Treatment of COVID-19 Pneumonia: the Case for Placenta-derived Cell Therapy

Abstract

Nearly 500'000 fatalities due to COVID-19 have been reported globally and the death toll is still rising. Most deaths are due to acute respiratory distress syndrome (ARDS), as a result of an excessive immune response and a cytokine storm elicited by severe SARS-CoV-2 lung infection, rather than by a direct cytopathic effect of the virus. In the most severe forms of the disease therapies should aim primarily at dampening the uncontrolled inflammatory/immune response responsible for most fatalities. Pharmacological agents-antiviral and anti-inflammatory molecules-have not been able so far to achieve compelling results for the control of severe COVID-19 pneumonia. Cells derived from the placenta and/or fetal membranes, in particular amniotic epithelial cells (AEC) and decidual stromal cells (DSC), have established, well-characterized, potent anti-inflammatory and immune-modulatory properties that make them attractive candidates for a cell-based therapy of COVID19 pneumonia. Placenta-derived cells are easy to procure from a perennial source and pose minimal ethical issues for their utilization. In view of the existing clinical evidence for the innocuousness and efficiency of systemic administration of DSCs or AECs in similar conditions, we advocate for the initiation of clinical trials using this strategy in the treatment of severe COVID-19 disease.

Human placenta/umbilical cord derivatives in regenerative medicine – Prospects and challenges

“…179 Improvement in the collection methods, donor selection, engraftment techniques and inclusion of other therapeutic approaches could lead to reduced hospital costs. [181][182][183][184][185][186][187][188][189][190][191][192] This strategy has been reviewed from many aspects in the search for a viable treatment option against COVID-19. 193,194 The presence of SARS-CoV-2 within the body elicits too many pro-inflammatory factors like IL-6, IL-8, IL-10, IFN-γ and TNF-α, ultimately causing severe hypercytokinemia, or the cytokine storm.…”

“…The potential of perinatal tissues like human PMSCs, UCMSCs and Wharton's Jelly-derived MSCs in COVID-19 therapeutics has been reflected in a number of clinical studies marching ahead from a single case report to Phase 2 clinical trials as per the published data on PubMed up to 9 th June, 2021. 181–192 This strategy has been reviewed from many aspects in the search for a viable treatment option against COVID-19. 193,194…”

Current Status and Future Prospects of Perinatal Stem Cells

“…SARS-CoV-2 mainly affects the respiratory system, although it is a very complex disease in which other organs, such as kidneys, heart, nervous system, liver, gastrointestinal tract, and skin, can also be affected, and various pathophysiological mechanisms are also involved [ 186 ]. Most deaths are due to acute respiratory distress syndrome (ARDS) caused by an over activation of the immune system struggling to kill the virus, leading to a significant production of inflammatory factors resulting in severe cytokine storm [ 187 ]. High levels of inflammatory markers in blood which include C-reactive protein, ferritin, and D-dimers, and increased serum levels of several inflammatory cytokines and chemokines such as IL-6, TNF, GCSF, MCP-1 among others, have been associated with disease severity and death [ 188 ].…”

Placenta-derived mesenchymal stem cells (P-MSCs) for COVID-19 pneumonia—a regenerative dogma

“…MSCs possess the intrinsic ability to curb the infection with pre-defined cytokines, chemokines, and growth factors. On this horizon, placental stem cells with MSC activity play a vital role in curbing COVID-19 pneumonia with improved lung compliance (4). Being considered as medical waste, the placenta serves as a temporary immune-tolerant unit to maintain the pregnancy and feto-maternal circuit.…”