Acute SARS-CoV-2 viral load and systemic inflammation are associated with neuropsychiatric and musculoskeletal symptoms in long COVID

DOI record: { "DOI": "10.1371/journal.pone.0346978", "ISSN": [ "1932-6203" ], "URL": "http://dx.doi.org/10.1371/journal.pone.0346978", "abstract": "<jats:sec id=\"sec001\">\n <jats:title>Background</jats:title>\n <jats:p>Long after recovery from acute-COVID illness, many patients show persistent multi-organ dysfunction consistent with Long COVID. Biochemical profile and measurements of inflammatory markers in these individuals can help to understand the underlying pathophysiology. This study aims to evaluate biochemical markers and their association with symptoms of Long COVID. We, in a retrospective analysis, also examined whether the Long COVID symptom persistence is associated with the SARS-CoV-2 viral load documented during the acute infection.</jats:p>\n </jats:sec>\n <jats:sec id=\"sec002\">\n <jats:title>Methods</jats:title>\n <jats:p>A total of 300 participants with previously diagnosed mild COVID-19 were recruited at 10 months post-infection. Brief clinical history was taken based on persistent symptoms after COVID-19 and categorized as Long COVID (n = 177) and controls group (n = 123) based on WHO defined criteria. Biochemical parameters in blood like complete blood count (RBC and WBC indices) were compared between the groups. Other measurements including inflammatory markers such as IL-6, IL-10, ferritin and C-reactive protein along with electrolytes, vitamin D3 and B12, and lipid profile, were also compared. SARS-CoV-2 viral load was assessed retrospectively. Data was analyzed through SPSS v.26.</jats:p>\n </jats:sec>\n <jats:sec id=\"sec003\">\n <jats:title>Results</jats:title>\n <jats:p>The findings of our study revealed that 59% (177) of individuals had symptoms of Long COVID. The most frequently reported symptoms of Long COVID were related to neuropsychiatry (35%), followed by musculoskeletal system (32.2%). The Hemoglobin, RBC counts and MCHC were decreased in Long COVID as compared to control group (p &lt; 0.05). While Lymphocytes, IL-6 and ferritin levels were raised in Long COVID group (p &lt; 0.05). In multivariable logistic regression analyses adjusted for age and sex, neuropsychiatric symptoms were independently associated with higher lymphocyte counts (aOR 1.19, 95% CI 1.12–1.51), IL-6 (aOR 1.16, 95% CI 1.10–1.86), ferritin (aOR 1.42, 95% CI 1.10–1.53), and vitamin D deficiency (aOR 1.45, 95% CI 1.22–2.01). Musculoskeletal symptoms were strongly associated with vitamin D deficiency (aOR 2.30, 95% CI 1.20–4.50) and ferritin levels (aOR 0.98, 95% CI 0.97–0.99). Moreover, higher SARS-CoV-2 viral load (CT ≤ 20) during acute infection was also associated with neuropsychiatric and musculoskeletal symptoms of Long COVID.</jats:p>\n </jats:sec>\n <jats:sec id=\"sec004\">\n <jats:title>Conclusion</jats:title>\n <jats:p>We identified Long COVID in 59% of the participants, the highest reported percentage in studies in the middle-aged individuals. Compared to controls, we found differential biochemical markers in the Long COVID group indicating a different metabolic status in these individuals. Moreover, the association of raised inflammatory markers at ten months follow up and acute-phase SARS-CoV-2 viral load were also seen to be associated with musculoskeletal and neuropsychiatric symptoms of the Long COVID. These significant clinical and biochemical changes warrant thorough monitoring and follow-ups for extended time.</jats:p>\n </jats:sec>", "author": [ { "ORCID": "https://orcid.org/0000-0003-0517-247X", "affiliation": [], "authenticated-orcid": true, "family": "Abbas", "given": "Uzair", "sequence": "first" }, { "affiliation": [], "family": "Laghari", "given": "Rabeel Nawaz", "sequence": "additional" }, { "affiliation": [], "family": "Ahmed", "given": "Ishfaque", "sequence": "additional" }, { "affiliation": [], "family": "Musawwir", "given": "Usama Abdul", "sequence": "additional" }, { "affiliation": [], "family": "Riaz", "given": "Hina", "sequence": "additional" }, { "affiliation": [], "family": "Anwar", "given": "Khadija", "sequence": "additional" }, { "affiliation": [], "family": "Hussain", "given": "Niaz", "sequence": "additional" }, { "affiliation": [], "family": "Mubeen", "given": "Muhammad", "sequence": "additional" }, { "affiliation": [], "family": "Khan", "given": "Mahtab", "sequence": "additional" }, { "affiliation": [], "family": "Khalid", "given": "Muhib Ullah", "sequence": "additional" }, { "affiliation": [], "family": "Ashraf", "given": "Shizrah", "sequence": "additional" } ], "container-title": "PLOS One", "container-title-short": "PLoS One", "content-domain": { "crossmark-restriction": false, "domain": [ "www.plosone.org" ] }, "created": { "date-parts": [ [ 2026, 4, 15 ] ], "date-time": "2026-04-15T17:31:58Z", "timestamp": 1776274318000 }, "deposited": { "date-parts": [ [ 2026, 4, 15 ] ], "date-time": "2026-04-15T17:32:05Z", "timestamp": 1776274325000 }, "editor": [ { "affiliation": [], "family": "Notarte", "given": "Kin Israel", "sequence": "first" } ], "indexed": { "date-parts": [ [ 2026, 4, 15 ] ], "date-time": "2026-04-15T18:12:20Z", "timestamp": 1776276740176, "version": "3.50.1" }, "is-referenced-by-count": 0, "issue": "4", "issued": { "date-parts": [ [ 2026, 4, 15 ] ] }, "journal-issue": { "issue": "4", "published-online": { "date-parts": [ [ 2026, 4, 15 ] ] } }, "language": "en", "license": [ { "URL": "http://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2026, 4, 15 ] ], "date-time": "2026-04-15T00:00:00Z", "timestamp": 1776211200000 } } ], "link": [ { "URL": "https://dx.plos.org/10.1371/journal.pone.0346978", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "340", "original-title": [], "page": "e0346978", "prefix": "10.1371", "published": { "date-parts": [ [ 2026, 4, 15 ] ] }, "published-online": { "date-parts": [ [ 2026, 4, 15 ] ] }, "publisher": "Public Library of Science (PLoS)", "reference": [ { "key": "pone.0346978.ref001", "unstructured": "JHU. 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