Lancaster Physician Fall 2020 - 24

L A N C A S T E R M E D I C A L S O C I E T Y.O R G

Healthy Communities

Remdesivir (antiviral): This is a prodrug
of a nucleoside analogue that has a broad
antiviral spectrum, covering coronaviruses
[including Middle East Respiratory Syndrome coronavirus (MERS-CoV), Severe
Acute Respiratory Syndrome (SARS), SARS
CoV-2], hemorrhagic fever viruses (Ebola,
Marburg), filoviruses, paramyxoviruses, and
pneumoviruses. A preliminary report regarding the use of remdesivir in the treatment
of COVID-19 was published in the New
England Journal of Medicine (NEJM) in May
2020. The report discussed the findings of a
double-blind, randomized, placebo-controlled
trial involving 1,063 patients with evidence
of lower respiratory tract involvement. They
concluded that remdesivir was superior to
placebo in decreasing time to recovery in
hospitalized adults with COVID-19 and evidence of lower respiratory tract infection. The
FDA issued an Emergency Use Authorization
(EUA) on May 1, 2020 to allow the use of
remdesivir on a larger scale, as the medication
is still considered to be an investigational
drug and is not readily available. A five-day
course is recommended if patients are not on
mechanical ventilation, this is extended to
a 10-day course in mechanically-ventilated
patients. It is only available in intravenous
(IV) form. Other antivirals such as lopinavir-ritonavir, ribavirin, and favipravir have not
shown benefit when compared with standard
care. Danuranivir/cobcistat is being studied
for use in COVID-19 in three randomized
clinical trials.
Dexamethasone (anti-inflammatory):
This is a corticosteroid that was shown to
lower 28-day mortality in 2,104 patients that
received the medication compared to 4,321
patients that received usual care. It was studied in an open-label randomized controlled
trial conducted in the United Kingdom,
the findings of which were published in the
NEJM, July 2020. It is available as IV and
oral (PO).The Infectious Disease Society of
America (IDSA) suggests use in patients with
severe COVID-19; it is not recommended
for patients without hypoxemia.
Other anti-inflammatory agents such as
interleukin-6 (IL-6) inhibitors (tocilizumab,
sarilumab) are currently being studied in
randomized clinical trials. Tocilizumab is

currently only recommended for use by the
IDSA guideline panel in hospitalized patients
enrolled in clinical trials. Immunomodulatory
agents such as IL-1 inhibitors (anakinra),
Janus kinase inhibitors (baritinib, ruxolitinib),
and GM-CSF inhibitors (mavrilimumab) are
currently being investigated.
Convalescent Plasma (antibodies): In
the 1918 Spanish flu pandemic, transfusion
of plasma obtained from patients who had
recovered from the viral infection was used
in the treatment of acutely ill patients.In the
decades following the pandemic, possible
therapeutic efficacy has been claimed for
the use of convalescent plasma in measles,
chickenpox, influenza, Argentine hemorrhagic
fever, cytomegalovirus infections, parvovirus
B19, MERS-CoV, H1N1 and H5N1 avian
flu, and SARS viruses.
A small multicenter, open-label, randomized clinical trial published in JAMA
June 2020, including 103 patients with
severe COVID-19 in China, did not find
any statistical difference in time to clinical
improvement within 28 days among patients
randomized to receive convalescent plasma
or standard care only.
Recently, a pre-print, uncontrolled,
non-randomized trial conducted by the Mayo
Clinic included 35,322 hospitalized patients
with COVID-19. It found that earlier use of
convalescent plasma (three or less days after
diagnosis) and administration of plasma with
higher antibody titers were associated with
improved seven-day and thirty-day mortality,
compared to later use (four or more days after
diagnosis). This was discussed in a non-peer
reviewed article published August 12, 2020 on
a preprint server for Health Sciences (medRxiv).
The FDA issued an EUA for convalescent
plasma on August 23, 2020, which allowed
the distribution and use of convalescent
plasma in hospitalized COVID-19 patients
and removed the previous restrictions of
convalescent plasma use to clinical trials. The
National Institutes of Health (NIH) COVID19 Treatment Guidelines Panel on September
1, 2020 state that there is insufficient data
to recommend for or against convalescent
plasma use and it should not be considered

LANCASTER

24

PHYSICIAN

the standard of care for the treatment of
COVID-19 patients.
The use of intravenous immunoglobulin
(IVIg) has also been studied, as the presence
of protective antibodies in IVIg is highly
likely as the numbers of people recovering
from COVID-19 in the community increases.
However, there is not enough data to suggest
any benefit.
There are multiple ongoing clinical trials
regarding the use of monoclonal antibodies
for treatment or prophylaxis, some of which
involve the use of convalescent plasma-derived
hyperimmune globulin and monoclonal
antibodies targeting SARS-CoV-2.
Low Molecular Weight Heparin (anticoagulant): The International Society of
Thrombosis and Haemostasis (ISTH) released
an interim guidance on recognition and management of coagulopathy in COVID-19. This
was published March 2020 in the Journal of
Thrombosis and Haemostasis, with recommendations for thromboembolic prophylaxis with
subcutaneous low molecular weight heparin
in all hospitalized patients with COVID-19.
Tyrosine Kinase inhibitors (antifibrotics):
The possibility of preventing pulmonary
vascular leakage in COVID-19 patients is
the focus of studies involving imatinib and
others in this group of medications.
Vitamin C, Vitamin D, and Zinc (adjunctive therapies): There is currently insufficient
data to recommend for or against vitamin C,
vitamin D or zinc use, per the NIH COVID19 Treatment Guidelines Panel.
The progression of COVID-19 research has
been quite remarkable. However, the search
for definitive treatment options continues, as
there is none available as of September 2020.


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Lancaster Physician Fall 2020

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