Clinical Nutrition ESPEN 55 (2023) 212e220

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Clinical Nutrition ESPEN

journal homepage: http://www.clinicalnutritionespen.com

Original article

COVID-19 infection in patients on long-term home parenteral

nutrition for chronic intestinal failure*
Loris Pironi a, b, *, Denise Jezerski c, Jacek Sobocki d, Simon Lal e, Tim Vanuytsel f,
Miriam Theilla g, Anna S. Sasdelli b, Cecile Chambrier h, Konrad Matysiak i,
Umberto Aimasso j, Henrik H. Rasmussen k, Amelia Jukes l, Marek Kunecki m,
David Seguy n, Ste
phane M. Schneider o, Joanne Daniels p, Florian Poullenot q,
Manpreet S. Mundi r, Przemysław Matras s, Marcin Folwarski t, Adriana Crivelli u,
Nicola Wyer v, Lars Ellegard w, Lidia Santarpia x, Marianna Arvanitakis y,
Corrado Spaggiari z, Georg Lamprecht aa, Francesco W. Guglielmi ab, Antonella Lezo ac,
Sabrina Layec ad, Esther Ramos Boluda ae, Anat Guz-Mark af, ag, Paolo Gandullia ah,
Cristina Cuerda ai, Emma Osland aj, Maria I. Spagnuolo ak, Zeljko Krznaric al,
Luisa Masconale am, Brooke Chapman an, María Maíz-Jime
nez ao, Paolo Orlandoni ap,
Mariana Hollanda Martins da Rocha , M. Nuria Virgili-Casas ar,
aq

Maryana Doitchinova-Simeonova as, Laszlo Czako at, Andre  Van Gossum au,
Lorenzo D'Antiga , Looi C. Ee , Daruneewan Warodomwichit ax, Marina Taus ay,
av aw

Sanja Kolacek az, Ronan Thibault ba, Giovanna Verlato bb, Aurora E. Serralde-Zún ~ iga bc,

I. Botella-Carretero bd, Pilar Serrano Aguayo be, Gabriel Olveira bf,
Jose
Sirinuch Chomtho bg, bh, Veeradej Pisprasert bi, Georgijs Moisejevs bj,
Ana Zugasti Murillo bk, Ma Estrella Petrina Ja
uregui bl, Marta Bueno Díez bm,
Mohammad Shukri Jahit , Narumon Densupsoontorn bo, Ali Tamer bp, Giorgia Brillanti a,
bn

Francisca Joly bq
a
University of Bologna, Department of Medical and Surgical Sciences, Italy
b
Centre for Chronic Intestinal Failure, Clinical Nutrition and Metabolism Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy
c
Home Nutrition Support, Cleveland Clinic Foundation, Cleveland, OH, USA
d
Centre of Postgraduate Medical Education, Warsaw, Poland
e
Intestinal Failure Unit, Salford Royal Foundation Trust, Salford, UK
f
University Hospital Leuven, Leuven Intestinal Failure and Transplantation (LIFT), Leuven, Belgium
g
Rabin Medical Center, Petach Tikva, Sackler School of Medicine, Tel Aviv University, Tel Aviv-Yaffo Academic College School for Nursing Sciences, Israel
h
Unit
^pital Lyon Sud, Lyon, France
e de Nutrition Clinique Intensive, Hospices Civils de Lyon, Ho
i
University of Medical Science, Poznan
Centre for Intestinal Failure, Department of General, Endocrinological and Gastroenterological Surgery, Poznan
,
Poland
j  della Salute e della Scienza, Turin, Italy
Citta
k
Centre for Nutrition and Bowel Disease, Department of Gastroenterology, Aalborg University Hospital, Aalborg, Denmark
l
University Hospital of Wales, Cardiff, United Kingdom
m
M. Pirogow Hospital, Lodz, Poland
n
Service de Nutrition, CHRU de Lille, Lille, France
o
Gastroenterology and Clinical Nutrition, CHU of Nice, Universit
^te d’Azur, Nice, France
e Co
p
Nottingham University Hospital NHS Trust, Nottingham, United Kingdom
q
Service de Gastroent
erologie, Ho^pital Haut-L
ev^
eque, CHU de Bordeaux, Pessac, France
r
Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic College of Medicine, Rochester, MN, USA
s
Department of General and Transplant Surgery and Clinical Nutrition, Medical University of Lublin, Lublin, Poland

*
The Home Artificial Nutrition and Chronic Intestinal Failure Special Interest
Group of ESPEN, The European Society for Clinical Nutrition and Metabolism.
* Corresponding author. University of Bologna, Department of Medical and Sur-
gical Sciences, Bologna, Italy.
E-mail address: [email protected] (L. Pironi).

