Article Type : Review Article
Authors : Weimer LE, Cattari G, Fanales Belasio E, Cuccuru E and Vidili Gianpaolo
Keywords : Orgn-Injury; Comorbility; New treatment; SARS-Cov-2; Ederly and Immunocompromised
The global pandemia of Omicron and the latest Variants again puts all the scientific community in big problems. Risk factors for COVID-19 include obesity, older age, underlying medical conditions such as diabetes, inadequate vaccination, and/or being immunocompromised. Elderly living with immunocompromizing conditions including but not limited to active treatment for solid tumor and hematologic malignancies, solid organ transplant recipients, or people living with human immunodeficiency virus, even with appropriate vaccination, are at a greater risk for adverse outcomes from COVID-19 including hospitalization, time in the intensive care unit (ICU), and mechanical ventilation and Severe Side Effects. It is of utmost importance to look at the possible risk of Organn-Injury in Elderly and Immunoompromized patients with COVID-19 and after the sieropositivity. It is essential to understand how co-morbid conditions increase the chance of SARS-CoV-2 infection subsequently increase mortality among elderly patients. It is an emergent need to take precautionary measures to avoid morbidity and mortality. The present literature review demonstrates the impact of COVID-19 on comorbidities and describe the latest farmacacological options .Information provided in the review will play an important role in the management and decision-making efforts to tackle such complications to reduce the further burden of the COVID-19 pandemic in the older population with pre-existing comorbidities
The global pandemia of Omicron and the latest
Variants again puts all the scientific community in big problems. Risk factors
for COVID-19 include obesity, older age, underlying medical conditions such as
diabetes, inadequate vaccination, and/or being immunocompromised [1].
Elderly living with
immunocompromizing conditions including but not limited to active treatment for
solid tumor and hematologic malignancies, solid organ transplant recipients, or
people living with human immunodeficiency virus, even with appropriate
vaccination, are at a greater risk for adverse outcomes from COVID-19 including
hospitalization, time in the intensive care unit (ICU), and mechanical
ventilation and Severe Side Effects [2-3].
It is of utmost importance to look at the possible
risk of Organn-Injury in Elderly and Immunoompromized patients with COVID-19
and after the sieropositivity. It is essential to understand how co-morbid
conditions increase the chance of SARS-CoV-2 infection subsequently increase
mortality among elderly patients. It is an emergent need to take precautionary
measures to avoid morbidity and mortality.
Recognizing these intricate factors
is crucial for effectively tailoring public health strategies to protect these
vulnerable populations [4]. The present literature review demonstrates the
impact of COVID-19 on comorbidities and describe the latest farmacacological
options. Information provided in the review will play an important role in the
management and decision-making efforts to tackle such complications to reduce
the further burden of the COVID-19 pandemic in the older population with
pre-existing comorbidities.
Recents Updates for Combating the
Impact of COVID-19 on Comorbidities
Patients with immunosuppressed
conditions, people with solid-organ trans-plants, metastatic cancers,
hematologic malignancies, advanced or untreated HIV (human immunodeficiency
virus) infection, primary immunodeficiency’s and secondary immunodeficiency,
those receiving cancer chemotherapy, and patients with autoimmune diseases
receiving immunosuppressive biologics and medications. This heterogonous group
of persons had a higher risk of COVID-19-related hospitalization, severe
COVID-19, or death and tend to have higher risk for opportunistic infections. In
addition, prolonged SARS-CoV-2 infection and persistent viral replication not
only cause long duration of symptoms but also risk of emergence of
antiviral-resistant or vaccine-escaped variants, prolonging the pandemic.
Immunocompromised individuals are
at higher risk of severe COVID-19 outcomes. Vaccination remains a critical
preventive mea-sure for this vulnerable population. Although some may have a reduced
response to vaccines, receiving the recommended doses can still provide some
level of protection and potentially mitigate severe disease.
Given the potential for diminished
vaccine response, immunocompromised individuals should be considered for
booster doses based on local guidelines and emerging data. In cases of exposure
to COVID-19, immunocompromised individuals may require specific isolation or quarantine
measures, depending on their risk profile. The management of COVID-19 necessitates
an individualized approach.
In severe COVID-19 cases, antiviral therapies
such as remdesivir may be considered. The decision to use antiviral drugs
should be based on clinical judgment and consultation with specialists from
multidisciplinary areas [5]. In severe COVID-19 cases with significant
inflammatory responses, corticoste-roids like dexamethasone may be used under
close medical supervision. The use drug therapy in specific severe cases of
COVID-19 among immunocompromised patients may be considered on a case-by-case
basis early in the pandemic.
