Page 77 - Mesenchymal Stem cells, Exosomes and vitamins in the fight aginst COVID

Pain Physician: August 2020 COVID-19 Special Issue 23:S391-S420

largement (16).The exact mechanism of cardiovascu- Renal Complications of COVID-19
lar complications is not clearly understood, however, Cheng et al (20) reported that most patients
there are some possible mechanisms, either single develop kidney injury within 7 days of admission.
or in combination, that seem to be responsible for The exact pathogenesis of kidney involvement in
the poor outcome. Some observed mechanisms are COVID-19 infection is unclear, however, it is reported
supported by the postmortem study of patients who to be due to a component of multiorgan failure sec-
had died due to SARS during the Toronto SARS out- ondary to systemic sepsis and shock, leading to acute
break. This study reported that the viral ribonucleic tubular necrosis (ATN). A study by Naicker et al (21)
acid (RNA) was detected in 35% of the human heart reported ATN to be based on single-cell transcrip-
samples, providing evidence for direct myocardial tome analysis of ACE2 receptor expression in kidney
injury by the virus (17). Regardless of the relative cells, suggesting the possibility of direct renal cellular
role of the different mechanisms described, the damage from SARS-CoV-2. This report was supported
direct (noncoronary) myocardial injury due to viral by the detection of the virus in a urine sample of an
myocarditis, and the direct effect of widespread in- infected patient (21).
flammation appear to be the most likely mechanisms.
Following are the likely mechanisms. Xiong et al (18) Liver and Other Gastrointestinal
reported that SARS-CoV-2 enters human cells by Complications of COVID-19
binding to angiotensin-converting enzyme 2 (ACE2), The injury to the gastrointestinal tract is not
an aminopeptidase highly expressed in myocardial well understood. However, a significant number of
and pulmonary cell membranes. ACE2 is important patients reported diarrhea, nausea, vomiting, and
for neurohumoral regulation of the cardiovascular abdominal pain. In some patients these symptoms
system in various disease conditions. The binding of were the only clinical presentation. This is supported
SARS-CoV-2 to ACE2 can result in alteration of ACE2, by detection of SARS-CoV-2 RNA in stool samples of
leading to acute myocardial and lung injury. The se- infected patients. It was postulated that ACE2 recep-
vere forms of COVID-19 are characterized by acute tors expressed in the gastrointestinal tract are also
systemic hyperinflammatory response and cytokine affected by COVID-19 (22). Liver injury has been re-
storm resulting in injury to multiple organ involve- ported in the study by Wong et al (22) starting from
ment, including myocardium, and ultimately leading mild liver injury to severe liver damage in COVID-19
to multiorgan failure. The studies have reported high patients. The blood chemistry had shown abnormal
levels of proinflammatory cytokines in patients with liver function tests (LFTs), including increased levels
severe COVID-19 (14). The systemic inflammation of alanine aminotransferase (ALT), aspartate amino-
due to cytokine surge causes hyperdynamic state, transferase (AST), and bilirubin, during the course of
which subsequently increases shear stress secondary the COVID-19 disease.
to increased coronary blood flow causing rupture
of coronary plaque, creating ideal setup for coro- Coagulopathy and Neurologic
nary thrombosis and precipitating acute myocardial Complications of COVID-19
infarction. The type of arrhythmia is variable, and Li et al (23) suggested that viral invasion of the
etiology can be multifactorial, ranging from hypoxic central nervous system by SARS-CoV-2 is possible and
state due to ARDS to myocarditis. The patients with can lead to several neurologic complications, includ-
severe COVID-19 are at the risk of developing hypo- ing seizures, unconsciousness, acute cerebrovascular
kalemia owing to interaction of SARS-CoV-2 with the disease, and encephalopathy. Early reports from Wu-
renin-angiotensin-aldosterone system. Hypokalemia han, China, described COVID-19 as a proinflammatory
increases susceptibility to various tachyarrhythmia. and prothrombotic disease, with an increased risk
Electrolyte imbalance is not uncommon in critically of pulmonary embolism, deep vein thrombosis, and
ill patients, especially in patients with underlying ischemic stroke (15). Massive systemic inflammatory
cardiac disorder (19). Increased basal metabolic process is responsible for disseminated intravascular
rate because of the systemic infection coupled with coagulation (DIC) as another common complication
hypoxia caused by acute respiratory illness, further of COVID-19. The study by Tang et al (24) reported
compromising myocardial oxygen supply, and even- a 71.4% incidence of DIC in nonsurvivors compared
tually altering myocardial demand-supply ratio . with only 0.6% in survivors. This study also reported

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