Received: 31 March 2023 | Accepted: 19 May 2023

DOI: 10.1111/bjh.18895

O R I G I N A L PA P E R

Oral anti-­viral therapy for early COVID-­19 infection in

patients with haematological malignancies: A multicentre
prospective cohort

Carla Minoia1 | Lucia Diella2 | Tommasina Perrone3 | Giacomo Loseto1 |

Carmen Pelligrino2 | Immacolata Attolico3 | Crescenza Pasciolla1 | Valentina Totaro2 |
Maria Stella De Candia1 | Vito Spada2 | Felice Clemente1 | Michele Camporeale2 |
Francesco Di Gennaro1,2 | Attilio Guarini1 | Pellegrino Musto3,4 | Annalisa Saracino2 |
Davide Fiore Bavaro2

1
Hematology Unit, IRCCS Istituto Tumori
“Giovanni Paolo II”, Bari, Italy
2
Clinic of Infectious Diseases, Department
of Precision and Regenerative Medicine and
Ionian Area, University of Bari “Aldo Moro”,
Bari, Italy
3
Unit of Hematology and Stem Cell
Transplantation, AOUC Policlinico, Bari, Italy
4
Department of Precision and Regenerative
Medicine and Ionian Area, “Aldo Moro”
University School of Medicine and Unit of
Hematology and Stem Cell Transplantation,
AOUC Policlinico, Bari, Italy
Correspondence
Carla Minoia, Hematology Unit, IRCCS
Istituto Tumori “Giovanni Paolo II”, v.le O.
Flacco, 65-­70124 Bari, Italy.
Email: carlaminoia980@gmail.com
Funding information
Ministry of Health, Italian Government, R.C.
Funds
Abstract
High rates of lung failure have been reported in haematological patients after SARS-­
CoV2 infection. An early administration of monoclonal antibodies or anti-­v irals
may improve the prognosis. Oral anti-­v irals may have a wider use independently
of the genetic variations of the virus. Prospective data on anti-­v irals in haemato-
logical malignancies (HMs) are still lacking. Outpatients diagnosed with HM and
early COVID-­19 infection were prospectively treated with the oral anti-­v irals nir-
matrelvir/ritonavir and molnupiravir. Incidence of lung failure, deaths and adverse
events was analysed. Long-­term outcome at third month was evaluated. Eighty-­two
outpatients were evaluable for the study objectives. All patients had been treated for
their HM within 12 months. COVID-­19-­related lung failure was 23.1%. Active HM
(aOR = 4.42; p = 0.038) and prolonged viral shedding (aOR = 1.04; p = 0.022) resulted
independent predictors of severe infection. The vaccination with three to four doses
(aOR = 0.02; p = 0.001) and with two doses (aOR = 0.06; p = 0.006) resulted protec-
tive. COVID-­19-­related deaths at 28 days were 6.1%. All-­cause mortality at 90-­day
follow-­up was 13.4% (n. 11) and included opportunistic infections and cardiovas-
cular events. In conclusion, this approach reduced the incidence of lung failure and
specific mortality compared to previous cohorts, but patients remain at high risk of
further complications.

K EY WOR DS
anti-­v iral, cancer, COVID-­19, haematological patients, molnupiravir, nirmatrelvir/ritonavir, SARS-­
CoV-­2

I N T RODUC T ION Serious complications were reported in up to 63% of cases

in this frail population, with a mortality rate up to 30%.1,2
The first wave of the severe acute respiratory syndrome Patients with markedly impaired immunity caused by the
coronavirus 2 (SARS-­CoV-­2) pandemic caused significant disease itself and by cancer treatments (in particular an-
issues in the management of onco-­haematological patients. ti-­CD20 monoclonal antibodies) were those at higher risk of

Carla Minoia and Lucia Diella equally contributed to this work.

© 2023 British Society for Haematology and John Wiley & Sons Ltd.

928 | wileyonlinelibrary.com/journal/bjh
 Br J Haematol. 2023;202:928–936.