Therapeutic recommendations for antiviral
or immunomodulator therapy of adults with varying severities of COVID-19 are
summarized in (Table 1).
Sars-Cov-2 and Cardiovascular Complications
The major concern is to conclude
whether people with Cardiovascular are at a greater risk for SARS-CoV-2.
Clinical Trials have established the association between cardiovascular
disorders with MERS and SARS infection. Analysis of 637 MERS-CoV revealed that
50 % of cases have a high prevalence of diabetes and high blood pressure, and
30% of cases have a high risk of Cardiovascular Diseases. The interaction of
SARS-CoV-2 with ACE-2 receptors (largely expressed in the heart, in the lungs,
Gastrointestinal System, kidneys) is well documented. It is found that with the
help of ACE-2 receptor interaction, virus reaches cardiac myocytes and
epithelial cells lining the alveolar tissue.
Moreover, ACE-2 has a crucial role
in the neurohumoral regulation of the Cardiovascular System. The engagement of
SARS-CoV-2 with cardiac and alveolar ACE-2 resulted in alteration of ACE-2
signaling that leads to acute injury to the lungs and heart. ACE-2 shields the
heart from the innervation of RAAS, which is involved in the conversion of
Angiotensin-II (Ang II) to Angiotensin (I-VII). Ang II is a powerful
vasoconstriction with proinflammatory activity that induces capillary
endothelial damage, while Angiotensin (I–VII) has opposite action. The entry of
the virus down-regulates the ACE-2 and elevates levels of Ang II, which enhanced
the risk of cardiac injury [6].
Therefore, elevated ACE-2 receptors
will enhance the virus content but have a cardiprotective potential. There is
an alarming escalation in comorbidities among Cardiovascular Disease patients.
The infection intervenes with biochemical pathways relevant to the
Cardiovascular System like ACE-2 pathway, cardiac muscle integrity, fibrinogen
pathways, redox homeostasis, induces breakage of plaques present in the stent,
and finally, aggravates myocardial damage and dysfunction (Figure 1). Heart
injury in patients elderly, immunocompromized, with hypertension, diabetes and
cardiovascular persistent damage are the basic heart illnesses associated with
SARS-CoV-2 infection (Tables 2 -3).
Sars-Cov-2 and Cardiovascular Disease
Underlying cardiovascular diseases
may be more mutual in the geriatric subjects, persons with weakened
immunological systems, high ACE-2 concentrations Individuals with
Cardiovascular had a greater death rate with SARS-CoV-2 infection. SARS-CoV-2
contamination can exacerbate Myocardia Infarction and necrosis, aggravating
myocardial infarction. The exact mechanism contributing to heart injury in
COVID-19 individuals is unknown but assumed to be the involvement of ACE-2. In
a mouse model, lung infection produced ACE-2 dependent cardiac complications in
subjects with SARS-CoV-2 infection. In Toronto, post mortem analysis of
SARS-CoV-2 patient’s revealed SARS coronavirus RNA's existence in heart
samples. Other studies demonstrated that SARS-CoV-2 associated cardiac
complications are distinguished by a cytokine crisis caused by misbalance in
helper T-cell subtype responses and intracellular calcium overload due to
hypoxia, which leads to cardiomyocyte death [7].
Sars-Cov-2
and Myocarditis
Troponin levels (cut-off of 28
pg/mL) representing one of the earliest cardiac damage linked to SARS-CoV-2. A
study with 41 COVID-19 subjects in Wuhan concluded that 12 % of subjects had an
elevated troponin level. In later trials, cardiac injury associated with an
elevated troponin concentration was seen in several hospitalized COVID-19 subjects,
and 22–31% were admitted to the ICU. Myocarditis also has been linked to
elevated virus load with mononuclear invasion in the autopsy samples of
COVID-19 patients, which accounts for 7% of COVID-19-related fatalities.
Sars-Cov-2
and Hypertension
Drugs like ACE-2 inhibitors and
Angiotensin receptors blockers were administered to patients with
cardiovascular disorders, including congestive heart failure and hypertension.
