ArticlePDF Available

Phospholipase enzymes as potential biomarker for SARS CoV-2 virus


Abstract and Figures

Severe acute respiratory syndrome corona virus 2 (SARS CoV-2) is the responsible pathogenic RNA virus which is responsible for current ongoing pandemic covid 19. This review provides an updated summary of the current knowledge of phospholipase enzymes and its role on SARS CoV-2 virus, discussing the reported evidence as a potential bio marker and future directions that could be used to develop PLAs as a therapeutic target for covid 19 pandemic.
Content may be subject to copyright.
International Journal of Scientific and Research Publications, Volume 11, Issue 1, January 2021 189
ISSN 2250-3153
This publication is licensed under Creative Commons Attribution CC BY.
Phospholipase enzymes as potential biomarker for SARS
CoV-2 virus
D.V.D. Hemalika
Department of Chemistry, Faculty of Natural Sciences, The Open University of Sri Lanka
DOI: 10.29322/IJSRP.11.01.2021.p10919
Severe acute respiratory syndrome corona virus 2 (SARS CoV-2) is the responsible pathogenic RNA virus which is responsible for
current ongoing pandemic covid 19. This review provides an updated summary of the current knowledge of phospholipase enzymes
and its role on SARS CoV-2 virus, discussing the reported evidence as a potential bio marker and future directions that could be used
to develop PLAs as a therapeutic target for covid 19 pandemic.
Index terms- bio marker, covid 19, LpPLA2, SARS CoV-2, sPLA2, therapeutic target
The covid 19 pandemic is a global health crisis which has grown exponentially to a disastrous scale. This is the greatest challenge we
have faced since world war two.
Corona virus disease 2019 (covid 19) is an infectious disease which is caused by novel SARS CoV-2 , Severe acute respiratory
syndrome. Considering the epidemiology of covid 19, WHO declared it as a global pandemic on 11th March 2020 [1]. Up to now
more than 79,100,000 reported covid 19 infected cases with around 1700000 deaths have been reported [2].
SARS CoV-2 is the seventh corona virus that infect human. Until 2020, six corona viruses were known to infect human namely 229E,
NL63 (genus Alpha-), OC43, HKU1, SARS-CoV, and MERS-CoV (Beta-)[3]. Among them in 2002 and 2012 we experienced severe
out breaks of SARS-CoV and MERS with high mortality [4].Those two viruses and SARS CoV- 2 are beta corona viruses which
infect lower respiratory tract and pneumonia in human. Corona viruses can cause common cold to more severe pneumonia condition
in human. However compared to SARS CoV and MERS, covid 19 shows less severe pathogenesis, but very rapid transmission whole
over the world [5].
This review summarizes the importance of phospholipase enzyme as therapeutic target for both noninfectious diseases and towards
that its possibility to use as a potential biomarker for the covid 19 current pandemic situation.
Information for this review were obtained from previous research findings regarding phospholipase enzymes, SARS CoV-2 virus, use
of phospholipase A2 (PLA2) as therapeutic targets for non-infectious diseases, role of PLA2 in corona viruses, studies of SARS CoV-
2 virus related to phospholipase enzyme from available literatures published in scientific databases such as Web of Science, Science
Direct, PubMed, JSTOR and Google Scholar. Primary search terms like, PLA2, Covid 19, SARS CoV-2, enzymes as therapeutic
targets are used to collect the information.
Pathogenic RNA viruses become most important group of zoonotic disease transmission among all pathogens. Biological diversity,
rapid inter transmission rates and epidemiology of recently developed Chikungunya(CHIKV) and Zika (ZIKV) viruses, Lassa fever,
Ebolavirus, Middle East respiratory syndrome (MERS), SARS, and Influenza A virus (IAV) are all RNA viruses [5]. Coronaviruses
International Journal of Scientific and Research Publications, Volume 11, Issue 1, January 2021 190
ISSN 2250-3153
This publication is licensed under Creative Commons Attribution CC BY.
belong to the family coronaviridae, (subfamily Coronavirinae), which represent major group of viruses which responsible for
respiratory and neurological diseases [6].
Coronaviruses are single stranded positive sense RNA genome. Coronaviruses encode four major structural proteins, namely, spike
(S), membrane (M), envelope (E), and nucleocapsid (N) [5]. As its name implies this virus contain large, multifunctional
transmembrane S glycoprotein on the virion surface, make crown like appearance [7]. Those glycoproteins are responsible for the
viral attachment to the host cells. When we consider about our concern, SARS corona virus, in 2004 it is suggested that increasing
international wildlife trade in countries like China and Vietnam may played an important role in SARS outbreak in 2002 [8].
Unfortunately, same incident is repeat in Wuhan, China in 2019 and now the outcome SARS CoV-2 is unable to anticipate by modern
medical technologies even.
Using genome sequencing study of isolated viruses, it had been found that SAARS CoV- 2 is a new human infecting beta corona virus
[9]. Covid 19 is a zoonotic disease and based on phylogenetic studies bats might be the original host of covid 19 virus. It was also
found that Malayan pangolins (wild life mammal) are the intermediate host of SARS CoV-2 [10]. It had also been found that s
glycoprotein which is contribute for the receptor binding is almost similar in both pangolin CoV and SARS CoV-2 [10].
Covid 19 emerged in china and now it is rapidly spread all over the world. This public health burden is now become supreme
challenge to whole universe. Therefore, strong investigations towards development of drugs and effective vaccines are highly needed
for the society.
Up to date scientists in all over the world are eager to find therapeutic targets for this disastrous virus and few treatment strategies are
identified and developed [11].
Severity and mortality of covid 19 patients are linked to excessive production of cytokines, called “cytokine storm” induce by the
virus. It leads to wide spread tissue damage, multiple organ failure and death, Therefore it is important to target the inflammatory
response as a therapeutic target for covid 19 virus [11].
In 2007, it had been shown another strategy that glycoproteins which is contain on the surface of the virus can be used as attractive
target to develop as antiviral agents against corona viruses [12].
Developing neutralizing antibodies that targeting S protein on covid 19 virus surface, using oligonucleotides against covid 19 virus,
Repurposing currently available antiviral medications [13] (viral polymerase and viral protease inhibitors [14]) against covid 19
viruses and development of vaccines (live vaccines with vector viruses, mRNA based vaccines, inactivated vaccines with viral
proteins) are still under ongoing clinical trials [15].
Enzymes are biological macromolecules, which are essential for all life. Enzyme catalysis is vital for the vast majority of biological
reactions including synthesis of biomacromolecules (proteins, polysaccharides, and nucleic acids), intercellular communication and
immune responses [16].
