Coronavirus disease (COVID-19) is an emerging global pandemic that is threatening the viability of healthcare systems worldwide. The virus responsible for the disease is also known as severe acute respiratory syndrome coronavirus 2 and abbreviated as SARS-CoV-2. The eruption started in China on December 29, 2019 and by March 2020 it was reported that it had spread to several countries across the world.
In the final days of 2019, Chinese doctors identified a number of similar cases of pneumonia in the city of Wuhan in China. Wuhan is the capital city of Hubei Province in China accommodating 11 million inhabitants. Soon, it was discovered that the disease was caused by a new strain of virus which was named SARS-CoV-2.
The first cases of Coronavirus infection outside of China were reported on January 13 in Thailand and January 16 in Japan. Since January 23, 2020, the Chinese government has placed Wuhan and other nearby cities on lockdown. However, the disease has now spread to another 121 countries.
The Latin word ‘corona’ means ‘crown’ since the virus looks like a crown under an electron microscope.
The Symptoms of Coronavirus
According to WHO, the most common symptoms in the laboratory confirmed cases are fever and dry cough. Nearly 87.9% of the confirmed cases had fever and 67.7% had a dry cough. The third and fourth most common symptoms were fatigue and sputum production accounting for 38.1% and 33.4% respectively. The fifth and sixth most common symptoms were shortness of breath (dyspnoea) and muscle and joint pain accounting for 18.6% and 14.8% respectively.
Most of these symptoms are also seen in patients with common flu or cold. However, COVID-19 infection does not usually cause running nose.
The symptoms of the COVID-19 develop and progress over time. In most cases, the symptoms start with a fever, followed by a dry cough. After a few days, some patients start experiencing shortness of breath. In severe and critical cases, particularly with old individuals, it can lead to severe pneumonia, respiratory failure, septic shock, multiple organ dysfunction and failure. Thus, severely affected patients may meet a fatal end.
The symptoms of COVID-19 have been classified into mild, severe and critical cases as shown below:
- Mild cases: About 81% of the confirmed cases are mild cases and they have no pneumonia or only mild pneumonia
- Severe cases: This category includes patients with shortness of breath, respiratory frequency ≥ 30/minute, blood oxygen saturation ≤93%, PaO2 ratio <300 and/or lung infiltrates >50% within 24-48 hours
- Critical cases: This category includes patients with respiratory failure, septic shock, and/or multiple organ dysfucnction/failure
Global Healthcare Response to COVID-19
Globally, the healthcare industry is trying to use every weapon in its armory to suppress the global threat from the virus, using approaches that include vaccines, drugs, stem cells and even exosomes. While many approaches are being investigated, mesenchymal stem cells (MSCs) are showing intriguing potential for the treatment of COVID-19.
MSCs are receiving notable attention because past studies have found the secretions from MSCs to be effective at treating inflammation and cytokine storms.
From early-stage studies, it appears that MSC may exert beneficial effects, potentially by improving the lung microenvironment, inhibiting immune system over-activation, promoting tissue repair, protecting lung alveoli epithelial cells, preventing pulmonary fibrosis, or improving lung function.
In the recent months, there has been increased activity in the clinical trial sector using stem cells and other living therapies against COVID-19. The majority of the current stem cells trials are being undertaken in China.
Cell Therapy Companies Tackling Coronavirus
In response to the global swell of COVID-19 cases which have surpassed 1 million worldwide, numerous cell therapy companies are exploring potential approaches to the treatment and prevention of COVID-19.
The following cell therapy companies are involved in the global response:
- Allovir (in partnership with Baylor College of Medicine)
- Athersys, Inc.
- Aspire Health Science, LLC
- CAR-T (Shanghai) Biotechnology Co., Ltd.
- Celltex Therapeutics Corporation
- Celularity, Inc. (in partnership with Seattle’s Infectious Disease Research Institute)
- Citius Pharmaceuticals (in-licensing deal with Novellus, Inc.)
- Cynata Therapeutics
- GC LabCell
- Lattice Biologics
- Mesoblast Ltd.
