 2 (5.9)
Mechanical ventilation requirement
No 32 (94.1) 33 (97.1) 1.0000
Yes 2 (5.9) 1 (2.9)

COVID-19), one (9.1%) permanently discontinued the treatment, (6, 85.7% respiratory, 2, 28.6% others). A stage migration from
five (45.4%) resumed the treatment following a regime/dose non-advanced to advanced disease in-between infections was
adjustment, and four (36.4%) continued the same regimen reported for only 1 (2.9%) patient.
without changes. Viral genome sequencing was not available in our database.
Among the 29 patients who underwent a clinical assessment Paired exact timings for each of the first/second infections are
between the two infections, 7 (25%) reported COVID-19 sequelae reported in Supplementary Table 3; most of the first infections

British Journal of Cancer (2022) 127:1787 – 1792

 A. Cortellini et al.
1790
a b
100

91.2
100
First infection First infection
Symptomatic patients Second infection Second infection
80
80

67.6

61.3
52.9

60
60

50.0
(%)

(%)
41.9

41.9
38.9

35.3
33.3

33.3
40 29.0 40
29.4

29.4
27.8

23.5
20.6
19.3

17.6
16.7

14.7
20

11.8
11.1
20

9.7
6.4

6.4

6.4

6.4
5.6
3.2

3.2
0

0
0 0
s

y
ia

y
ia
An a

9
gh

ps

a
ps

ue

9
ng
r
om

ap

ap
ve

er
ch
i

-1
oe

oe

-1
lg
m
us
om
om

ou
t ig

it i

th

D
D
Fe

ya

er

er
da
os
pn

rrh
pt

ge

VI
Fa

VI
C

th

th
pt
pt

M
m

ea

vo
ys

ia
ys

O
O
m
m
sy

n
D

a/
D

C
C
D

-1

ge
sy
sy

se
9

to
m
D

xy
-1

al
≥2

au

fro
VI

e
yz
D

du
O
N
VI

ns
or

C
O

n
C

io
of

io
C

at

at
d

ic
ee

lis
pl

ta
N

om

pi
os
C

H
Fig. 2 Histogram plot reporting COVID-19 symptoms and surrogates of COVID-19 severity for first and second infections. Visual summary
of COVID-19 symptoms (a) and proxies of COVID-19 severity (b) prevalence across infections. The prevalence of each specific symptom is
computed using the number of symptomatic patients as the denominator.

Patients with cancer experiencing SARS-CoV-2 reinfection Among patients who died within 14 days from the second
Dead
infection, most prevalent primary disease were gastrointestinal
Alive tumours [2], followed by breast cancer [1] and thoracic
malignancy [1], while three patients (75%) had advanced-stage
cancer.

DISCUSSION
This study is the first to report on SARS-CoV-2 breakthrough
Unvaccinated infections in patients with cancer who developed prior natural
14-days CFR: 13%
Partially vaccinated immunity, suggesting that ~2% of patients with cancer can
Fully vaccinated experience reinfections. Although outpacing the initial <1% rate
Fig. 3 COVID-19 mortality according to vaccination status. Visual reported among the general population [18], this result should be
summary of the 14-day case fatality rates among patients experien- seen in the context of the study recruitment timeframe, which
cing SARS-CoV-2 reinfection. covers infections contracted up to December 2021, when the
reported reinfection rates for the general population ranged from
were diagnosed in 2020 (27, 79.4%), while most of reinfections in 1.4 and 6.1% [19, 20].
2021 (25, 73.5%). We found a high proportion of patients with haematological
Table 1 summarises COVID-19 symptoms and characteristics of malignancies amongst second infections, a finding that is aligned
COVID-19 severity prevalence across infections. A lower preva- to the lower seroconversion rate following natural infection in this
lence of symptoms (52.9% vs 91.2%, P = 0.0008) and need of population [21] and also reflects the evidence of at least partially
COVID-19 specific therapy (11.8% vs 50%, P = 0.0013) was impaired immunogenicity of COVID-19 vaccines in patients with
reported for the second infection as compared to the first (Fig. 2), cancer, especially in those with haematological malignancies
while no difference in terms of hospitalisation (P = 0.2636), [22, 23].
intensive care unit admission (P = 1.0000), oxygen therapy Another factor potentially involved in defining the incidence of
(P = 0.1552) and mechanical ventilation (P = 1.0000) requirements reinfections in patients with cancer is the deployment of periodic
were found. Of note, 11 patients (32.4%) and 3 (8.8%) were fully asymptomatic SARS-CoV-2 screening, which was largely recom-
and partially vaccinated against SARS-CoV-2 before the 2nd mended in the years 2020/2021 ahead of anticancer therapy or
infection, respectively. The prevalence of COVID-19 symptoms at other diagnostic/therapeutic procedures [24, 25], although clear
the second infection was slightly lower among fully vaccinated evidence of its clinical utility is still lacking [26–28].
patients (63.6%, 7/11) than unvaccinated patients (70.0%, 14/2), In our study, SARS-Cov-2 reinfections appear to lead to milder
while the need of COVID-19 therapy was slightly higher (18.2%, 2/ disease manifestations, characterised by a lower symptomatic
11 vs 15.0%, 3/20). The median follow-up from the second burden, reduced need for COVID-19 specific therapy mirrored by
infection was 115 days (95% CI: 27–196) and the 14-day CFR was lower rates of hospitalisations, complications and oxygen
11.8%, with 4 death events overall, none of which occurred therapy requirement. Whilst the reported 14-day CFR of 11.8%
among fully vaccinated patients. Among 20 unvaccinated patients from reinfection is lower than ~30% CFRs for primary COVID-19
prior to the second infection, 3 deaths occurred within 14 days reported from most Cancer & Covid registries, including
from COVID-19 diagnosis, with a 14-day CFR of 15% (Fig. 3). Oncovid, during the first phase of the pandemic [11] this is

