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Bergengren, L., Ryen, L., Flodström, C., Fadl, H., Udumyen, R., Karlsson, M. G. & Helenius, G. (2022). Effectiveness and costs of an implemented primary HPV cervical screening programme in Sweden: A population based cohort study. Preventive Medicine Reports, 25, Article ID 101675.
Open this publication in new window or tab >>Effectiveness and costs of an implemented primary HPV cervical screening programme in Sweden: A population based cohort study
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2022 (English)In: Preventive Medicine Reports, E-ISSN 2211-3355, Vol. 25, article id 101675Article in journal (Refereed) Published
Abstract [en]

Swedish guidelines recommend cervical screening with primary HPV for women ≥ 30 years of age. The aim of this study was to compare an implemented HPV cervical screening programme in the Region of Örebro County from September 1, 2016, with the former cytology-based screening programme.

The clinical effectiveness by means of number of high-grade squamous intraepithelial lesions (HSILs) and cervical cancer cases detected in histology within 12 months after the screening test, together with cost implications were the main outcomes. Data were retrieved from the Swedish National Cervical Screening Registry between the years 2014-2015 (cytology based screening) and 2017-2018(HPV based screening), including screening information such as invitations and cytology and histology diagnoses.

The detection rate of HSIL + among women ≥ 30 years of age was 1.2 times higher with HPV screening, but data revealed an increase in direct colposcopy referral rate by 54% and a higher percentage of irrelevant findings (≤LSIL). Screening based on HPV for women ≥ 30 has increased yearly cost from 1 to 1.3 million EUR, while increasing the number of HSIL + identified. Two thirds of the total costs are from visits for screening samples in the programme.

HPV screening detected more cases of HSIL + compared to cytology screening among women ≥ 30 although high colposcopy rate, high rate of clinical irrelevant findings and higher costs were shown in the HPV-based screening programme, which implies that alterations in the screening programme in the future are important to consider.

Place, publisher, year, edition, pages
Elsevier, 2022
Keywords
Cervical cancer, Health economy, Human papilloma virus (HPV), Screening
National Category
Cancer and Oncology Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:oru:diva-97298 (URN)10.1016/j.pmedr.2021.101675 (DOI)000748438200026 ()35127354 (PubMedID)2-s2.0-85121919588 (Scopus ID)
Funder
Region Örebro County, OLL-841131
Available from: 2022-02-08 Created: 2022-02-08 Last updated: 2024-01-02Bibliographically approved
Ranhem, C., Lillsunde-Larsson, G., Lindqvist, D., Sorbe, B., Karlsson, M., Farnebo, M., . . . Andersson, S. (2022). Evaluation of dyskerin expression and the Cajal body protein WRAP53β as potential prognostic markers for patients with primary vaginal carcinoma. Oncology Letters, 23(1), Article ID 30.
Open this publication in new window or tab >>Evaluation of dyskerin expression and the Cajal body protein WRAP53β as potential prognostic markers for patients with primary vaginal carcinoma
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2022 (English)In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 23, no 1, article id 30Article in journal (Refereed) Published
Abstract [en]

Primary vaginal cancer (PVC) is a rare gynaecological malignancy, which, at present, lacks appropriate biomarkers for prognosis. The proteins dyskerin and WD repeat containing antisense to TP53 (WRAP53β), both of which exert their functions in the telomerase holoenzyme complex, have been shown to be upregulated in different cancer types. These proteins have also been proposed as prognostic markers in some types of cancer. The aim of the present study was to examine the expression patterns of dyskerin and WRAP53β in patients with PVC. Moreover, as part of a search for effective biomarkers to evaluate prognosis in PVC, the expression of these two proteins and their potential association with clinical variables and survival were also evaluated. The expression of dyskerin and WRAP53β was assessed in PVC tumour samples from 68 patients using immunohistochemistry. The majority of tumour samples showed low and moderate expression levels of dyskerin. Upregulation of dyskerin in tumour samples was significantly associated with a shorter survival time and a poorer cancer-specific survival rate. WRAP53β was also expressed in most of the cells but was not significantly associated with clinical variables or survival. This study demonstrates that upregulation of dyskerin is significantly associated with poor prognosis. Thus, dyskerin may serve as a promising prognostic marker and a potential putative therapeutic target in PVC.