- NantKwest, ImmunityBio
- Organicell Regenerative Medicine
- Pluristem Therapeutics
- Sorrento Therapeutics
- Tianhe Stem Cell Biotechnologies (in partnership with its division in China, Jinan Tianhe Stem Cell Biotechnology Co., Ltd.)
- Vitro Biopharma
A brief description of each of these COVID-19 efforts is described below:
AlloVir, a T-cell immunotherapy company, is collaborating with Baylor College of Medicine to development of allogeneic, virus specific T-cell therapies to combat SARS-CoV-2, the virus that causes COVID-19.
Athersys is working to launch a pivotal trial of MultiStem®, its allogeneic “off-the-shelf” bone marrow-derived stem cell product for the treatment of COVID-19 induced acute respiratory distress syndrome (ARDS). The clinical program received a “Highly Relevant” designation for COVID-19 from the Biomedical Advanced Research and Development Authority (BARDA).
Aspire Health Science, LLC, has filed a pre-IND meeting request with the U.S. FDA and Pre-CTA (Clinical Trial Application) with Health Canada for a clinical study that would involve its product candidate, ACT-20. ACT-10 is an allogeneic cryopreserved cell preparation of human MSCs that are ex-vivo culture expanded from human umbilical cord tissue and conditioned media (MSC-CM) produced from the culture of the umbilical cord derived MSCs.
Caladrius Biosciences has an FDA approved IND application for the study of CLBS119, its CD34+ cell therapy for repair of COVID-19 induced lung damage. The study will target patients with severe SARS-CoV-2 infection that required ventilatory support due to respiratory failure.
CAR-T (Shanghai) Biotechnology Co., Ltd., has registered a clinical trial (NCT04302519) to evaluate the use of intravenously injected dental pulp MSCs for the treatment of COVID-19 induced severe pneumonia. The trial plans to enroll 24 patients.
Celltex Therapeutics is in contact with the FDA about a study involving autologous MSCs against COVID-19 induced pneumonia. The company states it has facilitated over 9,000 MSC therapies for various diseases without incurring any adverse events, including ARDS, inflammatory lung disease, influenza and viruses similar to COVID-19.
Celularity is evaluating the capacity of its cryopreserved allogeneic, off-the-shelf NK cell therapy developed from placental hematopoietic stem cells (CYNK-001) for the treatment and prevention of COVID-19 infections. On April 2, 2020, Celularity obtained IND clearance from the U.S. FDA to test CYNK-001 against COVID-19 in a human trial that will enroll 100 patients. The study is being coordinated in partnership with Seattle’s Infectious Disease Research Institute.
Citius Pharmaceuticals signed an exclusive six-month option agreement to in-license a stem-cell therapy for the treatment of ARDS from a subsidiary of Novellus. The patented process uses non-immunogenic synthetic mRNA molecules to create iPSC-derived MSCs.
Cynata Therapeutics is exploring the capacity of its Cymerus™ platform to manufacture iPSC-derived MSCs for the treatment of COVID-19 patients with severe symptoms, including ARDS, sepsis and cytokine release syndrome.
GC LabCell has begun research into a COVID-19 medication, with a hope to start a clinical trial by the second half of 2020 in Korea and the U.S. The company plans to develop a COVID-19 treatment based on natural killer (NK) cells. It will begin to develop the COVID-19 treatment through a joint study with a biotechnology company, KLEO Pharmaceuticals, using its NK and KLEO’s antibody recruiting molecules (ARMs).
GIOSTAR (Global Institute of Stem Cell Therapy and Research) has received FDA approval for a COVID-19 clinical trial led by their Medical Director Dr. Prabhat Soni. GIOSTAR will conduct the trial using stem cells to treat COVID-19 patients, under the approval of the United States Food and Drug Administration (FDA) “expanded access for compassionate use” program.
Lattice Biologics is enrolling 10 patients for its Phase 1 clinical trial in Seattle. The trial will address the safety and efficacy of its stem cell technology, AmnioBoost, for the treatment of severe acute respiratory syndrome (SARS) related to COVID-19 infection.
