<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Archiving and Interchange DTD with OASIS Tables with MathML3 v1.1 20151215//EN" "JATS-archive-oasis-article1-mathml3.dtd">
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" xmlns:oasis="http://www.niso.org/standards/z39-96/ns/oasis-exchange/table" id="jcsm12896" dtd-version="1.1" xml:lang="en" article-type="review-article" specific-use="VoR">
<front>
<journal-meta>
<journal-id journal-id-type="doi">10.1007/13539.2190-6009</journal-id>
<journal-id journal-id-type="publisher-id">JCSM</journal-id>
<journal-title-group>
<journal-title xml:lang="en">Journal of Cachexia, Sarcopenia and Muscle</journal-title>
<abbrev-journal-title abbrev-type="publisher" xml:lang="en">Journal of Cachexia, Sarcopenia and Muscle</abbrev-journal-title>
</journal-title-group>
<issn publication-format="ppub">2190-5991</issn>
<issn publication-format="epub">2190-6009</issn>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.1002/jcsm.12896</article-id>
<article-id pub-id-type="publisher-id">JCSM12896</article-id>
<article-id pub-id-type="society-id">JCSM-D-21-00426</article-id>
<article-categories>
<subj-group subj-group-type="overline" xml:lang="en">
<subject>Review</subject>
</subj-group>
<subj-group subj-group-type="heading" xml:lang="en">
<subject>Reviews</subject>
</subj-group>
</article-categories>
<title-group>
<article-title xml:lang="en">Skeletal muscle alterations in patients with acute Covid‐19 and post‐acute sequelae of Covid‐19</article-title>
<alt-title alt-title-type="right-running-head">Skeletal muscle and Covid‐19</alt-title>
<alt-title alt-title-type="left-running-head">M.N. Soares <italic>et al</italic>.</alt-title>
</title-group>
<contrib-group>
<contrib id="jcsm12896-cr-0001" contrib-type="author">
<name>
<surname>Soares</surname>
<given-names>Madu N.</given-names>
</name>
<xref ref-type="aff" rid="jcsm12896-aff-0001">
<sup>1</sup>
</xref>
</contrib>
<contrib id="jcsm12896-cr-0002" contrib-type="author">
<name>
<surname>Eggelbusch</surname>
<given-names>Moritz</given-names>
</name>
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4006-4063</contrib-id>
<xref ref-type="aff" rid="jcsm12896-aff-0001">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="jcsm12896-aff-0002">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="jcsm12896-aff-0003">
<sup>3</sup>
</xref>
</contrib>
<contrib id="jcsm12896-cr-0003" contrib-type="author">
<name>
<surname>Naddaf</surname>
<given-names>Elie</given-names>
</name>
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6212-1236</contrib-id>
<xref ref-type="aff" rid="jcsm12896-aff-0004">
<sup>4</sup>
</xref>
</contrib>
<contrib id="jcsm12896-cr-0004" contrib-type="author">
<name>
<surname>Gerrits</surname>
<given-names>Karin H. L.</given-names>
</name>
<xref ref-type="aff" rid="jcsm12896-aff-0001">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="jcsm12896-aff-0005">
<sup>5</sup>
</xref>
</contrib>
<contrib id="jcsm12896-cr-0005" contrib-type="author">
<name>
<surname>van der Schaaf</surname>
<given-names>Marike</given-names>
</name>
<xref ref-type="aff" rid="jcsm12896-aff-0006">
<sup>6</sup>
</xref>
<xref ref-type="aff" rid="jcsm12896-aff-0007">
<sup>7</sup>
</xref>
</contrib>
<contrib id="jcsm12896-cr-0006" contrib-type="author">
<name>
<surname>van den Borst</surname>
<given-names>Bram</given-names>
</name>
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4597-2722</contrib-id>
<xref ref-type="aff" rid="jcsm12896-aff-0008">
<sup>8</sup>
</xref>
</contrib>
<contrib id="jcsm12896-cr-0007" contrib-type="author">
<name>
<surname>Wiersinga</surname>
<given-names>W. Joost</given-names>
</name>
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2277-1343</contrib-id>
<xref ref-type="aff" rid="jcsm12896-aff-0009">
<sup>9</sup>
</xref>
<xref ref-type="aff" rid="jcsm12896-aff-0010">
<sup>10</sup>
</xref>
</contrib>
<contrib id="jcsm12896-cr-0008" contrib-type="author">
<name>
<surname>van Vugt</surname>
<given-names>Michele</given-names>
</name>
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8365-2482</contrib-id>
<xref ref-type="aff" rid="jcsm12896-aff-0010">
<sup>10</sup>
</xref>
</contrib>
<contrib id="jcsm12896-cr-0009" contrib-type="author">
<name>
<surname>Weijs</surname>
<given-names>Peter J.M.</given-names>
</name>
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8281-0426</contrib-id>
<xref ref-type="aff" rid="jcsm12896-aff-0002">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="jcsm12896-aff-0003">
<sup>3</sup>
</xref>
</contrib>
<contrib id="jcsm12896-cr-0010" contrib-type="author">
<name>
<surname>Murray</surname>
<given-names>Andrew J.</given-names>
</name>
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0929-9315</contrib-id>
<xref ref-type="aff" rid="jcsm12896-aff-0011">
<sup>11</sup>
</xref>
</contrib>
<contrib id="jcsm12896-cr-0011" contrib-type="author" corresp="yes">
<name>
<surname>Wüst</surname>
<given-names>Rob C.I.</given-names>
</name>
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3781-5177</contrib-id>
<email>r.wust@vu.nl</email>
<xref ref-type="corresp" rid="correspondenceTo">*</xref>
<xref ref-type="aff" rid="jcsm12896-aff-0001">
<sup>1</sup>
</xref>
</contrib>
</contrib-group>
<aff id="jcsm12896-aff-0001">
<label>
<sup>1</sup>
</label>

