ArticlePDF Available


| a rchiv eu romed ica |  | ol.  | num.  |
erYtHroCYtes as a tarGet
oF sars CoV-2 in PatHoGenesis
oF CoVid-19
abstraCt — e paper considers the possible mechanism
of the pathogenesis of COVID-19 caused by SARS-
COV-2, associated with damage to red blood cells, which
the authors attribute to the main key target that triggers a
cascade of reactions leading to multiple organ failure. e
paper presents morphological evidence for the presence
of pathological forms of erythrocytes characteristic of
various anemias in the blood vessels and parenchyma of
damaged lungs of patients with COVID-19. e death
of red blood cells leads to cell ischemia and anemia. e
defeat of brain neurons, blood vessels and hematotissue
barriers in organ systems is a consequence of ischemia
due to the impossibility of transferring hemoglobin by
damaged erythrocytes and ends at the terminal stages of
the development of the disease with their dysfunction.
Adaptive erythropoiesis with an increase in erythropoietin
secretion is especially dangerous for patients suering from
hypertension, and then it is impossible, since all organs
involved in the synthesis of erythropoietin are damaged. In
this case, the synthesis of hemoglobin is also disrupted due
to a deciency of iron and cyancobolamin, whereas toxic
iron and hemosiderin are deposited in the tissues.
KEywords — COVID-19, SARS-COV-2, erythrocytes,
hemoglobin, erythropoiesis, viruses, pathogenesis of
Ivan Reva1 , Tatsuo Yamamoto1 ,
Mariya Rasskazova2, Tatyana Lemeshko3,
Victor Usov2 , Yuriy Krasnikov2, Anna Fisenko3,
Evgeniy Kotsyurbiy3, Vladislav Tudakov3,
Ekaterina Tsegolnik3, Olesya Oleksenko3,
Anatoly Korobkin2, Ellada Slabenko2,
Anastasiya Shindina2, Kseniya Gordzievskaya2,
Anna Furgal2, Galina Reva1,2 ,
1 International Medical Research Center, Niigata, Japan,
2 Far Eastern federal university, Vladivostok;
3 Pacic State Medical University, Vladivostok, Russia
r e l e V a n C e
In the world, the number of cases of COVID-19
has reached 16.4 million. e number of coronavirus
victims worldwide exceeds 600 thousand, including
children [1, 5, 16]. Madabhavi I., Sarkar M., Kadakol
N. (2020) identied the pandemic as a catastrophe
Received 01 July 2020;
Received in revised form 05 August 2020;
Accepted 07 August 2020
Editor’s ChoiCE
of global signicance [6], which indicates the high
urgency of the problem under study [9, 12, 21]. It is
generally accepted that viruses multiply in the cell,
specializing in certain cell types: HIV infects -
lymphocytes, the inuenza virus infects the epithe-
lium of the larynx and lungs, coronavirus destroys
the epithelium of the upper respiratory tract, lungs
and gastrointestinal tract, herpes aects the nerves
and causes neuroinfections, hepatitis viruses infect
liver cells, etc. [17, 20]. With COVID-19 caused by
SARS-COV-2, multiple organ disorders occur in
various structures, including nerve structures [3, 14].
Burness A. T. and Pardoe I. U. (1981) established the
possibility of attachment of the inuenza virus to
human erythrocytes, followed by hemagglutination of
the cells [4]. Allaway G.P., Burness A.T. (1986) showed
that the main type of glycophorins, glycophorin A, is a
receptor for the attachment of inuenza and encepha-
lomyocarditis (EMS) viruses to human erythrocytes
[2, 4]. e attachment of the EMS virus to glycoph-
orin A includes a region containing amino acids 35 to
about 70 (numbered from the end of NH2), four of
which (amino acids 37, 44, 47 and 50) are glycosylated.
In addition, there is evidence that segments contain-
ing amino acids 35 to 39 with an oligosaccharide side
chain on threonine-37 are particularly important for
the attachment of EMS virus. However, in the avail-
able scientic literature against the background of the
available pathomorphological data on the destruction
of lung tissue, death of alveolocytes, brotic changes
in the lungs, there is no assessment of erythrocytes
located both in the lumen of blood vessels and released
into the parenchyma of aected organs [5, 19, 24].
Given the multiple organ failure that develops in
COVID-19 [7, 18], the absence of a key morphologi-
cal target for SARS-COV-2 [8], as well as controver-
sial data on the nature of the virus itself, we directed
our research to study changes in the red blood cell
pool against the background of COVID-19. Accord-
ing to Rodríguez-Nóvoa S., Morello J., González M.,
et al (2008), the use of antiviral drugs causes hemolysis
and increases hyperbilirubinemia [13]. According to
them, treatment of HIV/hepatitis-C infected patients
led to an increase in hyperbilirubinemia from 9% to
45% aer starting treatment for hepatitis C. Anemia
has a multifactorial nature [10, 15], which explains the
6| a rchiv eu romed ica |  | ol.  | num.  |Editor’s ChoiCE
cases of unsuccessful attempts to empirically use eryth-
ropoietin in the treatment of patients with hepatitis C
and HIV-infected [11]. All this dictates an expansion
of the range of measures aimed at studying the etiology
and pathogenesis of COVID-19 for the development
of pathogenetically justied prevention and treatment
that is absent at the present stage [22, 23].
Purpose of the study:
To study the role of red blood cells in the patho-
genesis of COVID-19.
m at e r ia l an d m et H o d s
e paper analyzes and discusses the results of
our own studies of lung biopsies of 11 patients who
died from COVID-19 caused by SARS-CoV-2, with
PCR conrmation, obtained in accordance with the
order of the Ministry of Healthcare of the Russian
Federation dated 04.29.94 N 82 On the procedure for
conducting pathological autopsies, which regulates the
procedure for autopsies in medical institutions. e
control group consisted of 14 patients who died as a
result of injuries incompatible with life, presumably
without somatic pathology at the age of 24 to 76
years. e biopsy specimens were xed immediately
aer collection in accordance with the preparation
protocol for histological examination. e exclusion
of possible artifacts is based on data obtained during
a special study on dogs, indicating that when corpses
are stored at a temperature of 4–7° C for 4–6 hours,
microscopically visible changes in the morphology
of various organ systems are not observed, except for
a slight decrease in the intensity of specic reactions
on enzymatic activity. We used classical histological
research methods with hematoxylin-eosin staining to
obtain a general morphological picture.
e material was analyzed using an Olympus-
Bx82 microscope and a CDx82 digital camera with
proprietary soware. e morphological method of
the study consisted in the preparation of sections from
paran blocks of lung biopsies from SARS-CoV-2
victims, followed by staining with hematoxylin and
eosin in accordance with the classical protocol. Analy-
sis of preparations and production of illustrations were
carried out using an Olympus Bx52 microscope and a
DP25 digital camera.