MINOIA et al.
hospitalization for pneumonia and mortality.2 In this popu-
lation, the booster dose of anti-­SARS-­CoV-­2 vaccine allowed
recovery of T-­cellular and humoral immunity in a signifi-
cant percentage of patients receiving anti-­tumour treatment
for haematological malignancies (HMs), also in those not
responding to the first two doses of vaccine.3–­5 However, the
incidence of severe CoronaVirus Disease-­19 (COVID-­19) re-
mained high despite three doses of vaccination. The advent of
Omicron variant of concern (+VOCs) and its sublineages led
to a greater spread of the infection in the general population
as well as in cancer patients, with the risk of severe complica-
tions and mortality for onco-­haematological individuals es-
tablished at around 16% in matching statistics.6 COVID-­19
infection could also indirectly alter the prognosis, by forcing
the interruption or delay of cancer treatment for a variable
period of time. Thus, an appropriate and timely treatment
of SARS-­CoV-­2 infection is essential for this category of
patients.7 In order to reduce the risk of COVID-­19 progres-
sion, a series of therapies have been proposed over time for
the general population and for frail subjects.8 Several anti-­
viral molecules for intravenous and oral use were developed,
and proved to directly hamper viral replication in the early
stages of the infection.8,9 The intravenous anti-­v iral remde-
sivir has been widely used in hospitalized patients.9 The oral
preparations nirmatrelvir/ritonavir (NIR/r) and molnupira-
vir (MOL) have seen an increase in their use especially for
non-­hospitalized subjects at risk of developing severe forms
of COVID-­19. This kind of treatment may be quickly ad-
ministered completely at home soon after the diagnosis of
SARS-­Cov2 infection, independently of hospitalization or
day-­service admission, and could therefore have a wide-
spread use.8–­12 In a recent phase III randomized study, NIR/r
was administered within 5 days of the onset of symptoms to
patients at higher risk of severe infection development, and
obtained a rate close to 1% of hospitalization for COVID-­19
and no deaths at 28 days, compared with the placebo group
which obtained 6.7% of hospitalized and 1.6% of deaths.10 A
significant risk reduction of hospitalization and mortality in
non-­vaccinated COVID-­19 patients with early disease was
also evidenced in the latest trial on MOL, but with minor
efficacy if compared with NIR/r.12
Cohorts of patients diagnosed with HM treated with anti-­
virals or monoclonal antibodies (MABs) against COVID-­19
are quite limited. This is particularly true in the setting of
outpatients, who represent the majority of cases reported
to the referral oncologist or primary care physician. Recent
retrospective data on outpatients with HM showed a signif-
icant activity of various neutralizing anti-­Spike MABs in
the control of early infection, with a hospitalization rate of
12% and a mortality rate of 3.3%.6 Therefore the use of neu-
tralizing MABs appears to be the therapy of first choice in
the early phase of the infection in the onco-­haematological
patient. However, this approach presents some limitations
due to both the accessibility of the drug and the genetic vari-
ability of the virus.13,14 Treatment with MABs requires pa-
tient access to day service and therefore the availability of
a structure suitable for its widespread administration, given
13652141, 2023, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/bjh.18895 by Christian Medical College, Wiley Online Library on [10/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
   | 929
the high prevalence of infection. Furthermore, the high ge-
netic variability of the virus itself is known, making it neces-
sary to develop MABs with different binding activities and
therefore not readily available in clinical practice, especially
in peripheral/spots hospitals.14 With this perspective, the
use of oral anti-­v iral drugs which have a direct action on the
viral RNA replication could represent a more widespread
and easier-­to-­access approach.
Limited experiences have been reported on the use of NIR/r
and MOL in the setting of HM, independently of the admin-
istration of MABs. In fact, this population was underrepre-
sented in the phase III randomized controlled trials, which
predominantly included patients with metabolic comorbidi-
ties.10,12 A recent retrospective multicentre study showed the
outcome of early treatment with anti-­virals of mild/moderate
COVID-­19 infection in patients with HM, underlining a high
risk of failure of this approach especially in elderly patients.
With the limit of the retrospective nature of the study, a com-
parison between anti-­virals (remdesivir, NIR/r or MOL) and
MABs was proposed and an advantage for the anti-­viral ther-
apy in terms of lung failure was shown (5.8% for anti-­virals
and 11.8% for MABs in the Omicron infection period).15
The purpose of this prospective cohort study, born
from the close collaboration between Hematologists and
Infectious diseases specialists, was to analyse the efficacy
and safety of the oral anti-­v iral drugs NIR/r and MOL, as-
sociated or not with MABs, in outpatients diagnosed with
HM presenting asymptomatic or paucisymptomatic early
COVID-­19 infection. The study hypothesis was to quickly
offer an anti-­v iral treatment to a greater number of frail pa-
tients and regardless of the change of VOCs, and to iden-
tify predictors of severe infection. The study also presents a
3-­month follow-­up analysis for this population, evaluating
COVID-­19 recurrence or reinfection, secondary infections
and non-­infective complications.
PAT I E N T S A N D M ET HODS
Study design
This is a prospective cohort study. From 10 February to 30
September 2022 consecutive outpatients with HM and pre-
senting asymptomatic or paucisymptomatic SARS-­ Cov2
infection were prospectively treated with NIR/r or MOL,
associated or not with MABs. Inclusion criteria were: age
>/=18 years old, diagnosis of HM and undergoing or with re-
cent (less than 12 months) anti-­tumour therapy (chemother-
apy, chemo-­immunotherapy, targeted therapies) or immune
suppressive treatment (any line), positivity at molecular or
antigenic swab test for COVID-­19, no contraindication to
anti-­viral administration, asymptomatic or paucisympto-
matic COVID-­19 infection. In order to accurately assess the
patient's illness severity, the WHO clinical progression scale
has been used.16 The scale ranges from 0 (not infected) to 10
(death) in relation to the required assistance, need for oxy-
gen therapy and type of ventilation. It includes the following