<named-content content-type="organisation-division">Laboratory for Myology, Faculty of Behavioural and Movement Sciences</named-content>

<institution>Amsterdam Movement Sciences, Vrije Universiteit Amsterdam</institution>

<city>Amsterdam</city>
 <country country="NL">The Netherlands</country>

</aff>
<aff id="jcsm12896-aff-0002">
<label>
<sup>2</sup>
</label>

<named-content content-type="organisation-division">Department of Nutrition and Dietetics</named-content>

<institution>Amsterdam UMC, Location VUmc, Amsterdam Movement Sciences</institution>

<city>Amsterdam</city>
 <country country="NL">The Netherlands</country>

</aff>
<aff id="jcsm12896-aff-0003">
<label>
<sup>3</sup>
</label>

<named-content content-type="organisation-division">Faculty of Sports and Nutrition, Center of Expertise Urban Vitality</named-content>

<institution>Amsterdam University of Applied Sciences</institution>

<city>Amsterdam</city>
 <country country="NL">The Netherlands</country>

</aff>
<aff id="jcsm12896-aff-0004">
<label>
<sup>4</sup>
</label>

<named-content content-type="organisation-division">Department of Neurology</named-content>

<institution>Mayo Clinic</institution>

<city>Rochester</city>
 <named-content content-type="country-part">MN</named-content>
 <country country="US">USA</country>

</aff>
<aff id="jcsm12896-aff-0005" content-type="private-address">
<label>
<sup>5</sup>
</label>

<institution>Merem Medical Rehabilitation</institution>

<city>Hilversum</city>
 <country country="NL">The Netherlands</country>

</aff>
<aff id="jcsm12896-aff-0006">
<label>
<sup>6</sup>
</label>

<named-content content-type="organisation-division">Department of Rehabilitation</named-content>

<institution>Amsterdam UMC, University of Amsterdam, Amsterdam Movement Sciences</institution>

<city>Amsterdam</city>
 <country country="NL">The Netherlands</country>

</aff>
<aff id="jcsm12896-aff-0007">
<label>
<sup>7</sup>
</label>

<named-content content-type="organisation-division">Faculty of Health, Center of Expertise Urban Vitality</named-content>

<institution>Amsterdam University of Applied Sciences</institution>

<city>Amsterdam</city>
 <country country="NL">The Netherlands</country>

</aff>
<aff id="jcsm12896-aff-0008">
<label>
<sup>8</sup>
</label>

<named-content content-type="organisation-division">Department of Pulmonary Diseases</named-content>

<institution>Radboud University Medical Center</institution>

<city>Nijmegen</city>
 <country country="NL">The Netherlands</country>

</aff>
<aff id="jcsm12896-aff-0009">
<label>
<sup>9</sup>
</label>

<named-content content-type="organisation-division">Center for Experimental and Molecular Medicine (CEMM)</named-content>

<institution>Amsterdam University Medical Centers ‐ Location AMC, University of Amsterdam</institution>