British Journal of Cancer (2022) 127:1787 – 1792

 A. Cortellini et al.
1791
comparable to more modern estimates of COVID-19 mortality, 5. Dan JM, Mateus J, Kato Y, Hastie KM, Yu ED, Faliti CE, et al. Immunological
where a reduction in CFR to ~14% was seen as a likely result of memory to SARS-CoV-2 assessed for up to 8 months after infection. Science.
increased testing capacity and improved disease management 2021;371:eabf4063.
[17], factors that in turn could even be linked to the lower rate of 6. Harvey WT, Carabelli AM, Jackson B, Gupta RK, Thomson EC, Harrison EM, et al.
SARS-CoV-2 variants, spike mutations and immune escape. Nat Rev Microbiol.
COVID-19 symptoms and therapy requirement reported during
2021;19:409–24.
the second infection. On the other hand, the reinfected 7. Harrington D, Kele B, Pereira S, Couto-Parada X, Riddell A, Forbes S, et al. Con-
population carries an inherent selection towards negative firmed reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-
baseline features for COVID-19 outcomes compared to primary CoV-2) variant VOC-202012/01. Clin Infect Dis. 2021;73:1946–7.
infections reports, being haematological malignancies more 8. Zucman N, Uhel F, Descamps D, Roux D, Ricard J-D. Severe reinfection with South
represented [29]. African severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant
Although this is a preliminary analysis with a limited sample 501Y.V2. Clin Infect Dis. 2021;73:1945–6.
size, it is important to note that no deaths were reported within 9. Gyssens IC, Netea MG. Heterologous effects of vaccination and trained immunity.
14 days from infection among fully vaccinated patients. On the Clin Microbiol Infect. 2019;25:1457–8.
10. Cohen JI, Burbelo PD. Reinfection with SARS-CoV-2: implications for vaccines. Clin
other hand, the 14-days CFR for unvaccinated patients was 13%.
Infect Dis. 2020;73:e4223–8.
These results, placed on the background of vaccine hesitancy, 11. Desai A, Mohammed TJ, Duma N, Garassino MC, Hicks LK, Kuderer NM, et al.
which can affect a considerable population of patients with cancer COVID-19 and cancer: a review of the registry-based pandemic response. JAMA
[30, 31], further highlight the importance of immunisation Oncol. 2021;7:1882–90.
campaigns even in patients who gained natural immunity after 12. Patel M, Felip E, Sharkey R, Krengli M, Chester JD, Sita-Lumsden A, et al. 1588P
a previous infection. At the same time, ~50% of reinfections were SARS-CoV-2 antibody seroprevalence and safety of vaccines in cancer patients
diagnosed during late 2020/early 2021, when first immunisation who recovered from COVID-19. Ann Oncol. 2021;32:S1142.
campaigns were still ongoing in European countries. 13. Esperança-Martins M, Gonçalves L, Soares-Pinho I, Gomes A, Serrano M, Blan-
In our study, reinfections were diagnosed in absence of a pre- kenhaus B, et al. Humoral immune response of SARS-CoV-2-infected patients with
cancer: influencing factors and mechanisms. Oncologist. 2021;26:e1619–32.
defined, prospectively planned re-testing strategy: a clear
14. Cortellini A, Gennari A, Pommeret F, Patel G, Newsom-Davis T, Bertuzzi A, et al.
limitation that may have led to the underestimation of COVID-19 sequelae and the host proinflammatory response: an analysis from the
reinfection rates. On the other hand, patients with cancer are OnCovid registry. JNCI: J Natl Cancer Institute. 2022;114:979–87. https://doi.org/
used to undergo regular asymptomatic SARS-CoV-2 screening, as 10.1093/jnci/djac057.
above-mentioned [26–28]. In addition, our analysis lacked viral 15. Cortellini A, Salazar R, Gennari A, Aguilar-Company J, Bower M, Bertuzzi A, et al.
genomic data, an important factor to consider given the Persistence of long-term COVID-19 sequelae in patients with cancer: an analysis
different capacities of viral strains to evade immunity. None- from the OnCovid registry. Eur J Cancer. 2022;170:10–6.
theless, our detailed reconstruction of timing of infection 16. Pinato DJ, Tabernero J, Bower M, Scotti L, Patel M, Colomba E, et al. Prevalence
supports that most reinfections occurred when new variants, 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
including the B1.351 and B.1.617.2, were at their peak of
retrospective, multicentre registry study. Lancet Oncol. 2021;22:1669–80.
community transmission, suggesting viral immune escape to be 17. OnCovid Study G, Pinato DJ, Patel M, Scotti L, Colomba E, Dolly S et al. Time-