r e s ult s o F ou r o wn r e se a r C H
We have found that erythrocytes are one of the
targets damaged by SARS-COV-2. Anisocytosis and
poikilocytosis of erythrocytes are noted, macrophages
with hemosiderin, hypochromic and hyperchromic
erythrocytes are identied. Erythrocytes in the form
of a sickle are identied (in Fig. 1 it is indicated by an
arrow), as well as spherocytes, macro and microcytes.
e appearance of sickle erythrocytes may be as-
sociated with disturbances in the B-chains of globin
and the replacement of glutamine with valine. e
solubility of such globin decreases 25 times, depending
on the partial pressure of oxygen in the blood and the
concentration of HbS in the erythrocyte. e distribu-
tion of hemoglobin in the cytoplasm of erythrocytes is
uneven, bright oxyphilia is observed both in the center
of erythrocytes and in the periphery. ickening of
the erythrocyte membrane, chromophobic courtyard
around the red blood cells. Kebot's rings are identied,
staining red. Kebot's rings are characteristic and are
found mainly in megaloblastic anemia and metal in-
toxication (Pb). Under COVI-19 conditions, this toxic
eect is exerted by the hemoglobin of dying erythro-
cytes, transferrin and iron, as well as hemosiderin. We
have established that Howell-Jolly bodies are identied
on lung preparations, which are small round violet-red
inclusions 1–2 microns in size, less oen found in 2–3
in one erythrocyte. It is known that Howell-Jolly bod-
ies are the remainder of the erythrocyte nucleus aer
removal of its RES. Revealed more oen with intense
hemolysis and with megaloblastic anemia (Fig. 1).
Some of the erythrocytes have a swollen mem-
brane at one of the poles with the formation of a vacu-
ole (Figure 1, indicated by blue arrows). In addition, all
degenerative forms of erythrocytes with a characteris-
tic location of hemoglobin are observed: hypochromic
with a hole, ring, and also in the form of shadows,
indicating iron deciency and B12 anemia; hyperchro-
mic with an arrangement of hemoglobin in the form of
a ring with and without enlightenment (Fig. 2).
is explains the severity of clinical manifesta-
tions when the gastrointestinal tract is involved in
the pathological process, since the participation of
cyancobolamine in the normalization of erythropoi-
esis is inhibited. e presence of spherocytes in the
lung parenchyma and in the lumen of blood vessels
indicates hyperhydration of the erythrocyte, increased
permeability of the erythrocyte membrane for Na+
and Ca2+ ions, followed by the acquisition of spheri-
cal erythrocytes with the inability to plasticity and
deformation in the microvasculature, with a decrease
in life expectancy. It is known that with such changes,
the developing membranopathy is mainly due to a
signicant change in the content of the spectrin pro-
tein, a violation of its binding to other proteins of the
erythrocyte membrane. Since glycolysis is the leading
pathway for ATP resynthesis in erythrocytes, a lack of
ATP energy causes a violation of the transmembrane
transfer of ions, a decrease in the activity of enzymes
of the pentose phosphate cycle. eir imbalance
develops, leading to overhydration and swelling of
| a rchiv eu romed ica |  | ol.  | num.  |
Editor’s ChoiCE
erythrocytes. In addition, we noted the distribution
of hemoglobin at opposite poles of cells or at one of
the poles, typical for erythrocytes located both in the
lumen of blood vessels and in the parenchyma of the
lung. Also, cell nuclei are identied, the morphology
of which is characteristic of those damaged by viruses,
has a ring-shaped shape, or inclusions (Fig. 3).
Damage to erythrocytes does not have the
character of artifacts resulting from non-technological
implementation of methods in violation of the recom-
mended protocol, as evidenced by the presence of nor-
mocytes, as well as a clear morphology of macrophages
and other cells containing hemosiderin, a product of
erythrocyte destruction (Fig. 4).
In addition, hemosiderin is contained not only in
the cytolasm of macrophages, but also in the lumen of
blood vessels (Fig. 5, 6).
e presence of macrophages with hemosiderin
in the cytoplasm, as well as free hemosiderin in the
lumen of blood vessels, indicate that the death of
erythrocytes begins not in the lung parenchyma, but
at the stage of circulation and oxygen delivery to the
tissues. e consequence of this is the generalization
of the pathological process, leading to multiple organ
failure. us, for the causative agent of COVID-19
SARS COV-2 in starting the cascade of pathogenesis,
one of the main targets is the erythrocyte, in which
membranopathy, fermentopathy and hemoglobinopa-
thy are clearly manifested. Adaptive erythrocytosis,
an increase in the number of reticulocytes and arterial
hypertension are accompanied by a decrease in blood
plasma volume when the body loses uid as a result of
diarrhea, vomiting, and plasmorrhage. In our observa-
tions, 3 out of 11 patients developed anemia with a
Fig. 1. Lung parenchyma of patients a) 53 years old; b) 74 years old with COVID-19. Staining with hematoxylin and eosin. Microphoto, ×400.
Howell-Jolly bodies are identied (indicated by black arrows)
Fig. 2. Lung parenchyma of patients a) 56 years old; b) 64 years old with COVID-19. Staining with hematoxylin and eosin. Microphoto, ×400. Sphero-
cytes, microcytes, hypo- and hyperchromic erythrocytes are identied
8| a rchiv eu romed ica |  | ol.  | num.  |
Fig. 3. Lung parenchyma of patients a) 39 years old; b) 56 years old; c) 64 years old; d) 71 years old with COVID-19. Staining with hematoxylin and eosin.
Microphoto, ×400. Spherocytes, microcytes, hypo- and hyperchromic erythrocytes are identied. The uneven distribution of hemoglobin at the poles of
eryrocytes is indicated by blue arrows, and the nuclei of cells aected by viral RNA are indicated by green arrows
Fig. 4. Lung parenchyma of patients a) 51 years old; b) 56 years old with COVID-19. Staining with hematoxylin and eosin. Microphoto
Editor’s ChoiCE
| a rchiv eu romed ica |  | ol.  | num.  |
Fig. 5. Lung parenchyma of patients a) 51 years old; b) 56 years old; c)
64 years old; d, e) 74 years old with COVID-19. Staining with hematoxylin
and eosin. Microphoto, ×400. Macrophages with hemosiderin granules
in cytolasm are identied against the background of degenerative forms
of erythrocytes
decrease in Hb and erythrocyte count to 2.12  1012/L.
It is these facts that explain the multiple organ struc-
tural disorders in the human body, as well as the death
of the air-blood barrier structures, which results in the
uselessness of resuscitation measures with the help of
mechanical ventilation devices (IVL) against the back-
ground of defective, with a shortened life cycle, dying
or missing oxygen carriers.