Although enzymes are crucial for most essential life processes, dysregulated enzyme activity can lead to disease conditions. As a
result of these biological and pathophysiological implications, by modifying the action of enzymes, they become attractive targets for
drug discovery. This strategy has been applied in the development of a substantial amount of antibiotic and antiviral drugs that exist
today. In the year 2000, Hopkins and Groom reported that around 47% of drugs inhibit enzymes as their molecular targets. Nowadays
major pharmaceutical companies are seeking new drugs through selective enzyme inhibition since enzymes are susceptible to be
inhibited by small molecular weight drug-like molecules [17].
Viral enzymes also play a possible way to develop new anti-viral targets since each step of viral infection, viral enzymatic reactions
are involved [13].
International Journal of Scientific and Research Publications, Volume 11, Issue 1, January 2021 191
ISSN 2250-3153
This publication is licensed under Creative Commons Attribution CC BY.
Lipids have long been known as structural component in biological membranes of all living organisms. Lipids play a central role at
different stages in viral replication including cell entry and exit by viruses. Virus entry is a specific process which is depend on viral
surface proteins and host cell receptors[18]. Lipids also can function as host cell receptor for the viruses. Since lipids play a crucial
role in viral life cycle it is good to investigate whether the enzymes which related to lipid metabolism can be used as drug target for
viral infections.
Therefore, this lipid metabolic pathways become an important role in drug targets. Lipid related anti-viral strategies are promising
since lipoids play a crucial role in viral replication. Identification of host directed anti-viral that inhibit host factors is most promising.
It had been already reported that development of anti-viral drug for zika virus can drive through host directed anti-viral, since zika
virus having a different aspects of lipid metabolism to complete their life cycle [19].
Since SARS CoV -2 virus replication is occur within the host cell, virus first should be enter to the host via intracellular membranes
and create double membrane vesicles encoding with lipid bilayer and replicative organelles which are needed for the viral genome
amplification [18].
Not only lipid mediators that produce through lipid metabolic pathways, but also the enzymes which involved is used as promising
drug targets. Phospholipase enzymes may be considered as one such novel approach for fighting against SARS CoV-2 virus as well.
Phospholipases are a group of enzymes that lead to cleaving the various bonds in phospholipids, which are the major component of all
biological membranes in living organisms.
Phospholipases are categorized based on the bond cleavage in phospholipid substrates.
Figure 1: Site of action of various phospholipases on phospholipid. X = phospholipid common base (Choline, ethanol amine)
Based on the site of hydrolytic cleavage as depicted above, there are five types of phospholipases namely PLA1, PLA2, PLB, PLC,
and PLD. Up to date, phospholipase A2 (PLA2) is the most extensively studied group of phospholipases [20].
PLA2 enzymes vary in size, function, location, substrate specificity, and calcium requirement. Based on the structure, catalytic
mechanism, localization, and evolutionary relationships, PLA2s are subdivided into six subgroups as follows [21].
1. Cytosolic PLA2 - cPLA2
2. Secretory PLA2 - sPLA2 (Ca2+ dependent)
3. iPLA2 - Ca2+ independent PLA2
4. LyPLA2 - lysosomal PLA2
International Journal of Scientific and Research Publications, Volume 11, Issue 1, January 2021 192
ISSN 2250-3153
This publication is licensed under Creative Commons Attribution CC BY.
5. PAFAH - PAF acetylhydrolase
6. AdPLA2 - adipose PLA2
Among them, sPLA2 is the first discovered group of PLA2 enzymes, which was discovered as a component of cobra venom [22].
PLA2 has been identified as one of the main components of animal venom. Elapidae and Viperidae family snakes having sPLA2
group IA, IIA or IIB as the main component in snake venom [23]. Snake venom PLA2s induce pathophysiological alterations in the
victim by hydrolyzing phospholipids in membranes [23].
Among all existing isoforms of phospholipase enzymes, sPLA2 mainly play a major role in developing drug target as inhibitors since
it involves in many inflammatory conditions [24].
Studies about this sPLA2 enzyme and its function, hold great importance since PLA2 catalyzes the release of arachidonic acid, which
is believed to be the rate-limiting event in the generation of pro-inflammatory lipid mediators (prostaglandins, leukotrienes, lipoxins)
and platelet-activating factor [25]. Release of these mediators initiates the pain, swelling, and other unpleasant symptoms we
experience as part of an inflammatory response [26].
Figure 2: Phospholipid hydrolysis by sPLA2
Therefore, the inhibition of these phospholipase enzymes will be the good therapeutic target, as it leads to inhibit the production of
inflammatory lipid mediators.
sPLA2 enzymes are responsible for a large variety of physiological functions as well in many disease conditions. They help to
maintain membrane structure and function by removing oxidized and damaged phospholipids under physiological conditions [22].
It is important to discuss the cause of pathological conditions that are initiated by sPLA2. Lysophospholipids and free fatty acids
(arachidonic acid) are the main products of hydrolysis of the phospholipid cell membrane. Arachidonic acid initiates the production of
numerous metabolites through cyclooxygenase or lipoxygenase enzymatic pathways, especially eicosanoids including prostaglandins
and leukotrienes, which mediate various pathological conditions [27].
Under pathological conditions, overexpression of sPLA2 activity can be observed in a variety of diseases. Especially increased
activity of sPLA2 is associated with inflammatory diseases such as arthritis and sepsis [28], different types of cancer [29] and
atherosclerosis [30].
International Journal of Scientific and Research Publications, Volume 11, Issue 1, January 2021 193
ISSN 2250-3153
This publication is licensed under Creative Commons Attribution CC BY.
These studies have implicated a role of sPLA2 IIA known as inflammatory sPLA2, in disease pathogenesis, since it promotes the
production of inflammatory lipid mediators, mainly eicosanoids [31]. Moreover, it has been suggested that increased activity of
sPLA2-IIA can be used as a biomarker for the detection of sepsis and the presence of bacterial infection in adults [27]. The increased
sPLA2 activity has also been shown in the plasma or serum of patients with acute pancreatitis, septic shock, adult respiratory distress
syndrome and inflammatory bowel diseases including Chron’s disease and ulcerative colitis [22]. It had been shown that sPLA2 IIA ,
V, and X was overexpressed in transgenic mice with atherosclerosis [30]. A recent study had shown that an increase in the activity of
sPLA2 IIA was a significant risk factor in the occurrence of coronary artery disease.
sPLA2 IIA and sPLA2 X are the most studied sPLA2s in cancer so far [22]. It was determined that the sPLA2 X is expressed at high
levels in colon cancer by promoting cell proliferation and releasing various lipid mediators in other steps in progression and
development of cancer [33]. Several in-vitro studies had shown that human sPLA2 IIA activity is high in serum or in the tumor
microenvironment of patients with prostate, esophageal and lung cancer cells [35]. The previous study had suggested that plasma
sPLA2 IIA is a potential biomarker for lung cancer diagnosis since it is elevated in all most all lung cancer types [36]. sPLA2 IIA and
sPLA2 X are the most studied sPLA2s in cancer so far. Several in-vitro studies had shown that human sPLA2 IIA activity is high in
serum or in the tumor microenvironment of patients with prostate, esophageal and lung cancer cells [35]. It had been also reported that
sPLA2 group II is overexpressed in a variety of human breast, gastric and hepatocytic carcinomas and prostate cancers [37].