930 |    ORAL ANTI-­V IRALS FOR COVID-­19 IN HAEMATOLOGICAL MALIGNANCIES
stages of severity: ambulatory -­mild disease (1–­3), hospi-
talized -­moderate disease (4, 5) and hospitalized -­severe
disease (6–­9). In our cohort, patients with score 1–­3 on the
WHO clinical progression scale were included. Patients were
enrolled independently of their COVID-­19 vaccination sta-
tus (not vaccinated/uncompleted/completed). Consecutive
outpatients who communicated positivity to the COVID-­19
infection to their referent haematologist at the two Italian
hospitals (one Cancer Center and one University) were re-
ferred via email to the COVID-­19 service at the University
Clinic of Infectious Diseases. Infectious disease specialists
assessed for each patient: medical history, COVID-­19 symp-
toms and date of first positive nasopharyngeal swab. The pa-
tients were then instructed about the route of administration
of the oral anti-­v iral drug, the possible adverse events and
the monitoring of the evolution of symptoms.
The choice of anti-­v iral (NIR/r or MOL) was made by the
Infectious diseases specialists in relation to comorbidities
and drug interference. NIR/r was always considered the first
choice of treatment. Treatment was started within 5 days of
the onset of symptoms or a positive swab. The recommended
dosage for NIR/r was 300 mg nirmatrelvir (two 150 mg tab-
lets) with 100 mg of ritonavir (one 100 mg tablet) per os BID
(bis in die) for 5 days; for MOL it was 800 mg orally per os
BID for 5 days.17 According to the availability of neutralizing
MABs, patients could also receive it in association with the
anti-­v iral.
Patients were then followed until 3 months from the start
of anti-­v iral treatment.
Primary end-­ points of the study were: (i) lung fail-
ure (≥score 5 at the WHO clinical progression scale); (ii)
COVID-­19-­related deaths; and (iii) safety assessment. The
WHO clinical progression scale was used to define the se-
verity of lung insufficiency, namely score 5: hospitalized, ox-
ygen by mask or nasal prongs; score 6: hospitalized, oxygen
by non-­invasive ventilation (NIV) or high flow; score 7: intu-
bation and mechanical ventilation, pO2/FiO2 ≥ 150 or SpO2/
FiO2 ≥ 200; score 8: mechanical ventilation pO2/FIO2 < 150
(SpO2/FiO2 < 200) or vasopressors; and score 9: mechani-
cal ventilation pO2/FiO2 < 150 and vasopressors, dialysis or
ExtraCorporeal Membrane Oxygenation.16
Secondary end-­points were: (i) timing for the viral shed-
ding; (ii) to identify predictive factors for lung failure; and
(iii) long-­term outcome (at third month).
Data collection
Clinical data on the HM and infection were collected in a
dedicated database, which included disease history, comor-
bidities, vaccination status, previous prophylaxis with tixa-
gevimab/cilgavimab, anti-­v iral therapy, MABs, safety and
efficacy assessment and infection complications.
Approval for the study was obtained from the local ethics
committee at the Policlinico/University of Bari, Italy (study
approval code 6357/2021) and patients signed informed con-
sent for data collection.
13652141, 2023, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/bjh.18895 by Christian Medical College, Wiley Online Library on [10/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Statistical analysis
Descriptive statistics were produced for demographic and
clinical characteristics of patients. Median and interquartile
range (q1–­q3) for non-­normally distributed variables, num-
ber and percentages for categorical variables. The distribu-
tion of outcomes between groups (patients developing or not
lung failure or treated with NIR/r or MOL) was analysed by
univariable parametric or nonparametric tests, Kruskal–­
Wallis or Mann–­W hitney U test (where appropriate) for con-
tinuous variables and with Pearson's χ2 test (Fisher's exact
test where appropriate) for categorical variables, according
to data distribution.
In order to assess predictors of hospitalization for
COVID-­ 19-­
related respiratory failure and death, a uni-
variate logistic regression model was produced; a stepwise
multivariate logistic regression was then applied including
only factors associated at univariate analysis (p < 0.1) or sup-
ported by literature evidence.
Finally, also Kaplan–­ Meier survival curves were pro-
duced for variable of interest.
In all cases, a value of p < 0.05 was considered statistically
significant. Statistical analysis was performed using STATA
‘Special Edition’ version 16.1 (STATA Corp.).
R E SU LT S
Patient characteristics
Overall, 128 outpatients were prospectively evaluated. Of
these, 46 patients resulted not eligible for anti-­v iral therapy
according to Italian Medicines Agency (AIFA) criteria and
according to the study inclusion criteria: 23 due to the pa-
tient's refusal, 13 for HM out of treatment for more than
12 months and patient asymptomatic for COVID-­19, and 10
for the absence of complete follow-­up data.
Finally, 82 outpatients were enrolled in the study (me-
dian [range] age of 61 [18–­85] years; males in 58.6% of cases).
Patients were treated in the Omicron infection period, ac-
cording to the data from the Italian Institute of Healthcare
(ISS).18,19 As regards the vaccination status, 65 of 82 patients
(79.3%) had received three to four doses of anti-­SARS-­CoV2
vaccine, nine patients (11%) had received two doses, while
the remaining eight patients (10%) had received less than two
doses. Median time elapsed since the last vaccination and in-
fection (data of the first positive nasopharyngeal swab) was
110 days (range: 78–­168). Overall, 11 patients (13.4%) received
prophylaxis with tixagevimab/cilgavimab before contract-
ing the infection.20 At referral, patients presented an ambu-
latory mild disease defined as grade 1 to 3 according to the
WHO clinical progression scale.14 Symptoms of COVID-­19
infection at onset were: cough (n. 28, 34.1%), fever >38°C (n.
21, 25.6%) and constitutional symptoms (n. 46, 56%).
Regarding the HM, n. 51 patients (62.1%) were affected by
non-­Hodgkin lymphoma (NHL), n. one by Hodgkin's lym-
phoma (HL), n. 6 (7.3%) by chronic lymphocytic leukaemia
 13652141, 2023, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/bjh.18895 by Christian Medical College, Wiley Online Library on [10/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
MINOIA et al.    | 931

TA BL E 1 Patient characteristics.
(CLL), n. 6 (7.3%) by acute myeloid leukaemia (AML), n. 6
(7.3%) by myelodysplastic syndrome (MDS), n. 2 (2.4%) by Patients' characteristics n = 82
chronic myeloid leukaemia (CML), n. 5 (6%) by acute lym- Age at COVID-­19 infection, years (median, range) 61 (18–­85)
phoblastic leukaemia (ALL) and n. 5 (6%) by multiple my-
Sex, n (%)
eloma (MM). All patients were on anti-­cancer or immune
Female 34 (41.4)
suppressive treatment or had received it within 12 months
of COVID-­19 infection. The median number of lines of on- Male 48 (58.6)
cologic therapy was 1 (range, 1–­4). The disease status was: Haematological diagnosis, n (%)
active disease as defined as partial response, stable disease, Non-­Hodgkin lymphoma 51 (62.1)
progressive disease (n. 28, 34.1%) and disease remission (n. Hodgkin lymphoma 1 (1)
54, 65.9%). In relation to the type of anti-­cancer therapy, Chronic lymphocytic leukaemia 6 (7.3)
the patient population was differentiated in six subgroups:
Acute myeloid leukaemia 6 (7.3)
(a) haematopoietic stem cell transplant (HSCT), Chimeric
Antigen Receptor T cell therapies (CAR-­T therapy) n. 10, Myelodysplastic syndrome 6 (7.3)
12.1%; (b) anti-­ CD20 MAB rituximab or obinutuzumab Chronic myeloid leukaemia 2 (2.4)
+/− chemotherapy n. 38, 46.4%; (c) chemotherapy without Acute lymphoblastic leukaemia 5 (6)
anti-­CD20 monoclonal antibody n. 12, 14.6%; (d) monoclo- Multiple myeloma 5 (6)
nal antibody other than anti-­CD20 n. 3, 3.7%; (e) oral anti-­ Haematological malignancy characteristics, n (%)
cancer therapy n. 6, 7.3%; and (f) no ongoing therapy n. 13,
Median lines of anti-­cancer therapy 1 (1–­4)
15.9%. Within the first subgroup, one patient had received
Disease remission 54 (65.9)
CAR-­T as last treatment, one autologous stem cell transplant
and eight allogeneic stem cell transplants (performed at Active disease 28 (34.1)
mean of 17.5 months, range 3–­60 months). Type of anti-­cancer treatment, n (%)
Among the 82 patients, n. 28 (34.1%) patients presented Haematopoietic stem cell transplant (HSCT)/ 10 (12.1)
at least one metabolic comorbidity, including: cardiovascu- chimeric antigen receptor T-­cell therapy
lar (ischaemic cardiomyopathy or chronic heart failure) n. (CAR-­T therapy)
7 (8.5%); peripheral vascular disease n. 7 (8.5%), uncompli- Anti-­CD20 monoclonal antibody rituximab or 38 (46.4)
cated mellitus type II diabetes n. 3 (3.6%), moderate to se- obinutuzumab +/− chemotherapy
vere chronic renal failure (glomerular filtration rate < 50 mL/ Chemotherapy without anti-­CD20 monoclonal 12 (14.6)
min) n. 3 (3.6%); and chronic obstructive pulmonary disease antibody
(COPD) n. 3 (3.6%). Monoclonal antibody other than anti-­CD20 3 (3.7)
Patient characteristics of the study cohort are described Oral anti-­cancer therapy 6 (7.3)
in Table 1. No ongoing therapy 13 (15.9)
Comorbidities, n (%)
At least one comorbidity 28 (34.1)
COVID-­19 anti-­viral treatment
Cardiovascular 7 (8.5)