<city>Amsterdam</city>
 <country country="NL">The Netherlands</country>

</aff>
<aff id="jcsm12896-aff-0010">
<label>
<sup>10</sup>
</label>

<named-content content-type="organisation-division">Department of Internal Medicine, Division of Infectious Diseases</named-content>

<institution>Amsterdam University Medical Centers ‐ Location AMC, University of Amsterdam</institution>

<city>Amsterdam</city>
 <country country="NL">The Netherlands</country>

</aff>
<aff id="jcsm12896-aff-0011">
<label>
<sup>11</sup>
</label>

<named-content content-type="organisation-division">Department of Physiology, Development and Neuroscience</named-content>

<institution>University of Cambridge</institution>

<city>Cambridge</city>
 <country country="GB">UK</country>

</aff>
<author-notes>
<corresp id="correspondenceTo"><label>*</label>Correspondence to: Rob C. I. Wüst, PhD, Laboratory for Myology, Faculty of Behavioural and Movement Sciences, Amsterdam Movement Sciences, Vrije Universiteit Amsterdam, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. Phone: +31 (0)20‐5983831, Email: <email>r.wust@vu.nl</email></corresp>
</author-notes>
<pub-date date-type="pub" publication-format="electronic"><day>07</day>
<month>01</month>
<year>2022</year>
</pub-date><fpage/><lpage/><history>

<date date-type="rev-recd">
<day>11</day>
<month>11</month>
<year>2021</year>
</date>

<date date-type="received">
<day>15</day>
<month>07</month>
<year>2021</year>
</date>

<date date-type="accepted">
<day>22</day>
<month>11</month>
<year>2021</year>
</date>

</history>
<permissions>
<copyright-statement content-type="issue-copyright">© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley &amp; Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders</copyright-statement>
<copyright-statement content-type="article-copyright">© 2021 The Authors. <italic>Journal of Cachexia, Sarcopenia and Muscle</italic> published by John Wiley &amp; Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.</copyright-statement>
<copyright-year>2021</copyright-year>
<copyright-holder>© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley &amp; Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.</copyright-holder>
<license>
<ali:license_ref>http://creativecommons.org/licenses/by-nc-nd/4.0/</ali:license_ref>
<license-p>This is an open access article under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc-nd/4.0/">Creative Commons Attribution‐NonCommercial‐NoDerivs</ext-link> License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.</license-p>
</license>
</permissions>
<abstract xml:lang="en" abstract-type="main">
<title>Abstract</title>
<p xml:lang="en">Skeletal muscle‐related symptoms are common in both acute coronavirus disease (Covid)‐19 and post‐acute sequelae of Covid‐19 (PASC). In this narrative review, we discuss cellular and molecular pathways that are affected and consider these in regard to skeletal muscle involvement in other conditions, such as acute respiratory distress syndrome, critical illness myopathy, and post‐viral fatigue syndrome. Patients with severe Covid‐19 and PASC suffer from skeletal muscle weakness and exercise intolerance. Histological sections present muscle fibre atrophy, metabolic alterations, and immune cell infiltration. Contributing factors to weakness and fatigue in patients with severe Covid‐19 include systemic inflammation, disuse, hypoxaemia, and malnutrition. These factors also contribute to post‐intensive care unit (ICU) syndrome and ICU‐acquired weakness and likely explain a substantial part of Covid‐19‐acquired weakness. The skeletal muscle weakness and exercise intolerance associated with PASC are more obscure. Direct severe acute respiratory syndrome coronavirus (SARS‐CoV)‐2 viral infiltration into skeletal muscle or an aberrant immune system likely contribute. Similarities between skeletal muscle alterations in PASC and chronic fatigue syndrome deserve further study. Both SARS‐CoV‐2‐specific factors and generic consequences of acute disease likely underlie the observed skeletal muscle alterations in both acute Covid‐19 and PASC.</p>
</abstract>
<kwd-group kwd-group-type="author-generated" xml:lang="en">
<kwd id="jcsm12896-kwd-0001">Covid‐19</kwd>
<kwd id="jcsm12896-kwd-0002">Skeletal muscle</kwd>
<kwd id="jcsm12896-kwd-0003">Inflammation</kwd>
<kwd id="jcsm12896-kwd-0004">Muscle wasting</kwd>
<kwd id="jcsm12896-kwd-0005">Metabolism</kwd>
</kwd-group>
<counts>
<fig-count count="2"/>
<table-count count="0"/>
<page-count count="12"/>
<word-count count="5424"/>
</counts>
</article-meta>
</front>
</article>