Place, publisher, year, edition, pages
Spandidos Publications, 2022
Keywords
Cajal body, WRAP53β, biomarker, dyskerin, primary vaginal carcinoma, prognosis, survival
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-95773 (URN)10.3892/ol.2021.13148 (DOI)000724187100001 ()34868367 (PubMedID)
Funder
Swedish Cancer Society, 110544 CAN2011/471Swedish Research Council, 521-2008-2899Stockholm County Council, 20130097 20160155
Note

Funding agencies:

Karolinska Institute Cancer Strategic Grants 5888-05722

Gustaf V Jubilee Fund 154022 151202 

Centre of Clinical Research, Västmanland County Council LTV-940144

Available from: 2021-12-07 Created: 2021-12-07 Last updated: 2022-02-11Bibliographically approved
Kaliff, M., Lillsunde-Larsson, G., Helenius, G., Karlsson, M. & Bergengren, L. (2022). Full genotyping and FAM19A4/miR124-2 methylation analysis in high-risk human papillomavirus-positive samples from women over 30 years participating in cervical cancer screening in Örebro, Sweden. PLOS ONE, 17(9), Article ID e0274825.
Open this publication in new window or tab >>Full genotyping and FAM19A4/miR124-2 methylation analysis in high-risk human papillomavirus-positive samples from women over 30 years participating in cervical cancer screening in Örebro, Sweden
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2022 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 17, no 9, article id e0274825Article in journal (Refereed) Published
Abstract [en]

Currently, cervical cancer prevention is undergoing comprehensive development regarding human papillomavirus (HPV) vaccination and cervical cancer screening. In Sweden and many other countries, high coverage vaccinated cohorts are entering screening within the next few years. This entails demands for baseline HPV genotype data across the screening age range for surveillance and a basis for screening program adjustment. In 2016, Örebro County, Sweden, changed to primary HPV screening using HPV mRNA testing followed by cytology triage. An alternative triage method to cytology could allow for a fully molecular screening algorithm and be implemented in a screening program where self-sampling is included. Hypermethylation analysis of the human genes FAM19A4/miR124-2 has been suggested as a promising triage method. HPV mRNA-positive screening samples (n = 529) were included and subjected to genotyping targeting a broad range of both low-risk and high-risk genotypes in addition to hypermethylation analysis of the two human genes FAM19A4/miR124-2. Data were connected to cytological and histological status and age. The most commonly detected genotypes were HPV31, 16, and 52. In addition, HPV18 was one of the most common genotypes in high-grade squamous intraepithelial lesions (HSILs) samples. In relation to available vaccines, 26% of the women with histological HSIL or cancer (≥HSIL) tested positive for only hrHPV included in the quadrivalent vaccine and 77% of the genotypes in the nonavalent vaccine. According to these figures, a relatively large proportion of the HSILs will probably remain, even after age cohorts vaccinated with the quadrivalent vaccine enter the screening program. Hypermethylation positivity was associated with increasing age, but no HPV-related independently predictive factors were found. Accordingly, age needs to be considered in development of future screening algorithms including triage with hypermethylation methodology.

Place, publisher, year, edition, pages
PLOS, 2022
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-101442 (URN)10.1371/journal.pone.0274825 (DOI)000892255200073 ()36137165 (PubMedID)2-s2.0-85138421382 (Scopus ID)
Funder
Region Örebro County, OLL-783961 OLL-929736
Available from: 2022-09-24 Created: 2022-09-24 Last updated: 2023-04-05Bibliographically approved
Dorofte, L., Grélaud, D., Fiorentino, M., Giunchi, F., Ricci, C., Franceschini, T., . . . Karlsson, M. G. (2022). Low level of interobserver concordance in assessing histological subtype and tumor grade in patients with penile cancer may impair patient care. Virchows Archiv, 480(4), 879-886
Open this publication in new window or tab >>Low level of interobserver concordance in assessing histological subtype and tumor grade in patients with penile cancer may impair patient care
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2022 (English)In: Virchows Archiv, ISSN 0945-6317, E-ISSN 1432-2307, Vol. 480, no 4, p. 879-886Article in journal (Refereed) Published
Abstract [en]

