Viral mapping in COVID-19 deceased in the Augsburg autopsy series of the first wave: A multiorgan and multimethodological approach

Abstract

Background COVID-19 is only partly understood, and the level of evidence available in terms of pathophysiology, epidemiology, therapy, and long-term outcome remains limited. During the early phase of the pandemic, it was necessary to effectively investigate all aspects of this new disease. Autopsy can be a valuable procedure to investigate the internal organs with special techniques to obtain information on the disease, especially the distribution and type of organ involvement. Methods During the first wave of COVID-19 in Germany, autopsies of 19 deceased patients were performed. Besides gross examination, the organs were analyzed with standard histology and polymerase-chain-reaction for SARS-CoV-2. Polymerase chain reaction positive localizations were further analyzed with immunohistochemistry and RNA-in situ hybridization for SARS-CoV-2. Results Eighteen of 19 patients were found to have died due to COVID-19. Clinically relevant histological changes were only observed in the lungs. Diffuse alveolar damage in considerably different degrees was noted in 18 cases. Other organs, including the central nervous system, did not show specific micromorphological alterations. In terms of SARS-CoV-2 detection, the focus remains on the upper airways and lungs. This is true for both the number of positive samples and the viral load. A highly significant inverse correlation between the stage of diffuse alveolar damage and viral load was found on a case and a sample basis. Mediastinal lymph nodes and fat were also affected by the virus at high frequencies. By contrast, other organs rarely exhibited a viral infection. Moderate to strong correlations between the methods for detecting SARS-CoV-2 were observed for the lungs and for other organs. Conclusions The lung is the most affected organ in gross examination, histology and polymerase chain reaction. SARS-CoV-2 detection in other organs did not reveal relevant or specific histological changes. Moreover, we did not find CNS involvement.

Impaired Dendritic Cell Homing in COVID-19

“…Interestingly, we found mDCs in stage 1 lung lobes also had failed to upregulate MHC class II. This is noteworthy as an inverse correlation between DAD stage and viral load has been described previously ( 23 ). Based on the data of this study, we attempted to fit a simple linear regression between the viral load and mDC maturation.…”

“…In this retrospective study, we performed an analysis of the immune cells involved in SARS-CoV-2 induced DAD based on 19 cases of the Augsburg autopsy series ( 23 ) using a multiplexed immunohistochemistry approach. We found an increased number of dendritic cells accumulating in later stages of DAD.…”

“…Samples presenting with collagenous fibrosis were assigned the fibrotic phase (or stage 3). Results of these analyses, among others, have been published recently ( 23 ).…”

“…We fit a simple linear regression model to correlate viral load and mDC maturation using GraphPad Prism. Data of viral load (Ct values of each lobe) were taken from the work by Hirschbühl et al ( 23 ) and are available in the Supplementary Material of this study.…”

Visceral fat inflammation and fat embolism are associated with lung’s lipidic hyaline membranes in subjects with COVID-19

“…We then aimed at assessing whether the observed VAT alterations were associated with SARS-CoV-2 presence in the tissue or if they were a consequence of the systemic inflammation. Although SARS-CoV-2 ability to infect human adipose tissue has been frequently speculated [ 8 , 13 , 18 , 23 ], direct evidence of such phenomenon are scarce in the literature [ 16 , 28 , 29 ]. While SARS-CoV-2 genomic RNA, nucleocapsid and spike proteins were not detectable in VAT samples of patients affected by COVID-19, virus-like structures with morphology and size resembling those present in SARS-CoV-2-infected VeroE6 cells (Fig.…”