an important determinant of the reinfection risk [32, 33], and dependent COVID-19 mortality in patients with cancer: an updated analysis of
supporting the need to monitor clinical outcomes from the OnCovid registry. JAMA Oncol. 2022;8:114–22. https://doi.org/10.1001/
recurrent infections in patients with cancer [34]. Lastly, as an jamaoncol.2021.6199.
additional source of bias, we need to acknowledge that despite 18. Vitale J, Mumoli N, Clerici P, De Paschale M, Evangelista I, Cei M, et al. Assessment
mortality outcome availability, not all COVID-19 survivors in our of SARS-CoV-2 reinfection 1 year after primary infection in a population in
study population were subsequently followed at participating Lombardy, Italy. JAMA Intern Med. 2021;181:1407–8.
centres, therefore we could not reconstruct the exact prevalence 19. Flacco ME, Acuti Martellucci C, Soldato G, Carota R, Fazii P, Caponetti A, et al. Rate
of reinfections after SARS-CoV-2 primary infection in the population of an Italian
of reinfections for the whole population.
province: a cohort study. J Public Health (Oxf). 2021:fdab346. https://doi.org/
Despite these limitations, this is, to our knowledge, the first 10.1093/pubmed/fdab346.
study to document SARS-CoV-2 reinfections in patients with 20. COVID-19 daily dashboard amended to include reinfections. https://www.gov.uk/
cancer. Whilst documenting comparable reinfection prevalence to government/news/covid-19-daily-dashboard-amended-to-include-reinfections.
the general population, our study highlights haemato-oncology 21. Passamonti F, Romano A, Salvini M, Merli F, Porta MGD, Bruna R, et al. COVID-19
patients to be at high risk of reinfection. The mortality rates in elicits an impaired antibody response against SARS-CoV-2 in patients with hae-
excess of 11%, occurring exclusively in unvaccinated patients matological malignancies. Br J Haematol. 2021;195:371–7.
experiencing a second infection, highlights the importance of 22. Becerril-Gaitan A, Vaca-Cartagena BF, Ferrigno AS, Mesa-Chavez F, Barrientos-
adequate vaccinal coverage in patients with cancer as a measure Gutierrez T, Tagliamento M, et al. Immunogenicity and risk of severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) infection after coronavirus
to protect from adverse consequences from COVID-19.
disease 2019 (COVID-19) vaccination in patients with cancer: a systematic review
and meta-analysis. Eur J Cancer. 2022;160:243–60.
23. Fendler A, Shepherd STC, Au L, Wilkinson KA, Wu M, Byrne F, et al. Adaptive
DATA AVAILABILITY immunity and neutralizing antibodies against SARS-CoV-2 variants of concern
Study data made available upon reasonable request. following vaccination in patients with cancer: the CAPTURE study. Nat Cancer.
2021;2:1305–20.
24. NCCN Best Practices Guidance: Management of COVID-19 Infection in Patients
REFERENCES with Cancer. https://www.nccn.org/docs/default-source/covid-19/2021-covid-
1. Seow J, Graham C, Merrick B, Acors S, Pickering S, Steel KJA, et al. Longitudinal infectious-disease-management.pdf?sfvrsn=63f70c30_7.
observation and decline of neutralizing antibody responses in the three months 25. Guidance on SARS-CoV-2 antigen testing for asymptomatic heathcare workers
following SARS-CoV-2 infection in humans. Nat Microbiol. 2020;5:1598–607. (HCW) and patients in non-surgical oncology in the UK. https://www.rcr.ac.uk/
2. Muecksch F, Wise H, Batchelor B, Squires M, Semple E, Richardson C, et al. sites/default/files/guidance-covid19-testing-asymptomatic-hcw-patients-
Longitudinal serological analysis and neutralizing antibody levels in coronavirus oncology.pdf.
disease 2019 convalescent patients. J Infect Dis. 2020;223:389–98. 26. Haradaa G, Antonacio FF, Gongora AB, Behar MH, Capareli FC, Bastos DA, et al.
3. Crawford KHD, Dingens AS, Eguia R, Wolf CR, Wilcox N, Logue JK, et al. Dynamics SARS-CoV-2 testing for asymptomatic adult cancer patients before
of neutralizing antibody titers in the months after severe acute respiratory syn- initiating systemic treatments: a systematic review. Ecancermedicalscience.
drome coronavirus 2 infection. J Infect Dis. 2020;223:197–205. 2020;14:1100.
4. Rodda LB, Netland J, Shehata L, Pruner KB, Morawski PA, Thouvenel CD, et al. 27. Shah MA, Mayer S, Emlen F, Sholle E, Christos P, Cushing M, et al. Clinical
Functional SARS-CoV-2-specific immune memory persists after mild COVID-19. screening for COVID-19 in asymptomatic patients with cancer. JAMA Netw Open.
Cell. 2021;184:169–83. 2020;3:e2023121.