C o n C l u s i o n
Hemolytic anemia in COVID-19, which devel-
ops at the rst stage as a reaction to the SARS COV-2
viral microorganisms, causes cascading reactions to
toxic erythropoietin and hemoglobin released from
erythrocytes in the bloodstream, and then to hemosi-
derin released due to the death of erythrocytes in the
tissue. e process ends with a decrease in the synthe-
sis of erythropoietin in the decaying liver and kidneys,
in the absence of the necessary vitamin B12 due to the
pathology of its secretion in the gastrointestinal tract.
e characteristic signs of damage to red blood cells
in conditions of infection with COVID-19 indicate
Editor’s ChoiCE
10 | a rchiv eu romed ica |  | ol.  | num.  |
Fig. 6. Lung parenchyma of patients a) 64 years old; b) 71 years old with COVID-19. Staining with hematoxylin and eosin. Microphoto, ×400. (Green
arrow indicates sickle-shaped erythrocyte. Orange arrows indicate viral inclusions in cell nuclei)
disruption of erythropoiesis, with developing iron
deciency and B12 anemia. e synthesis of hemo-
globin lags behind the dierentiation of erythrocytes,
which in the initial period of the disease induces an
increase in the secretion of erythropoietin, which has a
hypertensive eect; increases blood viscosity and leads
to impaired blood microcirculation, which is why
patients with essential hypertension are the main risk
group. is underlies the inability to use erythropoi-
etin-based drugs to treat patients with anemia in the
context of COVID-19 infection. Pathological changes
in erythrocytes infected with viruses are caused by
specic and non-specic processes. Reactions caused
by the conguration of the permeability of the plasma
membrane of erythrocytes, margination of chromatin
in the form of Howell-Jolly bodies, and vacuolization
of the cytoplasm are nonspecic. SARS COV-2, like
SV40, can be attributed to vacuolizing viruses, but only
erythrocytes, since the virus has a particularly peculiar
and pronounced character of inducing vacuolization.
Specic changes are oxyphilic viral inclusions in cell
nuclei, leading to cell destruction through a rapid and
deep eect on the synthesis of cellular proteins.
C o n C l u s i o n s
1. e key target for SARS COV-2 is erythrocytes.
2. Multiorgan failure is the result and consequence
of SARS COV-2 virus damage to erythrocytes,
which develops against this background of
ischemia and anemia with cell death of various
organ systems.
3. e use of erythrocyte mass for the treatment of
COVID-19 is pathogenetically substantiated.
e study was carried out within the amework of
the state assignment 17.5740.2017 / 6.7, the international
Russian-Japanese grant of the FEFU (agreement No. 13-
09-0602-m_a dated 06.11.2013) and the execution of the
grant om the Russian Science Foundation 19-14-00260
r e F e r e n C e s
1. Ahn D.G., Shin H.J., Kim M.H., Lee S., Kim H.S.,
Myoung J., Kim B.T., Kim S.J. Current Status of
Epidemiology, Diagnosis, erapeutics, and Vaccines
for Novel Coronavirus Disease 2019 (COVID-19).//J
Microbiol Biotechnol. 2020 Mar 28;30(3):313–324.
doi: 10.4014/jmb.2003.03011.
2. Allaway G.P., Burness A.T.J Site of attachment
of encephalomyocarditis virus on human erythro-
cytes.//Virol. 1986 Sep;59(3):768–70. doi: 10.1128/
3. Buja L.M., Wolf D.A., Zhao B., Akkanti B.,
McDonald M., Lelenwa L., Reilly N., Ot-
taviani G., Elghetany M.T., Trujillo D.O.,
Aisenberg G.M., Madjid M., Kar B. e emerg-
ing spectrum of cardiopulmonary pathology of the
coronavirus disease 2019 (COVID-19): Report of 3
autopsies from Houston, Texas, and review of autopsy
ndings from other United States cities.//Cardiovasc
Pathol. 2020 Sep-Oct;48:107233. doi: 10.1016/j.
4. Burness A. T., Pardoe I. U. Eect of enzymes
on the attachment of inuenza and encephalomyo-
carditis viruses to erythrocytes.// J Gen Virol. 1981
Aug;55(Pt 2): 275–88. doi: 10.1099/0022-1317-55-2-
275. DOI: 10.1099/0022-1317-55-2-275
5. Jiang F., Deng L., Zhang L., Cai Y., Cheung
C.W., Xia Z. Review of the Clinical Characteristics of
Coronavirus Disease 2019 (COVID-19).Version 2.//
J. Gen Intern Med. 2020 May;35(5):1545–1549. doi:
6. Joob B, Wiwanitkit V. Pulmonary Pathology of
Early Phase 2019 Novel Coronavirus Pneumonia.//J.
Editor’s ChoiCE
| a rchiv eu romed ica |  | ol.  | num.  |
orac Oncol. 2020 May;15(5):e67. doi: 10.1016/j.
jtho.2020.03.013.PMID: 32340677
7. Kannan S., Shaik Syed Ali P., Sheeza A.,
Hemalatha K. COVID-19 (Novel Coronavirus
2019) – recent trends. //Eur Rev Med Pharmacol
Sci. 2020 Feb;24(4):2006–2011. doi: 10.26355/eur-
8. Li Y.C., Bai W.Z., Hashikawa T. J. e neuroin-
vasive potential of SARS-CoV2 may play a role in the
respiratory failure of COVID-19 patients.//Med Vi-
rol. 2020 Jun;92(6):552–555. doi: 10.1002/jmv.25728.
9. Madabhavi I., Sarkar M., Kadakol N.
COVID-19: a review.//Monaldi Arch Chest Dis.
2020 May 14;90(2). doi: 10.4081/monaldi.2020.1298.
10. Ochoa D., Redondo T., Moreno-Rueda G.
Mizutama: A uick, Easy, and Accurate Method for
Counting Erythrocytes.//Physiol Biochem Zool. 2019
Mar/Apr;92(2):206–210. doi: 10.1086/702666.
11. Reva I.V., Reva G.V., Yamamoto T.T., Ole-
ksenko O.M., Rasskazova M.E., Reva G.V.,
Oleksenko O.M., Rasskazova M.E., Reva I V.V.,
Reva G.V., Yamamoto T.T., Gulkov A.N., Ole-
ksenko O.M., Rasskazova M.E., Danilenko
M.V., Vershinina S.S., Shmelev M.E., Tyasto
V.A. e role of ischemia in the pathogenesis of
hepatitis c complicated by glomerulonephritis and
carcinogenesis // Modern problems of science and
education. – 2015. – No. 5; URL: http://science-edu-; DOI: 10.17513/
12. Rico-Mesa J.S., White A., Anderson A.S.
Outcomes in Patients with COVID-19 Infection
Taking ACEI/ARB.//Curr Cardiol Rep. 2020 Apr
14;22(5):31. doi: 10.1007/s11886-020-01291-4.