https://doi.org/10.1016/j.clnesp.2023.03.008
2405-4577/© 2023 The Authors. Published by Elsevier Ltd on behalf of European Society for Clinical Nutrition and Metabolism. This is an open access article under the CC BY
license (http://creativecommons.org/licenses/by/4.0/).
L. Pironi, D. Jezerski, J. Sobocki et al. Clinical Nutrition ESPEN 55 (2023) 212e220

t
Department of Clinical Nutrition and Dietetics, Medical University of Gdansk, Home Enteral and Parenteral Nutrition Unit, Copernicus Hospital, Gdansk,
Poland
u
Unidad de Soporte Nutricional, Rehabilitacio
n y Trasplante de Intestino, Hospital Universitario Fundacion Favaloro, Buenos Aires, Argentina
v
University Hospitals Coventry & Warwickshire NHS Trust, Coventry, United Kingdom
w
Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg,
Sweden
x
Internal Medicine and Clinical Nutrition Unit, Federico II University, Naples, Italy
y
Department of Gastroenterology, HUB Erasme, Brussels, Belgium
z
AUSL Parma, Parma, Italy
aa
University Medical Center Rostock, Rostock, Germany
ab
Gastroenterology Unit, Monsignor di Miccoli Hospital, Barletta, Italy
ac
Department of Clinical Nutrition, OIRM-S. Anna Hospital, Citta  della Salute e della Scienza, Turin, Italy
ad
Digestive and Nutritional Rehabilitation Unit/Artificial Nutrition Unit, Clinique Saint-Yves, Rennes, France
ae
Pediatric Gastrointestinal and Nutrition Unit, University Hospital La Paz, Madrid, Spain
af
Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Petach-Tikva, Israel
ag
Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
ah
Pediatric Gastroenterology and Endoscopy, IRCCS G. Gaslini Institute, Genoa, Italy
ai
University Complutense. Department of Medicine, Nutrition Unit, Hospital General Universitario Gregorio Maran ~ on, Madrid, Spain
aj
Royal Brisbane and Women's Hospital, Herston, Australia
ak
Section of Paediatrics, Department of Translational Medical Science, University of Naples Federico II, Naples, Italy
al
Centre of Clinical Nutrition, Department of Medicine, University Hospital Centre, Zagreb, Croatia
am
Ospedale Orlandi, Bussolengo (VR), Italy
an
Austin Health, Melbourne, Australia
ao
Department of Endocrinology and Nutrition, Hospital 12 de Octubre, Madrid, Spain
ap
Nutrizione Clinica-Centro di Riferimento Regionale NAD, IRCCSeINRCA, Ancona, Italy
aq
Hospital das Clinicas da Faculdade de Medicina da Universidade de Sa ~o Paulo, Sa
~o Paulo, Brazil
ar
Department of Endocrinology and Nutrition, Hospital Universitari de Bellvitge, Barcelona, Spain
as
Bulgarian Association of Patients with Malnutrition, Sofia, Bulgaria
at
First Department of Internal Medicine, Szeged, Hungary
au
Department of Gastroenterology, HUB Erasme, Brussels
av
Paediatric Hepatology, Gastroenterology and Transplantation. “Papa Giovanni XXIII” Hospital, Bergamo, Italy
aw
Queensland Children's Hospital, Brisbane, Australia
ax
Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
ay
SOD Dietetica e Nutrizione Clinica, Centro Riferimento Regionale NAD, Ospedali Riuniti di Ancona, Italy
az
Children's Hospital Zagreb, Zagreb Medical University, Zagreb, Croatia
ba
CHU Rennes, Nutrition Unit, Home Parenteral Nutrition Centre, INRAE, INSERM, Univ Rennes, Nutrition Metabolisms and Cancer, NuMeCan, Rennes,
France
bb
Paediatric Nutrition Service-Neonatal Intensive Care Unit, University Hospital of Padova, Padova, Italy
bc
Instituto Nacional de Ciencias M

n, Salvador Zubira
edicas y Nutricio
n, M

exico, Mexico
bd
Department of Endocrinology and Nutrition-Hospital Universitario Ramo
n y Cajal, & IRyCIS Madrid, Spain
be
Hospital Universitario Virgen del Rocío, Sevilla, Spain
bf
Hospital Regional Universitario de Ma
laga, IBIMA, Universidad de Ma
laga, Spain
bg
Pediatric Nutrition Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
bh
Division of Nutrition, Department of Pediatrics, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
bi
Division of Clinical Nutrition, Department of Medicine, Khon Kaen University, Srinagarind Hospital, Khon Kaen, Thailand
bj
Riga East University Hospital, Riga, Latvia
bk
Hospital Virgen del Camino, Pamplona, Spain
bl
Complejo Hospitalario de Navarra, Pamplona, Spain
bm
Hospital Universitari Arnau de Vilanova, Lleida, Spain
bn
National Cancer Institute/Institut Kanser Negara, Putrajaya Wilayah Persekutuan, Malaysia
bo
Division of Nutrition, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
bp
Internal Medicine, Sakarya Unıversity Medical Faculty Education and Research Hospital, Sakarya, Turkey
bq
Centre for Intestinal Failure, Department of Gastroenterology and Nutritional Support, Ho ^pital Beaujon, Clichy, France