British Journal of Cancer (2022) 127:1787 – 1792

 A. Cortellini et al.
1792
28. Meti N, Tahmasebi H, Leahey A, Boudreau A, Thawer A, Stewart J, et al. SARS-CoV- (BRC). The views expressed are those of the author(s) and not necessarily those of the
2 testing for asymptomatic patients with cancer prior and during treatment: a NIHR or the Department of Health and Social Care. Neither sponsor nor the funders of
single centre experience. Curr Oncol. 2021;28:278–82. the study had any role in study design, data collection, data analysis, data
29. Lee LYW, Cazier JB, Starkey T, Briggs SEW, Arnold R, Bisht V, et al. COVID-19 interpretation, or writing of the report. All authors had access to all the data reported
prevalence and mortality in patients with cancer and the effect of primary in the study.
tumour subtype and patient demographics: a prospective cohort study. Lancet
Oncol. 2020;21:1309–16.
30. Nguyen M, Bain N, Grech L, Choi T, Harris S, Chau H, et al. COVID-19 vaccination rates, ETHICS APPROVAL AND CONSENT TO PARTICIPATE
intent, and hesitancy in patients with solid organ and blood cancers: a multicenter OnCovid was granted central approval by the United Kingdom Health Research
study. Asia-Pacific J Clin Oncol. 2022. https://doi.org/10.1111/ajco.13754. Authority (20/HRA/1608) and by the corresponding research ethics committees at
31. Villarreal-Garza C, Vaca-Cartagena BF, Becerril-Gaitan A, Ferrigno AS, Mesa-Chavez each participating institution. Full waiver of consent due to the retrospective nature
F, Platas A, et al. Attitudes and factors associated with COVID-19 vaccine hesi- of the study was granted by the UK HRA in accordance with UK law.
tancy among patients with breast cancer. JAMA Oncol. 2021;7:1242–4.
32. Planas D, Bruel T, Grzelak L, Guivel-Benhassine F, Staropoli I, Porrot F, et al.
Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing
antibodies. Nat Med. 2021;27:917–24. CONSENT TO PUBLISH
33. Mlcochova P, Kemp SA, Dhar MS, Papa G, Meng B, Ferreira IATM, et al. SARS-CoV- Informed consent was waived by competent authorities due to the anonymized
2 B.1.617.2 Delta variant replication and immune evasion. Nature. nature of patient data and the retrospective design of the study.
2021;599:114–9.
34. Pinato DJ, Aguilar-Company J, Ferrante D, Hanbury G, Bower M, Salazar R, et al.
Outcomes of the SARS-CoV-2 omicron (B.1.1.529) variant outbreak among vac- COMPETING INTERESTS
cinated and unvaccinated patients with cancer in Europe: results from the ret- AC received consulting fees from MSD, BMS, AstraZeneca, Roche; speakers’ fee from
rospective, multicentre, OnCovid registry study. Lancet Oncol. 2022;23:865–75. AstraZeneca, MSD, Novartis and Eisai. AG has declared consulting/advisory role for
https://doi.org/10.1016/S1470-2045(22)00273-X. Roche, MSD, Eli Lilly, Pierre Fabre, EISAI and Daichii Sankyo; speakers bureau for Eisai,
Novartis, Eli Lilly, Roche, Teva, Gentili, Pfizer, AstraZeneca, Celgene and Daichii
Sankyo; research funds: EISAI, Eli Lilly, and Roche. DJP received lecture fees from ViiV
Healthcare, Bayer Healthcare, BMS, Roche, EISAI, Falk Foundation, travel expenses
ACKNOWLEDGEMENTS
from BMS and Bayer Healthcare; consulting fees for Mina Therapeutics, EISAI, Roche,
OnCovid received direct project funding and infrastructural support by the NIHR
DaVolterra and AstraZeneca; research funding (to institution) from MSD and BMS. The