Above studies were evidenced that sPLA2s are considered as pro-inflammatory enzymes and their inhibition has long been
recognizing as a desirable therapeutic target.
Previous literature was cited that phospholipase enzyme act as key role of producing inflammatory lipid mediators in host during viral
It had been reported that dengue virus (DENV) of neuroblastoma cell lines leads to increase in the activity of the sPLA2 enzyme
leading to cell apoptosis. Increase in sPLA2 activity resulted in the increased production of prostaglandin E2 (PGE2), prostacyclin
(PGI2) , thromboxane and leukotriene, which could lead to the endothelial dysfunction leading to increased vascular permeability
It was demonstrated that dengue shock syndrome (DSS) patients had higher sPLA2 levels than healthy individuals [39]. Another
study has shown that the sPLA2 activity was significantly higher in patients with DHF, especially in the very early phase of the
illness. The activity of sPLA2 diminished towards 120132 hours of illness and was similar to the sPLA2 activity seen in patients
with DF [40].
Role of Phospholipace C (PLC) signaling had been reported for the bovine herpesvirus 1 infection which enhance the generation of
inflammatory mediator reactive oxygen species [41].
It had been also evidenced that PLA2 host enzyme and lysophosphatidylcholins are contributed to form west Nile virus replication
complex [42]. Moreover phospholipase D activity is stimulated by infection of influenza virus [43].
There are some evidence that elevated level of PLA2 is patients with lung infections and respiratory problems. Pulmonary surfactant
is important to maintain alveolar stability by lowering surface tension along the alveolar epithelium. Destruction of this surface
tension will results in lung injury (Acute Respiratory distress Syndrome ARDS) [44].
sPLA2 enzyme leads to hydrolyze phospholipid surfactant and destruction of surface tension. It had been found that inhibition of
sPLA2 activity play a protective role in lung injury by maintaining surfactant integrity [45]. It was also reported that various sPLA2
isoforms are produced in lungs by macrophages and epithelial cells [46].
Using multicenter translational study including several pediatric and neonatal intensive care units suggested that sPLA2 might be the
main cross road between inflammation and surfactant dysfunction in lungs [47].
Moreover it had been suggested that sPLA2 V and X participated to the lung injury by lipid mediator production and surfactant
hydrolysis [48].There are patients with severe asthma showed increasing sPLA2 activity [49].
International Journal of Scientific and Research Publications, Volume 11, Issue 1, January 2021 194
ISSN 2250-3153
This publication is licensed under Creative Commons Attribution CC BY.
Studies related to PLA2 and covid 19 is already done by few scientists. As initial step it had been found that plasma sPLA2 level of
moderate and acute covid 19 patients significantly increase compare to the covid 19 negative patients. They also observed the
dramatic depletion of plasma phospholipids concentration with the elevation of sPLA2 [50]. That is may be due to hydrolysis of
phospholipids and formation of lyso phospholipids. Resultant lysophospholipds may stimulate the cytokine production and this
cytokine storm will lead the severity of SARS CoV-2.
This is further supported by recent finding that several circulating lipids and PLA2 activity can be used as potential biomarkers in the
pathogenesis of covid 19. It is mainly due to the down regulation of glycerophospholipids and upregulation of lysophospholipids
which produced by PLA2 activity [51]. It would suggest the strong influence of PLA2 in progression of pathogenesis of covid 19.
Previous reports were highlighted that cPLA2α is critically involved in RNA replication of some viruses. This enzyme also important
in corona virus replication by producing lysophospholipids that required to form double membrane vesicle formation, that is proven
by both electron microscopy studies and lipidomic studies [52],[18].
In another study, age dependent increase of PLA2 Group IID in lungs of mice had been shown that it is linked with more than 80 %
lethality of SARS CoV in mice than mice with lacking PLA2 Group IID [53].
There are some studies done to evaluate the relationship between mortality of covid 19 patients with gender, sex, BMI, cholesterol
level, Asthma and cardiovascular diseases. By analyzing the results of those studies, it was observed that PLA2 showed an important
biological link in that patients.
One study had clearly shown that increased BMI levels were associated with higher risk of contracting SARS CoV-2 [54]. Higher
BMI level is associated with increased sPLA2 activity in patients with stable asthma [49]. There is also an evidence that serum PLA2
level is higher in both asthma patients with and without attacks, when compared to the control group [56]. Therefore it can be
suggested sPLA2 activity is interrelated in the patients having higher BMI and asthma towards the susceptibility of severe covid 19
While both men and women have the same prevalence to SARS CoV-2 without any gender discrimination, men is more susceptible to
face more complications and death [55]. Study [49] was evidenced the inverse correlation of sPLA2 activity with vitamin c
concentration in covid 19 patients. Interestingly the vitamin C concentration in plasma is lower in males than females [49]. It also
links with the severity of covid 19 in males with the correlation of increasing sPLA2 activity and the decrease in vitamin C content.
LpPLA2 is a member of the GVII family of PLA2 enzymes. This enzyme was named for its ability to cleave the acetyl group from
the sn-2 position of PAF, as well as its association with lipoproteins [57] . It was well established that increasing LPPLA2 is a reliable
marker for the risk of cardiovascular events. It had been evidenced that LpPLA2 level upregulation is mainly found in non-
hospitalized covid 19 patients. This abnormal increase LpPLA2 was observed in covid 19 re-positive patients as well [58], [59], [60].
Those patients are not showed promising symptoms of pneumonia, however sometimes they first experienced cardiovascular
symptoms [61]. The limited medical care of these patients may follow up cardiovascular diseases.
Another study was revealed that Increasing rates of LpPLA2 were positively correlated with not only viral loads in patients with
COVID-19 but also severity of pneumonia in non-COVID-19 patients. Therefore it could be suggested that increased levels of Lp-
PLA2 in plasma could provide insights to higher mortality was seen in patients underlying comorbidities (e.g. hypertension, diabetes
mellitus, cardiovascular disease) [62].
Moreover proteomics studies of covid 19 infected host cell showed a potential link with inflammatory response supported by
increasing of PLA2 at 24h after virus infection [63].