a r t i c l e i n f o s u m m a r y

Article history:
Background and aims: To investigate the incidence and the severity of COVID-19 infection in patients
Received 29 January 2023
enrolled in the database for home parenteral nutrition (HPN) for chronic intestinal failure (CIF) of the
Accepted 11 March 2023
European Society for Clinical Nutrition and Metabolism (ESPEN).
Methods: Period of observation: March 1st, 2020 March 1st, 2021. Inclusion criteria: patients included in
Keywords:
the database since 2015 and still receiving HPN on March 1st, 2020 as well as new patients included in
COVID-19
SARS-CoV-2 the database during the period of observation. Data related to the previous 12 months and recorded on
Pandemic March 1st 2021: 1) occurrence of COVID-19 infection since the beginning of the pandemic (yes, no,
Home parenteral nutrition unknown); 2) infection severity (asymptomatic; mild, no-hospitalization; moderate, hospitalization no-
Intestinal failure ICU; severe, hospitalization in ICU); 3) vaccinated against COVID-19 (yes, no, unknown); 4) patient
Epidemiology outcome on March 1st 2021: still on HPN, weaned off HPN, deceased, lost to follow up.
Results: Sixty-eight centres from 23 countries included 4680 patients. Data on COVID-19 were available
for 55.1% of patients. The cumulative incidence of infection was 9.6% in the total group and ranged from
0% to 21.9% in the cohorts of individual countries. Infection severity was reported as: asymptomatic
26.7%, mild 32.0%, moderate 36.0%, severe 5.3%. Vaccination status was unknown in 62.0% of patients,
non-vaccinated 25.2%, vaccinated 12.8%. Patient outcome was reported as: still on HPN 78.6%, weaned off
HPN 10.6%, deceased 9.7%, lost to follow up 1.1%. A higher incidence of infection (p ¼ 0.04), greater
severity of infection (p < 0.001) and a lower vaccination percentage (p ¼ 0.01) were observed in deceased
patients. In COVID-19 infected patients, deaths due to infection accounted for 42.8% of total deaths.

213
L. Pironi, D. Jezerski, J. Sobocki et al. Clinical Nutrition ESPEN 55 (2023) 212e220

Conclusions: In patients on HPN for CIF, the incidence of COVID-19 infection differed greatly among
countries. Although the majority of cases were reported to be asymptomatic or have mild symptoms
only, COVID-19 was reported to be fatal in a significant proportion of infected patients. Lack of vacci-
nation was associated with a higher risk of death.
© 2023 The Authors. Published by Elsevier Ltd on behalf of European Society for Clinical Nutrition and
Metabolism. This is an open access article under the CC BY license (http://creativecommons.org/licenses/
by/4.0/).

1. Introduction presence of active malignant disease [3]. Data were collected in a

structured questionnaire embedded in an Excel (Microsoft Co., 2013)
The coronavirus SARS-CoV-2 (COVID-19) has been a challenging database, termed “the CIF Action day” [3,9].
worldwide pandemic in recent years [1]. The clinical spectrum of For each patient, the following data were collected at first in-
COVID-19 ranges from an asymptomatic infection or mild upper clusion in the database (baseline): age and gender; body weight
respiratory tract symptoms to severe pneumonia with acute res- and height; underlying disease and its benign or malignant nature;
piratory distress syndrome (ARDS) [1,2]. Older age and the presence pathophysiological mechanism of CIF; HPN requirements (dura-
of comorbidities, such as diabetes, cardiovascular diseases and tion, number of days of infusion per week, type of parenteral
obesity, were reported to be risk factors for progression of pul- nutrition admixture, intravenous supplementation (IVS) volume
monary disease as well as for death [3,4]. Patients affected by and energy for each day of infusion). The pathophysiological
chronic organ failure are particularly vulnerable subgroups mechanisms of IF were classified as short bowel syndrome with
requiring epidemiological investigation to better understand their end-jejunostomy (SBS-J), with jejuno-colic anastomosis (SBS-JC) or
associated morbidity and mortality risk and to devise prevention with jejuno-ileal anastomosis and total colon in continuity (SBS-
and treatment strategies. JIC), intestinal dysmotility (dysmotility), intestinal fistulas (fistulas),
In May 2020, a few months after the beginning of the pandemic, mechanical obstruction (obstruction) and extensive small bowel
the Home Artificial Nutrition and Chronic Intestinal Failure mucosal disease (mucosal disease). The severity of CIF was divided
(HAN&CIF) special interest group of the European Society for into eight categories, based on the type (Fluid and electrolyte alone,
Clinical Nutrition and Metabolism (ESPEN) carried out a survey of FE; parenteral nutrition including macronutrients, PN) and volume
centres looking after patients on home parenteral nutrition (HPN) of IVS, calculated as daily mean of the total volume infused per
for Chronic Intestinal Failure (CIF) [5] to assess the impact of the week (volume per day of infusion  number of infusions per week/
COVID-19 pandemic on patient care [6]. A total of 78 centers from 7 (mL/day)): FE1 or PN1, 1000 mL; FE2 or PN2, 1001e2000 mL;
around the world contributed to the survey, representing 3500 FE3 or PN3, 2001e3000 mL; FE4 or PN4, >3000 mL [8]. At the end
patient experiences from both adult and pediatric centers; at that of the 12-month follow-up period, patient outcome was classified
time, 53 centres (67.95%) reported to have no known COVID-19 as still on HPN, weaned off HPN or deceased. Weaning from HPN
infected patients, 7 (8.97%) centres were aware that some pa- equated to stopping IVS. The causes of death were grouped as HPN/
tients had been infected but were unsure of the exact number of IF-related, underlying disease-related and other causes (neither
cases, while 18 (23.08%) centres reported that a total of 37 patients HPN/IF nor underlying disease-related).
had been infected with COVID-19 [6]. For the present study, the period of observation was March 1st,
In 2015, the HAN&CIF group developed an international multi- 2020 (baseline) to March 1st 2021 (end of follow-up) and the date
center research project to develop consensus criteria for the of data collection was March 1st 2021. Patients included at baseline
severity of CIF; the study protocol involved annual prospective data were those already in the database still requiring HPN on March 1st,
collection of HPN-dependent patients using a structured database 2020 and new patients who started HPN between March 1st, 2020
[7,8]. As part of the project, data collection in 2021 was used to and March 1st, 2021. In order to evaluate occurrence and outcomes
perform an international multicenter survey to investigate the associated with COVID-19 infection, a section was added to the
incidence and severity of COVID-19 infection in patients on long- ESPEN CIF database including three questions:1) had the patient
term HPN for CIF. suffered from COVID-19 infection? (answers: yes; no; unknown); 2)
if yes, what was the severity of infection? (answers: asymptomatic;
mild, no-hospitalization; moderate, with hospitalization not in the
2. Materials and methods intensive care unit; severe, hospitalization in the intensive care
unit); 3) has the patient been vaccinated against COVID-19 (an-
2.1. Study protocol, patient population and data collection swers: yes, no, unknown).