Mesoblast’s Remestemcel-L has proven itself to be effective in treating advanced respiratory distress. On March 9, 2020, Mesoblast announced its plans to evaluate its allogeneic MSC product candidate Remestemcel-L in patients with ARDS caused by COVID-19 in the U.S., Australia, China and Europe. On April 30, 2020, Mesoblast shared it would enroll up to 300 patients in its Phase 2/3 trial of Remestemcel-L in patients with COVID-19 ARDS.
NantKwest, ImmunityBio – For patients in the severe state of COVID-19 disease, NantKwest is exploring the use of bone marrow-derived allogenic mesenchymal stem cells (BM-Allo-MSC) to mitigate the ‘cytopathic storm’. NantKwest has proprietary isolation and expansion methods for growing MSCs and is using ImmunityBio’s automated, closed system (GMP-in-a-Box) to efficiently grow the MSCs from a bone marrow cell bank in ~7-9 days. NantKwest has filed an IND with the FDA and is on track to initiate trials in Q2 2020.
Organicell Regenerative Medicine has an FDA approved IND application for its lead product, Organicell Flow, for patients diagnosed with moderate to severe acute respiratory syndrome (SARS) due to COVID-19 infection. This trial will be the first randomized, double-blinded, placebo-controlled, phase I/II multi-center clinical trial investigating the safety and potential efficacy of amniotic fluid sourced components for COVID-19.
Pluristem Therapeutics is exploring its PLX cell product candidate for treating respiratory and inflammatory complications caused by the novel Coronavirus infection. The company has already dosed three patients in two different hospitals in Israel under a compassionate use program for the treatment of COVID-19, as approved by the Israeli Ministry of Health.
ReeLabs is involved in fast tracking a clinical trial using MSCs to treat patients suffering from COVID-19 health complications in conjunction with the Indian Health Ministry. The trial will be a randomized placebo-controlled Phase I and II study of the treatment of patients with COVID-19 pneumonia using an intravenous administration of a mixture of umbilical cord and placenta MSCs.
Sorrento Therapeutics is working on a novel decoy cellular vaccine for COVID-19 (STI-6991) and is in active discussions with the FDA’s Center for Biologics Evaluation and Research (IND# 019724) regarding its required IND-enabling studies, clinical protocol and end-points for potential accelerated approval. The company hopes to start enrolling for a clinical trial by mid-year 2020.
Tianhe Stem Cell Biotechnologies and its division in China (Jinan Tianhe Stem Cell Biotechnology Co., Ltd.) registered a clinical trial (NCT04299152) for evaluating its “Stem Cell Educator Therapy” against COVID-19.
Vitro Biopharma is positioning its scalable manufacturing platform to provide stem cell therapies for Coronavirus infections, working with the U.S. government to present its AlloRx™ stem cell therapy option.
Many other companies are also exploring the potential of living therapies to manage the global surge of Coronavirus infections.
Stem Cell Trials for COVID-19
Currently, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) report a combined 29 trials exploring the potential of stem cells for treating COVID-19.
Interestingly, not all of the filed trials are being pursued. In recent weeks, five trials with Chinese Clinical Trial Register (“ChiCTR”) numbers and one trial from ClinicalTrials.gov (with a “National Clinical Trial”) number have been marked as “Cancelled by the Investigator.” Four of the six withdrawn trials were submitted by the same Chinese company, Guangzhou Reborn Health Management Consultation Co., LTD.
Thus, there are 23 active stem cell trials for COVID-19, the vast majority of which utilize MSCs. 16 of the ongoing trials have Chinese Clinical Trial Register (“ChiCTR”) numbers and 7 have National Clinical Trial (NCT) numbers.
When all trial types are considered, there are over 400 studies worldwide exploring approaches to diagnosing, treating or managing COVID-19.
Dozens of companies are also rushing vaccine development and proceeding toward clinical trials.
As select examples, the U.S. NIH initiated a Phase 1 trial in Seattle evaluating an investigational vaccine (mRNA-1273) created by NIAID scientists and their collaborators at Moderna. Sanofi and Regeneron launched a Phase 2/3 trial in New York evaluating the IL-6 targeted Kevzara. Inovio Pharmaceuticals announced that it will move its vaccine into human trials by April within the United States.
Numerous other vaccines are also moving rapidly through development, sponsored by companies in the United States, China and worldwide.