Patients were referred by the reference onco-­haematologist to Peripheral vascular disease 7 (8.5)
the COVID-­19 service at the University Clinic of Infectious Type II diabetes mellitus 3 (3.6)
Diseases. A telemetric evaluation of medical history, phar- Moderate -­severe chronic renal failure 3 (3.6)
macological therapy and symptoms was conducted. After COPD 3 (3.6)
multidisciplinary evaluation, n. 49 (59.7%) and n. 33 (40.3%) Anti-­COVID-­19 vaccination status, n (%)
were treated with NIR/r and MOL respectively. Among them,
Vaccinated with three -­four doses 65 (79.3)
n. 9 (10.9%) patients also received neutralizing MABs (n. 7
sotrovimab and n. 2 tixagevimab/cilgavimab).20,21 Median Vaccination with two doses 9 (11)
(q1–­q3) time from diagnosis of COVID-­19 to the start of the Prophylaxis with tixagevimab/cilgavimab 11 (13.4)
anti-­v iral therapy was of 1 (1, 2) day, thus quick access to the Symptoms of COVID-­19 infection at onset, n (%)
drug was guaranteed. The patients were educated about the Cough 28 (34.1)
possible evolution of the symptoms and therefore the need to Fever (>38°C) 21 (25.6)
go to the hospital.
Constitutional symptoms 46 (56)
Anti-­v iral therapy, n (%)

Efficacy and safety analysis Nirmatrelvir/ritonavir 49 (60)

Molnupiravir 33 (40)
In response to the primary end-­points of the study, COVID-­ Monoclonal antibody (MABs), n (%) 9 (11)
19-­related lung failure, defined as score 5 or more on the Length of viral shedding, days (q1–­q3) 12 (7–­22)
WHO clinical progression scale,16 was reported in 19
 13652141, 2023, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/bjh.18895 by Christian Medical College, Wiley Online Library on [10/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
932 |    ORAL ANTI-­V IRALS FOR COVID-­19 IN HAEMATOLOGICAL MALIGNANCIES

TA BL E 2 Predictors of COVID-­19-­related lung failure (WHO clinical progression scale >5) at univariate and multivariate Cox regression analyses.

OR 95% CI p value aOR 95% CI p value

Age, per 1 year increase 1.02 0.99–­1.06 0.121 \
Male sex versus female sex 0.96 0.34–­2 .73 0.948 \
At least one metabolic comorbidity 0.86 0.28–­2 .57 0.788 \
Active HM 5.03 1.69–­14.99 0.004 4.42 1.08–­17.99 0.038
NHL/CLL versus other diseases 1.87 0.55–­6.35 0.313 \
Anti-­CD20 MAB within 6 months 1.83 0.64–­5.17 0.253 \
Doses of vaccine for SARS-­CoV2
Two doses of vaccine 0.04 0.02– ­0.56 0.017 0.06 0.01– ­0.22 0.006
Three to four doses of vaccine 0.02 0.01– ­0.23 0.001 0.02 0.01– ­0.21 0.001
Prophylaxis with tixagevimab/cilgavimab 0.29 0.03–­2 .46 0.259 \
Type of anti-­v iral therapy
Molnupiravir 1 \ \ \
Nirmatrelvir/ritonavir 0.51 0.18–­1.45 0.213 \
Therapy with MAB 0.94 0.17–­4.96 0.943 \
Length of viral shedding, per 1 day increase 1.02 0.99–­1.05 0.063 1.04 1.00–­1.08 0.022

Abbreviations: aOR, adjusted OR; CI, confidential interval; CLL, chronic lymphocytic leukaemia; HM, haematological malignancy; MAB, monoclonal antibody; NHL, non-­
Hodgkin's lymphoma; OR, odds ratio.
Bold values are statistically significat (p < 0.05)

patients (23.1%) of whom n. 9 (10.9%) in the NIR/r group
and n. 10 (12.1%) in the MOL group (n.s). Specifically, n. 14
(17%) required low flux oxygen therapy or non-­invasive ven-
tilation, while n. 5 (6%) required admission to the intensive
care unit (ICU) with invasive ventilation. The median time
between the start of oral anti-­v iral therapy and the onset of
respiratory failure was 5 days (range = 2–­11 days). In accord-
ance with NIH guidelines, all patients completed 5 days of
oral anti-­v iral.17
Univariate and multivariate logistic regression were
performed to explore predictors of COVID-­19-­related lung
failure. Interestingly, active HM (aOR = 4.42, 95% CI = 1.08–­
17.99 p = 0.038) and prolonged viral shedding (aOR = 1.04;
95% CI = 1.00–­1.08; p = 0.022) resulted independent predic-
tors of severe COVID-­19 infection. The vaccination with
three -­four doses (aOR = 0.02; 95% CI = 0.01–­0.21; p = 0.001)
and to a lesser extent with two doses (aOR = 0.06; 95%
CI = 0.01–­0.22; p = 0.006) resulted protective (Table 2).
The hospitalization rate for pulmonary complications of
COVID-­19 infection at 28 days was 23.1% as all patients who
developed lung failure were hospitalized at that time point.
COVID-­19-­related deaths at 28 days were 5 (6.1%), n. 2 oc-
curring in the NIR/r group and n. 3 MOL group (n.s.).
Finally, no grade 3–­4 adverse events related to anti-­v iral
or neutralizing MABs were reported, and all patients com-
pleted the planned treatment.
Viral shedding
Viral shedding was evaluated by molecular nasopharynx
swab which was viewable on an online centralized regional
system. The median (q1–­q3) duration of viral shedding was
12 days (range 7–­22), comparable in the two treatment arms.
By performing a univariate Cox regression, factors re-
ducing viral clearance were increased age (HR = 0.98, 95%
CI = 0.96–­0.99 p = 0.025) and being affected by NHL/CLL
(HR = 0.46, 95% CI = 0.28–­0.76 p = 0.003); on the contrary,
NIR/r resulted in a faster viral clearance compared with
MOL (HR = 1.60, 95% CI = 1.00–­2.58 p = 0.049). At multi-
variate analysis, only the diagnoses of NHL/CLL resulted
independently associated with a slower viral shedding
(aHR = 0.50, 95% CI = 0.30–­0.83 p = 0.003; Table 3). Finally,
these results were graphically explored by Kaplan–­Meier
survival analysis, confirming previous findings (Figure 1).
Long-­term outcome at 90 days
Patients were evaluated at 90 days from the start of anti-­v iral
treatment. The following aspects were analysed: (a) all-­cause
mortality at 90 days; (b) COVID-­19 recurrence/reinfection;
(c) onset of an opportunistic infection; (d) non-­infectious
pneumonia; and (e) cardiovascular complications.
All-­cause mortality at 90 days was 13.4% (n. 11).
Out of 82 patients, follow-­up clinical data were available for
71 patients. The most frequently occurring complication was
COVID-­19 recurrence/reinfection observed in n. 13 (18.3%).
Furthermore, two (2.8%) patients developed a fatal opportunis-
tic infection (Aspergillosis), two a non-­infectious pneumonia
(pulmonary inflammatory disease manifesting with dys-
pnoea, tachypnoea and hyperpyrexia), one (1.4%) a pulmonary
microembolism recovered with anticoagulant therapy and
1 a fatal ischaemic cardiac event. Median time to COVID-­19
 13652141, 2023, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/bjh.18895 by Christian Medical College, Wiley Online Library on [10/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
MINOIA et al.    | 933