The ESPEN international multicenter survey for CIF is based on

the retrospective analysis of data prospectively recorded during 12- 2.2. Ethical statement
month follow-up periods. The study started on March 1st, 2015, and
data collection was performed on March 1st of each subsequent year, The research was based on anonymized information taken from
analysing data recorded during the previous 12 months for those patient records at the time of data collection. The study was con-
patients already included in the database and for new patients who ducted with full regard to confidentiality of the individual patient.
started HPN for CIF during the preceding 12 months. Center invita- Ethical committee approval was obtained by the individual HPN
tion to participate in the study occurred via representatives of the centers according to local regulations.
national Parenteral and Enteral Nutrition (PEN) societies of the
ESPEN Council, who were asked to send the study protocol to 2.3. Statistical analysis
members of their PEN societies. Both pediatric (18-year-old) and
adult patients who were dependent on HPN for either benign-CIF or Data are reported as absolute and relative frequencies. The fre-
malignant-CIF were included. The term ‘malignant-CIF’ indicates the quency of COVID-19 infection was reported as “cumulative annual
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L. Pironi, D. Jezerski, J. Sobocki et al. Clinical Nutrition ESPEN 55 (2023) 212e220

incidence”. Pearson chi-square test and Fisher's exact test were Table 2
used to analyze frequencies where appropriate. All analyses were Patient demographic and clinical characteristics at baseline enrollment on March
1st, 2020.
carried out using Stata v.15.1, and the significance level was set to
p < 0.05. Patient categories % of patients

Sex (n. 4860)

Males 42.0
3. Results Females 58.0
Age category (n. 4815)
3.1. Patient cohort Children (18 years) 6.1
Adults 93.9
Disease category (n. 4849)
Sixty-eight HPN centers from 23 countries included 4860 pa- Benign 79.7
tients (Tables 1 and 2). Malignant (presence of active cancer) 20.3
Mechanism of CIF (n. 4182)
SBS 59.0
3.2. COVID-19 infection Dysmotility 15.2
Obstruction 13.6
COVID-19 infection was reported as known (answer: yes or no) Fistulas 7.5
Mucosal Disease 4.7
in 2503 (51.5%) patients, unknown in 2039 (42.0%) and was not Underlying disease (n. 4749)
reported in 318 (6.5%). COVID-19 infection occurred in 241 patients, Cancer 16.9
corresponding to an annual cumulative incidence rate of 9.6% of the Crohn's disease 16.4
2503 patients for whom the item was known. Among contributing Mesenteric Ischemia 13.8
CIPO-primary 7.3
countries, the calculated annual cumulative incidence ranged from
Radiation enteritis 3.8
0 (Australia) to 21.9% (Israel) (Supplemental Table 1). Figure 1 Carcinomatosis 2.8
shows the incidence of infections in countries that included in Other 25.0
the study at least 10 patients with known infection status. The IVS category (L/d) (n. 3949)
infection rate was 6.1% in children and 10.2% in adults (p ¼ 0.036), FE  1 4.3
FE 1e2 1.9
10.3% in benign disease and 7.0% in active cancer (p ¼ 0.032) and FE 2e3 0.3
did not differ between sex (p ¼ 0.891), mechanisms of CIF FE > 3 0.1
(p ¼ 0.743) or IVS (p ¼ 0.170) categories. Total FE 7.0
PN  1 22.0
PN 1e2 38.3
3.3. COVID-19 infection severity PN 2e3 21.3
PN > 3 9.6
Total PN 93.0
The clinical severity of COVID-19 infection was reported for 172
of the 241 infected patients. Infection was asymptomatic in 26.7%, Abbreviations: CIF, chronic intestinal failure; SBS, short bowel syndrome; CIPO,
chronic intestinal pseudo-obstruction; IVS, intravenous supplementation; FE, fluids
mild in 32.0%, moderate in 36.0% and severe in 5.3% (Fig. 2). The
and electrolytes; PN, parenteral nutrition.
severity of infection did not differ between sex (p ¼ 0.864), age
(p ¼ 0.720), underlying disease (0.564), mechanism of CIF
(p ¼ 0.603) and IVS categories (p ¼ 0.378). 3.4. Vaccination against COVID-19