13. Rodríguez-Nóvoa, S., Morello, J., González,
M., Vispo, E., Barreiro, P., González-Pardo,
G., Jiménez-Nácher, I., Gonzalez-Lahoz, J.,
Soriano, V. Increase in serum bilirubin in HIV/
hepatitis-C virus-coinfected patients on atazanavir
therapy following initiation of pegylated-interferon
and ribavirin.//AIDS. 2008 Nov 30;22(18):2535–7.
doi: 10.1097/QAD.0b013e3283177f38.
14. Shanmugaraj B., Siriwattananon K.,
Wangkanont K., Phoolcharoen W. Perspec-
tives on monoclonal antibody therapy as potential
therapeutic intervention for Coronavirus disease-19
(COVID-19).//Аsian Pac J Allergy Immunol. 2020
Mar;38(1):10–18. doi: 10.12932/AP-200220-0773.
15. Shaz B.H. Red blood cells: beyond the transfusion.//
Blood. 2019 Jun 20;133(25):2627–2628. doi: 10.1182/
16. She J, Liu L, Liu W. COVID-19 epidemic: Dis-
ease characteristics in children.//J Med Virol. 2020
Jul;92(7):747–754. doi: 10.1002/jmv.25807.
17. Sun P., Lu X., Xu C., Sun W., Pan B. Understand-
ing of COVID-19 based on current evidence.//J
Med Virol. 2020 Jun;92(6):548–551. doi: 10.1002/
18. Tian S., Hu W., Niu L., Liu H., Xu H., Xiao
S.Y. Pulmonary Pathology of Early-Phase 2019
Novel Coronavirus (COVID-19) Pneumonia in Two
Patients With Lung Cancer.//J. orac Oncol. 2020
May;15(5):700–704. doi: 10.1016/j.jtho.2020.02.010.
19. Tian S., Xiao S.Y. Pathology of 2019 Novel Coro-
navirus Pneumonia: A Dynamic Disease Process.//J.
orac Oncol. 2020 May;15(5):e67–e68. doi:
20. Wajcman H., Kiger L.C. R. Hemoglobin, from
microorganisms to man: a single structural motif, mul-
tiple functions// Biol. 2002 Dec;325(12):1159–74.
doi: 10.1016/s1631-0691(02)01537-8.
21. Wang Y., Wang Y., Chen Y., Qin Q. Unique
epidemiological and clinical features of the emerging
2019 novel coronavirus pneumonia (COVID-19)
implicate special control measures./J Med Virol. 2020
Jun;92(6):568–576. doi: 10.1002/jmv.25748.
22. Wu Y., Xu X., Chen Z., Duan J., Hashimoto K.,
Yang L., Liu C., Yang C. Nervous system involvement
aer infection with COVID-19 and other coronavi-
ruses.//Brain Behav Immun. 2020 Jul;87:18–22. doi:
23. Yang L., Tian D., Liu W. Strategies for vaccine de-
velopment of COVID-19.//Sheng Wu Gong Cheng
Xue Bao. 2020 Apr 25;36(4):593–604. doi: 10.13345/j.
24. Zhang L, Jiang Y, Wei M, Cheng BH, Zhou
XC, Li J, Tian JH, Dong L, Hu RH. Analysis of
the pregnancy outcomes in pregnant women with
COVID-19 in Hubei Province.//Zhonghua Fu Chan
Ke Za Zhi. 2020 Mar 25;55(3):166–171. doi: 10.3760/
Editor’s ChoiCE
... 7-KCh exerts a toxic effect and induces cell damage [16]. Because of these different toxic activities, 7-KCh has been suggested to contribute to the pathogenesis of COVID-19 [22]. ...
... The characterized analytes were quantitatively determined since these metabolites have been reported as erythrocytic pathogenic biomarkers released due to their harmful impact on biological cells [10,21,25,38]. The summary of the results we obtained is consistent with the report published by Reva et al. [22]. The virus causing COVID-19 has been reported to target human red blood cells for replication and cause cell damage. ...
Full-text available
Background Due to the high risk of COVID-19 patients developing thrombosis in the circulating blood, atherosclerosis, and myocardial infarction, it is necessary to study the lipidome of erythrocytes. Specifically, we examined the pathogenic oxysterols and acylcarnitines in the erythrocyte homogenate of COVID-19 patients. These molecules can damage cells and contribute to the development of these diseases. Methods This study included 30 patients and 30 healthy volunteers. The erythrocyte homogenate extract was analyzed using linear ion trap mass spectrometry combined with high-performance liquid chromatography. The concentrations of oxysterols and acylcarnitines in erythrocyte homogenates of healthy individuals and COVID-19 patients were measured. Elevated levels of toxic biomarkers in red blood cells could initiate oxidative stress, leading to a process known as Eryptosis. Results In COVID-19 patients, the levels of five oxysterols and six acylcarnitines in erythrocyte homogenates were significantly higher than those in healthy individuals, with a p-value of less than 0.05. The mean total concentration of oxysterols in the red blood cells of COVID-19 patients was 23.36 ± 13.47 μg/mL, while in healthy volunteers, the mean total concentration was 4.92 ± 1.61 μg/mL. The 7-ketocholesterol and 4-cholestenone levels were five and ten times higher, respectively, in COVID-19 patients than in healthy individuals. The concentration of acylcarnitines in the red blood cell homogenate of COVID-19 patients was 2 to 4 times higher than that of healthy volunteers on average. This finding suggests that these toxic biomarkers may cause the red blood cell death seen in COVID-19 patients. Conclusions The abnormally high levels of oxysterols and acylcarnitines found in the erythrocytes of COVID-19 patients were associated with the severity of the cases, complications, and the substantial risk of thrombosis. The concentration of oxysterols in the erythrocyte homogenate could serve as a diagnostic biomarker for COVID-19 case severity. Graphical abstract
... Наиболее важные механизмы развития полиорганной дисфункции при COVID-19 об-условлены, как прямым, так и косвенным воздействием вируса SARS-CoV-2 на клетки и ткани макроорганизма. Один из возможных механизмов запуска каскада реакций, ведущих к полиорганной недостаточности, рассматривается через повреждение эритроцитов [22]. Изменение структуры мембраны и метаболизма эритроцитов при различных патологических состояниях, проявляется нарастанием полиморфизма клеток в популяции и появлением трансформированных Клетки крови после COVID- 19 Blood cells after COVID-19 2022, Vol. 24, 4 2022 форм [4]. ...
