DISCUSION
SARS-CoV2 is a single-stranded RNA virus from the coronavirus group with
an unusual property of penetration in the cell and the ability to break
down the beta-1 chain of hemoglobin so that the iron separates as free
and hemoglobin loses its ability to bind oxygen, which leads to
resistant hypoxemia and multiorganic dysfunction named pediatric
multisystem inflammatory disease, COVID-19 related7,8.
Compensatory, the organism increases the synthesis of hemoglobin and
ferritin, which explains their increased concentration in the serum, and
it should be borne in mind that this compensation continues because too
much hemoglobin has lost the ability to carry oxygen. High ferritin
(non-toxic iron storage) is a bad prognostic sign7,8.
As soon as iron is separated from hemoglobin and it found in the
circulation, the level of ferritin increases and the toxic effect of
free iron manifests with strong oxidative damage to the lungs, what
results in inflammation by alveolar macrophages i.e. incitement of
inflammatory storm, and all listed changes in the lungs are
radiographically presented as multiple peripheral
atelectasis7,8. The high concentration of iron and
increased hemoglobin synthesis affect on rise of blood viscosity, which
results in disseminated micro- and macro-circulatory thrombosis and
embolization of tissues and organs, followed by a fast increase in
D-dimmer and a sudden clinical patient deterioration and, eventual,
deathly outcome7,8.
During the early compensatory reaction of the organism, a larger number
of monocytes are released from the bone marrow because they want to
remove the excess iron from the organism. Differentiation and
proliferation of the monocyte line is favored, what for developed a
lymphopenia5. However, in asymptomatic covid19
patients included in our serial case reports, lymphocytosis was found in
7 of 8 patients (7/8), with normal white blood cell (Le) count in 7/8
patients, monocytosis in 8/8, and eosinophilia in 3/8 patients
asymptomatic covid19 examinees of child age.
We compared this findings with findings related to influenza-like
illness. In those likely to have H1N1 virus infection exist relative
lymphopenia with or without monocytosis7, while in our
asymptomatic covid19 patients exist monocytosis with lymphocytosis and
normal or increased leukocyte count predominate, what is important
differential diagnostic characteristic between these two infections. For
the suspicion on SARS-COV-2 infection and before the arrival of PCR
results, it is useful to determine the relationship between lymphocytes
and monocytes. This ratio of lymphocytes to monocytes less than 2 with
normal or low leukocytes is found in 90% of patients with
influenza-like illness and has been suggested as a replacement instead
of a rapid influenza test7. Unlike influenza carriers,
SARS-CoV-2 carriers have a lymphocyte-monocyte ratio greater than 2 with
normal or increased leukocytes. Given that the covid19 pandemic is
ongoing and there are indices that a new waves will occur in the future,
it is important to establish clear hematological differences between
this two viral infections.
The rise of the hemoglobin (Hb), which were seen in symptomatic covid19
patients were not found in any asymptomatic patients. In most children
(6/8) without symptoms and carriers of SARS-CoV-2, there were no changes
in erythrocyte indices, which is an important difference in relation to
symptomatic covid19 patients. A fall of certain erythrocyte indices was
found in a pair of children carriers of SARS-CoV-2, and that are: a fall
of the mean corpuscular Hb (MCH) in 1/8 and of mean corpuscular volume
(MCV) in 2/8 asymptomatic covid19 patients (carriers of SARS-CoV-2).
Mean corpuscular Hb concentration (MCHC) was within normal limits in all
asymptomatic pediatric covid19 patients. Found values of erythrocyte
indices and their mutual relations in a pair of patients (2/8) indicate
the initial accelerated consumption of Hb and the change in the volume
of erythrocytes into microcytic and hypochromic, in children who are
carriers of SARS-CoV-2. These findings indicate that carriers of
SARS-CoV-2 had, presumably, “silent” or “minimal” inflammation that
induced microcytic anemia.
The determined relationship between the number of monocytes, lymphocytes
and eosinophils with normal white blood cells (WBC) number, normal Hb
concentration and showed changes in erythrocyte indices in the complete
blood count may be a pattern for the suspicion on the SARS-CoV-2
infection and predictive factors of asymptomatic covid19 in children,
what has important practical significance in pediatrics.
The presented hematological changes were followed with a multiple rise
of lactate dehydrogenase (LDH) in serum in all asymptomatic covid19
children (carriers of SARS-CoV-2). Strong oxidative lung damage and
resistant hypoxemia during covid19 were accompanied by an rise of
concentration of LDH in serum6,9. The initial damage
on cells (erythrocyte hemolysis)and tissues caused with SARS-CoV-2 is
accompanied by significant activity of this enzyme (LDH) in the
blood6,8,9. A multiple increase of LDH levels in serum
was found in all (8/8) asymptomatic covid19 subjects (carriers of
SARS-CoV-2), which means that the increase in LDH is an early
biochemical sign of this infection in children. In all (8/8)
asymptomatic covid19 children (carriers of SARS-CoV-2), it was found
multiple rise of serum LDH values with a normal red blood cell (Er)
count, without an increase in Hb, already fall of erithrocyte indices,
and the distinctive ratio between lymphocytes and monocytes, with
occasional eosinophila. Such a haematological and biochemical finding
may be a predictive factors of SARS-CoV-2 in asymptomatic children. The
carriers of SARS-CoV-2, in contrast to carriers of influenza virus, have
other changes in leukocyte formula6, and high LDH
values6. This finding suggests the need to analyze the
values of five specific serum LDH isoenzymes in order to quickly predict
and set of suspicion on SARS-CoV-2 infection in patients named the
”contact from covid19 patients” or the ”reservoir of
SARS-CoV-2”6. Biochemical analysis of specific LDH
isoenzymes is a rapid method in contrast to the PCR test for SARS-CoV-2,
the result of which is often waiting for more than 24
hours6.
Low-income countries have a frequent problem with a shortage of tests
for rapid diagnosis of SARSCoV2 (antigen or PCR-real-time), so our
suggestion would be useful for fast and effectiv triage of asymptomatic
patients and the implementation of stricter isolation for children of
any age from 0 to 14 years. Asymptomatic covid19 children (carriers of
SARS-CoV-2) stay at home and do not cough, haven’t a fever, shortness of
breath, difficulty breathing, or other characteristic symptoms and signs
but there is a characteristic relationship between their the basic
hematological and biochemical changes. The suspicion on asymptomatic
covid19 children (carriers of SARS-CoV-2) may be, presumably, based on
the factors which implies hematological changes in the complete blood
count (monocytosis, lymphocytosis, eosinophilia, the fall of erithrocyte
indices-MCH and MCV) and a rapid and strong increase in serum LDH value.
The practical applicability of the lymphocyte-to-monocyte ratio (more
than 2) with normal or increased leukocytes for fast and cheap
identification (finger prick) of asymptomatic covid19 children needs to
be considered in the future, as and for simple distinguishing from H1N1
influenza-like illness.