TA BL E 3 Predictors of prolonged viral shedding in HM at univariate and multivariate Cox regression analyses.

HR 95% CI p value aHR 95% CI p value

Age, per 1 year increase 0.98 0.96– ­0.99 0.025 0.98 0.97–­1.00 0.213
Male sex versus female sex 1.05 0.66–­1.67 0.813 \
Active HM 0.80 0.49–­1.29 0.367 \
NHL/CLL versus other diseases 0.46 0.28– ­0.76 0.003 0.50 0.30– ­0.83 0.008
Anti-­CD20 MAB within 6 months 0.68 0.43–­1.08 0.107
Doses of vaccine for SARS-­CoV2
Two doses of vaccine 0.71 0.25–­2 .04 0.540 \
Three to four doses of vaccine 0.72 0.34–­1.52 0.390 \
Prophylaxis with tixagevimab/cilgavimab 0.69 0.36–­1.32 0.267
COVID-­19-­associated lung failure 0.55 0.31–­1.00 0.050 0.73 0.38–­1.36 0.327
Type of anti-­v iral therapy
Molnupiravir 1 \ \
Nirmatrelvir/ritonavir 1.60 1.00–­2 .58 0.049 1.36 0.82–­2 .25 0.231
Therapy with MAB 0.58 0.28–­1.17 0.132

Abbreviations: aHR, adjusted HR; CI, confidential interval; CLL, chronic lymphocytic leukaemia; HM, haematological malignancy; HR, hazard ratio; MAB, monoclonal
antibody; NHL, non-­Hodgkin lymphoma.
Bold values are statistically significat (p < 0.05)

(A) (B)

F I G U R E 1 Kaplan–­Meier analyses reporting days from infection to viral clearance according to: (A) type of HM (NHL/CLL vs. others); (B) type of
anti-­v iral therapy (NIR/r vs. MOL). HM, Haematological malignancy; NHL, non-­Hodgkin's lymphoma, HL; Hodgkin lymphoma. [Colour figure can be
viewed at wileyonlinelibrary.com]

recurrence/reinfection was 35 days (range, 4–­71) from the first
negative nasopharyngeal swab. Vascular events occurred after
77 days (pulmonary microembolism) and 84 days (ischaemic
cardiac event). Of the entire cohort, two patients died for HM
progression and one for an unknown cause.
By evaluating the risk factors for COVID-­19 recurrence/
reinfection, only being affected by active HM (OR = 3.66,
95% CI = 1.05–­12.73 p = 0.041) and occurrence of COVID-­19-­
related lung failure during the previous infection (OR = 4.55,
95% CI = 1.15–­17.89 p = 0.030) resulted significant (Table 4).
Logistic regression was performed to evaluate predictors of
90-­day mortality; in this case, the only independent risk factor
for mortality was the development of COVID-­19-­related lung
failure (aOR = 6.94, 95% CI = 1.54–­31.3 p = 0.012; Table 5).
DISC US SION
In this study we describe a prospective cohort of HM pa-
tients presenting with early COVID-­19 infection and treated
in the Omicron VOC diffusion phase of the pandemic with
oral anti-­v irals with or without neutralizing anti-­ Spike
MABs. The study was born from the need to treat an ever-­
wider number of patients for COVID-­19 infection in a vast
territory of about 1 500 000 inhabitants. Access to MABs was
not always rapid, and was affected by drug availability in
relation to VOCs and the patient's possibility to reach the
hospital.22,23 This is therefore an unselected real-­life cohort
of patients who were treated on an outpatient basis with
NIR/r or MOL. NIR/r was the first choice, but MOL could
 13652141, 2023, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/bjh.18895 by Christian Medical College, Wiley Online Library on [10/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
934 |    ORAL ANTI-­V IRALS FOR COVID-­19 IN HAEMATOLOGICAL MALIGNANCIES