... На эритроциты приходится до 98% объема клеточной популяции в кровяном русле [3], поэтому любые изменения морфологии этих клеток ведут к нарушениям реологии крови. Доказанным является факт накопления в крови пациентов с COVID-19 патологических форм эритроцитов (эхиноциты, сфероциты, овалоциты, шизоциты, акантоциты, дрепаноциты) [22]. Так, у пациентов с анемией на фоне тяжелого течения COVID-19, в 70% случаев в крови регистрировали трансформированные формы эритроцитов [12], образование которых было обусловлено структурными повреждениями мембраны эритроцитов [14]. ...
Full-text available
Complexity and multifactorial nature of potential pathogenic consequences of SARS-CoV-2 infection in human body, discovery of new virus-induced mechanisms triggering a cascade of pathological responses in the cells of host organism leading to development of multiple organ failure elicited increasing interest in morpho-functional state of blood cells in reconvalescent persons after COVID-19 infection. The aim of the present work is to characterize morphofunctional pattern of blood cells at different periods of recovery, depending on the severity of COVID-19. We examined 55 convalescents after bearing COVID-19 infection: Group I included the convalescents 30 days after the disease (n = 39); Group II consisted of the persons 60 days after recovery (n = 16); Group III included clinically healthy volunteers with no history of clinical SARS-CoV-2 infection (n = 11). The cells were examined by means of Olympus CX41 microscope (Olympus, Japan), and VZ-C31S digital videocamera (VideoZavr, Russia) using the VideoZavr software (version 1.5). Assessment of neutrophil populations in the whole blood samples was performed with BD Accuri C6 Plus flow cytometer (USA) with automatic differentiation of cells between lymphocytes and monocytes, according to the degree of granularity. Cytokine production was determined using commercial kits for detection of IFNγ, TNFα, IL-4, IL-8, IL-10 (JSC Vector-Best, Russia), IL-17A (eBioscience, Austria) was assayed with automatic enzyme immunoassay analyzer “LAZURIT” (Dynex Technologies, USA). Among the convalescents who suffered the moderate-degree COVID-19 (45.5% and 50% of cases, respectively) on days +30 and +60 after clinical recovery, a significantly increased ratio of morphologically altered forms of erythrocytes (echinocytes, ovalocytes, dacryocytes, codocytes) was noted as compared with group III (p = 0.00001 and p = 0.001, respectively). Regardless of clinical severity of the disease; a mean of 40.6% convalescents from groups I and II had moderate disturbances in the neutrophil morphology (cytoplasmic vacuolization, chromatin decondensation at the pre-netosis stage, transformation of cells by the netosis type), and, in 27.4% of cases, the areas of neutrophilplatelet aggregation were seen. In blood supernates from recovered patients, we have revealed a significantly decreased content of IFNγ (P = 0.02), TNFα (p = 0.03), IL-10 (p = 0.04) and IL-17A (p = 0.02). The revealed morphological and functional changes in blood cells in the persons who underwent COVID-19 infection suggest long-term maintenance of toxic damage to erythrocytes, neutrophils and lymphocytes over the recovery period. The effects of the detected morphological and functional disorders of blood cells following COVID-19 recovery leading to increase in blood viscosity and microcirculation, formation of neutrophil-platelet aggregates, may cause higher risks of thrombotic complications at the long-range period as well as decreased levels of regulatory cytokines, thus confirming slow recovery of the lymphocyte populations (Th1, Th2, Th17) of the immune system.
... Another finding of our study is the increased standard deviation of brightness in RBCs after SARS-CoV-2 infection. As this parameter reflects structural changes within the cells, it may be the result of various implications of SARS-CoV-2 on RBCs such as direct infection of RBCs or changes in hemoglobin 11,39,54,56 . ...
Full-text available
Severe coronavirus disease 2019 (COVID-19) is associated with hyperinflammation, hypercoagulability and hypoxia. Red blood cells (RBCs) play a key role in microcirculation and hypoxemia and are therefore of special interest in COVID-19 pathophysiology. While this novel disease has claimed the lives of many older patients, it often goes unnoticed or with mild symptoms in children. This study aimed to investigate morphological and mechanical characteristics of RBCs after SARS-CoV-2 infection in children and adolescents by real-time deformability-cytometry (RT-DC), to investigate the relationship between alterations of RBCs and clinical course of COVID-19. Full blood of 121 students from secondary schools in Saxony, Germany, was analyzed. SARS-CoV-2-serostatus was acquired at the same time. Median RBC deformation was significantly increased in SARS-CoV-2-seropositive compared to seronegative children and adolescents, but no difference could be detected when the infection dated back more than 6 months. Median RBC area was the same in seropositive and seronegative adolescents. Our findings of increased median RBC deformation in SARS-CoV-2 seropositive children and adolescents until 6 months post COVID-19 could potentially serve as a progression parameter in the clinical course of the disease with an increased RBC deformation pointing towards a mild course of COVID-19.
... Thus, assessment of the biochemical diversity of RBCs in patients of different age groups, inevitably leading to different levels of adaptive response to hypoxic conditions [163,164], is useful for predicting the severity of COVID-19 and selecting individual therapies. Moreover, there is a need to identify potential reasons for inconsistent experimental results and the existing opposing views about the role of RBCs in disrupting convective oxygen transport in SARS-CoV-2 infection [20,40,165], associated not only with the patient's age but also with the use of nonunified experimental design that does not permit the researcher to consider a myriad of variables affecting the results. ...
Full-text available
Coronavirus disease 2019 (COVID-19) is a rapidly spreading acute respiratory infection caused by SARS-CoV-2. The pathogenesis of the disease remains unclear. Recently, several hypotheses have emerged to explain the mechanism of interaction between SARS-CoV-2 and erythrocytes, and its negative effect on the oxygen-transport function that depends on erythrocyte metabolism, which is responsible for hemoglobin-oxygen affinity (Hb-O2 affinity). In clinical settings, the modulators of the Hb-O2 affinity are not currently measured to assess tissue oxygenation, thereby providing inadequate evaluation of erythrocyte dysfunction in the integrated oxygen-transport system. To discover more about hypoxemia/hypoxia in COVID-19 patients, this review highlights the need for further investigation of the relationship between biochemical aberrations in erythrocytes and oxygen-transport efficiency. Furthermore, patients with severe COVID-19 experience symptoms similar to Alzheimer’s, suggesting that their brains have been altered in ways that increase the likelihood of Alzheimer’s. Mindful of the partly assessed role of structural, metabolic abnormalities that underlie erythrocyte dysfunction in the pathophysiology of Alzheimer’s disease (AD), we further summarize the available data showing that COVID-19 neurocognitive impairments most probably share similar patterns with known mechanisms of brain dysfunctions in AD. Identification of parameters responsible for erythrocyte function that vary under SARS-CoV-2 may contribute to the search for additional components of progressive and irreversible failure in the integrated oxygen-transport system leading to tissue hypoperfusion. This is particularly relevant for the older generation who experience age-related disorders of erythrocyte metabolism and are prone to AD, and provide an opportunity for new personalized therapies to control this deadly infection.