Differentiation between penile squamous cell carcinoma patients who can benefit from limited organ-sparing surgery and those at significant risk of lymph node metastasis is based on histopathological prognostic factors including histological grade and tumor histological subtype. We examined levels of interobserver and intraobserver agreement in assessment of histological subtype and grade in 207 patients with penile squamous cell carcinoma. The cases were assessed by seven pathologists from three hospitals located in Sweden and Italy. There was poor to moderate concordance in assessing both histological subtype and grade, with Fleiss kappas of 0.25 (range: 0.02-0.48) and 0.23 (range: 0.07-0.55), respectively. When choosing HPV-associated and non-HPV-associated subtypes, interobserver concordance ranged from poor to good, with a Fleiss kappa value of 0.36 (range: 0.02-0.79). A re-review of the slides by two of the pathologists showed very good intraobserver concordance in assessing histological grade and subtype, with Cohen's kappa values of 0.94 and 0.91 for grade and 0.95 and 0.84 for subtype. Low interobserver concordance could lead to undertreatment and overtreatment of many patients with penile cancer, and brings into question the utility of tumor histological subtype and tumor grade in determining patient treatment in pT1 tumors. 

Place, publisher, year, edition, pages
Springer, 2022
Keywords
Histological grading, Interobserver agreement, Penile cancer, Penile carcinoma subtypes
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-95898 (URN)10.1007/s00428-021-03249-5 (DOI)000729009000001 ()34889977 (PubMedID)2-s2.0-85120917734 (Scopus ID)
Note

Funding agency:

Örebro University

Available from: 2021-12-13 Created: 2021-12-13 Last updated: 2023-07-05Bibliographically approved
Dorofte, L., Davidsson, S., Lillsunde-Larsson, G. & Karlsson, M. (2022). Reliability of histological subtyping of penile squamous cell carcinoma in assessing HPV tumour status. Paper presented at 34th European Congress of Pathology (ECP 2022), Basel, Germany, September 3-7, 2022. Virchows Archiv, 481(Suppl. 1), S168-S168, Article ID PS-26-003.
Open this publication in new window or tab >>Reliability of histological subtyping of penile squamous cell carcinoma in assessing HPV tumour status
2022 (English)In: Virchows Archiv, ISSN 0945-6317, E-ISSN 1432-2307, Vol. 481, no Suppl. 1, p. S168-S168, article id PS-26-003Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Background & objectives: HPV-positive penile tumours have been associated with higher survival rates. However, HPV analysis is unavailable in many low-income countries. We investigated if histological assessment of penile squamous cell carcinoma subtypes can replace HPV testing in determining HPV-related/non-HPV-related tumour status.

Methods: We reviewed paraffin-embedded tumour tissue from 345 penile cancer patients, surgically treated between 2009 and 2018 at Örebro University Hospital, Sweden. The histological subtype of squamous cell carcinoma was assessed according to the WHO criteria and ISUP recommendations. HPV-DNA genotyping was performed using the PCR method Anyplex II HPV28. Concordance was assessed by calculating Cohen’s kappa (κ).

Results: A good concordance was found between histological subtype of squamous cell carcinoma and HPV tumour-status with a Cohen’s kappa (κ) of 0,72 corresponding to 86,6% agreement. Of the 46 discordant cases, five had HPV-related histology (mixed subtypes) but were HPV-negative. The remaining 41 cases had non-HPV- related histology (85% usual subtype, 15% mixed subtypes) but were HPV-positive. Noteworthy is that in 21 of the cases with non-HPV-related histology, foci of undifferentiated PeIN was found. In addition, four cases with both undifferentiated PeIN and lichen sclerosus et atrophicus in the tumour margin, 14 cases with both differentiated PeIN and lichen sclerosus et atrophicus and two cases without preneoplastic lesion were identified.

Conclusion: Good concordance between histological subtype of penile squamous cell carcinoma and HPV genotyping shows that when necessary, histological assessment is a good alternative, at least in less resourceful settings, to PCR-based HPV analysis in determining if penile tumours are HPV or non-HPV-related. Discordant cases most likely depend on subjectivity in histological assessment but can also suggest a HPV infection in a non-HPV-related tumour.

