COVID-19 Diagnosis, Differential
Diagnosis, and Treatment.
Diagnosis of COVID-19,
largely has been accomplished,
by nucleic acid amplification testing or "NAAT,"
typically, by reverse transcriptase
polymerase chain reaction,
an (RT-PCR) assay.
Antigen testing can be performed,
it is certainly rapid, it can be
performed as a point of care test,
so, at the site of a clinic
or emergency department,
but it is less sensitive than NAAT.
Serology or antibody detection
of course will be adequate
for diagnosing prior infection
or infection at least three to four weeks prior
to the time of testing,
however, there is variable
sensitivity and specificity,
keeping in mind that the antibody, assay,
must be specific to a component
of the SARS-Coronavirus II
and not creating a false positive
result in reaction to something else.
Also important, in the diagnosis of COVID-19,
is, to exclude as best as
one is able other etiologies
or even coexisting processes such
as other respiratory infections,
congestive heart failure,
multi-organ failures, exacerbations
of underlying reactive airway disease
or asthma or even COPD, and anxiety.
There is, as you would
imagine an extensive overlap,
between the presentation and symptoms of COVID-19
and many other respiratory illnesses, such as,
influenza, rhinovirus or even other coronaviruses,
as the cause of the common cold,
pertussis, causing whooping cough
and even atypical pneumonia, caused
by such bacteria as mycoplasma
or even tuberculosis.
With that extensive overlap,
you can imagine an initial presentation,
is completely non-specific,
patients with COVID-19 and
other respiratory illnesses,
will start off with a flu-like illness,
they will likely have lymphopenia, especially,
if one is having an initial robust presentation,
with elevated white blood cells
and a neutrophil predominance,
so-called left shift, if
that response also includes,
bands or metamyelocytes.
However, lymphopenia, can be quite prominent
several days even several weeks into COVID-19
and maybe a suggestion that
the patient has COVID-19,
versus other respiratory illnesses.
Certainly, development of pneumonia can
be seen in all respiratory illnesses,
that's part of the name and including COVID-19
and all these can progress to severe disease,
also can have critical complications,
especially, if an initial,
viral respiratory disease
other than SARS-Coronavirus II,
develops a secondary bacterial pneumonia
as a complication.
So, whereas the initial
presentation is nonspecific,
One, can use a specific testing
which will help distinguish COVID-19,
from other respiratory illnesses.
So, in that patient with a
and in whom one suspects COVID-19,
one, can perform RT-PCR testing
or a quick antigen test,
followed by PCR confirmation
for SARS-Coronavirus II.
If the patient is sick enough
to require hospitalization
and potentially other interventions,
then a chest computed tomography or a CT scan,
may demonstrate bilateral ground glass opacities
and diffused pneumonia or even
unilateral patchy processes,
in patients with COVID-19, versus other findings
and other types of respiratory illnesses.
In kidneys, one can develop or one
can see elevated BUN and creatinine
or evidence of acute kidney injury,
again, this doesn't distinguish COVID-19,
from other infections or respiratory illnesses,
but it is more commonly seen in
patients earlier on in their COVID-19,
than you might anticipate in other illnesses.
Similarly, cardiac abnormalities,
keeping in mind that the virus does
have tropism for among other organs,
the heart, one can see elevated troponin,
so, evidence, of myocardial damage
or injury as well as an abnormal EKG,
so, showing a dysrhythmia
or even sometimes access deviation on the EKG.
Liver function abnormalities,
so elevated liver enzymes such as,
AST, ALT, GGT, lactite dehydrogenase,
the alpha-HBDH, all these can be
seen early on in acute COVID-19,
which is, on the way to becoming severe,
but again, keep in mind there is still an
overlap with other respiratory illnesses.
What about treatment,
so, in patients who are
outpatients, so, mild disease,
or mild about to become severe
if they have comorbidities,
there are several monoclonal
antibody cocktail therapies,
typically, two monoclonal
antibodies in combination,
which target, as two separate antigens,
expressed by SARS-Coronavirus II,
typically, these are two
components of the spike protein,
created or expressed by SARS-Coronavirus II.
In the United States as well
as elsewhere in the world,
these monoclonal cocktails, antibody cocktails,
have been approved for patients
with mild to moderate disease
and risk factors for progression
and continuing studies demonstrate their efficacy,
the challenge of course is in parts of the world,
which now, is everywhere in which a variance,
mutant variants have emerged,
not all of the monoclonal
antibodies remain efficacious,
against the newest variants and
especially against the delta variant.
Other therapies of course are being evaluated,
as prophylactic interventions but
none has been proven to be helpful,
in patients who have mild disease only.
What about those patients who have severe disease
and are hospitalized.
Again, there is emerging
evidence in this this field
and the ideal management continues to evolve,
however, absolutely oxygen therapy is a necessary,
because patients principally present with hypoxia
and decreased peripheral oxygenation,
there are several series
now which have demonstrated
benefit for those patients with moderate
to severe disease with tocilizumab,
which is, a monoclonal antibody,
targeting the interleukin-6 receptor.
Prophylactic anticoagulation, some
benefit has been shown there as well,
keeping in mind that a
complication of COVID-19 is,
thrombosis due in part to the
immune reaction to the virus itself.
Those patients who are moderate to severe,
progressing to severe critical disease,
also qualify for use of dexamethasone therapy,
while, other steroids have been tried
and also found to be efficacious
and then the antiviral drug remdesivir,
however, if these patients rapidly
proceed to mechanical ventilation,
it is unclear that either of these interventions,
has any ability to prevent that,
once they've actually presented and
presented with respiratory failure.
Those severest of the severe patients,
may require intubation, mechanical
ventilation and even sometimes,
“ECMO,” “Extracorporeal membrane oxygenation.”
So, this is of course I guess
the scary part of the pandemic,
knowing that while 80% of
patients have mild disease,
there is still a 15% severe
and a 5% critical component,
who can develop very, very,
so, it is good to have ways to diagnose them early
and hopefully provide some sort of
intervention to prevent progression to,
that point were,
they require ventilation,
intubation and potentially ECMO.