... A possible limitation of this study is that experiments with red blood cells were carried out using 2D in vitro cultures, with blood obtained from healthy donors and not with COVID-19 patients. This could be important since damage and clumps of red blood cells in blood vessels have been reported in COVID-19 patient biopsies (32,33). In addition, complement activation products and S protein binding have been detected in the erythrocyte membrane COVID-19 patients (34). ...
Full-text available
The co-occurrence and the similarities between malaria and COVID-19 diseases raise the question of whether SARS-CoV-2 is capable of infecting red blood cells and, if so, whether these cells represent a competent niche for the virus. In this study, we first tested whether CD147 functions as an alternative receptor of SARS-CoV-2 to infect host cells. Our results show that transient expression of ACE2 but not CD147 in HEK293T allows SARS-CoV-2 pseudoviruses entry and infection. Secondly, using a SARS-CoV-2 wild type virus isolate we tested whether the new coronavirus could bind and enter erythrocytes. Here, we report that 10,94% of red blood cells had SARS-CoV-2 bound to the membrane or inside the cell. Finally, we hypothesized that the presence of the malaria parasite, Plasmodium falciparum , could make erythrocytes more vulnerable to SARS-CoV-2 infection due to red blood cell membrane remodelling. However, we found a low coinfection rate (9,13%), suggesting that P. falciparum would not facilitate the entry of SARS-CoV-2 virus into malaria-infected erythrocytes. Besides, the presence of SARS-CoV-2 in a P. falciparum blood culture did not affect the survival or growth rate of the malaria parasite. Our results are significant because they do not support the role of CD147 in SARS-CoV-2 infection, and indicate, that mature erythrocytes would not be an important reservoir for the virus in our body, although they can be transiently infected.
... The summary of the results we obtained is consistent with the report published by Reva et al. It has been described that COVID-19 virus considered the human erythrocytes as a preferred target's host for multiplication and cell damage [47]. Table 1 shows the calibration parameters of the assayed targeted analytes. ...
Full-text available
Background: Due to the high risk of COVID-19 patients to the formation of thrombosis in the circulating blood, atherosclerosis, and myocardial infarction, it was necessary to study the lipidomic of the erythrocytes. The aim of this work was to analyze the pathogenic oxysterols and acylcarnitines in the erythrocyte’s homogenate of COVID-19 patients and to estimate the case severity from the level of oxysterols. Methods: A linear ion trap mass spectrometry coupled with high-performance liquid chromatography was used to investigate the extract of erythrocytes homogenate. The toxic biomarkers that primarily induce the generation of dead red blood cells, were characterized, and quantified in the erythrocytes of COVID-19 patients and matched with healthy volunteers. Results: A total of 30 patients and 30 healthy volunteers were enrolled. The concentration of five oxysterols and six acylcarnitines in the erythrocyte’s homogenate of COVID-19 patients was significantly upregulated matching with healthy subjects at p <0.05. The average total concentration of oxysterols was 23.36 ± 13.47 μg/mL in the erythrocytes of COVID-19 patients, while samples of healthy volunteers showed a total concentration of 4.92 ± 1.61 μg/mL. The average concentration level of 7-ketocholesterol and 4-cholestenone in the COVID-19 patients was higher by five and ten-fold compared to the healthy subjects. Also, the average concentration of acylcarnitines in the erythrocyte's homogenate of COVID-19 patients was high by 2-to-4-fold in comparison with the healthy volunteers. Conclusions: The abnormally high levels of oxysterols and acylcarnitines found in the erythrocytes of COVID-19 patients were associated with the severity of the case's complications and substantial risk of thrombosis. The concentration of oxysterols in the erythrocyte homogenate could be useful as a diagnostic biomarker to stand on the COVID-19 case severity.
... Many patients show reduced blood oxygen levels that some experts describe as "incompatible with life", while lung scans show little to no abnormalities and patients do not display symptoms of shortness of breath or difficulty breathing 44 . Virus-induced changes in hematopoiesis, altered turnover of erythrocytes, and the presence of malfunctioning erythrocytes in the lungs may contribute to silent hypoxia and could be the key players in determining the severity of COVID illness 45,46 . Analysis of early events of SARS-CoV-2 infection in cotton rats suggests that SARS-CoV-2 infection may cause BM hyperplasia that is accompanied by a reduced proportion of erythroid cells in the BM of facial bones. ...
Full-text available
Heterogeneity of COVID-19 manifestations in human population is vast, for reasons unknown. Cotton rats are a clinically relevant small animal model of human respiratory viral infections. Here, we demonstrate for the first time that SARS-CoV-2 infection in cotton rats affects multiple organs and systems, targeting species- and age-specific biological processes. Infection of S. fulviventer, which developed a neutralizing antibody response and were more susceptible to SARS-CoV-2 replication in the upper respiratory tract, was accompanied by hyperplasia of lacrimal drainage-associated lymphoid tissue (LDALT), a first known report of mucosa-associated lymphoid tissue activation at the portal of SARS-CoV-2 entry. Although less permissive to viral replication, S. hispidus showed hyperplasia of bone marrow in the facial bones and increased pulmonary thrombosis in aged males. Augmentation of these features by SARS-CoV-2 infection suggests a virus-induced breach in regulatory mechanisms which could be devastating for people of all ages with underlying conditions and in particular for elderly with a multitude of ongoing disorders.
... It has been reported that, compared to moderate cases, severe COVID-19 cases had lower red blood cell counts and hemoglobin levels [47]. It has also been stated that COVID-19 is associated to red blood cell (RBC) damage and that the virus negatively affects the process of RBC formation; thus, being responsible for multiple organ damage [48]. Indeed, the statistical analysis showed that, in the cohort of study, the percentage of patients with under range values of erythrocytes max was 45.2% (23.9%) in deceased (alive) patients and 41.1% (26.2%) in patients admitted (not admitted) to the ICU [49]. ...
Full-text available
The coronavirus disease 2019 (COVID-19) pandemic has affected hundreds of millions of individuals and caused millions of deaths worldwide. Predicting the clinical course of the disease is of pivotal importance to manage patients. Several studies have found hematochemical alterations in COVID-19 patients, such as inflammatory markers. We retrospectively analyzed the anamnestic data and laboratory parameters of 303 patients diagnosed with COVID-19 who were admitted to the Polyclinic Hospital of Bari during the first phase of the COVID-19 global pandemic. After the pre-processing phase, we performed a survival analysis with Kaplan–Meier curves and Cox Regression, with the aim to discover the most unfavorable predictors. The target outcomes were mortality or admission to the intensive care unit (ICU). Different machine learning models were also compared to realize a robust classifier relying on a low number of strongly significant factors to estimate the risk of death or admission to ICU. From the survival analysis, it emerged that the most significant laboratory parameters for both outcomes was C-reactive protein min; HR=17.963 (95% CI 6.548–49.277, p < 0.001) for death, HR=1.789 (95% CI 1.000–3.200, p = 0.050) for admission to ICU. The second most important parameter was Erythrocytes max; HR=1.765 (95% CI 1.141–2.729, p < 0.05) for death, HR=1.481 (95% CI 0.895–2.452, p = 0.127) for admission to ICU. The best model for predicting the risk of death was the decision tree, which resulted in ROC-AUC of 89.66%, whereas the best model for predicting the admission to ICU was support vector machine, which had ROC-AUC of 95.07%. The hematochemical predictors identified in this study can be utilized as a strong prognostic signature to characterize the severity of the disease in COVID-19 patients.