be administered according to comorbidities and pharma- 12 months. Patients treated with CAR-­T as last treatment
cological interferences. All patients had HM treated with were also included. We evaluated the progression of the in-
anti-­cancer or immunosuppressive drugs after HSCT within fection and the possible factors predisposing the evolution.
The patients presented a COVID-­19-­related lung failure,
T A B L E 4 Predictive factors for COVID-­19 recurrence/reinfection at
corresponding to a grade equal to or greater than 5 on the
90-­day follow-­up in HM.
WHO clinical progression scale, in 23.1% of cases. Even with
OR 95% CI p value the limitation of the number of samples, no differences were
Age, per 1 year increase 0.99 0.95–­1.02 0.599 observed in terms of onset of pulmonary insufficiency in re-
lation to the anti-­v iral drug. According to our analysis, the
Male sex versus female sex 0.88 0.26–­2 .95 0.841
predisposing factor for clinical worsening in lung failure was
At least one metabolic comorbidity 1.10 0.31–­3.80 0.879
the presence of an active HM, defined as PR, SD, PD and a
Active HM 3.66 1.05–­12.73 0.041 prolonged viral shedding. Vaccination with three–­four doses
NHL/CLL versus other diseases 1.75 0.43–­7.10 0.431 and to a lesser extent with two doses was protective against
Anti-­CD20 MAB within 6 months 1.21 0.36–­4.06 0.753 this event. These results are in line with previous evidence
Doses of vaccine for SARS-­CoV2 on HM patients who could benefit from additional doses
Two doses of vaccine 1.01 0.18–­11.30 0.798 of vaccine in the development of a more effective humoral
and T-­cell-­mediated immune response.3–­5,24–­26 Moreover,
Three to four doses of vaccine 1.33 0.14–­12.51 0.801
our study confirmed that viral shedding in these patients
At least three doses of vaccination 3.46 0.41–­29.2 0.253
can be prolonged, especially in elderly patients and in those
for SARS-­CoV2
treated for NHL and CLL. Treatment with NIR/r appears
Prophylaxis with tixagevimab/ 0.98 0.18–­5.23 0.990
to result in faster viral clearance compared to MOL. The
cilgavimab
COVID-­19-­related mortality at 28 days was 6.1% in our pop-
COVID-­19-­associated lung failure 4.55 1.15–­17.89 0.030
at first infection
ulation, a rate moderately higher than that reported in the
literature case series of patients treated for COVID-­19 in the
Type of anti-­v iral therapy
early phase in an outpatient regimen and affected by HM. Of
Molnupiravir 1 \ \ note, in our population, 34% of patients presented an active
Nirmatrelvir/ritonavir 1.47 0.40–­5.37 0.552 HM, 12% underwent HSCT or CAR-­T, 46% were on therapy
Therapy with MAB 2.6 0.55–­12.1 0.225 including anti-­CD20 MAB and all had been treated within
Length of viral shedding, per 1 day 0.99 0.96–­1.02 0.732 12 months of the infection. In addition, 34% had at least one
increase comorbidity, predominantly cardiovascular.
Abbreviations: CI, confidential interval; CLL, chronic lymphocytic leukaemia;
In a retrospective series by the Gruppo Italiano Malattie
HM, haematological malignancy; MAB, monoclonal antibody; NHL, non-­Hodgkin Ematologiche dell'Adulto (GIMEMA group), Marasco et al.
lymphoma; OR, odds ratio. reported on 91 haematological patients treated with different
Bold values are statistically significat (p < 0.05)
types of neutralizing anti-­Spike MABs, finding an incidence

TA BL E 5 Predictors of all-­cause mortality at 90 days after COVID-­19 infection in HM at univariate and multivariate Cox regression analyses.

OR 95% CI p value aOR 95% CI p value

Age, per 1 year increase 0.98 0.95–­1.02 0.484 \
Male sex versus female sex 2.06 0.50–­8.44 0.312 \
At least one metabolic comorbidity 0.38 0.07–­1.91 0.244 \
Active HM 2.67 0.73–­9.69 0.135 1.44 0.31–­6.50 0.634
NHL/CLL versus other diseases 2.15 0.43–­10.7 0.350 \
Anti-­CD20 MAB within 6 months 3.64 0.89–­14.8 0.072 3.25 0.72–­14.5 0.123
Doses of vaccine for SARS-­CoV2
Two doses of vaccine 0.37 0.02–­5.16 0.464 \
Three to four doses of vaccine 0.42 0.07–­2 .45 0.336 \
COVID-­19-­associated lung failure 8.60 2.17–­34.1 0.002 6.94 1.54–­31.3 0.012
Type of anti-­v iral therapy
Molnupiravir 1 \
Nirmatrelvir/ritonavir 0.51 0.14–­1.83 0.304 \
Therapy with MAB 0.78 0.08– ­6.98 0.830 \
Length of viral shedding, per 1 day increase 0.99 0.96–­1.03 0.908 \

Abbreviations: aOR, adjusted OR; CI, confidential interval; CLL, chronic lymphocytic leukaemia; HM, haematological malignancy; MAB, monoclonal antibody; NHL, non-­
Hodgkin lymphoma; OR, odds ratio.
Bold values are statistically significat (p < 0.05)