Place, publisher, year, edition, pages
Springer, 2022
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-101307 (URN)000842770700538 ()
Conference
34th European Congress of Pathology (ECP 2022), Basel, Germany, September 3-7, 2022
Available from: 2022-09-22 Created: 2022-09-22 Last updated: 2022-09-22Bibliographically approved
Gebregzabher, E., Seifu, D., Tigneh, W., Bokretsion, Y., Bekele, A., Abebe, M., . . . Karlsson, M. (2021). Detection of High- and Low-Risk HPV DNA in Archived Breast Carcinoma Tissues from Ethiopian Women. International Journal of Breast Cancer, 2021, Article ID 2140151.
Open this publication in new window or tab >>Detection of High- and Low-Risk HPV DNA in Archived Breast Carcinoma Tissues from Ethiopian Women
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2021 (English)In: International Journal of Breast Cancer, ISSN 2090-3170, E-ISSN 2090-3189, Vol. 2021, article id 2140151Article in journal (Refereed) Published
Abstract [en]

Background: Human papilloma virus (HPV) is involved in the development of cancer of the cervix, mouth and throat, anus, penis, vulva, or vagina, but it has not been much considered as a cause of breast cancer. Recently, a number of investigations have linked breast cancer to viral infections. High-risk HPV types, predominantly HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59, are established as carcinogens in humans. In this study we aimed to detect 19 high-risk and 9 low-risk HPVs from archived breast tumor tissue among Ethiopian women.

Methods: In this study, 75 breast cancer patients from Tikur Anbassa Specialized Hospital in Addis Ababa (Ethiopia) were included. HPV detection and genotyping were done using the novel Anyplex™ II HPV28 Detection Assay at the Orebro University Hospital, Sweden. The Anyplex™ II PCR System detects 19 high-risk HPV types (16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 69, 73, and 82) and 9 low-risk HPV types (6, 11, 40, 42, 43, 44, 54, 61, and 70). IHC for p16 was done using an automated system, the Dako Autostainer Link.

Results: Out of the 75 valid tests, two were found to be positive (2.7%) for HPV. One of the cases was positive for the high-risk HPV16 genotype while the other was positive both for the high-risk HPV39 and the low-risk HPV6. The cell cycle protein p16 was highly expressed in the case positive for the high-risk HPV16, but it was not expressed in the case positive for HPV39.

Conclusion: The prevalence of HPV is low in Ethiopian breast cancer patients, but the role played by HPV in breast carcinogenesis among Ethiopian breast cancer patients cannot be commented based on these observations.

Place, publisher, year, edition, pages
Hindawi Publishing Corporation, 2021
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-95150 (URN)10.1155/2021/2140151 (DOI)000716652500001 ()34671492 (PubMedID)2-s2.0-85118388939 (Scopus ID)
Available from: 2021-10-22 Created: 2021-10-22 Last updated: 2022-03-11Bibliographically approved
Kaliff, M., Louise, B. M., Helenius, G., Karlsson, M. & Lillsunde-Larsson, G. (2021). Optimization of droplet digital PCR assays for the type specific detection and quantification of five HPV genotypes, also including additional data on viral load of nine different HPV genotypes in cervical carcinomas. Journal of Virological Methods, 294, Article ID 114193.
Open this publication in new window or tab >>Optimization of droplet digital PCR assays for the type specific detection and quantification of five HPV genotypes, also including additional data on viral load of nine different HPV genotypes in cervical carcinomas
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2021 (English)In: Journal of Virological Methods, ISSN 0166-0934, E-ISSN 1879-0984, Vol. 294, article id 114193Article in journal (Refereed) Published
Abstract [en]

The droplet digital PCR (ddPCR) system enables high-sensitivity detection of nucleic acids and direct absolute quantification of the targets. The aim of this research was to evaluate this system for viral load (VL) analysis of the human papillomavirus (HPV) genotypes HPV31, 35, 39, 51 and 56 measured in number of viral particles per cell. The sample types used for the optimization of the ddPCR assay were formalin-fixed paraffin-embedded (FFPE) tissues and cervical liquid cytology samples. The presently optimized ddPCR assays, together with assays optimized previously for HPV16, 18, 33 and 45, with the same ddPCR method, were used for the VL analysis of cervical tumor samples. Results published previously on the present study cohort showed that women with a cervical tumor containing multiple high-risk HPV genotypes had a worse prognosis compared to women with single-genotype-infected tumors. The VL was therefore analyzed in this study for the same cohort, as a possible explanatory factor to the prognostic differences. The results of the optimization part of the study, with analysis of VL using ddPCR in DNA from varying sample types (FFPE and liquid cytology samples), showed that each of the five assays demonstrated good inter- and intra-assay means with a coefficient of variation (CV) under 8% and 6% respectably. The cohort results showed no difference in VL between tumors with multiple and single HPV infections, and therefore did most likely not constitute a contributing factor for prognostic differences observed previously. However, tumors from women aged 60 years or older or containing certain HPV genotypes and genotype genera were associated with a higher VL.