The administered drugs lead to overexpression of ACE-2, thus resulting in an increased
risk of devastating COVID-19. The Word Cardiovascular Society proposed that
subjects administered with ACE-2 elevating drugs for hypertension, diabetes, or
cardiac diseases have a higher risk of SARS-CoV-2 infection and, therefore,
should be monitored [8]. It is unclear whether elevated Blood Pressure in an
uncontrolled manner is a risk factor for acquiring COVID-19 or whether
controlled blood pressure among patients with hypertension. Lippy et al.
demonstrated a 2.5-fold more risk of lethality in COVID-19 with high Blood
Pressure, predominantly in geriatric patients. During the infection, the ACE-2
receptor mediates the entry of the virus into the lung, and patients with high
blood pressure have more devastating results than other clinical conditions.
Sars-Cov-2
and Acute Myocardial Infarction and chronic Myocardial Infarction
Cardiac injury is manifested in
multiple ways in Sars-Cov-2 patients. Contamination, inflammation and febrile
conditions turn the vascular system more vulnerable to clot formation and
interferes with the body's ability to dissolve a clot. Despite arteries being
devoid of fatty acids calcified flow-limiting blockages, chances of cardiac
injury similar to the injury induced by a heart attack (Myocardial Infarction
type 2). The pathology occurs when there is a lack of oxygen supply to the
cardiac myocytes, one of the predominant clinical conditions associated with
SARS-CoV-2 infection. During fever and inflammation, the oxygen demands of
various organs get increased. Suppose the infection is localized in the lung,
the stress level increases, affecting the gaseous exchange, resulting in a
drastic reduction in the supply of O2 to the cardiac muscles. Since
the virus targets the heart, COVID-19 positive patients experience inflammation
in the cardiac muscles, along with those individuals who had been formerly
healthy with no heart problems. This very characteristic of the inflammatory
pathway leads to damage to the cardiac muscle, dysrhythmia, and heart failure.
High systemically mediated inflammation increases both atherosclerotic plaques
breakdown and Acute Myocardial Infarction. In a study, viral infections were
associated with an elevated risk of Acute Myocardial Infarction between the
first seven days of diagnosis of the illness, with 6.1 being the incidence
ratio for influenza and other viruses having a 2.8 ratio. COVID-19 individuals
are at higher risk for AMI due to significant inflammatory responses and
hypercoagulability. The therapy of Acute Myocardial Infarction in COVID-19 subjects
remains questionable. While fibrinolysis may be contemplated in individuals
with a STEMI with COVID-19. According to the ACC, fibrinolysis should be
avoided in those with “low-risk STEMI.” Several facilities conduct PCI more
frequently, and it remains the therapy of preference for lower STEMI with no
right ventricular inclusion or lateral Acute Myorcardial Infarction, mostly
with no hemodynamic instability. If PCI is done, personnel must adopt suitable
PPE, and the catheterization laboratories must be fully disinfected.
Individuals with NSTEMI who are hemodynamically vulnerable must be addressed in
the same way STEMI individuals [9].
Sars-Cov-2 and Cardiomyopathy
In acute Congestive failure (CF),
COVID-19 contamination is the predominantly manifested. Acute Heart Failure
evident in 23 % of COVID-19 subjects at the time of diagnosis, with
cardiomyopathy appearing in 33% of the individual. A study reported that Heart
Failure was detected in 24 % of subjects and associated with an increased
fatality rate. Almost half of the patients with Heart Failure had no prior
history of Hypertension or Cardiovascular Disease. It is unknown whether this
Heart Failure results from nascent cardiomyopathy or deterioration of formerly
undiscovered Heart Failure. Right Heart Failure can also happen, especially in
a population with acute respiratory distress syndrome and acute lung injury.
Sars-Cov-2 and Neurological Diseases
The structural features of the
human corona virus and the mechanism of inducing infection make it a potential
host for CNS. The exact mechanism of the human corona virus entering the CNS
remains unclear. The distribution of ACE-2 receptors in the neuronal tissue is
insufficient to describe viral neurotropism. Another possible mechanism could
be axonal transport, which leads to neuronal damage.
The aerosol droplets facilitate the
human corona virus to enter the nasal mucosa of the infected host; thereby, the
virus gains access to the CNS. Once in the CNS, the membrane-bound ACE-2
receptor, ubiquitously present in cerebral capillary endothelium, glial cells,
and neurons, assures SARS-CoVs to fuse with cell surface via spike proteins.