... Recently, 2 separate studies demonstrated structural damage and morphological alteration of erythrocytes in serious COVID-19 patients. 30,31 However, further studies are needed to identify the diagnostic or prognostic utility of MCHC in COVID-19. ...
Full-text available
Objectives: To validate C-reactive protein (CRP), red cell distribution width (RDW), and neutrophil lymphocyte ratio (NLR) for both serious outcomes and length of hospital stay (LOS) among hospitalized coronavirus disease-19 (COVID-19) patients. Methods: Laboratory data of adult COVID-19 patients (n=74) was collected in this retrospective cohort. Logistic regression was employed for risk factor evaluation and receiver operating curve was used for comparison of these risk factors for the prediction of serious outcome. Multiple regression was applied to determine the association between routine analytes and LOS. Results: Higher levels of CRP (3 times), white blood cells (20%), and neutrophil counts (40%) were seen in the serious category. Odds ratio for CRP for the serious outcome was 1.052 (p=0.007) and RDW for the serious outcome was 1.218 (p=0.040) in unadjusted model and odds ratio for CRP for the serious outcome was 1.048 (p=0.024) and for RDW 1.286 (p=0.023) in adjusted model. In a multivariate regression analysis for the LOS of the unadjusted models consisting of NLR, monocyte lymphocyte ratio (MLR) and platelet lymphocyte ratio (PLR), the beta coefficients (BC) for the CRP were 0.006 (NLR), 0.005 (MLR) and 0.006 (PLR), whereas -0.029 (NLR), -0.034 (MLR) and -0.027 (PLR) were BCs for mean corpuscular hemoglobin concentration (MCHC). Additionally, in adjusted models, the BCs for MCHC were -0.044 (NLR), -0.047 (MLR) and -0.043 (PLR). However, the CRP was consistent with 0.004 (BC) in all models. Conclusion: We observed that CRP is a better predictor than RDW and NLR for serious outcome among COVID-19 patients. Besides, CRP was positively, whereas MCHC was negatively associated with LOS.
Представлен обзор по коронавирусной инфекции с описанием клинических проявлений и лечения постковидного синдрома. Сделано предположение о возможности применения кавинтона ввиду его широкого спектра фармакологического действия при постковидном синдроме. An overview of the coronavirus infection is presented. Clinical manifestations of the postcovid syndrome are presented. An assumption was made about the possibility of using cavinton due to its wide spectrum of pharmacological action in postcovid syndrome.
Full-text available
The enduring epidemic outbreak which started in Wuhan city of China, in December 2019 caused by the 2019 novel coronavirus (COVID- 19) or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has created a dangerous and deadly Public Health disaster of International apprehension, with cases confirmed in several countries. This novel community health trouble is frightening the universe with clinical, psychological, emotional, collapse of health system and economical slowdown in each and every part of the world infecting nearly 200 countries. A highly virulent and pathogenic COVID-19 viral infection with incubation period ranging from two to fourteen days, transmitted by breathing of infected droplets or contact with infected droplets, belongs to the genus Coronavirus with its high mutation rate in the Coronaviridae. The likely probable primary reservoir could be bats, because genomic analysis discovered that SARSCoV-2 is phylogenetically interrelated to SARS-like bat viruses. The transitional resource of origin and transfer to humans is not known, however, the rapidly developing pandemic has confirmed human to human transfer. Approximately 1,016,128 reported cases, 211,615 recovered cases and 53,069 deaths of COVID-2019 have been reported to date (April 2, 2020). The symptoms vary from asymptomatic, low grade pyrexia, dry cough, sore throat, breathlessness, tiredness, body aches, fatigue, myalgia, nausea, vomiting, diarrhea, to severe consolidation and pneumonia, acute respiratory distress syndrome (ARDS) and multiple organ dysfunction leading to death with case fatality rate ranging from 2 to 3%.
Full-text available
This paper collates the pathological findings from initial published autopsy reports on 23 patients with Coronavirus Disease 2019 (COVID-19) from 5 centers in the United States of America, including 3 cases from Houston, Texas. Findings confirm that COVID-19 is a systemic disease with major involvement of the lungs and heart. Acute COVID-19 pneumonia has features of a distinctive acute interstitial pneumonia with: a diffuse alveolar damage (DAD) component, coupled with microvascular involvement with intra- and extra-vascular fibrin deposition and intravascular trapping of neutrophils, and, frequently, with formation of microthombi in arterioles. Major pulmonary thromboemboli with pulmonary infarcts and/or hemorrhage occurred in 5 of the 23 patients. Two of the Houston cases had interstitial pneumonia with DAD pattern. One of the Houston cases had multiple bilateral segmental pulmonary thromboemboli with infarcts and hemorrhages coupled with, in non-hemorrhagic areas, a distinctive interstitial lymphocytic pneumonitis with intra-alveolar fibrin deposits and no hyaline membranes, possibly representing a transition form to acute fibrinous and organizing pneumonia (AFOP). Multifocal acute injury of cardiac myocytes was frequently observed. Lymphocytic myocarditis was reported in 1 case. In addition to major pulmonary pathology, the three Houston cases had evidence of lymphocytic pericarditis, multifocal acute injury of cardiomyocytes without inflammatory cellular infiltrates, depletion of splenic white pulp, focal hepatocellular degeneration and rare glomerular capillary thrombosis. Each had evidence of chronic cardiac disease: hypertensive left ventricular hypertrophy (420 gram heart), dilated cardiomyopathy (1070 gram heart), and hypertrophic cardiomyopathy (670 gram heart). All three subjects were obese (BMIs of 33.8, 51.65 and 35.2 Kg/m²). Overall, the autopsy findings support the concept that the pathogenesis of severe COVID-19 disease involves direct viral-induced injury of multiple organs, including heart and lungs, coupled with the consequences of a procoagulant state with coagulopathy.