MINOIA et al.
of hospitalization for COVID-­19 of 12% and a mortality rate
of 3.3%.6 In the retrospective series by Mikulska et al, the
incidence of lung failure was 5.8% for patients treated with
anti-­v irals (remdesivir or oral anti-­v irals NIR/r and MOL)
and 11.8% for MABs.15 Evaluating patients' characteristics,
the study of the GIMEMA group presented patients pre-
dominantly with active and recently treated HM, a preva-
lent diagnosis of lymphoma, and a comparable median age
and prevalence of patients after transplantation or CAR-­T
therapy to our cohort, while patients' comorbidities for
this study were not described. Compared to the cohort re-
ported by Mikulska et al, although the median age, num-
ber of comorbidities and distribution of HMs were similar
to that of our study, 66.5% had received anti-­cancer treat-
ment and 12.8% HSCT or CAR-­T therapy within 12 months
of COVID-­19, while the remaining patients had been out of
therapy for longer. Compared to the cohorts of HM patients
reported prior to the availability of anti-­v iral therapies and
MABs, early treatment of the infection is confirmed to be
effective in reducing infection progression and COVID-­
19-­related mortality rate by approximately 10%. Our data
therefore strengthen the need to have a defined pathway for
HM patients to initiate drug therapy in the early stages of
COVID-­19 infection.
Despite the limit of the number of patients, we wanted
to extend the observation period of the study to 90 days
after infection. This evaluation also arose from the clini-
cal observation outside the study of the onset of opportu-
nistic infections and reinfections from COVID-­19. In the
3 months following the infection, reinfection/recurrence of
COVID-­19 was the most observed event in the study, and
this was correlated with the presence of an active HM. The
onset of opportunistic infections and cardiovascular events
was also observed, some of which were fatal, with a mortal-
ity rate that reached 13.1% for all-­cause mortality at 90 days.
This observation reinforces the need for careful monitoring
of the haematological patients who contract COVID-­19 as
they could develop both severe pulmonary and cardiovas-
cular sequelae.
To the best of our knowledge, this is the first prospec-
tive study exploring the safety and efficacy of the oral
anti-­v iral drugs NIR/r and MOL for the treatment of early
COVID-­19 in HM. The use of an oral and home treatment
is certainly more widespread and rapid but, although it is
associated with a reduction in the risk of lung failure and
mortality compared to the pretreatment cohorts, it is still
associated with a non-­negligible rate of failure. For these
high-­r isk patients, a combined treatment with anti-­v irals
and MABs or the use of more prolonged anti-­v iral therapy
schedules could be hypothesized, in relation to the pro-
longed viral clearance. We must point out that complete
vaccination is the strategy that has allowed the greatest
rate of improvement in the prognosis of haematological
patients in general, and that this is confirmed as a pro-
tective factor of respiratory failure in our cohort. It would
also be desirable to strengthen the factors predisposing
the progression of the infection in more numerous series,
13652141, 2023, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/bjh.18895 by Christian Medical College, Wiley Online Library on [10/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
   | 935
thus allowing for risk stratification for each patient. In our
population, active HM and incomplete vaccination were
the main risk factors, as were old age and the use of im-
mune suppressive drugs such as anti-­CD20 MABs in other
cohorts.
AU T HOR C ON T R I BU T ION S
CM, LD and DFB were responsible for the conceptual-
ization, methodology, writing original draft and formal
analysis. CM, TP, GL, IA, CP, FC and MSDC collected and
evaluated clinical data for the haematological part. CP, VT,
VS and MC collected and evaluated clinical data for the in-
fective part. FDG, AG, PM and AS revised the study process
and final analyses. All authors reviewed and approved the
final manuscript.
AC K N O​W L E​D G E​M E N T S
The authors are thankful to patients and nurses of the in-
volved departments.
F U N DI N G I N F OR M AT ION
Supported by Ministry of Health, Italian Government, R.C.
Funds 2021, to the IRCCS Istituto Tumori ‘Giovanni Paolo
II’, Bari-­Italy (del. 153/21).
C ON F L IC T OF I N T E R E S T S TAT E M E N T
The authors declare no conflict of interest regarding the
topic of the study.
DATA AVA I L A BI L I T Y S TAT E M E N T
Raw data were generated at Clinic of Infectious Diseases,
Department of Precision and Regenerative Medicine and
Ionian Area, University of Bari “Aldo Moro”, 70124 Bari,
Italy. Derived data supporting the findings of this study are
available from the corresponding author C.M. on request.
E T H IC S A PPROVA L S TAT E M E N T
Approval for the study was obtained from the local ethics
committee at the Policlinico/ University of Bari, Italy (study
approval code 6357/2021).
PAT I E N T C ON S E N T S TAT E M E N T
Patients signed informed consent for data collection.
ORC I D
Carla Minoia https://orcid.org/0000-0002-5707-0689
Immacolata Attolico https://orcid.
org/0000-0002-3527-3151
R EFER ENCES
1. Passamonti F, Cattaneo C, Arcaini L, Bruna R, Cavo M, Merli
F, et al. Clinical characteristics and risk factors associated with
COVID-­19 severity in patients with haematological malignancies in
Italy: a retrospective, multicentre, cohort study. Lancet Haematol.
2020;7(10):e737–­45. https://doi.org/10.1016/S2352​-­3026(20)30251​-­9.
Epub 2020 Aug 13. PMID: 32798473; PMCID: PMC7426107.
2. Pagano L, Salmanton-­ García J, Marchesi F, Busca A, Corradini
P, Hoenigl M, et al. COVID-­ 19 infection in adult patients with