Strong adhesion subsequently leads to further axonal transport resulting in the
spread of infection to the piriform cortex and other regions associated with
olfaction. Within days after the viral entry, it diffuses into the CNS and is
observed in the neuronal region of infected mice or healthy subjects after the
acute manifestation of the infection [10].
Many neurologic complications, including confusion, stroke, and neuromuscular disorders, also manifest during acute COVID-19. Furthermore, disorders such as impaired concentration, headache, sensory disturbances, depression, and even psychosis may persist for months after SARS-CoV-2 infection, as part of a constellation of symptoms now called Long COVID. Even young people with mild disease can develop acute COVID-19 and Long COVID neuropsychiatric syndrome.
Sars-Cov-2 Clinical Manifestations
Neurological manifestations in
COVID-19 positive individuals have become more evident with the prior existence
of neurological problems associated with more intense SARS-CoV-2 infections. In
a study, Sars-Cov-2 hospitalized patients, 8% had pre-existing neurological
disorders, especially pre-existing strokes. Moreover, there was a considerable
increase in Acute Respiratory Distress Syndrome risk devoid of neurological
complications. In another study where 179 subjects were diagnosed with
SARS-CoV-2 pneumonia, prior cardiovascular complications significantly enhanced
mortality. Within the hospitalized group of patients, 6-36% of subjects had
neurological manifestations.
Moreover, 20% of patients were
inflicted with hypoxic-ischemic encephalopathy. Rigorous efforts made to
investigate neurotropism of Covid-19 to address extensive brainstem-mediated
manifestations in both pulmonary and cardiovascular systems [11]. The
identifying features of Covid-19 virus include an envelope, non-segmented,
single-stranded, positive-sense RNA. The multifaceted pathways through which
the virus inflicts neurological damage directly injure particular receptors,
like ACE-2, 2° hypoxic injury, cytokines storm and anti-retrograde traveling to
the nerve fibers.
Unlike lung epithelia, ACE-2
receptors are also expressed on the Blood Brain Barrier endothelium that links
the viral access to the CNS and damages the vascular system. The coalition of
the SARS-CoV-2 with the lungs epithelia produces a universal Systemic
inflammatory response syndrome that enhances the levels of IL-2, IL-6, IL-15,
TNF- ?; activation of glial cells leads to extensive production of
proinflammatory state in CNS. Specifically, IL-6 levels correlate with the
enhanced intensity of the COVID-19 illness.
This alveolar injury and systemic
implications cause severe hypoxia, leading to vasodilation in cerebral vessels,
resulting in decompensated cerebral edema and ischemia. Eventually, the viruses
proceed backward through the bulb and olfactory nerves, generating a pathway
joining the epithelial cells in the nasal cavity and CNS which may also
elucidate the common symptom of anosmia.
Impact of COVID-19 on acute
cerebrovascular disease with neurological indications: strocke, ictus,
tromboembolism. One of the most prevalent and significant neurological
manifestations observed in COVID-19 patients includes acute cerebrovascular
disease. SARS-CoV-2 produce a universal inflammatory response and hyper
coagulation, resulting from enhanced D-dimers, prolonging prothrombin time and
disseminated intravascular coagulation.
In an Italian cohort, the rate of
ischemic stroke was 2.5% in hospitalized COVID-19 patients, despite prophylaxis
thromboembolism admission. In comparison, the Chinese cohort reported a 5%
higher rate of ischemic stroke. Comparably, in Dutch, the prevalence of
ischemic stroke was found to be 3.7% in ICUs admitted patients despite the
prophylaxis of thromboembolism. Notably, in younger patients, ischemic stroke
with large vessel occlusions was reported. Moreover, COVID-19 patients are
prone to severe hypoxia in the cerebral region and infarcts, especially in
patients with a prior cerebrovascular disorder. Inflammation and hyper
coagulation can significantly enhance the chances of ischemic stroke, the
greater risk associated with older patients.
The protection of front-line
workers during the evaluation of COVID-19 patients with stroke-like symptoms is
of utmost importance. However, continuous medical care is required for patients
diagnosed with ischemic stroke based on their institution laying special
attention to intravenous thrombolytic medicaments and endovascular thrombectomy
in the appropriate clinical scenarios without altering intervention criteria
[12].
Sars-Cov-2
and Parkinson Disease and Associated Symptoms
Early reports describe worsening of
parkinsonian symptoms during infection and poor prognosis. SARS-CoV-2 infection
increased both motor and non-motor symptoms of Parkinson Disease, including
stiffness, tremor, trouble walking, mood problems, cognition, and exhaustion.