COVID-19 vaccination status was reported for 3962 patients as

Table 1
Contributing home parenteral nutrition (HPN) centers and patients with chronic follows: vaccinated 12.8%, not vaccinated 25.2% and unknown
intestinal failure enrolled in the study, grouped by country of origin. 62.0%. The vaccination rate was 2.6% in children and 39.7% in adults
(p < 0.001), 31.7% in benign disease and 44.9% in malignant disease
HPN Centers Patients
(p < 0.001), 38.3% in SBS-J, 29.7% in SBS-JC, 18.6% in SBS-JIC, 42.4% in
Country n n %
fistulas, 21.2% in dysmotility, 14.8% in mechanical occlusion and
France 7 887 18.25 25.0% in mucosal disease (p < 0.001), and did not differ between sex
Poland 5 806 16.58 (p ¼ 0.248), mechanisms of CIF (p ¼ 0.743) and IVS categories
Italy 13 675 13.89
(p ¼ 0.800).
USA 2 639 13.15
UK 4 626 12.88
Belgium 3 304 6.26
Israel 2 239 4.92
Denmark 1 145 2.98
Spain 10 128 2.63 3.5. Association between COVID-19 incidence, severity and
Australia 4 82 1.69 vaccination status and patient outcome
Argentina 1 68 1.40
Sweden 1 57 1.17 At the end of the 12-month follow up period, the outcomes of
Germany 1 46 0.95
Croatia 2 32 0.66
2454 patients were reported as follows: still on HPN 78.6%, weaned
Finland 1 32 0.66 off HPN 10.6%, deceased 9.7%, lost to follow up 1.1%. The infection
Thailand 4 28 0.58 rate was significantly higher in the deceased and in those lost to
Brazil 1 17 0.35 follow up (p ¼ 0.042), while infection severity was higher in the
Bulgaria 1 16 0.33
deceased group (p < 0.001) and those still requiring HPN p ¼ 0.017)
Hungary 1 15 0.31
Mexico 1 9 0.19 (Table 3).
Latvia 1 5 0.10 Twenty-nine patients infected with COVID-19 died, with causes
Malaysia 1 3 0.06 of deaths shown in Table 4. No death was HPN-related. Deaths due
Turkey 1 1 0.02 to COVID-19 infection accounted for the 42.8% of the 29 deaths
Total 68 4860 100
occurred in patients who had the infection.
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L. Pironi, D. Jezerski, J. Sobocki et al. Clinical Nutrition ESPEN 55 (2023) 212e220

Fig. 1. Annual cumulative incidence of COVID-19 infection in the total cohort of 2503 patients on home parenteral nutrition for chronic intestinal failure and in the cohorts of
countries that included in the study at least 10 patients with known infection status.

Fig. 2. Percentages of clinical severity of COVID-19 infection in 172 patients on home parenteral nutrition for chronic intestinal failure. Mild, no-hospitalization; Moderate, with
hospitalization not in intensive care unit; Severe, hospitalization in intensive care unit.

Table 3
COVID-19 infection incidence, severity of infection, and COVID-19 vaccination in the 12-month outcome categories of patients on home parenteral nutrition (HPN) for chronic
intestinal failure.

COVID-19 infection COVID-19 infection severity COVID-19 vaccination

n. Infected n. (%) p n.* Asymptomatic n. (%) Mild n. (%) Moderate n. (%) Severe n. (%) p n. ** Vaccinated n. (%) p

Outcome 0.042 <0.001 0.017

Still on HPN 1930 183 (9.5) 129 38 (29.5) 47 (36.4) 42 (32.6) 2 (1.6) 1376 480 (34.9)
Weaned off HPN 258 19 (7.4) 15 5 (33.3) 5 (33.3) 5 (33.3) 0 45 10 (22.2)
Deceased 239 29 (12.1) 20 0 1 (5.0) 12 (60.0) 7 (35.0) 43 8 (18.6)
Lost to follow-up 27 6 (22.2) 4 2 (50.0) 0 2 (50.0) 0 14 2 (14.3)

*Number of infected patients for whom the severity of infection was reported.
**Number of patients for whom the vaccination status (yes or no) was known.

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L. Pironi, D. Jezerski, J. Sobocki et al. Clinical Nutrition ESPEN 55 (2023) 212e220