936 |    ORAL ANTI-­V IRALS FOR COVID-­19 IN HAEMATOLOGICAL MALIGNANCIES
hematological malignancies: a European Hematology Association
Survey (EPICOVIDEHA). J Hematol Oncol. 2021;14(1):168. https://
doi.org/10.1186/s1304​5-­021-­01177​- ­0. PMID: 34649563; PMCID:
PMC8515781.
3. Griffiths EA, Segal BH. Immune responses to COVID-­19 vaccines in
patients with cancer: promising results and a note of caution. Cancer
Cell. 2021;39(8):1045–­7.
4. Herishanu Y, Avivi I, Aharon A, Shefer G, Levi S, Bronstein Y, et al.
Efficacy of the BNT162b2 mRNA COVID-­19 vaccine in patients with
chronic lymphocytic leukemia. Blood. 2021;137(23):3165–­73.
5. Benjamini O, Rokach L, Itchaki G, Braester A, Shvidel L, Goldschmidt
N, et al. Safety and efficacy of the BNT162b mRNA COVID-­19 vac-
cine in patients with chronic lymphocytic leukemia. Haematologica.
2022;107(3):625–­34. https://doi.org/10.3324/haema​tol.2021.279196.
PMID: 34320789; PMCID: PMC8883569.
6. Marasco V, Piciocchi A, Candoni A, Pagano L, Guidetti A, Musto P,
et al. Neutralizing monoclonal antibodies in haematological patients
paucisymptomatic for COVID-­19: the GIMEMA EMATO-­0321 study.
Br J Haematol. 2022;199(1):54–­60. https://doi.org/10.1111/bjh.18385.
Epub 2022 Jul 30. Erratum in: Br J Haematol. 2023 Mar;200(5):680.
PMID: 35906881; PMCID: PMC9796521.
7. Bafunno D, Romito F, Lagattolla F, Delvino VA, Minoia C, Loseto
G, et al. Psychological well-­ being in cancer outpatients during
COVID-­19. J Buon. 2021;26(3):1127–­34. PMID: 34268981.
8. Drożdżal S, Rosik J, Lechowicz K, Machaj F, Szostak B, Przybyciński
J, et al. An update on drugs with therapeutic potential for SARS-­
CoV-­2 (COVID-­19) treatment. Drug Resist Updat. 2021;59:100794.
https://doi.org/10.1016/j.drup.2021.100794. Epub 2021 Dec 9. PMID:
34991982; PMCID: PMC8654464.
9. Angamo MT, Mohammed MA, Peterson GM. Efficacy and safety
of remdesivir in hospitalised COVID-­19 patients: a systematic re-
view and meta-­ a nalysis. Infection. 2022;50(1):27–­41. https://doi.
org/10.1007/s1501​0 -­021-­01671​- ­0
10. Hammond J, Leister-­ Tebbe H, Gardner A, Abreu P, Bao W,
Wisemandle W, et al. Oral Nirmatrelvir for high-­risk, nonhospital-
ized adults with Covid-­19. N Engl J Med. 2022;386(15):1397–­408.
https://doi.org/10.1056/NEJMo​a 2118542. Epub ahead of print. PMID:
35172054; PMCID: PMC8908851.
11. Fischer WA 2nd, Eron JJ Jr, Holman W, Cohen MS, Fang L, Szewczyk
LJ, et al. A phase 2a clinical trial of molnupiravir in patients with
COVID-­19 shows accelerated SARS-­CoV-­2 RNA clearance and elim-
ination of infectious virus. Sci Transl Med. 2022;14(628):eabl7430.
https://doi.org/10.1126/scitr​a nslm​ed.abl7430. Epub 2022 Jan 19.
PMID: 34941423.
12. Jayk Bernal A, Gomes da Silva MM, Musungaie DB, Kovalchuk E,
Gonzalez A, Delos Reyes V, et al. Molnupiravir for oral treatment of
Covid-­19 in nonhospitalized patients. N Engl J Med. 2022;386(6):509–­
20. https://doi.org/10.1056/NEJMo​a 2116044. Epub 2021 Dec 16.
PMID: 34914868; PMCID: PMC8693688.
13. World Health Organization. vol edition 67. Geneva PP; Geneva. 2021.
Weekly Epidemilogical Update on COVID-­19-­23 November.
14. Arora P, Kempf A, Nehlmeier I, Schulz SR, Jäck HM, Pöhlmann S,
et al. Omicron sublineage BQ.1.1 resistance to monoclonal antibod-
ies. Lancet Infect Dis. 2023;23(1):22–­3. https://doi.org/10.1016/S1473​
-­3099(22)00733​-­2. Epub 2022 Nov 18. Erratum in: Lancet Infect Dis.
2022 Nov 29; PMID: 36410372; PMCID: PMC9707647.
15. Mikulska M, Testi D, Russo C, Balletto E, Sepulcri C, Bussini L, et al.
Outcome of early treatment of SARS-­C oV-­2 infection in patients
with haematological disorders. Br J Haematol. 2023;201:628–­39.
https://doi.org/10.1111/bjh.18690. Epub ahead of print. PMID:
36806152.
13652141, 2023, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/bjh.18895 by Christian Medical College, Wiley Online Library on [10/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
16. WHO working group on the clinical characterisation and manage-
ment of COVID-­19 infection. A minimal common outcome measure
set for COVID-­ 19 clinical research. The Lancet. 2020;20:e192–­ 7.
https://doi.org/10.1016/S1473​-­3099(20)30483​-­7
17. https://www.covid​19tre​atmen​t guid​elines.nih.gov/table​s/thera​peuti​
c-­manag​ement​-­of-­nonho​spita ​lized​-­adult​s/
18. SARS-­CoV-­2 variants in Italy from the Italian Institute of Healthcare
(ISS) from 03/01/2022. https://www.iss.it/docum​ents/20126/​0/
Report_flash​Varia ​nti_14gen​naio22.pdf/b44b1​a7d-­a 0c1- ­67fd- ­4 4b7-­
34c8b​775c0​88?t=16421​62662435
19. SARS-­CoV-­2 variants in Italy from the Italian Institute of Healthcare
(ISS) from 07/03/2022. https://www.iss.it/docum​ents/20126/​0/
Rel+tecni​c a+Flash​++7+Marzo.pdf/f082f​e1b-­f 06e-­2d4a-­9 056-­9 4ba8​
3eb67​41?t=16484​52994970
20. Stuver R, Shah GL, Korde NS, Roeker LE, Mato AR, Batlevi CL,
et al. Activity of AZD7442 (tixagevimab-­cilgavimab) against omicron
SARS-­CoV-­2 in patients with hematologic malignancies. Cancer Cell.
2022;40(6):590–­1. https://doi.org/10.1016/j.ccell.2022.05.007. Epub
2022 May 16. PMID: 35598602; PMCID: PMC9108069.
21. Gupta A, Gonzalez-­Rojas Y, Juarez E, Crespo Casal M, Moya J, Falci
DR, et al. Early treatment for Covid-­19 with SARS-­CoV-­2 neutraliz-
ing antibody Sotrovimab. N Engl J Med. 2021;385(21):1941–­50.
22. O'Brien MP, Forleo-­Neto E, Sarkar N, Isa F, Hou P, Chan KC, et al.
Effect of subcutaneous Casirivimab and imdevimab antibody combi-
nation vs placebo on development of symptomatic COVID-­19 in early
asymptomatic SARS-­CoV-­2 infection: a randomized clinical trial.
JAMA. 2022;327(5):432–­41. https://doi.org/10.1001/jama.2021.24939.
PMID: 35029629; PMCID: PMC8808333.
23. RECOVERY Collaborative Group. Casirivimab and im-
devimab in patients admitted to hospital with COVID-­ 19
(RECOVERY): a randomised, controlled, open-­ label, platform
trial. Lancet. 2022;399(10325):665–­76. https://doi.org/10.1016/S0140​
-­6736(22)00163​-­5. PMID: 35151397; PMCID: PMC8830904.
24. Rinaldi I, Pratama S, Wiyono L, Tandaju JR, Wardhana IL, Winston
K. Efficacy and safety profile of COVID-­19 mRNA vaccine in pa-
tients with hematological malignancies: systematic review and
meta-­a nalysis. Front Oncol. 2022;12:951215. https://doi.org/10.3389/
fonc.2022.951215. PMID: 36003763; PMCID: PMC9393790.
25. Teh JSK, Coussement J, Neoh ZCF, Spelman T, Lazarakis S, Slavin
MA, et al. Immunogenicity of COVID-­19 vaccines in patients with
hematologic malignancies: a systematic review and meta-­a nalysis.
Blood Adv. 2022;6(7):2014–­ 34. https://doi.org/10.1182/blood​advan​
ces.20210​06333. PMID: 34852173; PMCID: PMC8639290.
26. Mai AS, Lee ARYB, Tay RYK, Shapiro L, Thakkar A, Halmos B,
et al. Booster doses of COVID-­19 vaccines for patients with haema-
tological and solid cancer: a systematic review and individual pa-
tient data meta-­a nalysis. Eur J Cancer. 2022;172:65–­75. https://doi.
org/10.1016/j.ejca.2022.05.029. Epub 2022 Jun 3. PMID: 35753213;
PMCID: PMC9163022.
How to cite this article: Minoia C, Diella L, Perrone
T, Loseto G, Pelligrino C, Attolico I, et al. Oral
anti-­viral therapy for early COVID-­19 infection in
patients with haematological malignancies: A
multicentre prospective cohort. Br J Haematol.
2023;202(5):928–936. https://doi.org/10.1111/bjh.18895