Full-text available
Purpose of review: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the aggressive coronavirus disease (COVID-19) pandemic. Recently, investigators have stipulated that COVID-19 patients receiving angiotensin-converting-enzyme inhibitors (ACEI) may be subject to poorer outcomes. This editorial presents the available evidence to guide treatment practices during this pandemic. Recent findings: Recent studies from Wuhan cohorts provide valuable information about COVID-19. A cohort with 52 critically ill patients revealed cardiac injury in 12% of patients. Worse outcomes appear to be more prevalent in patients with hypertension and diabetes mellitus (DM), possibly due to overexpression of angiotensin-converting enzyme 2 (ACE2) receptor in airway alveolar epithelial cells. Investigators suspect that SARS-CoV-2 uses the ACE2 receptor to enter the lungs in a mechanism similar to SARS-CoV. Several hypotheses have been proposed to date regarding the net effect of ACEI/ARB on COVID-19 infections. Positive effects include ACE2 receptor blockade, disabling viral entry into the heart and lungs, and an overall decrease in inflammation secondary to ACEI/ARB. Negative effects include a possible retrograde feedback mechanism, by which ACE2 receptors are upregulated. Even though physiological models of SARS-CoV infection show a theoretical benefit of ACEI/ARB, these findings cannot be extrapolated to SARS-CoV-2 causing COVID-19. Major cardiology scientific associations, including ACC, HFSA, AHA, and ESC Hypertension Council, have rejected these correlation hypotheses. After an extensive literature review, we conclude that there is no significant evidence to support an association for now, but given the rapid evolvement of this pandemic, findings may change.
Full-text available
Coronavirus disease 2019 (COVID-19), which causes serious respiratory illness such as pneumonia and lung failure, was first reported in Wuhan, the capital of Hubei, China. The etiological agent of COVID-19 has been confirmed as a novel coronavirus, now known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is most likely originated from zoonotic coronaviruses, like SARS-CoV, which emerged in 2002. Within a few months of the first report, SARS-CoV-2 had spread across China and worldwide, reaching a pandemic level. As COVID-19 has triggered enormous human casualties and serious economic loss posing global threat, an understanding of the ongoing situation and the development of strategies to contain the virus's spread are urgently needed. Currently, various diagnostic kits to test for COVID-19 are available and several repurposing therapeutics for COVID-19 have shown to be clinically effective. In addition, global institutions and companies have begun to develop vaccines for the prevention of COVID-19. Here, we review the current status of epidemiology, diagnosis, treatment, and vaccine development for COVID-19.
Full-text available
Last decade witnessed the outbreak of many life-threatening human pathogens including Nipah, Ebola, Chikungunya, Zika, Middle East respiratory syndrome coronavirus (MERS-CoV), Severe Acute respiratory syndrome coronavirus (SARS-CoV) and more recently novel coronavirus (2019-nCoV or SARS-CoV-2). The disease condition associated with novel coronavirus, referred to as Coronavirus disease (COVID-19). The emergence of novel coronavirus in 2019 in Wuhan, China marked the third highly pathogenic coronavirus infecting humans in the 21st century. The continuing emergence of coronaviruses at regular intervals poses a significant threat to human health and economy. Ironically, even after a decade of research on coronavirus, still there are no licensed vaccines or therapeutic agents to treat coronavirus infection which highlights an urgent need to develop effective vaccines or post-exposure prophylaxis to prevent future epidemics. Several clinical, genetic and epidemiological features of COVID-19 resemble SARS-CoV infection. Hence, the research advancements on SARS-CoV treatment might help scientific community in quick understanding of this virus pathogenesis and develop effective therapeutic/prophylactic agents to treat and prevent this infection. Monoclonal antibodies represent the major class of biotherapeutics for passive immunotherapy to fight against viral infection. The therapeutic potential of monoclonal antibodies has been well recognized in the treatment of many diseases. Here, we summarize the potential monoclonal antibody based therapeutic intervention for COVID-19 by considering the existing knowledge on the neutralizing monoclonal antibodies against similar coronaviruses SARS-CoV and MERS-CoV. Further research on COVID-19 pathogenesis could identify appropriate therapeutic targets to develop specific anti-virals against this newly emerging pathogen.
In mid‐December 2019, a disease caused by infection with severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), which began in Wuhan, China, has spread throughout the country and many countries around the world. The number of children with coronavirus disease‐2019 (COVID‐19) has also increased significantly. Although information regarding the epidemiology of COVID‐19 in children has accumulated, relevant comprehensive reports are lacking. The present article reviews the epidemiological characteristics of COVID‐19 in children. This article is protected by copyright. All rights reserved.
Viral infections have detrimental impacts on neurological functions, and even to cause severe neurological damage. Very recently, coronaviruses (CoV), especially severe acute respiratory syndrome CoV 2 (SARS-CoV-2), exhibit neurotropic properties and may also cause neurological diseases. It is reported that CoV can be found in the brain or cerebrospinal fluid. The pathobiology of these neuroinvasive viruses is still incompletely known, and it is therefore important to explore the impact of CoV infections on the nervous system. Here, we review the research into neurological complications in CoV infections and the possible mechanisms of damage to the nervous system.
Objective: To study the effect of COVID-19 on pregnancy outcomes and neonatal prognosis in Hubei Province. Methods: A retrospective comparison of the pregnancy outcomes was done between 16 women with COVID-19 and 45 women without COVID-19. Also, the results of laboratory tests, imaging examinations, and the 2019-nCoV nucleic acid test were performed in 10 cases of neonatal deliverd from women with COVID-19. Results: (1) Of the 16 pregnant women with COVID-19, 15 cases were ordinary type and 1 case was severe type. No one has progressed to critical pneumonia. The delivery method of the two groups was cesarean section, and the gestational age were (38.7±1.4) and (37.9±1.6) weeks, there was no significant difference between the two groups (P> 0.05). Also, there wee no significant differences in the intraoperative blood loss and birth weight of the newborn between the two groups (all P>0.05). (2) Ten cases of neonates delivered from pregnant women with COVID-19 were collected. The 2019-nCoV nucleic acid test were all negative. There were no significant differences in fetal distress, meconium-stained amniotic fluid, preterm birth, and neonatal asphyxia between the two groups (all P>0.05). (3) In the treatment of uterine contraction fatigue, carbetocin or carboprost tromethamine was used more in cesarean section for pregnant women with COVID-19 (1.3±0.6), compared with Non-COVID-19 group (0.5±0.7), the difference was statistically significant (P=0.001). Conclusions: If there is an indication for obstetric surgery or critical illness of COVID-19 in pregnant women, timely termination of pregnancy will not increase the risk of premature birth and asphyxia of the newborn, but it is beneficial to the treatment and rehabilitation of maternal pneumonia. Preventive use of long-acting uterotonic agents could reduce the incidence of postpartum hemorrhage during surgery. 2019-nCoV infection has not been found in neonates deliverd from pregnant women with COVID-19.