Viral infected Parkinson Disease patients report worsening Parkinson Disease
symptoms, contribute to systemic inflammation, altered dopaminergic signaling,
or changes in drug pharmacokinetics. Direct infection of the CNS by SARS-CoV-2
is unlikely to worsen symptoms. Although COVID-19 has been linked to
alterations in neuroimaging and SARS-CoV-2 RNA has been found in the cerebral
fluid. Exacerbation of Parkinson Diseases symptoms during COVID-19 could be
partially attributed to the disease's inflammatory response. The widespread
occurrence of COVID-19-related symptoms exacerbation in Parkinson Disease
patients underscores the need to consider COVID-19 as a possible explanation
for rapidly increasing Parkinson Disease-related symptoms.
A higher percentage of women with
Parkinson Disease affceted by COVID-19 than men. Women were not overrepresented
in other case studies of patients with Parkinson Disease and COVID-19. COVID-19
has been shown to cause more severe disease in men than in women [13], but
women may be more vulnerable.
Many Parkinson Disease-related symptoms
worsened with COVID-19 infection. 18% of SARS-COV-2 patients reported new motor
symptoms, while 55% indicated worsening at least one previous motor symptom.
Non-motor symptoms were reported as new or deteriorating in all domains: mood
(20 % new, 51 % worsening), cognitive (7.8% new, 41 % worsening), sleep (12 %
new, 59 % worsening), and autonomic dysfunction (12 % new, 59 % worsening).
Impact
of COVID?19 on encephalitis and encephalopathy
SARS-CoV-2 related encephalitis
have been rarely found. Encephalitis is characterized by convulsions, nausea,
unconsciousness the onset of febrile conditions. The pathophysiology remains
unknown but is believed from secondary edema to inflammation-induced injury
versus direct viral infection.
Acute Necrotizing Encephalopathy is
a rare brain condition resulting from cytokine crisis and Blood Brain Barrier
damage, characterized by the absence of demyelination. Initially, a
Non-contrast head CT scan illustrates symmetric, widespread lesions, whereas
MRI with T2-weighted FLAIR shows hyperintense signal and internal hemorrhage.
The most commonly affected regions are the thalamus, brainstem, cerebellum,
cerebral white matter. Acute Necrotizing Encephalopathy is more associated with
influenza or zika infection, but this condition is also observed with
SARS-CoV-2 [15].
COVID-19 and Guillain-Barre’ Syndrome
Guillain Barre’ Syndrome is a
symmetrical, escalating flaccid paralysis, often caused by bacterial or viral
illnesses of the pulmonary or GIT. This progressive neuropathy has been
identified to be analogous with SARS-CoV-2 contamination, with five incidents
found in Italy and two more incidents from Wuhan (China). All subjects felt a
prelude of upper respiratory infections spanning from 1 to 14 days before the
progression of symptomatic weakness; respiratory failure was reported in three
patients. All subjects had a positive nose swab PCR test and lung scanning
feature of SARS-CoV-2, but all CSF specimens were negative for SARS-CoV-2.
Since all subjects were administered with IVIG, others that suffered pulmonary
insufficiency fared poorly. Notably, brain and spine MRI failed to reveal
discrepancies in 50 % of the patients, indicating the requirement of more profound
tests and consultations, like studies based on the conduction of nerves, when
there is a significant therapeutic concern even in the lack of radiological
data [16].