Above studies revealed the contribution of phospholipase enzymes to SARS CoV-2 into some extent. However, it would be further
investigated beyond the current understanding.
This review summarizes the PLA2 and its role in SARS CoV-2 infection. The increasing of phospholipase enzyme is linked with
progression of disease from mild to severe and it is related with other associated complications like pneumonia, cardiovascular disease
International Journal of Scientific and Research Publications, Volume 11, Issue 1, January 2021 195
ISSN 2250-3153
This publication is licensed under Creative Commons Attribution CC BY.
and towards the mortality. Therefore, this valuable information has unveiled potential antiviral targets that are now starting to be
Further understanding of interfacial activation mechanisms of PLA2s on lipid surface will also uncover the new therapeutic target.
Future studies with larger number of subjects is need to develop novel PLA2 inhibitors as therapeutic target for not only for covid 19,
but also other related diseases. Optimization of existing PLA2 inhibitors will also be a good approach to develop therapeutics for not
only infectious diseases but also for non-infectious disease.
[1] WHO, “Listings of WHO’s response to COVID-19,” WHO, 2020.
[2] worldometer, “COVID-19 CORONAVIRUS PANDEMIC,” 2020.
[3] N. Zhu et al., “A Novel Coronavirus from Patients with Pneumonia in China, 2019,” N. Engl. J. Med., vol. 382, no. 8, pp. 727733, 2020, doi:
[4] Y. Chen, Q. Liu, and D. Guo, “Emerging coronaviruses: Genome structure, replication, and pathogenesis,” J. Med. Virol., vol. 92, no. 4, pp. 418423, 2020,
doi: 10.1002/jmv.25681.
[5] M. A. Dhama K, Khan S, Tiwari R, Sircar S, Bhat S, Malik Y.S, Singh K P, Chaicumpa W, Aldana DKB, “Coronavirus Disease 2019 COVID-19,” Clin.
Microbiol. Rev., vol. 33, no. 4, pp. 148, 2020.
[6] A. Gaurav and M. Al-Nema, “Polymerases of coronaviruses: Structure, function, and inhibitors,” in Viral Polymerases Structures, Functions and Roles as
Antiviral Drug Targets, Elsevier Inc., 2019, pp. 271300.
[7] David A.J. Tyrrell and Steven H. Myint., “Coronaviruses,” in Medical microbiology, 1996, p. chapter 60.
[8] H. P. Bell D, Roberton S, “Animal origins of SARS coronavirus: Possible links with the international trade in small carnivores.,” Philos Trans R Soc L. B
Biol Sci, vol. 359, no. 1447, pp. 11071114, 2004.
[9] R. Lu et al., “Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding,” Lancet, vol. 395,
pp. 565574, 2020, doi: 10.1016/S0140-6736(20)30251-8.
[10] K. Xiao et al., “Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins,” Nature, vol. 583, pp. 286289, 2020, doi: 10.1038/s41586-020-
[11] R. L. Kruse, “Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China,” F1000Research, vol. 9, no. 72, pp.
114, 2020, doi: 10.12688/f1000research.22211.2.
[12] F. G. U. M. van der Meer et al., “The carbohydrate-binding plant lectins and the non-peptidic antibiotic pradimicin A target the glycans of the coronavirus
envelope glycoproteins,” J. Antimicrob. Chemother., vol. 60, no. 4, pp. 741749, 2007, doi: 10.1093/jac/dkm301.
[13] H. Ferriz and R. Buchet, “Coronavirus and Enzymes: What the Past Told us?,” Open Enzym. Inhib. J., vol. 5, no. 1, pp. 11, 2020, doi:
[14] C.-H. Tsai, P.-Y. Lee, V. Stollar, and M.-L. Li, “Antiviral Therapy Targeting Viral Polymerase,” Curr. Pharm. Des., vol. 12, no. 11, pp. 13391355, 2006,
doi: 10.2174/138161206776361156.
[15] G. association of research based pharmaceutical Company, “Vaccines to protect against Covid-19, the new coronavirus infection,” VFA, 2020.
[16] C. GM., “The Central Role of Enzymes as Biological Catalysts,” in The Cell: A Molecular Approach. 2nd edition, 2000.
[17] R. R, “Inhibitors of Secretory Phospholipase A2 Group IIA,” Curr. Med. Chem., vol. 12, no. 25, pp. 30113026, 2005.
[18] M. Abu-Farha, T. A. Thanaraj, M. G. Qaddoumi, A. Hashem, J. Abubaker, and F. Al-Mulla, “The role of lipid metabolism in COVID-19 virus infection and
as a drug target,” Int. J. Mol. Sci., vol. 21, no. 3544, pp. 111, 2020, doi: 10.3390/ijms21103544.
[19] M. A. Martín-Acebes, N. J. de Oya, and J. C. Saiz, “Lipid metabolism as a source of druggable targets for antiviral discovery against zika and other
flaviviruses,” Pharmaceuticals, vol. 12, no. 2, 2019, doi: 10.3390/ph12020097.
[20] M. . Aloulou, A, Ali Y.B, Bezzine, S, Gargouri, Y, Gelb, “Chapter 4 Phospholipases : An Overview,” in Lipases and phospholipases: Methods and
protocoal, methods in molecular biology, 2012, pp. 6385.
[21] and B. S. C. Nhat D. Quach, Robert D. Arnold, “Secretory Phospholipase A2 Enzymes as Pharmacological Targets for Treatment of Disease,” Biochem.
Pharmacol., vol. 90, no. 4, pp. 338348, 2015.
[22] V. M. Edward A. Dennis, Jian Cao, Yuan-Hao Hsu, “Phospholipase A2 Enzymes: Physical Structure, Biological Function, Disease Implication, Chemical
Inhibition, and Therapeutic Intervention,” Chem Rev, vol. 111, no. 10, pp. 61306185, 2012.
[23] Y. Zambelli, V.O., Picolo, G., Fernandes, C.A .H., Fontes, M.R .M., Cury, “Pain and Analgesia,” Toxins (Basel)., vol. 9, no. 406, pp. 127, 2017.
International Journal of Scientific and Research Publications, Volume 11, Issue 1, January 2021 196
ISSN 2250-3153
This publication is licensed under Creative Commons Attribution CC BY.
[24] T. C. R. Thais A. Sales, Silvana Marcussi, “Current Anti-Inflammatory Therapies and the Potential of Secretory Phospholipase A2 Inhibitors in the Design of
New Anti-Inflammatory Drugs: A Review of 2012 - 2018No Title,” Curr. Med. Chem., vol. 27, no. 3, pp. 477497, 2020.