Table 4 cases per 100 thousand population since the beginning of the
Causes of death in patients on home parenteral nutrition infected with COVID-19 pandemic [13]. In many countries, the calculated incidence of
during the 12-month follow up period.
infection in HPN-dependent patients appeared at least two-fold
Death in patients on HPN infected with COVID-19, n. 29 higher than that in the general population (Fig. 3), suggesting
Cause of death, n. (%) either greater susceptibility and/or risk of exposure to COVID-19
Not reported 1 (3.4) infection and/or a greater rate of testing in patients on HPN for
Underlying disease-related 14 (48.3) CIF. The incidence of infection was significantly higher in adults
 Cancer 7
than in children and in patients with benign rather than malignant
 Cancer þ COVID-19 1
 Not reported 6 disease. The reasons for these differences are not evident from our
Other 14 (48.3) data. However, as expected, vaccination rates were higher in pa-
 COVID-19 11 tients with cancer and lower in children; it is, of course, possible
 Intracerebral hemorrage 2
that both adults and patients with benign disease were at greater
 Renal failure 1
risk of exposure to the infection as they spent more time in contact
with others outside of their homes. Overall, our data confirm that
4. Discussion patients on HPN are a fragile population to be timely protected by
repeated vaccination against COVID-19.
This study reports the incidence and severity of COVID-19 COVID-19 infection was asymptomatic or led to only mild
infection as well as the vaccination status of a large cohort of pa- symptoms without the need for hospitalization in the majority of
tients requiring HPN for CIF during the early phase of the pandemic cases; notably, these data are comparable to the impact of the
(March 1st, 2020eMarch 1st, 2021). In the whole group of patients, disease on the general population observed at the beginning of the
the annual incidence of COVID-19 infection was 9.7%. By compari- pandemic and suggest that HPN-dependence for CIF was not a risk
son, a recent review of 145 articles, largely based on single-centre factor for developing more severe clinical features following
experiences in high-income countries, revealed an incidence of infection [14,15].
COVID-19 among patients on hemodialysis (HD) for chronic kidney Only 12.8% of patients were reported to be vaccinated at the
disease (CKD) ranging from 0% to 37.6% [9]. Sosa et al. reported a time of data collection, although this was more frequent in adults,
COVID-19 infection incidence rate of 102 per 1000 patients on HD in those with active cancer and for some underlying CIF patho-
(10.2%) between May 1st to July 31st, 2020, in Guatemala, physiological mechanisms. That said, this low rate of vaccination
compared with 3/1000 (0.3%) in the general population [10]. The would, of course, fit with the study's time frame since the first
United States Renal Data System (USRDS) 2021 annual data report vaccine was approved in December 2020 and therefore only
showed that, among Medicare beneficiaries in February 2020 un- available during the latter two months of the survey, and not in all
dergoing HD, the cumulative incidence of COVID-19 infection by countries. Furthermore, differences in country policies to prevent
the end of 2020 was 15.8% [11]. The 2022 USRDS report went on to COVID-19 infection could have impacted on the incidence rates of
show that patients with CKD had consistently higher COVID-19 both infection and vaccination status. Differences between age
testing rates than those without CKD, and rates were higher still categories were due to the initial approval of the vaccine for adults
for patients undergoing dialysis, suggesting that patients with CKD only, while difference between diseases and mechanisms of CIF
were consistently more likely to be diagnosed with COVID-19 than may have related to vaccine prioritization for those with frailty in
those without CKD [12]. We also compared our data with the some countries.
epidemiological update published by the World Health Organiza- Both the frequency and severity of COVID-19 infection were
tion (WHO) on February 28th, 2021, which reported cumulative greater in the deceased and in those lost to follow up, with

Fig. 3. Cumulative cases of COVID-19 infection in patients on home parenteral nutrition (HPN), from March 1st, 2020 to March 1st, 2021 and cumulative cases per 100 thousand
population from the beginning of the pandemic (January 2020) to February 28th, 2021, as reported by the World Health Organization (WHO), in the individual countries.