Place, publisher, year, edition, pages
Elsevier, 2021
Keywords
Human papilloma virus, Papillomaviridae, cervical cancer, droplet digital PCR, uterine cervical neoplasms, viral load
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-91909 (URN)10.1016/j.jviromet.2021.114193 (DOI)000661415300006 ()34022300 (PubMedID)2-s2.0-85106372888 (Scopus ID)
Note

Funding Agency:

Örebro County Council Research Committee  

Available from: 2021-05-24 Created: 2021-05-24 Last updated: 2022-02-11Bibliographically approved
Hadgu, E., Seifu, D., Tigneh, W., Bokretsion, Y., Bekele, A., Abebe, M., . . . Karlsson, M. G. (2020). Distribution and characteristics of androgen receptor (AR) in breast cancer among women in Addis Ababa, Ethiopia: A cross sectional study. PLOS ONE, 15(5), Article ID e0232519.
Open this publication in new window or tab >>Distribution and characteristics of androgen receptor (AR) in breast cancer among women in Addis Ababa, Ethiopia: A cross sectional study
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2020 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 15, no 5, article id e0232519Article in journal (Refereed) Published
Abstract [en]

Evaluation of the role of androgen receptor (AR) in the biology of breast cancer is an emerging area of research. There are compelling evidences that AR expression may be used to further refine breast cancer molecular subtyping with prognostic and therapeutic implications. Many studies indicated co-expression of AR with the hormonal receptors in breast cancer has a favorable prognosis. AR is also investigated by many researchers as a potential therapeutic target in treatment of breast cancer. Studies on the frequency and distribution of AR in breast cancer among Africans is barely available. Given the heightened interest to understand its role in breast cancer, we determined AR expression and assessed its association with clinicopathological parameters among Ethiopian women. In this study, 112 newly diagnosed patient with invasive breast cancer at Tikur Anbessa Specialized Hospital were enrolled. Immunohistochemical assessment of AR, ER, PR, Ki67 and HER2 were performed using tissue microarrays (TMA) constructed from their primary tumor block. Out of the 112 participants, 91 (81%) were positive for AR expression and the remaining 21 participants (19%) were negative for AR expression. Expression of AR in ER+, HER2+ and TNBC cases were 93%, 83% and 48% respectively. Our study reveals AR is expressed in a significant number of breast cancers patients and this may indicate that breast cancers cases in Ethiopia have favorable prognosis and could benefit from progresses in AR targeted treatments. Since AR expression has important consequences on the prognosis and treatment of breast cancer, further studies with an increased number of participants is necessary to confirm our reports.

Place, publisher, year, edition, pages
Public Library Science, 2020
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-81776 (URN)10.1371/journal.pone.0232519 (DOI)000537283500038 ()32374753 (PubMedID)2-s2.0-85084409140 (Scopus ID)
Note

Funding Agencies:

Addis Ababa University, School of Graduate Studies, thematic research group "clinico-epidemiological characterization of breast cancer in Ethiopia"  

Armauer Hansen Research Institute (AHRI)  

AHRI from Swedish International Developmental Agency (SIDA), Sweden 

Available from: 2020-05-11 Created: 2020-05-11 Last updated: 2023-12-08Bibliographically approved
Kaliff, M., Karlsson, M., Sorbe, B., Bohr Mordhorst, L., Helenius, G. & Lillsunde-Larsson, G. (2020). HPV-negative Tumors in a Swedish Cohort of Cervical Cancer. International Journal of Gynecological Pathology, 39(3), 279-288
Open this publication in new window or tab >>HPV-negative Tumors in a Swedish Cohort of Cervical Cancer
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2020 (English)In: International Journal of Gynecological Pathology, ISSN 0277-1691, E-ISSN 1538-7151, Vol. 39, no 3, p. 279-288Article in journal (Refereed) Published
Abstract [en]