[25] K. B. Glaser, “Regulation of Phospholipase A2 Enzymes: Selective Inhibitors and their Pharmacological Potential BTNo Title,” Adv. Pharmacol., vol. 32, pp.
3166, 1995.
[26] T. great plains Laboratory, Phospholipase A2 (PLA2) And Viruses How Lowering PLA2 May Help Stifle The Impact Of Serious Viral Infections Like
Coronavirus GENERAL,” 2020. [Online]. Available:
[27] Y. Y. Tan, T. L. and Goh, “The role of group IIA secretory phospholipase A2 (sPLA2-IIA) as a biomarker for the diagnosis of sepsis and bacterial infection
in 173 adults—A systematic reviewNo Title,” PLoS One, vol. 12, no. 7, pp. 113, 2017.
[28] and B. S. C. Nhat D. Quach, Robert D. Arnold, “Secretory Phospholipase A2 Enzymes as Pharmacological Targets for Treatment of DiseaseNo Title,”
Biochem. Pharmacol., vol. 90, no. 4, pp. 338348, 2015.
[29] V. Petan, T. and Brglez, “Secreted phospholipases A 2 in cancer : Diverse mechanisms of actionNo Title,” Biochimie, vol. 107, pp. 114123, 2014.
[30] M. H. Rosenson, R. S. and Gelb, “Secretory phospholipase A2: A multifaceted family of proatherogenic enzymesNo Title,” Curr. Cardiol. Rep., vol. 11, no.
6, pp. 445451, 2009.
[31] K. Murakami, M., Taketomi, Y., Sato, H., Yamamoto, “Secreted phospholipase A 2 revisitedNo Title,” J. Biochem., vol. 150, no. 3, pp. 233255, 2011.
[32] D. Yedgar, S., Cohen, Y. and Shoseyov, “Control of phospholipase A2activities for the treatment of inflammatory conditionsNo Title,” Biochim. Biophys.
Acta - Mol. Cell Biol. Lipids, vol. 1761, no. 11, pp. 13731382, 2006.
[33] K. . Surrel, F., Jemel, I., Boilard, E., Bollinger, J.G., Payre, C., Mounier, C.M., Talvinen and M. H. Laine, V.J. O., Nevalainen, T.J., Gelb, “Group X
Phospholipase A 2 Stimulates the Proliferation of Colon Cancer Cells by Producing Various Lipid MediatorsNo Title,” Mol. Pharmacol., vol. 76, no. 4, pp.
778790, 2009.
[34] W. . Hallstrand, T. S., Chi, E.Y., Singer, A.G., Gelb, M.H., Henderson, “Secreted Phospholipase A 2 Group X Overexpression in Asthma and Bronchial
HyperresponsivenessNo Title,” Am. J. Respir. Crit. Care Med., vol. 176, pp. 10721078, 2007.
[35] B. Sved, P., Scott, K.F., Mcleod, D., King, N.J.C., Singh, J., Tsatralis, T., Nikolov, B. and P. J. J., Nallan, L., Gelb, M.H., Sajinovic, M., Graham, G. G.,
Russell, “Oncogenic Action of Secreted Phospholipase A 2 in Prostate CancerNo Title,” Cancer Res., vol. 64, pp. 69346940, 2006.
[36] W. Kupert, E., Anderson, M., Liu, Y., Succop, P., Levin, L., Wang, J. and S. K., Chen, P., Pinney, S.M., Macdonald, T., Dong, Z., Starnes, S., Lu, “Plasma
secretory phospholipase A2-IIA as a potential biomarker for lung cancer in patients with solitary pulmonary nodulesNo Title,” Bio med Cent., vol. 11, no.
513, pp. 110, 2011.
[37] B. M. Graff, J.R., Konicek, B.W., Chedid, M., Neubauer, B.L., Deddens, J.A., Hurst and J. H. Colligan, B., Carter, H.W., Carter, “Expression of group IIA
secretory phospholipase A2 increases with prostate tumor grade,” Clin. Cancer Res., vol. 7, no. 12, pp. 38573861, 2001.
[38] H. Jan, J., Chen, B., Ma, S., Liu, C., Tsai, “Potential Dengue Virus-Triggered Apoptotic Pathway in Human Neuroblastoma Cells : Arachidonic Acid ,
Superoxide Anion , and NF-ƘB are Sequentially Involved,” J. Virol., vol. 74, no. 18, pp. 86808691, 2000.
[39] L. G. Juffrie, M., Meer, G M., Hack, C E., Haasnoot, K., Sutaryo., Veerman, A.J., Thijs, “Inflammatory mediators in dengue virus infection in children:
interleukin-6 and its relation to C-reactive protein and secretory phospholipase A2,” Am. J. Trop. Med. Hyg., vol. 65, no. 1, pp. 7075, 2001.
[40] G. S. Jeewandara, C., Gomes, L., Udari, S., Paranavitane, S. A., Shyamali, N. L.A., Ogg and G. . Malavige, “Secretory phospholipase A2 in the pathogenesis
of acute dengue infection,” Immunity, Inflamm. Dis., vol. 5, no. 1, pp. 715, 2017.
[41] L. Zhu, C. Yuan, X. Ding, C. Jones, and G. Zhu, “The role of phospholipase C signaling in bovine herpesvirus 1 infection,” Vet. Res., vol. 48, no. 1, pp. 110,
2017, doi: 10.1186/s13567-017-0450-5.
[42] S. Liebscher et al., “Phospholipase A2 activity during the replication cycle of the flavivirus West Nile virus,” PLoS Pathog., vol. 14, no. 4, pp. 120, 2018,
doi: 10.1371/JOURNAL.PPAT.1007029.
[43] T. H. Oguin et al., “Phospholipase D facilitates efficient entry of influenza virus, allowing escape from innate immune inhibition,” J. Biol. Chem., vol. 289,
no. 37, pp. 2540525417, 2014, doi: 10.1074/jbc.M114.558817.
[44] L. Arbibe et al., “Generation of lyso-phospholipids from surfactant in acute lung injury is mediated by type-II phospholipase A2 and inhibited by a direct
surfactant protein A-phospholipase A2 protein interaction,” J. Clin. Invest., vol. 102, no. 6, pp. 11521160, 1998, doi: 10.1172/JCI3236.
[45] S. Chabot et al., “ Inhibitory Effects of Surfactant Protein A on Surfactant Phospholipid Hydrolysis by Secreted Phospholipases A 2 ,” J. Immunol., vol. 171,
no. 2, pp. 9951000, 2003, doi: 10.4049/jimmunol.171.2.995.
[46] R. Carrasco-Hernandez, R. Jácome, Y. L. Vidal, and S. P. de León, “Are RNA viruses candidate agents for the next global pandemic? A review,” ILAR J.,
vol. 58, no. 3, pp. 343358, 2017, doi: 10.1093/ilar/ilx026.
