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\begin{document}

\title{Coronavirus 19 (COVID-19) infection and vaccination in patients with
Shwachman-Diamond syndrome}



\author[1]{Thomas Galletta}%
\author[1]{Sara Loveless}%
\author[2]{Maggie Malsch}%
\author[3]{Akiko Shimamura}%
\author[1]{Kasiani Myers}%
\affil[1]{Cincinnati Children's Hospital Medical Center}%
\affil[2]{Boston Children's Hospital}%
\affil[3]{Dana-Farber/Boston Children's Cancer and Blood Disorders Center}%


\vspace{-1em}



  
  \date{May 21, 2024}


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\begin{abstract}
Because they can experience neutropenia due to bone marrow failure,
patients with Shwachman-Diamond syndrome (SDS) carry increased risk for
serious infections compared to the general population; however, it has
been unknown whether this predisposes them to COVID-19 infection or more
significant complications. We compiled results from a survey distributed
to participants in the Shwachman-Diamond Syndrome Registry between May
and June 2021. In this report we describe the characteristics and
outcomes of patients with SDS who had COVID-19. Patients reported a
short clinical course without significant complications or severe
cytopenias. Additionally, COVID-19 vaccines were well tolerated with
only minor side effects.%
\end{abstract}%



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\textbf{Introduction:}

The Coronavirus 19 (COVID-19) pandemic has had significant implications
for patients with chronic medical conditions, particularly those who are
immunocompromised due to malignancy or bone marrow failure (BMF).
Shwachman-Diamond syndrome (SDS) is an inherited BMF disorder
characterized by cytopenias, particularly neutropenia, exocrine
pancreatic dysfunction, and predisposition to myeloid malignancies. Its
manifestations are variable and can affect many body systems, including
the skeletal, cardiac, endocrine, nervous, hepatic, and immune systems.
In most cases SDS is due to recessive mutations in the
Shwachman-Bodian-Diamond Syndrome (\emph{SBDS} ) gene located on
chromosome 7q11. Because patients with SDS can experience neutropenia
due to BMF, they carry a higher risk for serious infections compared to
the general population; however, it has been unknown whether this
predisposes them to developing COVID-19 or experiencing greater
complications related to COVID-19.

\textbf{Methods:}

A survey was distributed to patients participating in the
Shwachman-Diamond Syndrome Registry, and responses were anonymous.
Results were compiled between May and June 2021. In this cohort study we
report the baseline characteristics and clinical outcomes of these ten
patients with SDS who had a COVID-19 infection.

\textbf{Results:}

Of the 73 survey respondents, 10 patients experienced COVID-19 infection
(13.7\%) {[}Table 1{]}. Seven of these ten patients (70\%) reported
germline \emph{SBDS} mutations. The median age of the COVID-19 positive
patients at time was diagnosis was 16.5 years (range 1-37 years). Of the
three patients who both developed COVID-19 infection and received a
COVID-19 vaccine, all of them received the vaccine following COVID-19
infection, two to six months following infection (median 5 months). None
of them experienced serious vaccine-related adverse events. All
vaccinated patients received two mRNA vaccine doses. All patients in the
SDS Registry who developed COVID-19 were symptomatic of infection with
the most common symptoms being respiratory, such as congestion or cough
(70\%), or fever (60\%). The median duration of symptoms was 4.5 days
(range 2-100 days; excluding an outlier of 100 days, range 4-14 days).
Only one of ten patients required hospitalization, and this patient was
one year-old (PT-6). She was hospitalized two days after symptom onset
and was hospitalized for four days. She did not require supplemental
oxygen, noninvasive positive-pressure ventilation, or intubation and
mechanical ventilation. She did not require admission to the intensive
care unit.

Of the survey respondents who developed COVID-19 infection, none of them
reported having a pre-existing condition other than SDS. Pre-existing
conditions listed in the survey included hypertension, diabetes
mellitus, asthma, and routine need for immune globulin (IVIG).
Respondents were able to report other conditions that were not listed.
No patients who developed COVID-19 infection reported a history of
tobacco use or vaping. Six of them (60\%) reported regularly taking
pancreatic enzymes, and two of them (20\%) reported regularly
administering granulocyte colony-stimulating factor (G-CSF) prior to
COVID infection (PT-8 and PT-9). One patient reported a history of a
hematopoietic stem cell transplant over 15 years ago (PT-4).

Survey respondents were asked if they received any of the following
COVID-19 infection treatments: remdesivir,
hydroxychloroquine/chloroquine, azithromycin, anakinra, tocilizumab,
corticosteroids, immune globulin, or the investigational COVID-19
monoclonal antibody, bamlanivimab. One patient (PT-10) received
remdesivir, and one patient (PT-4) received systemic corticosteroids.
One patient (PT-5) developed ``COVID toes'' -- swelling, discoloration,
and/or pain of the toes associated with COVID-19 -- and was treated with
aspirin and topical corticosteroids. She also reported the longest
duration of symptoms out of all respondents, 100 days. No patients
required pRBC or platelet transfusion during COVID-19 infection, or new
administration of G-CSF. No patients developed a venous thromboembolism,
multisystem inflammatory syndrome in adults (MIS-A), or children
(MIS-C).

In the cohort of SDS registry patients described, most reported having a
short duration of symptoms that did not require hospitalization or
result in serious virus-related complications. Although the Centers for
Disease Control and Prevention (CDC) recommends receiving the COVID-19
vaccine even after developing COVID-19 infection, only 30\% of patients
with SDS and COVID-19 infection subsequently received the vaccine; three
of whom were ineligible to receive the vaccine at the time of survey due
to age less than 12. Of the 63 survey respondents who had not developed
COVID-19 infection, 18 (28.6\%) of them received at least one dose of
the COVID-19 vaccine; 15 of whom (83.3\%) received two doses. Of the 18
respondents who received at least one COVID-19 vaccine dose, arm pain
was the most common side effect (66.7\%), followed by fatigue (50\%),
fever and/or chills (38.9\%), and muscle aches (33.3\%). Other side
effects listed in the survey were rash and anaphylaxis; no respondents
reported experiencing these symptoms. Five of 18 recipients (27.8\%)
reported experiencing no side effects. Thirteen (72.2\%) of 18
vaccinated respondents received the Pfizer vaccine while the remainder
received the Moderna vaccine.

\textbf{Discussion:}

In this report we describe the largest cohort to date of patients with
SDS and COVID-19 infection. Most patients reported a short clinical
course with few requiring COVID-19 directed therapy, and only one
requiring hospitalization; none experienced significant complications or
severe cytopenias. However, these results cannot be generalized to
patients with more severe comorbidities. COVID-19 vaccines were well
tolerated with only minor expected side effects, suggesting that
vaccination should be encouraged according to CDC guidelines during this
ongoing global pandemic.

\textbf{Conflict of Interest:} The authors would like to highlight a
potential conflict of interest as Drs. Akiko Shimamura and Kasiani Myers
work closely with Dr. Peter Newburger on the Severe Congenital
Neutropenia International Registry.

\textbf{Acknowledgments:} The authors gratefully acknowledge all
patients and families participating in the SDS Registry as well as
physician colleagues who referred patients to the Registry.

\textbf{References:} None

\textbf{Legends:} None

\textbf{Hosted file}

\verb`COVID SDS Figure PBC 12.28.21.docx`  available at \url{https://authorea.com/users/453372/articles/551221-coronavirus-19-covid-19-infection-and-vaccination-in-patients-with-shwachman-diamond-syndrome}

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