Early postmortem mapping of SARS-CoV-2 RNA in patients with COVID-19 and correlation to tissue damage

Abstract

<jats:title>Abstract</jats:title><jats:p>Clinical observations indicate that COVID-19 is a systemic disease. An investigation of the viral distribution within the human body in correlation to tissue damage can help understanding the pathophysiology of SARS-CoV-2 infection.</jats:p><jats:p>We present a detailed mapping of viral RNA in 61 tissues and organs of 11 deceased patients with the diagnosis COVID-19. The autopsies were performed within the (very) early postmortem interval (mean: 5.6 hours) to avoid bias due to viral RNA and tissue degradation. Viral loads, blood levels of cytokines, prothrombotic factors as well as macro- and micro-morphology were correlated.</jats:p><jats:p>Very high (&gt; 10<jats:sup>4</jats:sup> copies/ml) viral loads were detected in the lungs of most patients and then correlated to severe tissue damage. Intact viral particles could be verified in the lung tissue by transmission electron microscopy. Viral loads in the lymph nodes were associated with a loss of follicular architecture. Viral RNA was detected throughout further extra-pulmonary tissues and organs without visible tissue damage. Inflammatory cytokines as well as the prothrombotic factors were elevated in all patients.</jats:p><jats:p>In conclusion, the dissemination of SARS-CoV-2-RNA throughout the body supports the hypothesis of a maladaptive host response with viremia and multi-organ dysfunction.</jats:p>

SARS-CoV-2 causes severe alveolar inflammation and barrier dysfunction

“…Taken together, these results indicate that endothelial cells of the lung model are not the primary target cells of SARS-CoV-2 which is in agreement with previous studies (Bar-On et al, 2020). Further, it is in line with the observation that endothelial layer of the alveolar capillaries of deceased COVID-19 patients were still intact but epithelial tissue was found seriously damaged (Deinhardt-Emmer et al, 2020b). Although the mechanism is not clear the increased proinflammatory cytokine release might cause an endothelial dysfunction.…”

“…Clinical studies revealed that the virus primarily replicates in the lung, which can cause severe lung damage up to necrotic destruction of large areas of the lung tissue (Carsana et al, 2020). In autopsies of deceased COVID-19 patients, it has been observed that particularly in severe cases viral particles can disseminate throughout the body (Deinhardt-Emmer et al, 2020b;Wichmann et al, 2020). Additionally, systemic complications have been reported, such as the massive release of proinflammatory cytokines and thromboembolic events in various organs (Becker, 2020).…”

Bone marrow haemophagocytosis indicates severe infection with severe acute respiratory syndrome coronavirus 2

“…Even though SARS‐CoV‐2 is also detectable in the bone marrow, it has not been demonstrated whether haemophagocytosis in COVID‐19 patients is caused by direct viral infection of phagocytes or indirectly by a systemic immune response 2 . To elucidate this, histological bone marrow analysis and additional SARS‐CoV‐2 RNA determination in these bone marrow samples would be required.…”

“…The pathophysiology and mechanisms of the immune response in COVID‐19 patients have not yet been completely elucidated. Although respiratory symptoms such as dyspnoea or cough are predominant, the virus affects the entire host organism, and has been detected in many organs by the use of molecular techniques 1,2 . Especially in patients with severe COVID‐19, dysregulation of the immune system, with elevated levels of proinflammatory cytokines, increased numbers of neutrophils, and decreased numbers of lymphocytes, has been reported 3 .…”

Physical phenotype of blood cells is altered in COVID-19

“…Thus, neutrophil alterations observed in our recovered cohort were induced after the successful displacement of the virus by the immune system. This might be indicative for SARS-CoV-2 causing long-term immunological signals or even targeting bone marrow stem cells, as viral RNA was found post-mortem in patient bone marrow (53).…”