Despite the common perception that the human papilloma virus (HPV) is a requirement for the development of cervical cancer (CC), a considerable number of CCs test HPV negative. Presently, many countries are shifting to HPV primary CC screening, and it is of importance to increase the knowledge about the group of CCs that test HPV negative. The aim of this study was to reinvestigate a proportion of cervical tumors with a primary negative or invalid test result. Reinvestigation with repeated genotyping (targeting L1) was followed by analysis with an alternative target method (targeting E6/E7) on existing or additional tumor material. Consistently negative tumors were histologically evaluated, and cases with low or lacking tumor cell content, consistent invalid test results, or with suspicion of other than cervical origin were excluded. HPV-negative cases were thereafter subjected to immunohistochemistry (Cytokeratin 5, pan cytokeratin, protein 63, P16, and P53). The HPV-negative proportion could after reinvestigation be reduced by one-half (14%-7%). Additional positive samples were often detected in late polymerase chain reaction cycles, with an alternative (E6/E7) or the same (L1) target, or with a method using shorter amplicon lengths. Confirmed HPV negativity was significantly associated with worse prognosis, high patient age, longer storage time, and adenocarcinoma histology. Some of the HPV-negative cases showed strong/diffuse p16 immunoreactivity, indicating some remaining false-negative cases. False HPV negativity in this cohort was mainly linked to methodological limitations in the analysis of stored CC material. The small proportion of presumably true HPV-negative adenocarcinomas is not a reason for hesitation in revision to CC screening with primary HPV testing.

Place, publisher, year, edition, pages
Wolters Kluwer, 2020
Keywords
Uterine cervical neoplasms, Papillomaviridae, Human papillomavirus DNA tests, Formalin-fixed paraffin-embedded tissues, False-negative reactions
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-79634 (URN)10.1097/PGP.0000000000000612 (DOI)000526400700012 ()31206367 (PubMedID)
Note

Supported by Örebro country council research committee in Sweden.

Available from: 2020-01-31 Created: 2020-01-31 Last updated: 2022-02-11Bibliographically approved
Hellman, U., Karlsson, M. G., Engström-Laurent, A., Cajander, S., Dorofte, L., Ahlm, C., . . . Blomberg, A. (2020). Presence of hyaluronan in lung alveoli in severe Covid-19: an opening for new treatment options?. Journal of Biological Chemistry, 295(45), 15418-15422
Open this publication in new window or tab >>Presence of hyaluronan in lung alveoli in severe Covid-19: an opening for new treatment options?
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2020 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 295, no 45, p. 15418-15422Article in journal (Refereed) Published
Abstract [en]

Severe corona virus disease 2019 (Covid-19) is characterized by inflammation of the lungs with increasing respiratory impairment. In fatal Covid-19, lungs at autopsy have been filled with a clear liquid jelly. However, the nature of this finding has not yet been determined.The aim of the study was to demonstrate if the lungs of fatal Covid-19 contain hyaluronan as it is associated with inflammation and acute respiratory distress syndrome (ARDS) and may have the appearance of liquid jelly.Lung tissue obtained at autopsy from three deceased Covid-19 patients was processed for hyaluronan histochemistry using a direct staining method and compared with staining in normal lung tissue.Stainings confirmed that hyaluronan is obstructing alveoli with presence in exudate and plugs, as well as in thickened perialveolar interstitium. In contrast, normal lungs only showed hyaluronan in intact alveolar walls and perivascular tissue. This is the first study to confirm prominent hyaluronan exudates in the alveolar spaces of Covid-19 lungs, supporting the notion that the macromolecule is involved in ARDS caused by SARS-CoV-2. The present finding may open up for new treatment options in severe Covid-19, aiming at reducing the presence and production of hyaluronan in the lungs.

Place, publisher, year, edition, pages
American Society for Biochemistry and Molecular Biology, 2020
Keywords
COVID-19, autopsy, coronavirus, extracellular matrix, glycosaminoglycan, hyaluronan, lung, virus
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:oru:diva-86047 (URN)10.1074/jbc.AC120.015967 (DOI)000591839400022 ()32978255 (PubMedID)2-s2.0-85095861098 (Scopus ID)
Funder
Swedish Heart Lung Foundation, 20200366
Available from: 2020-09-28 Created: 2020-09-28 Last updated: 2024-01-10Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-6881-237X

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