Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin
Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection, the cause of coronavirus disease 2019 (COVID-19), is characterized by acute clinical pathologies, including various coagulopathies that may be accompanied by hypercoagulation and platelet hyperactivat...
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| Format: | Article |
| Language: | English |
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BMC
2021-08-01
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| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12933-021-01359-7 |
| _version_ | 1818358174968709120 |
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| author | Etheresia Pretorius Mare Vlok Chantelle Venter Johannes A. Bezuidenhout Gert Jacobus Laubscher Janami Steenkamp Douglas B. Kell |
| author_facet | Etheresia Pretorius Mare Vlok Chantelle Venter Johannes A. Bezuidenhout Gert Jacobus Laubscher Janami Steenkamp Douglas B. Kell |
| author_sort | Etheresia Pretorius |
| collection | DOAJ |
| description | Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection, the cause of coronavirus disease 2019 (COVID-19), is characterized by acute clinical pathologies, including various coagulopathies that may be accompanied by hypercoagulation and platelet hyperactivation. Recently, a new COVID-19 phenotype has been noted in patients after they have ostensibly recovered from acute COVID-19 symptoms. This new syndrome is commonly termed Long COVID/Post-Acute Sequelae of COVID-19 (PASC). Here we refer to it as Long COVID/PASC. Lingering symptoms persist for as much as 6 months (or longer) after acute infection, where COVID-19 survivors complain of recurring fatigue or muscle weakness, being out of breath, sleep difficulties, and anxiety or depression. Given that blood clots can block microcapillaries and thereby inhibit oxygen exchange, we here investigate if the lingering symptoms that individuals with Long COVID/PASC manifest might be due to the presence of persistent circulating plasma microclots that are resistant to fibrinolysis. Methods We use techniques including proteomics and fluorescence microscopy to study plasma samples from healthy individuals, individuals with Type 2 Diabetes Mellitus (T2DM), with acute COVID-19, and those with Long COVID/PASC symptoms. Results We show that plasma samples from Long COVID/PASC still contain large anomalous (amyloid) deposits (microclots). We also show that these microclots in both acute COVID-19 and Long COVID/PASC plasma samples are resistant to fibrinolysis (compared to plasma from controls and T2DM), even after trypsinisation. After a second trypsinization, the persistent pellet deposits (microclots) were solubilized. We detected various inflammatory molecules that are substantially increased in both the supernatant and trapped in the solubilized pellet deposits of acute COVID-19 and Long COVID/PASC, versus the equivalent volume of fully digested fluid of the control samples and T2DM. Of particular interest was a substantial increase in α(2)-antiplasmin (α2AP), various fibrinogen chains, as well as Serum Amyloid A (SAA) that were trapped in the solubilized fibrinolytic-resistant pellet deposits. Conclusions Clotting pathologies in both acute COVID-19 infection and in Long COVID/PASC might benefit from following a regime of continued anticlotting therapy to support the fibrinolytic system function. |
| first_indexed | 2024-12-13T20:24:49Z |
| format | Article |
| id | doaj.art-13c4062367104010a66d20345dbc31d5 |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-12-13T20:24:49Z |
| publishDate | 2021-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-13c4062367104010a66d20345dbc31d52022-12-21T23:32:34ZengBMCCardiovascular Diabetology1475-28402021-08-0120111810.1186/s12933-021-01359-7Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasminEtheresia Pretorius0Mare Vlok1Chantelle Venter2Johannes A. Bezuidenhout3Gert Jacobus Laubscher4Janami Steenkamp5Douglas B. Kell6Department of Physiological Sciences, Faculty of Science, Stellenbosch UniversityCentral Analytical Facility: Mass Spectrometry, Stellenbosch UniversityDepartment of Physiological Sciences, Faculty of Science, Stellenbosch UniversityDepartment of Physiological Sciences, Faculty of Science, Stellenbosch UniversityMediclinic StellenboschDepartment of Physiological Sciences, Faculty of Science, Stellenbosch UniversityDepartment of Physiological Sciences, Faculty of Science, Stellenbosch UniversityAbstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection, the cause of coronavirus disease 2019 (COVID-19), is characterized by acute clinical pathologies, including various coagulopathies that may be accompanied by hypercoagulation and platelet hyperactivation. Recently, a new COVID-19 phenotype has been noted in patients after they have ostensibly recovered from acute COVID-19 symptoms. This new syndrome is commonly termed Long COVID/Post-Acute Sequelae of COVID-19 (PASC). Here we refer to it as Long COVID/PASC. Lingering symptoms persist for as much as 6 months (or longer) after acute infection, where COVID-19 survivors complain of recurring fatigue or muscle weakness, being out of breath, sleep difficulties, and anxiety or depression. Given that blood clots can block microcapillaries and thereby inhibit oxygen exchange, we here investigate if the lingering symptoms that individuals with Long COVID/PASC manifest might be due to the presence of persistent circulating plasma microclots that are resistant to fibrinolysis. Methods We use techniques including proteomics and fluorescence microscopy to study plasma samples from healthy individuals, individuals with Type 2 Diabetes Mellitus (T2DM), with acute COVID-19, and those with Long COVID/PASC symptoms. Results We show that plasma samples from Long COVID/PASC still contain large anomalous (amyloid) deposits (microclots). We also show that these microclots in both acute COVID-19 and Long COVID/PASC plasma samples are resistant to fibrinolysis (compared to plasma from controls and T2DM), even after trypsinisation. After a second trypsinization, the persistent pellet deposits (microclots) were solubilized. We detected various inflammatory molecules that are substantially increased in both the supernatant and trapped in the solubilized pellet deposits of acute COVID-19 and Long COVID/PASC, versus the equivalent volume of fully digested fluid of the control samples and T2DM. Of particular interest was a substantial increase in α(2)-antiplasmin (α2AP), various fibrinogen chains, as well as Serum Amyloid A (SAA) that were trapped in the solubilized fibrinolytic-resistant pellet deposits. Conclusions Clotting pathologies in both acute COVID-19 infection and in Long COVID/PASC might benefit from following a regime of continued anticlotting therapy to support the fibrinolytic system function.https://doi.org/10.1186/s12933-021-01359-7COVID-19Long COVID/PASCFibrin(ogen)MicroclotsProteomicsAntiplasmin |
| spellingShingle | Etheresia Pretorius Mare Vlok Chantelle Venter Johannes A. Bezuidenhout Gert Jacobus Laubscher Janami Steenkamp Douglas B. Kell Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin Cardiovascular Diabetology COVID-19 Long COVID/PASC Fibrin(ogen) Microclots Proteomics Antiplasmin |
| title | Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin |
| title_full | Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin |
| title_fullStr | Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin |
| title_full_unstemmed | Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin |
| title_short | Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin |
| title_sort | persistent clotting protein pathology in long covid post acute sequelae of covid 19 pasc is accompanied by increased levels of antiplasmin |
| topic | COVID-19 Long COVID/PASC Fibrin(ogen) Microclots Proteomics Antiplasmin |
| url | https://doi.org/10.1186/s12933-021-01359-7 |
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