3. Other therapies and future perspectives
Many other drugs with disparate mechanisms of actions are evaluated in
patients with COVID-19. For instance, a PD-1 immune checkpoint inhibitor
monoclonal antibody, camrelizumab, which recently received a conditional
approval in China for the treatment of relapsed or refractory classical
Hodgkin lymphoma, is evaluated in a phase 2 study involving patients
with SARS-Cov-2 infection. PD-1 and its ligand (PD-L1) are key mediators
in T cell depletion in patients with sepsis. Preclinical studies have
demonstrated that the blockade of PD-1 or PD-L1 can prevent T cell
death, regulate cytokine production and reduce organ dysfunction
[97,98 ]. The study was launched on February 2020 to verify
its efficacy in combination with thymosin in 120 patients with severe
pneumonia associated with lymphocytopenia [99 ].
A further experimental monoclonal antibody for the treatment of COVID-19
is bevacizumab, approved for the treatment of metastatic colorectal
cancer, non-small cell lung cancer, metastatic breast cancer and
advanced and/or metastatic renal cell carcinoma. By binding to the
growth factor of vascular endothelial cells (VEGF), a key promoter of
vasculogenesis and angiogenesis, bevacizumab is able to prevent its
biological activity [100,101 ]. A key role of VEGF in acute
lung injury and ARDS was confirmed [102 ]. Based on these
findings, two clinical trials are currently evaluating the efficacy and
safety of bevacizumab in patients with COVID-19 (BEST-RCT and BEST-CP)
[103,104 ].
Also for thalidomide, a drug widely used in the treatment of
Interstitial Pulmonary Fibrosis, lung damage from paraquat and myeloma,
a possible role for the treatment of COVID-19 was hypothesized. Indeed,
the drug has been reported to be effective against HIV
[105,106 ] by modulating TNF-a-induced replication.
Moreover, thalidomide suppresses the production of proinflammatory
cytokines such as TNF-alpha and IL-8 through the inhibition of NF-κB
[107 ]. Two studies are currently testing its efficacy in
patients with COVID19 [108,109 ].
In addition, other drugs are currently evaluated in Chinese clinical
trials involving patients with COVID-19, including fingolimod
[110 ], high-dose Vitamin C, adalimumab, piperaquine, and
leflunomide [111 ]. Lastly, considering the key role of ACE2
for the attachment and cell entry of SARS-Cov-2, researchers recently
suggested that the development of specific neutralizing monoclonal
antibodies that bind to ACE2 might block the virus entry
[112 ].
Lastly, given that the therapy for COVID-19 is dependent on the
patients’ immune system, researchers are evaluating two possible
engineering therapies: expanded umbilical cord mesenchymal stem cells in
critically ill patients [113 ] and intravenous
immunoglobulin purified from IgG antibodies of patients who recovered
from COVID-19 [114 ]. Finally, the development of a vaccine
against SARS-CoV-2 is urgently needed. However, according to Shang W et
al., researchers would bring a new SARS-CoV-2-based vaccine in
approximately 16–20 weeks [115 ]. On March 2020, there were
2 candidate vaccines in phase 1 development (studies ChiCTR2000030906
and NCT04283461) and 42 candidate vaccines in preclinical phase of
evaluation [116 ]. Researchers from the University of
Pittsburgh School of Medicine announced a potential vaccine against
SARS-CoV-2 that was tested in mice and produced antibodies specific to
SARS-CoV-2 able to neutralize the virus [117 ]. Furthermore,
an experimental mRNA vaccine against the pandemic coronavirus was
already administered to one person in US [118 ].