[47] D. De Luca et al., “Secretory phospholipase A2 pathway in various types of lung injury in neonates and infants: A multicentre translational study,” BMC
Pediatr., vol. 11, no. 1, p. 101, 2011, doi: 10.1186/1471-2431-11-101.
[48] S. Masuda et al., “Expression of secretory phospholipase A2 enzymes in lungs of humans with pneumonia and their potential prostaglandin-synthetic
function in human lung-derived cells,” Biochem. J., vol. 387, no. 1, pp. 2738, 2005, doi: 10.1042/BJ20041307.
[49] N. L. A. Misso, N. Petrovic, C. Grove, A. Celenza, J. Brooks-Wildhaber, and P. J. Thompson, “Plasma phospholipase A2 activity in patients with asthma:
Association with body mass index and cholesterol concentration,” Thorax, vol. 63, no. 1, pp. 2126, 2008, doi: 10.1136/thx.2006.074112.
International Journal of Scientific and Research Publications, Volume 11, Issue 1, January 2021 197
ISSN 2250-3153
This publication is licensed under Creative Commons Attribution CC BY.
[50] M. Y. O. Abdalla, Mohammed, Mohamed Ismail, NE, Mohamed AH, Borik R, ali A, “Plasma Levels of Phospholipids in Patients With COVID-19 ; A
Promising Simple Biochemical Parameter to Evaluate the Disease Severity,” 1811.
[51] E. Barberis et al., “Large-scale plasma analysis revealed new mechanisms and molecules associated with the host response to sars-cov-2,” Int. J. Mol. Sci.,
vol. 21, no. 22, pp. 125, 2020, doi: 10.3390/ijms21228623.
[52] C. Müller, M. Hardt, D. Schwudke, B. W. Neuman, S. Pleschka, and J. Ziebuhr, “Inhibition of cytosolic phospholipase A2α impairs an early step of
coronavirus replication in cell culture,” J. Virol., vol. 92, no. 4, pp. 120, 2018, doi: 10.1128/jvi.01463-17.
[53] R. Vijay et al., “Critical role of phospholipase A2 group IID in age-related susceptibility to severe acute respiratory syndrome-CoV infection,” J. Exp. Med.,
vol. 212, no. 11, pp. 18511868, 2015, doi: 10.1084/jem.20150632.
[54] C.-Y. Jung et al., “Association between Body Mass Index and Risk of Coronavirus Disease 2019 (COVID-19): A Nationwide Case-control Study in South
Korea,” Clin. Infect. Dis., vol. xx, no. Xx Xxxx, pp. 18, 2020, doi: 10.1093/cid/ciaa1257.
[55] J. M. Jin et al., “Gender Differences in Patients With COVID-19: Focus on Severity and Mortality,” Front. Public Heal., vol. 8, no. April, pp. 16, 2020, doi:
[56] T. T. N Kashima , H Nakajima, T Katsura, S Sugihara, A Fukaura, “Study of serum phospholipase A2 activity in bronchial asthmatic patients,” Allergy, vol.
42, no. 6, pp. 723727, 1993.
[57] John E. Burke and Edward A. Dennis, “Phospholipase A2 structure/function, mechanism, and signaling,” J Lipid Res, vol. 50, no. suppl, pp. s237s242,
[58] M. Madjid, M. Ali, and J. T. Willerson, “Lipoprotein-associated phospholipase A2 as a novel risk marker for cardiovascular disease: A systematic review of
the literature,” Texas Hear. Inst. J., vol. 37, no. 1, pp. 2539, 2010.
[59] A. M. N. N. G. Osmankulova, B.T. Kurmanbekova, “Evaluation of lipoprotein-associated phospholipase A2 levels in association with carotid atherosclerosis
in patients with coronary artery disease,” 2020.
[60] Sanja Stankovic and Milika Asanin, “Pathophysiological Role and Clinical Significance as a Cardiovascular Biomarker,” in Lipoprotein-Associated
Phospholipase A2, no. intech open, 2016, pp. 113135.
[61] R. M. Inciardi et al., “Cardiac Involvement in a Patient with Coronavirus Disease 2019 (COVID-19),” JAMA Cardiol., vol. 5, no. 7, pp. 819824, 2020, doi:
[62] M. L. Yang LI, Yongzhong JIANG, Yi ZHANG, Naizhe LI, Qiangling YIN, Linlin LIU, Xin LV, Yan LIU, Aqian LI, Bin FANG, Jiajia LI, Hengping YE,
Gang YANG, Xiaoxian CUI, Yang LIU, Yuanyuan QU, Chuan LI, Jiandong LI, Dexin LI, Shiwen WANG, Zhongtao GAI, Faxian ZHAN, “Abnormal
Upregulation of Cardiovascular Disease Biomarker PLA2G7 Induced by Proinflammatory Macrophages in COVID-19 patients,” 2020.
[63] J. O. Bock and I. Ortea, “Re-analysis of SARS-CoV-2-infected host cell proteomics time-course data by impact pathway analysis and network analysis: A
potential link with inflammatory response,” Aging (Albany. NY)., vol. 12, no. 12, pp. 1127711286, 2020, doi: 10.18632/aging.103524.
First author D.V.D. Hemalika, Ph.D, Faculty of Natural Sciences, The Open University of Sri Lanka
Correspondence Author - D.V.D. Hemalika, Ph.D, Faculty of Natural Sciences, The Open University of Sri Lanka, mobile no: +94711358415
... Citicoline, an essential substance for structural phospholipids of cell membranes, was found to have a neuroprotective effect on patients with neurological diseases [17][18][19][20][21]. Moreover, citicoline properties are also proposed to be able to limit inflammation and viral replication, leading to a cytokine storm, as happened in COVID-19 patients [17,[22][23][24][25][26][27][28][29][30]. There is some evidence for the use of citicoline in neurological studies involving traumatic brain injury patients [31,32]. ...
... The role of phospholipase A2 (PLA2) in the inflammation cascade of COVID-19 has recently begun to be discussed [23]. A study by Abdalla et al. reported a positive correlation between plasma phospholipids depletion, the elevation of secretory phospholipase A2 (member of phospholipase A2 enzymes superfamily), and the occurrence of cytokine storms with the severity of COVID-19 [62]. ...
... Concerning Abdalla et al.'s study, this result may occur because of phospholipid hydrolysis followed by the formation of lysophospholipids, which may, in turn, stimulate cytokine production [23]. PLA2 acts as a catalyzer of the arachidonic acid release, which generates pro-inflammatory lipid mediators such as prostaglandins, leukotrienes, lipoxins, and platelet-activating factors. ...
