A Novel Treatment Paradigm for the Treatment of COVID-19 Induced
Acute Respiratory Distress Syndrome (ARDS)
Acute respiratory distress syndrome due to the SARS-CoV-2 virus
(COVID-19 ARDS) demonstrates the same pathologic changes of diffuse
alveolar damage as classic ARDS, and ARDS develops in 33%-42% of
hospitalized patients with COVID-19 and in 61-81% of patients admitted
to the intensive care unit (ICU).1,2 Regardless of
etiology, ARDS treatment options are limited to supportive care with
mechanical ventilation (MV) and new, effective treatments are
needed.3ExoFloTM is an
acellular extracellular vesicle (EV) product isolated from a single
donor bone marrow mesenchymal stem cell (bmMSC) culture that confers the
promising anti-inflammatory and regenerative benefits of bmMSCs for
treatment of ARDS without the drawbacks associated with viable cell
therapy.4-12 We proposed that ExoFlo could safely
reduce lung injury from COVID-19, and possibly assist in the lung’s
recovery process. We describe the case of a patient with severe
respiratory failure and subsequent ARDS requiring prolonged mechanical
ventilation who recovered after receiving ExoFlo. This case highlights
this EV product as a novel therapeutic for the treatment of COVID-ARDS.
The patient is a 40-year-old female with a history of mild intermittent
asthma, diverticulosis, and a remote history of thyroid cancer status
post thyroidectomy. The patient had a prolonged ICU course due to
COVID-19 induced ARDS that started four days after delivering her second
child via a Cesarean section. Treatment for ARDS included mechanical
lung ventilation with prone positioning, treatment of secondary
infections with intravenous antibiotics, and supportive care for
multisystem organ failure. She also received standard supportive care
for COVID ARDS including lung protective ventilation, intermittent
neuromuscular blockade, and intravenous steroids.
After one month of supportive care failed to improve her status, an eIND
(IND #28207) was approved by the Food and Drug Administration (FDA) for
the administration of 15 mL of ExoFlo. At the time of ExoFlo
administration, she was sedated with an FiO2 of 100%
and PEEP of 15cm H2O, and she was receiving norepinephrine to maintain
adequate perfusion. She received two doses of ExoFlo on Day 1 and Day 2
with slight improvement. She was not considered a candidate for
extracorporeal membrane oxygenation (ECMO) due to the prolonged
mechanical ventilation. Seventeen days later, she continued having
febrile episodes and still required maximum ventilatory support. Her
FiO2 on the ventilator was 90% and her PEEP was at 14cm H2O. Since her
lung function had not improved, an additional treatment course of ExoFlo
was approved by the FDA. After the second day of her second course of
ExoFlo treatment, we were able to wean the PEEP, wean sedation and she
began to move her lower extremities again. Due to this clear
improvement, she continued the ExoFlo treatment course with 15 mL every
24 hours for a total of 5 days. By the fifth dose of ExoFlo, her
ventilatory requirements had improved to 55% FiO2 and a PEEP of 8. The
day after her fifth dose, two months from her ARDS diagnosis, she
underwent a bedside tracheostomy and PEG tube placement.
Two days following her second round of ExoFlo treatment, her sedation
continued to be weaned, her urine output began to increase, and she was
initiated on oral intake with ice chips. Two weeks following this
treatment course, the FDA approved a third treatment course with ExoFlo.
Following her third course of ExoFlo (5 days, 15 mL Q 24 hours) her
tracheostomy was downsized, ventilatory support was discontinued, and
she achieved 96% oxygen saturation on trach collar. (Figure 1. A. Chest
computed tomography (CT) imaging before five-day course of ExoFlo. B.
Chest CT showing improvement after five-day course of ExoFlo.)
Four days after her third treatment course with ExoFlo, she was
discharged from the hospital to a rehabilitation facility. She was still
regaining strength and remained on oxygen at rest. Eight months after
discharge from the hospital, she was able to return to work part time.
One year after discharge, she has regained most of her strength. She
still has some fine motor deficits in her right hand, and she still
requires oxygen with exertion. She has a mild restrictive pattern and
mild DLCO reduction on her pulmonary function tests, but her chest CT
and overall functional status have both greatly improved. Her most
recent CT shows improvement in the fibrotic injury appreciated on her
earlier chest CTs. (Figure 2. A. Chest CT before five-day course of
ExoFlo B. Chest CT one year after discharge from hospital).
Prior to her second course of ExoFlo, the ICU team was discussing
palliative care options with the family, since she was in the severe
COVID ARDS category of patients who often did not recover. Once she
started showing signs of major improvement during her second course of
treatment with ExoFlo, it became apparent that she had a good chance for
a meaningful recovery. The multiplicity of molecules contained within
ExoFlo may have promoted healing and regeneration of healthy lung tissue
in this patient who appeared to have irreversible ARDS. Currently a
Phase III, randomized, blinded trial is underway to evaluate the
efficacy of ExoFlo in patients with moderated to severe COVID related
ARDS.