Impact of Sars-Cov-2 on Diabetes Mellitus
Diabetes Mellitus is a
proinflammatory condition defined by an incorrect and excessive cytokine
reaction, as demonstrated in Sars-Cov-2 subjects, there are an increased blood
counts of IL-6, CRP, and ferritin. This shows that persons with diabetes are
vulnerable to an Inhaled corticosteroids, leading to shock, ARDS, and prompt
Sars-Cov-2 infection. Furthermore, COVID-19 individuals with diabetes had
greater D-dimer concentrations. The hypercoagulation cascade in COVID-19
results in catastrophic thromboembolism and probable fatality in the context of
a pre-existing latent pro-thrombotic hypercoagulable state predisposed
condition exacerbated by the presence of Diabetes Mellitus. Diabetes Mellitus
is linked to lower levels of ACE-2, subsequently decreased AT-II and to a
lesser extent AT-I, especially AT I-7 and AT 1–9 individually. The respiratory
ACE-2/AT 1-7 system has been demonstrated to possess anti-inflammatory and
antioxidant characteristics, and ACE-2 has also been demonstrated to protect
against deadly AIA H5N1 infections. As a result, the surge in prevalence of
serious injury to lungs and ARDS associated with COVID-19 could be explained by
reduced ACE-2 expression in Diabetes Mellitus. ARBs/ACEi are routinely utilized
as anti-hypertensive and renoprotective medicines in persons with diabetes. Enhanced
production of ACE-2 is linked to the utilization of ARBs/ACEi as an adaptable
reaction to the increasing concentrations of AT-II. However, SARS-CoV-2
requires ACE-2 as a receptor as an entrance into the pneumocytes of the host
cell. Therefore ACE-2 overexpression would make it easier for the coronavirus
to enter and multiply. When the viruses use the enzyme to access the host
tissue, ACE-2 is down regulated, and it can no longer defend the lungs from
infection [17]. According to a recent study, SARS-CoV-2 non-structural proteins
target hemoglobin's b1-chain, causing iron to dissociate from porphyrin and
decreasing hemoglobin's ability to deliver oxygen (Figure 2).
SARS-CoV-2
and pathophysiology of diabetes Mellitus
COVID-19 can increase insulin
resistance in Type 2 Diabwetes Mellitus and Type 1 Diabetes Mellitus
(particularly individuals who remain overweight and develop insulin
resistance). Even modest Sars-Cov-2 can induce proinflammatory effects, seen by
elevated IL-1b, IL-6, TNF?, MCP-1 & IP-10, leading to insulin resistance.
Furthermore, overweightness, which is usually related to T2 Diabetes Mellitus,
increases the cytokine reaction, exacerbating resistance to insulin.
Covid-19 also raises serum
concentrations of fetuin-A, an ?2- Hermans-Schmid glycoprotein linked to
insulin resistance. Finally, COVID-19 is frequently linked to hypokalaemia,
decreased pulmonary ACE-2, angiotensin-II deprivation, and increased
aldosterone secretion. Hypokalaemia, in turn, can exacerbate glucose regulators
in T1DM and T2DM patients. It is also important to estimate the indirect effect
of COVID-19 medicines on glycaemic control deterioration. Corticosteroids,
commonly given in subjects with ARDS and infection, can cause hyperglycemia
excursions. However, brief exposure in the current clinical context might not
be clinically meaningful; lopinavir-ritonavir may cause lipodystrophy and
consequent insulin resistance. More importantly, as ritonavir is an enzyme
inhibitor, it can lengthen the t1/2 of glucocorticoids, indirectly contributing
to an abnormal glycaemic profile. Interferon-b1 (type 1 interferon) has also
been found as a probable therapeutic approach for COVID-19, and interferon
treatment has been linked to ?-cell destruction. In COVID-19, Azithromycin was
also utilized in conjunction with HCQ. The macrolide antibiotic can raise the
likelihood of dysglycemia in DM patients. Data from Wuhan demonstrated that
roughly 10 % of individuals with COVID-19 and T2DM experienced at least one
incident of hypoglycaemic (3.9 mmol/L) episode in addition to worsening
hyperglycemia [18]. On the other hand, hypoglycemia provides an elevated
incidence of (CV) episodes in the diabetic population by over-activating the
SNS, mobilizing mononuclear cells that are proinflammatory, and raising
platelet activity. Thus, COVID-19 worsens the glycaemic profile in patients
with underlying DM, which further weakens the innate immune reaction and
stimulates the production of proinflammatory cytokines, creating a chain of
circumstances in following (Figure 3).
Impact of COVID-19 on gangrene
Gangrene is defined as
decomposition, and putrefaction of body tissues due to serious microbial
infection or lack of blood supply to the organs. Gangrene is usually associated
with the body extremities such as feet, toes, hands, or fingers but can affect
any body part. Very few reports have been published which relates dry and
intestinal gangrene with COVID-19, suggesting people developing dry gangrene in
toes and fingers due to Sars-Cov-2 associated blood coagulation issues.
Geriatric population with comorbidities
are more severely affected by COVID-19. COVID-19 patients on therapy for
anticoagulation, the subject’s AVT progressed, leading to ischemic necrosis and
dry gangrene of the lower extremities [18-20].
