Page 252 - IJB-8-4

3D Bioprinting for Lung Tissue Regeneration
infection . Numerous case reports have already been diabetes, cardiovascular disease, and cerebrovascular
[36]
published mentioning that lung cavity due to COVID-19 disease . Similarly, Zhang et al. reported disease
[56]
pneumonia as pneumonia weakens the patients’ immunity, severity in older adults (median age, 64 years) with
and secondary infection can occur during this period. pre-existing comorbidities . A study containing 548
[72]
However, a great concern has also been shown toward the COVID-19 patients revealed that the risk factors of
elevation of lung cavity size, which can damage the lung. severe and long-term complications include elder
Unfortunately, patients with pre-existing lung disease or age (surprisingly, males of elder age), underlying
risk factors, which could lead to worse prognosis, are hypertension, underlying cardiac injury, hyperglycemia,
more prone to cavitation [37-43] . and high LDH level, which is associated with sudden
Pulmonary fibrosis is another major threat to death . Interestingly, two comprehensive meta-analyses
[73]
COVID-19. According to research, around 40% of indicate the positive correlation between smoking habit
COVID-19 patients develop ARDS, and 20% have severe and disease progression in patients with critical illness of
ARDS that influence the development of pulmonary COVID-19.
fibrosis. Besides, cytokine storm and abnormal Moreover, males over 65 years with advanced
coagulopathy are the potential factors underlying the hypertension, diabetes, cardiovascular disease, and
development of pulmonary fibrosis. Although pulmonary respiratory diseases are at higher risk of having long-
fibrosis is found to recover in most patients, patients with term irreversible complications, a 6-time higher chance
risk factors of severe complications might develop the of getting hospitalized, and a 12-time higher chance
irreversible form of pulmonary fibrosis [44-49] . Persistent of death than healthy individuals [71,74-76] . Cao et al. and
post-COVID-19 pulmonary fibrosis can develop other researchers found that higher disease susceptibility
permanent pulmonary architectural distortion and occurred in males as a remarkable number of ICU patients
irreversible pulmonary dysfunction in elderly individuals were male compared to the non-ICU patients (89.5% vs.
and heavy cigarette smokers during follow-up compared 46.9%) [70,75,77,78] . Unexpectedly, obesity is another leading
to the mild COVID-19 patients [50,51] . A comparison in risk factor that causes poor outcomes in COVID-19-
pulmonary function between the control subjects and induced lung injury because of the high prevalence of
the COVID-19 survivors revealed decrease in total lung undiagnosed obstructive sleep apnea . Analysis of a
[79]
capacity (TLC), TLC %PRED, forced vital capacity, cohort containing COVID-19 patients admitted into ICU
forced expiratory volume in the first second (FEV1), demonstrates the relation between higher body mass
FEV1/FEV, and DLCO, along with a higher percentage index and intensive care requirements independent of age
of the restrictive lung in the post-COVID-19 group . and comorbidities, such as diabetes and hypertension,
[52]
[80]
3. Risk factors of COVID-19 associated with which is a matter of concern . Among all the
comorbidities, Ebinger et al. found a strong correlation
fatal disease courses between pre-existing diabetes and concerning outcomes
Specification of the risk factors along with disease in COVID-19 patients as lymphocyte counts, amount of
immunopathology related to severe outcomes in red blood cells, and hemoglobin level were comparatively
COVID-19 patients is advantageous for physicians lower in diabetic patients [58,81] . The increased blood
in identifying the high-risk patients who require glucose level caused impaired innate immunity in diabetic
immediate treatment to prevent disease progression and patients. Thus, cytokines’ glycosylation disrupts cytokine
[82]
adverse outcomes . Risk factors include demographic function dependent on type I helper T lymphocytes .
[53]
factors such as age [19,54-56] , diet and lifestyle habits [57,58] , In addition, higher expression of ACE2 in the lungs
underlying diseases and complications [59,60] , and and other tissues of type 2 diabetes mellitus patients is
laboratory indications [61,62] . These aspects can influence associated with chronic inflammation, insulin resistance,
disease severity, progression to critical stage, and long- and endothelial cell activation that, in turn, aggravate
term complications. [63,64] . alveolar-capillary barrier functionality [83,84] . A cohort
Although SARS-CoV-2 infects young, middle- of 54 COVID-19 patients demonstrates the threat of
aged, and older individuals, the dramatic elevation of hypertension toward the severe outcomes of COVID-19,
disease severity has been observed in older adults as such as ARDS, that is surprisingly independent of age .
[85]
activation of the acquired immune system is delayed in Moreover, based on the baseline characteristics of 1591
older people, thereby facilitating viral replication and ICU patients, the risk of hypertension with COVID-
stimulating increased production of pro-inflammatory 19-induced long-term complications and mortality by
response [9,65-71] . While observing the hospital inpatients, affecting lung function and disrupting oxygen delivery as
Wang et al. found that patients requiring ICU admission 49% of patients had pre-existing hypertension [70,82] . Thus,
(n = 36) are of older age (median age, 66 years) and COVID-19-mediated cardiovascular deaths correlate with
have pre-existing comorbidities, including hypertension, poor blood pressure control. Moreover, downregulated

244 International Journal of Bioprinting (2022)–Volume 8, Issue 4