217
L. Pironi, D. Jezerski, J. Sobocki et al. Clinical Nutrition ESPEN 55 (2023) 212e220

corresponding low vaccination rates in both latter groups. More- France); Consulting fees for Nestle
Health Science; Payment or
over, around half of all deaths were due to COVID-19 infection. honoraria for lectures for Baxter, BBraun, Fresenius-Kabi, Nutricia;
Again, these data are in keeping with observations in the general Support for attending meetings for Nutricia, NHC.
population and, of course, serve to highlight the importance of PS: none.
preventative measures, such as mask-wearing and handwashing, LE: none.
physical distancing, and timely vaccination to mitigate infection PO: none.
and its severity [15]. L D’A: none.
The strength of this study is based on the large patient cohort AT: none.
and its international and multicenter design. However, limitations ND: Leadership of Pediatric Nutrition Association of Thailand
may include missing data, which likely relate to difficulties Society of Parenteral Enteral Nutrition of Thailand.
encountered in monitoring outpatients, resultant from lockdown ASZ: Payment or honoraria for lectures for Siegfried;
restrictions brought into force in virtually all the countries during Consulting for Takeda; Support for attending meetings for Abbott
the follow-up period of the survey. Furthermore, our study design and Nestle .
did not investigate the country policies to prevent COVID-19 MF: Payment or honoraria for lectures for Fresenius Kabi, B
infection during the period of the data collection, a factor that Braun, Baxter.
could have contributed to the differences observed among coun- GV: none.
tries. Nevertheless, the results of this unique study on COVID-19 MIS: none.
infection in HPN-dependent patients are in keeping with the MT: none.
impact of the infection on the general population, as well as on ERB: none.
patients requiring HD for CKD, which is a useful proxy model of NVC: Payment or honoraria for lectures for Takeda, Nutricia;
disease. Payment for expert testimony, Support for attending meetings and
In conclusion, in patients on HPN for CIF, the incidence of Participation on a Data Safety Monitoring Board for Takeda.
COVID-19 infection differed greatly among countries and was AL: Consulting fees, Support for attending meetings, Participa-
asymptomatic or led to only mild symptoms in the majority of cases tion on a Data Safety Monitoring Board or Advisory Board for
but was the cause of death in a consistent number of infected pa- Nestle; Participation on a Data Safety Monitoring Board or Advisory
tients. COVID-19 infection, infection severity and lack of vaccination Board for Takeda; Payment or honoraria for lectures for baxter.
were associated with a higher risk of death. The results highlight LC: none.
the importance of measures to prevent infection. MA: none.
EO: none.
Funding source AGM: none.
AVG: none.
The project of the ESPEN database for Chronic Intestinal Failure VP: honoraria for lectures for Thai Otsuka Pharmaceutical Co.,
was promoted by the ESPEN Executive Committee in 2013, was Ltd., Abbott Laboratories Ltd., Nestle (Thai) Ltd., Fresenius Medical
approved by the ESPEN Council and was supported by an ESPEN Care (Thailand) Ltd., Baxter Healthcare (Thailand) Co., Ltd., Mega
grant. Lifesciences PTY Ltd., Novo Nordisk Thailand.
MSM: Grants or contracts from any entity for Fresenius Kabi,
Statement of authorship Nestle, Realfood Blends, VectivBio, Rockfield, Zealand; Consulting
fees, Northsea; Participation on a Data Safety Monitoring Board for
LP devised the study protocol, collected the data, analyzed the EndoBarrier.
results and drafted the manuscript. The Home Artificial Nutrition & M D-S: none.
Chronic Intestinal Failure Special Interest Group of ESPEN discussed TV: Grants or contracts from any entity for Vectiv Bio, Takeda;
and approved the protocol study, discussed the results and Consulting fees for Vectiv Bio, Zealand Pharma, Takeda, Baxter,
reviewed the manuscript before submission. Coordinators of the Hamni, NorthSea Therapeutics; Payment or honoraria for lectures
participating centers collected the data and reviewed the manu- for Vectiv Bio, Takeda, Baxter; Support for attending meetings for
script upon submission. All authors approved the final version of Takeda, Vectiv Bio, Zealand Pharma, Fresenius Kabi; Receipt of
the manuscript before submission. equipment, materials, drugs for VectivBio.
ZK: Support for attending meetings for Abbott, Fresenius,
Conflict of interest statements Nutricia, Nestle, Takeda; Leadership for Croatian Medical Associa-
tion- The President.
LP: Participation on a Data Safety Monitoring Board or Advisory FP: none.
Board for Takeda, Consulting fees for Takeda, Northsea, NAPO. LM: none.
SL: Participation on a Data Safety Monitoring Board or Advisory LCE: Consulting fees, Payment or honoraria for lecture and
Board for Baxter, Takeda, NorthSea, VectivBio; Grants or contracts Support for attending meetings for Takeda.
from any entity for Baxter, Takeda; Consulting fees for VectivBio, UA: Payment or honoraria for lectures for Takeda, Baxter; Sup-
Takeda, Northsea; Support for attending meetings and/or travel for port for attending meetings and Participation on a Data Safety
Takeda; Payment or honoraria for lectures for Takeda, Fresenius. Monitoring for Takeda.
PG: none. MK: none.
LS: none. MMJ: none.
PO: none. AC: none.
NW: none. DW: none.
RT: Royalties or licenses for Royalties for designing the Simple GO: none.
Evaluation of Food Intake® (SEFI®) (Knoe €, le Kremlin Bice^tre, CC: none.

218
L. Pironi, D. Jezerski, J. Sobocki et al. Clinical Nutrition ESPEN 55 (2023) 212e220

JS: Grants or contracts from any entity and for BBraun, Frese- Finland
niusKabi, Nestle; Payment or honoraria for lectures for BBraun, Laura Merras-Salmio, Mikko Pakarinen; Helsinki University
OlimpLabs, FreseniusKabi, Baxter, Nestle; Support for attending Hospital, Children's Hospital, Helsinki
meetings for FreseniusKabi. France
FWG: none. Cecile Chambrier; Hospices Civils de Lyon, Centre Hospitalier
CS: none. Lyon Sud, Lyon
MBD: none. Francisca Joly, Vanessa Boehm, Julie Bataille, Lore Billiauws;
DS: none. Beaujon Hospital, Clichy
SL: none. Sabrina Layec; Digestive and Nutritional Rehabilitation Unit/
SK: Payment or honoraria for lectures, for Abbott, Abela Farm, Artificial Nutrition Unit, Clinique Saint-Yves, Rennes
Danone/Nutricia, Fresenius, GM Pharma, Nestle, Nestle Nutrition Florian Poullenot; CHU de Bordeaux, Ho ^ pital Haut-Le

ve^que,
Institute, Oktal Pharma, Shire/Takeda; Non-restricted grant deliv- Pessac
ered to the hospital from BioGaia.
phane M. Schneider, He
Ste
le
ne Lapeyre; CHU Archet, Nice
BC: none. David Seguy; CHRU de Lille, Lille
GM: none. Ronan Thibault; Nutrition unit, CHU Rennes, Nutrition Metab-
MHMdC: Grants or contracts, Consulting fees, Payment or olisms and Cancer institute, NuMeCan, INRA, INSERM, Universite