Imperial Biomedical Research Centre (BRC). Alessio Cortellini is supported by the
remaining authors declare no competing interests.
National Institute for Health Research (NIHR) Imperial Biomedical Research Centre
(BRC). David J Pinato is supported by grant funding from the Wellcome Trust
Strategic Fund (PS3416) and from the Associazione Italiana per la Ricerca sul Cancro
(AIRC MFAG Grant ID 25697) and acknowledges support by the NIHR Imperial ADDITIONAL INFORMATION
Biomedical Research Centre (BRC), the Imperial Experimental Cancer Medicine Centre Supplementary information The online version contains supplementary material
(ECMC) and the Imperial College Tissue Bank. A. Gennari is supported by the AIRC IG available at https://doi.org/10.1038/s41416-022-01952-x.
Grant, No. 14230, Associazione Italiana per la Ricerca sul Cancro Foundation, Milan,
Italy. A. Gennari from the University of Piemonte Orientale (Novara, Italy) acknowl- Correspondence and requests for materials should be addressed to Alessio Cortellini.
edge support from the UPO Aging Project.
Reprints and permission information is available at http://www.nature.com/reprints

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims
AUTHOR CONTRIBUTIONS
in published maps and institutional affiliations.
All authors contributed to the publication according to the ICMJE guidelines for the
authorship. All authors read and approved the submitted version of the manuscript
(and any substantially modified version that involves the author’s contribution to the
study). Each author has agreed both to be personally accountable for the author’s
own contributions and to ensure that questions related to the accuracy or integrity of
Open Access This article is licensed under a Creative Commons
any part of the work, even ones in which the author was not personally involved, are
Attribution 4.0 International License, which permits use, sharing,
appropriately investigated, resolved, and the resolution documented in the literature.
adaptation, distribution and reproduction in any medium or format, as long as you give
Study concept and design: AC and DJP. Acquisition of the data: AC, JA-C, RS, MB, AS-L,
appropriate credit to the original author(s) and the source, provide a link to the Creative
Andrea Plaja, AJXL, AB, CT, ND, CM-V, Aleix Prat, EA, AG and DJP. Analysis and
Commons license, and indicate if changes were made. The images or other third party
interpretation of data: AC and DJP. Drafting of the manuscript: AC and DJP. Statistical
material in this article are included in the article’s Creative Commons license, unless
analysis: AC and DJP. Manuscript review and approval: AC, JA-C, RS, MB, AS-L, Andrea
indicated otherwise in a credit line to the material. If material is not included in the
Plaja, AJXL, AB, CT, ND, CM-V, Aleix Prat, EA, AG and DJP. Obtained funding: DJP.
article’s Creative Commons license and your intended use is not permitted by statutory
Study supervision: AC and DJP.
regulation or exceeds the permitted use, you will need to obtain permission directly
from the copyright holder. To view a copy of this license, visit http://
creativecommons.org/licenses/by/4.0/.
FUNDING
OnCovid is sponsored by Imperial College London and received direct project
funding and infrastructural support by the NIHR Imperial Biomedical Research Centre © The Author(s) 2022

British Journal of Cancer (2022) 127:1787 – 1792