Subjects of COVID-19, the disease could get more intricated by Acute Respiratory Distress Syndrome, sepsis, and multi-organ dysfunction. Non-vasculopathy patientS develops dried gangrene due to COVID-19?s coagulopathy and disseminated intravascular coagulation. Literature also supports that SARS-COV-2 infection leads to hypercoagulability in different forms like gangrene, stroke, pulmonary embolism, and other acute thrombotic complications, thus approving the use of anticoagulant drugs. In COVID-19 patients, the susceptibility of catching thrombosis appears to be multifactorial, including proinflammatory condition, cytokine crisis, hypoxia-induced thrombus, cytopathological effects, and endothelium cell inflammation resulting in the development of intra alveolar or systemic fibrin clots. Hypothesis about how blood clot formation (which can further advance into thrombosis and gangrene) takes place in the COVID-19 patients’ states that “Due to an internal injury in the endothelium of blood vessels either directly by SARS-CoV-2 infection or by the virus-mediated inflammatory immune response, may result in vasoconstriction and the activation of coagulation and blood clotting pathways, resulting in the formation of blood clots” [21], This hypothesis is further demonstrated in (Figure 4). As of now, very few cases have been seen where gangrene is associated with COVID-19. This symptom is considered one of the rarest and needs more research to reach any specific conclusion.
Impact of COVID-19 on endothelial
dysfunctioning
Endothelial
cellular damage participates in the pathology of multiple-organ collapse in
COVID-19 leads to high BP and nephrological disorders mediated by the
interaction with ACE-2 receptors present on the endothelial system. The
protection of the CVS is mediated by endothelial cells (ECs), releasing the
proteins that influence the blood clotting and immune system. Damage to the
Endothelial cells results in extensive cardiovascular tissues damage,
eventually causing spontaneous heart attacks in Sars-Cov-2. Moreover, injury to
the endothelial cells leads to inflammation in the blood vessels, causing
plaque rupture and heart attack, and subsequent cytokine storm to
inflammation-induced heart failure. The major contributing factors towards
endothelial damage includes disbalance between antioxidants and production of
ROS and RNS, left ventricle remodeling, fibrosis by releasing transforming
growth factor-beta (TGF?) by differentiated monocytes.
Drug Therapy for the Latest
Variants
Effectiveness of Monoclonal Antibody-based therapy
Against Covid Variants (June 2024)
Monoclonal antibodies against the
SARS-CoV-2 S protein act through mechanisms related to their structure. First,
the antigen-binding fragments (Fab) prevent the virus from binding to the ACE2
receptors, and second, the Fc fragment can activate the complement system and
bind to the Immunoglobulin Fc receptors (FcRs) on cytotoxic cells that can
eliminate virus-infected cells through Ab-dependent cell-mediated cytotoxicity
(ADCC). Unfortunately, some mAbs can bind to macrophage FcRs and induce a
hyperinflammatory response resulting from Ab-dependent enhancement (ADE) of
cytokine production.
The SARS-CoV-2 RBD has become the
main target of mAbs because of its crucial role in virus entry into host
cells (Table 4). Analysis of the structural relationship between RBD and
anti-RBD NAbs has led to the classification of these antibodies according to
structural features and mechanism of action. Class 1
NAbs, e.g., CT-P59 (regdanvimab), target the receptor binding motif
(RBM). They recognize the RBD in the up conformation, thus blocking the
interaction with the ACE2 receptor. Class 2 NAbs, e.g. LY-CoV1404
(bebtelovimab), target the ACE2 binding site of the RBD in both up and down
conformations. Class 3 antibodies, e.g., S309 (sotrovimab), target the
conserved core domain of the RBD without altering interactions with the ACE2
receptor. Class 4 antibodies, e.g., S2X259, target epitopes in both the
RBM and the core domain of the RBD. Unfortunately, frequent mutations in the
RBD have modified the epitopes recognized by mAbs, resulting in the emergence
of viral variants resistant to mAbs. To address this issue, researchers are
exploring other SRS-CoV-2 regions as potential targets for therapeutic mAbs.
Conclusion
Studying the adaptation trajectory
of SARS-CoV-2, it is crucial to anticipate possible future events rooted in the
molecular mechanisms that underpin the evolutionary success of SARS-CoV-2 is
essential. People with Sars-Cov-2 who have a past medical history of
cardiovascular disorder, elderly, immunocompromized, patients with cancer,
obesity, chronic lung disease, diabetes, or neurological disease had the worst
prognosis and are more likely to develop Acute Respiratory Stress Syndrome or
pneumonia.