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Published on: February 16, 2016
Comparative Study of the Myocardium of Patients from Four COVID-19 Waves
Lubov Borisovna Mitrofanova1, Igor Aleksandrovich Makarov1, Andrey Nikolaevich Gorshkov1,2
1Almazov National Medical Research Centre, St. Petersburg 197341, Russia.
Insights
This study found that cardiovascular complications like myocarditis decreased over time in COVID-19 patients. However, a direct link between SARS-CoV-2 infection and myocarditis remains unproven.
Area of Science:
- Pathology
- Virology
- Cardiology
Background:
- Limited research exists on comparing COVID-19 patients across different pandemic waves.
- Understanding clinical and morphological changes in deceased COVID-19 patients is crucial.
Purpose of the Study:
- To conduct a clinical and morphological analysis of patients who died from COVID-19 across four distinct waves.
- To compare the incidence of myocardial damage and cardiovascular complications over successive COVID-19 waves.
Main Methods:
- Autopsy myocardium samples from 276 deceased COVID-19 patients (across three waves) were histologically examined.
- Immunohistochemistry, immunofluorescence, RT-ddPCR, and electron microscopy were employed to detect viral presence and cellular changes.
- Analysis included markers for inflammation, endothelial damage, and viral proteins (enteroviral VP1, SARS-CoV-2 spike protein).
Main Results:
- Active myocarditis was diagnosed in 5% of cases; 86% expressed VP1, and 22% had SARS-CoV-2 spike protein in individual cells.
- Electron microscopy revealed potential SARS-CoV-2 virions on the endothelium of myocardial vessels.
- Incidence of hemorrhage, myocardial necrosis, blood clots, and myocarditis significantly decreased over the waves, with CD8-T-killers appearing.
Conclusions:
- Myocardial damage, including endotheliitis complications and myocarditis, decreased across the studied COVID-19 waves.
- The direct causal link between SARS-CoV-2 infection and the observed myocarditis in these cases remains unproven.
- Endotheliitis was confirmed in all immunohistochemically studied cases.
Background:
Few studies have compared COVID-19 patients from different waves. This study aims to conduct a clinical and morphological analysis of patients who died from COVID-19 during four waves.
Methods:
The study involved 276 patients who died from COVID-19 during four waves, including 77 patients in the first wave, 119 patients in the second wave, and 78 patients in the third wave. We performed a histological examination of myocardium samples from autopsies and additionally analyzed the samples by PCR. We conducted immunohistochemistry of the myocardium for 21 samples using antibodies against CD3, CD45, CD8, CD68, CD34, Ang1, VWF, VEGF, HLA-DR, MHC1, C1q, enteroviral VP1, and SARS-CoV-2 spike protein. We also did immunofluorescent staining of three myocardial specimens using VP1/SARS-CoV-2 antibody cocktails. Further, we ran RT-ddPCR analysis for 14 RNA samples extracted from paraffin-embedded myocardium. Electron microscopic studies of the myocardium were also performed for two samples from the fourth wave.
Results:
Among the 276 cases, active myocarditis was diagnosed in 5% (15/276). Of these cases, 86% of samples expressed VP1, and individual cells contained SARS-CoV-2 spike protein in 22%. Immunofluorescence confirmed the co-localization of VP1 and SARS-CoV-2 spike proteins. ddPCR did not confidently detect SARS-CoV-2 RNA in the myocardium in any myocarditis cases. However, the myocardium sample from wave IV detected a sub-threshold signal of SARS-CoV-2 by qPCR, but myocarditis in this patient was not confirmed. Electron microscopy showed several single particles similar to SARS-CoV-2 virions on the surface of the endothelium of myocardial vessels. A comparison of the cardiovascular complication incidence between three waves revealed that the incidence of hemorrhage (48 vs. 24 vs. 17%), myocardial necrosis (18 vs. 11 vs. 4%), blood clots in the intramural arteries (12 vs. 7 vs. 0%), and myocarditis (19 vs. 1 vs. 6%) decreased over time, and CD8-T-killers appeared. Immunohistochemistry confirmed the presence of endotheliitis in all 21 studied cases.
Conclusions:
This study compared myocardial damage in patients who died during three COVID-19 waves and showed a decrease in the incidence of endotheliitis complications (thrombosis, hemorrhage, necrosis) and myocarditis over time. However, the connection between myocarditis and SARS-CoV-2 infection remains unproven.
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