Full-text available
With growing concerns about COVID-19’s hyperinflammatory condition and its potentially damaging impact on the neurovascular system, there is a need to consider potential treatment options for managing short- and long-term effects on neurological complications, especially cognitive function. While maintaining adequate structure and function of phospholipid in brain cells, citicoline, identical to the natural metabolite phospholipid phosphatidylcholine precursor, can contribute to a variety of neurological diseases and hypothetically toward post-COVID-19 cognitive effects. In this review, we comprehensively describe in detail the potential citicoline mechanisms as adjunctive therapy and prevention of COVID-19-related cognitive decline and other neurologic complications through citicoline properties of anti-inflammation, anti-viral, neuroprotection, neurorestorative, and acetylcholine neurotransmitter synthesis, and provide a recommendation for future clinical trials.
... He emphasized the Sars CoV-2 upregulation of the LpPLA2 enzyme in the production of inflammatory fatty acids and subsequent over production of ROS. CDP choline provided a negative feedback/partial blockade of the PLA2 enzyme [35][36][37]. ...
An effective protocol for COVID-19 treatment was started at an internal medicine clinic in Gulf Breeze, FL and began with a local group of physicians using best practices from review of all the literature including the Sars CoV-1 at the turn of this century. There are limited studies on the early outpatient treatment of COVID-19 using intravenous-ozonated saline. The purpose of this report is to describe our experience.
Full-text available
This work aims at developing a diagnostic method based on Electron Paramagnetic Resonance (EPR) measurements of stable nitroxide radicals released from “EPR silent” liposomes. The liposome destabilisation and consequent radical release is enzymatically triggered by the action of phospholipase A2 (PLA2) present in the biological sample of interest. PLA2 are involved in a broad range of processes, and changes in their activity may be considered as a unique valuable biomarker for early diagnoses. The minimum amount of PLA2 measured “in vitro” was 0.09 U/mL. Moreover, the liposomes were successfully used to perform Overhauser-enhanced Magnetic Resonance Imaging (OMRI) in vitro at 0.2 T. The amount of radicals released by PLA2 driven liposome destabilization was sufficient to generate a well detectable contrast enhancement in the corresponding OMRI image.
Full-text available
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to nearly every continent, registering over 1,250,000 deaths worldwide. The effects of SARS-CoV-2 on host targets remains largely limited, hampering our understanding of Coronavirus Disease 2019 (COVID-19) pathogenesis and the development of therapeutic strategies. The present study used a comprehensive untargeted metabolomic and lipidomic approach to capture the host response to SARS-CoV-2 infection. We found that several circulating lipids acted as potential biomarkers, such as phosphatidylcholine 14:0_22:6 (area under the curve (AUC) = 0.96), phosphatidylcholine 16:1_22:6 (AUC = 0.97), and phosphatidylethanolamine 18:1_20:4 (AUC = 0.94). Furthermore, triglycerides and free fatty acids, especially arachidonic acid (AUC = 0.99) and oleic acid (AUC = 0.98), were well correlated to the severity of the disease. An untargeted analysis of non-critical COVID-19 patients identified a strong alteration of lipids and a perturbation of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, aminoacyl-tRNA degradation, arachidonic acid metabolism, and the tricarboxylic acid (TCA) cycle. The severity of the disease was characterized by the activation of gluconeogenesis and the metabolism of porphyrins, which play a crucial role in the progress of the infection. In addition, our study provided further evidence for considering phospholipase A2 (PLA2) activity as a potential key factor in the pathogenesis of COVID-19 and a possible therapeutic target. To date, the present study provides the largest untargeted metabolomics and lipidomics analysis of plasma from COVID-19 patients and control groups, identifying new mechanisms associated with the host response to COVID-19, potential plasma biomarkers, and therapeutic targets.
Full-text available
Background: Increased body mass index (BMI) has been associated with higher risk of severe coronavirus disease 2019 (COVID-19) infections. However, whether obesity is a risk factor for contracting COVID-19 has been hardly investigated so far. Methods: We examined the association between BMI level and the risk of COVID-19 infection in a nationwide case-control study comprised of 3,788 case patients confirmed with COVID-19 between January 24 and April 9, 2020 and 15,152 controls matched by age and sex, who were aged 20 years or more and underwent National Health Insurance Service (NHIS) health examinations between 2015-2017, using data from the Korean NHIS with linkage to the Korea Centers for Disease Control and Prevention data. Our primary exposure of interest was BMI level categorized into four groups; &18.5 (underweight), 18.5-22.9 (normal weight), 23-24.9 (overweight), and ≥25 kg/m 2 (obese). Results: Of the entire 18,940 study population, 11,755 (62.1%) were women, and the mean (SD) age of the study participants was 53.7 (13.8) years. In multivariable logistic regression models adjusted for sociodemographic, comorbidity, laboratory and medication data, there was a graded association between higher BMI levels and higher risk of COVID-19 infection; compared to normal weight individuals, the adjusted ORs in the overweight and obese individuals were 1.13 (95% CI, 1.03-1.25) and 1.26 (95% CI, 1.15-1.39), respectively. This association was robust across age and sex subgroups. Conclusions: Higher BMI levels were associated with higher risk of contracting COVID-19.
Full-text available
Coronavirus disease 2019 (COVID-19), caused by an outbreak of the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) in Wuhan, China, has led to an unprecedented health and economic crisis worldwide. To develop treatments that can stop or lessen the symptoms and severity of SARS-CoV-2 infection, it is critical to understand how the virus behaves inside human cells, and so far studies in this area remain scarce. A recent study investigated translatome and proteome host cell changes induced in vitro by SARS-CoV-2. Here, we use the publicly available proteomics data from this study to re-analyze the in vitro cellular consequences of SARS-CoV-2 infection by impact pathways analysis and network analysis. Notably, proteins linked to the inflammatory response, but also proteins related to chromosome segregation during mitosis, were found to be altered in response to viral infection. Upregulation of inflammatory response proteins is in line with the propagation of inflammatory reaction and lung injury that is observed in advanced stages of COVID-19 patients and which worsens with age.
Full-text available
The current Coronavirus disease 2019 or COVID-19 pandemic has infected over two million people and resulted in the death of over one hundred thousand people at the time of writing this review. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Even though multiple vaccines and treatments are under development so far, the disease is only slowing down under extreme social distancing measures that are difficult to maintain. SARS-COV-2 is an enveloped virus that is surrounded by a lipid bilayer. Lipids are fundamental cell components that play various biological roles ranging from being a structural building block to a signaling molecule as well as a central energy store. The role lipids play in viral infection involves the fusion of the viral membrane to the host cell, viral replication, and viral endocytosis and exocytosis. Since lipids play a crucial function in the viral life cycle, we asked whether drugs targeting lipid metabolism, such as statins, can be utilized against SARS-CoV-2 and other viruses. In this review, we discuss the role of lipid metabolism in viral infection as well as the possibility of targeting lipid metabolism to interfere with the viral life cycle.