honoraria, Support for attending meetings, Participation on a Data Rennes, Rennes
Safety Monitoring for lectures for Takeda Pharmaceutical Brazil. Germany
EPJ: none. Georg Lamprecht; University Medical Center Rostock, Rostock
FJ: none. Hungary
DJ: none. Laszlo Czako, First Department of Internal Medicine University
GL: none. of Szeged, Szeged
AZM: none. Israel
MT: none. Ana Guz Mark, Shamir Raanan; Institute of Gastroenterology,
DZ: none. Nutrition and Liver Diseases, Schneider Children's Medical Center
MK: Payment or honoraria for manuscript writing and educa- of Israel,Petach-Tikva
tional events for Nutricia, FreseniusKabi. Miriam Theilla, Pierre Singer; Rabin Medical Center, Petach Tikva
ASS: none. Italy
GB: none. Umberto Aimasso, Merlo F. Dario; Citta  della Salute e della Sci-
enza, Turin
Acknowledgements Lorenzo D'Antiga, Michela Bravi; Paediatric Hepatology,
Gastroenterology and Transplantation. “Papa Giovanni XXIII” Hos-
Contributing coordinators and centers by country pital, Bergamo
Argentina Luisa Masconale; ULSS 22 Ospedale Orlandi, Bussolengo (VE)
Adriana N. Crivelli, Hector Solar Mun ~ iz; Unidad de Soporte Paolo Gandullia, Tommaso Bellini; G. Gaslini Institute for Child
Nutricional, Rehabilitacio
n y Trasplante de Intestino, Hospital Health, Genoa
Universitario Fundacion Favaloro, Buenos Aires, Argentina Francesco W. Guglielmi, Nunzia Regano; Gastroenterology Unit,
Australia Monsignor di Miccoli Hospital, Barletta, Italy
Brooke R. Chapman; Austin Health, Melbourne Paolo Orlandoni; Nutrizione Clinica-Centro di Riferimento
Looi C. Ee; Queensland Children's Hospital, Brisbane, Australia Regionale NAD, IRCCSeINRCA, Ancona, Italy
Margie O'Callaghan; Flinders Medical Centre, Adelaide Antonella Lezo; Department of Clinical Nutrition, OIRM-S. Anna
Emma Osland; Royal Brisbane and Women's Hospital, Herston  della Salute e della Scienza, Turin
Hospital, Citta
Belgium Lidia Santarpia, Maria Carmen Pagano; Federico II University,
Marianna Arvanitakis; Erasme University Hospital, ULB, Brussels Napoli
Tim Vanuytsel, Nathalie Lauwers, Karlien Geboers, Marleen Anna Simona Sasdelli, Loris Pironi; IRCCS S. Orsola University
Pijpops; University Hospital Leuven; Leuven Intestinal Failure and Hospital, Bologna
Transplantation (LIFT), Leuven; Andre Van Gossum; Medico- Corrado Spaggiari; AUSL di Parma, Parma
Surgical Department of Gastroenterology, Ho ^pital Erasme, Free Maria I. Spagnuolo; Section of Paediatrics, Department of Trans-
University of Brussels, Belgium lational Medical Science, University of Naples Federico II, Naples
Brazil Marina Taus, Debora Busni; Ospedali Riuniti, Ancona
Mariana Hollanda Martins da Rocha; Hospital das Clinicas da Giovanna Verlato; Paediatric Nutrition Service-Neonatal Inten-
Faculdade de Medicina da Universidade de Sa ~o Paulo, S~
ao Paulo sive Care Unit, University Hospital of Padova, Padova, Italy
Bulgaria Latvia
Maryana Doitchinova-Simeonova; Bulgarian Association of Pa- Georgijs Moisejevs; Riga East University Hospital, Riga
tients with Malnutrition, Sofia Malaysia
Croatia Mohammad Shukri Jahit; National Cancer Institute/Institut
Zeljko Krznaric, Dina Ljubas Kelecic; University Hospital Centre Kanser Negara, Putrajaya Wilayah, Persekutuan, Putrajaya
Zagreb, Zagreb Me
xico
Sanja Kolacek; Children's Hospital Zagreb, Zagreb Aurora E. Serralde-Zún ~ iga; Instituto Nacional de Ciencias
Denmark Me
dicas y Nutricio
n Salvador Zubira
n, Me
xico City
Henrik Højgaard Rasmussen; Center for Nutrition and Bowel Poland
Disease, Aalborg University Hospital, Aalborg Marcin Folwarski; M. Kopernik Hospital, Gdan
sk

219
L. Pironi, D. Jezerski, J. Sobocki et al. Clinical Nutrition ESPEN 55 (2023) 212e220

Marek Kunecki; M. Pirogow Hospital, Lodz Denise Jezerski, Ezra Steiger; Cleveland Clinic Foundation,
Przemysław Matras; Department of General and Transplant Cleveland, OH.
Surgery and Clinical Nutririon, Medical University of Lublin, Lublin ESPEN CIF database manager and statistician: Giorgia Brillanti,
Konrad Matysiak; Centre for Intestinal Failure, Department of Department of Medical and Surgical Sciences; University of
General, Endocrinological and Gastroenterological Surgery, Poznan Bologna, Italy.
Univercity of Medical Science. Posnan
Jacek Sobocki, Zuzanna Zaczek; Centre of Postgraduate Medical Appendix A. Supplementary data
Education, Warsaw
Spain Supplementary data to this article can be found online at
Marta Bueno Díez; Hospital Universitari Arnau de Vilanova, https://doi.org/10.1016/j.clnesp.2023.03.008.
Lleida, Spain
Cristina Cuerda; Hospital General Universitario Gregorio Mar- References
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