SARS‐CoV‐2 cellular tropism and direct multiorgan failure in COVID‐19 patients: Bioinformatic predictions, experimental observations, and open questions

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 , has led to an unprecedented public health emergency worldwide. While common cold symptoms are observed in mild cases, COVID-19 is accompanied by multiorgan failure in severe patients. Organ damage in COVID-19 patients is partially associated with the indirect effects of SARS-CoV-2 infection (e.g., systemic inflammation, hypoxic-ischemic damage, coagulopathy), but early processes in COVID-19 patients that trigger a chain of indirect effects are connected with the direct infection of cells by the virus. To understand the virus transmission routes and the reasons for the wide-spectrum of complications and severe outcomes of COVID-19, it is important to identify the cells targeted by SARS-CoV-2. This review summarizes the major steps of investigation and the most recent findings regarding SARS-CoV-2 cellular tropism and the possible connection between the early stages of infection and multiorgan failure in COVID-19. The SARS-CoV-2 pandemic is the first epidemic in which data extracted from single-cell RNA-seq (scRNA-seq) gene expression data sets have been widely used to predict cellular tropism. The analysis presented here indicates that the SARS-CoV-2 cellular tropism predictions are accurate enough for estimating the potential susceptibility of different cells to SARS-CoV-2 infection; however, it appears that not all susceptible cells may be infected in patients with COVID-19.

Lung inflammation is associated with lipid deposition

“…Recently, different aspects of pneumonia have attracted special attention in the context of COVID-19, since the lung is the main target organ for SARS-CoV-2 [9]. The key change in lipid-modulating enzymes for COVID-19 reported to date is the elevation of secreted phospholipase A2 (sPLA2) and its activity in blood plasma [10].…”

“…Recently, different aspects of pneumonia have attracted attention in the context of COVID-19, as the lungs are one of the main target organs of SARS-CoV-2 [6]. However, the lipid metabolism in the context of this infection has not been thoroughly studied.…”

“…However, dysregulation of lipid metabolism associated with lung inflammation has been addressed much less, although lipid synthesis in general and lung surfactant specifically have an important role in lung diseases [5]. Recently, different aspects of pneumonia have attracted attention in the context of COVID-19, as the lungs are one of the main target organs of SARS-CoV-2 [6]. However, the lipid metabolism in the context of this infection has not been thoroughly studied.…”

Zebrafish models of COVID-19

“…SARS-CoV-2 cell tropism may explain COVID-19 pathogenicity (Valyaeva et al. 2022 ). Nasal epithelial cells has been found to be very susceptible to viral infection, since they express highest levels of viral entry factors among all studied cells in the respiratory tract.…”

“…In addition, SARS-CoV-2 has also been found to infect ocular tissues (corneal and limbal cells), heart (cardiomyocytes and interstitial cells), gastrointestinal tract (enterocytes), pancreas (α and β cells), kidney, olfactory epithelium (nonneuronal cell types), and brain (neurons and glia) (Valyaeva et al. 2022 ).…”