Full-text available
The outbreak of COVID-19 poses unprecedent challenges to global health1. The new coronavirus, SARS-CoV-2, shares high sequence identity to SARS-CoV and a bat coronavirus RaTG132. While bats may be the reservoir host for various coronaviruses3,4, whether SARS-CoV-2 has other hosts remains ambiguous. In this study, one coronavirus isolated from a Malayan pangolin showed 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S genes, respectively. In particular, the receptor-binding domain within the S protein of the Pangolin-CoV is virtually identical to that of SARS-CoV-2, with one noncritical amino acid difference. Results of comparative genomic analysis suggest that SARS-CoV-2 might have originated from the recombination of a Pangolin-CoV-like virus with a Bat-CoV-RaTG13-like virus. The Pangolin-CoV was detected in 17 of 25 Malayan pangolins analyzed. Infected pangolins showed clinical signs and histological changes, and circulating antibodies against Pangolin-CoV reacted with the S protein of SARS-CoV-2. The isolation of a coronavirus that is highly related to SARS-CoV-2 in pangolins suggests that they have the potential to act as the intermediate host of SARS-CoV-2. The newly identified coronavirus in the most-trafficked mammal could represent a future threat to public health if wildlife trade is not effectively controlled.
Full-text available
Objective: The recent outbreak of Novel Coronavirus Disease (COVID-19) is reminiscent of the SARS outbreak in 2003. We aim to compare the severity and mortality between male and female patients with COVID-19 or SARS. Study Design and Setting: We extracted the data from: (1) a case series of 43 hospitalized patients we treated, (2) a public data set of the first 37 cases of patients who died of COVID-19 and 1,019 patients who survived in China, and (3) data of 524 patients with SARS, including 139 deaths, from Beijing in early 2003. Results: Older age and a high number of comorbidities were associated with higher severity and mortality in patients with both COVID-19 and SARS. Age was comparable between men and women in all data sets. In the case series, however, men's cases tended to be more serious than women's (P = 0.035). In the public data set, the number of men who died from COVID-19 is 2.4 times that of women (70.3 vs. 29.7%, P = 0.016). In SARS patients, the gender role in mortality was also observed. The percentage of males were higher in the deceased group than in the survived group (P = 0.015). Conclusion: While men and women have the same prevalence, men with COVID-19 are more at risk for worse outcomes and death, independent of age.
Full-text available
A novel coronavirus (2019-nCoV) originating in Wuhan, China presents a potential respiratory viral pandemic to the world population. Current efforts are focused on containment and quarantine of infected individuals. Ultimately, the outbreak could be controlled with a protective vaccine to prevent 2019-nCoV infection. While vaccine research should be pursued intensely, there exists today no therapy to treat 2019-nCoV upon infection, despite an urgent need to find options to help these patients and preclude potential death. Herein, I review the potential options to treat 2019-nCoV in patients, with an emphasis on the necessity for speed and timeliness in developing new and effective therapies in this outbreak. I consider the options of drug repurposing, developing neutralizing monoclonal antibody therapy, and an oligonucleotide strategy targeting the viral RNA genome, emphasizing the promise and pitfalls of these approaches. Finally, I advocate for the fastest strategy to develop a treatment now, which could be resistant to any mutations the virus may have in the future. The proposal is a biologic that blocks 2019-nCoV entry using a soluble version of the viral receptor, angiotensin-converting enzyme 2 (ACE2), fused to an immunoglobulin Fc domain (ACE2-Fc), providing a neutralizing antibody with maximal breath to avoid any viral escape, while also helping to recruit the immune system to build lasting immunity. The ACE2-Fc therapy would also supplement decreased ACE2 levels in the lungs during infection, thereby directly treating acute respiratory distress pathophysiology as a third mechanism of action. The sequence of the ACE2-Fc protein is provided to investigators, allowing its possible use in recombinant protein expression systems to start producing drug today to treat patients under compassionate use, while formal clinical trials are later undertaken. Such a treatment could help infected patients before a protective vaccine is developed and widely available in the coming months to year(s).
Full-text available
In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed another clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.).
Importance Virus infection has been widely described as one of the most common causes of myocarditis. However, less is known about the cardiac involvement as a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objective To describe the presentation of acute myocardial inflammation in a patient with coronavirus disease 2019 (COVID-19) who recovered from the influenzalike syndrome and developed fatigue and signs and symptoms of heart failure a week after upper respiratory tract symptoms. Design, Setting, and Participant This case report describes an otherwise healthy 53-year-old woman who tested positive for COVID-19 and was admitted to the cardiac care unit in March 2020 for acute myopericarditis with systolic dysfunction, confirmed on cardiac magnetic resonance imaging, the week after onset of fever and dry cough due to COVID-19. The patient did not show any respiratory involvement during the clinical course. Exposure Cardiac involvement with COVID-19. Main Outcomes and Measures Detection of cardiac involvement with an increase in levels of N-terminal pro–brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T, echocardiography changes, and diffuse biventricular myocardial edema and late gadolinium enhancement on cardiac magnetic resonance imaging. Results An otherwise healthy 53-year-old white woman presented to the emergency department with severe fatigue. She described fever and dry cough the week before. She was afebrile but hypotensive; electrocardiography showed diffuse ST elevation, and elevated high-sensitivity troponin T and NT-proBNP levels were detected. Findings on chest radiography were normal. There was no evidence of obstructive coronary disease on coronary angiography. Based on the COVID-19 outbreak, a nasopharyngeal swab was performed, with a positive result for SARS-CoV-2 on real-time reverse transcriptase–polymerase chain reaction assay. Cardiac magnetic resonance imaging showed increased wall thickness with diffuse biventricular hypokinesis, especially in the apical segments, and severe left ventricular dysfunction (left ventricular ejection fraction of 35%). Short tau inversion recovery and T2-mapping sequences showed marked biventricular myocardial interstitial edema, and there was also diffuse late gadolinium enhancement involving the entire biventricular wall. There was a circumferential pericardial effusion that was most notable around the right cardiac chambers. These findings were all consistent with acute myopericarditis. She was treated with dobutamine, antiviral drugs (lopinavir/ritonavir), steroids, chloroquine, and medical treatment for heart failure, with progressive clinical and instrumental stabilization. Conclusions and Relevance This case highlights cardiac involvement as a complication associated with COVID-19, even without symptoms and signs of interstitial pneumonia.