2.1 Pneumonia
Pneumonia can be brought on by a wide range of microorganisms, including
bacteria, viruses, mycoplasma, and fungus. When microorganisms invade,
nonspecific immunity responds positively with the release of
inflammatory factors and other immunomodulators from macrophages, which
are the primary source of inflammatory factors. In the same time,
macrophages directly engulf and kill microorganisms. Following this,
neutrophils and other immune cells are recruited, then neutrophils
perform pathogen clearance by phagocytosis of lysosomes, formation of
neutrophil extracellular traps (NETs), and degranulation to release
myeloperoxidase (MPO), gelatines B (MMP9), while also producing
inflammatory factors and chemokines[30].Surface active proteins
(SP-A, SP-D, etc.) synthesized by alveolar II epithelial cells directly
inhibit microbial activity. The pulmonary immune system maintains a
balance between the clearance of invading pathogens and the functional
and ecological integrity.
The most common pathogens of hospital-acquired pneumonia are
Enterobacteriaceae, Staphylococcus aureus, Pseudomonas aeruginosa and
Acinetobacter baumannii[31]. In some cases, there may be multiple
bacterial infections, concurrent bacterial pneumonia and influenza, or
secondary bacterial infections after an exacerbation of a viral
infection. The most common pathogen for secondary bacterial infections
is Staphylococcus aureus, followed by Streptococcus pneumonia,
Haemophilus influenza, and group A streptococcus[32]. About 25% of
patients develop secondary bacterial infections after influenza A (H1N1)
infection[33].
Influenza A virus infection stimulates IFN-β transcription, which in
turn upregulates lnc-ISG20 expression. lnc-ISG20 acts as a ceRNA
competing with ISG20 to bind miR-326, reducing the inhibition of ISG20
translation and negatively regulating the replication of influenza
A[34]. There are also retroviruses known as Prototype foamy virus
(PFV) that cause no clinical symptoms after infection. Lnc-RP5 binding
to miR-129-5p and boost its expression as a result of the infection,
repressing Notch1 to increase the unique internal promoter of PFV, thus
active the expression of the viral transcriptional transactivator, be
critical to the replication, expression, and transportation of
virus[35].
Both lnc-ANRIL and miR-125a are associated with the severity and
pro-infammatory factors level of sepsis, also are high value predictive
biomaker for short‐term sepsis risk and 28‐day mortality[36].
Additionally, lnc‐ANRIL/miR‐125a axis shows more efficient in the
prediction of the sepsis risk, correlation with the organ damage and a
series of inflammatory factors of sepsis[37]. Overexpression of lnc
NKILA leads to the upregulation of miR-21, inhibition of JNK/NF-κB
pathway, and reduces immune response and lung fibroblast apoptosis and
cell viability in pediatric pneumonia[38].
Since Decemeber 2019, the rapid spread of the novel severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) transmitted via
respiratory droplets has led to a worldwide pandemic of the coronavirus
disease 2019 (COVID-19)[39]. Patients who are infected may show no
symptoms for a brief period of time, and rapidly developing a high fever
and severe respiratory symptoms (cough, shortness of breath, etc.),
along with other nonspecific symptoms including malaise, myalgia,
nausea, and vomiting[40].
It has been found that miR-146a-5p, miR-21-5p and miR-142-3p are
relatively lowly expressed and miR-15b-5p is highly expressed in the
serum of COVID-19 patients. Metastasis-associated lung adenocarcinoma
transcript 1 (MALAT1) can bind to miR-146a-5p and miR-142-3p and shows a
negative correlation with both[41]. Furthermore, patients with lower
miR-146a-5p expression levels responded to Tocilizumab less well [40).
MALAT1 and Nuclear-enriched autosomal transcript 1 (NEAT1) expression
was elevated in SARS-CoV-2-infected bronchial epithelial cells[42].
NEAT1 target miR-21 in allergic rhinitis to inhibit its
anti-inflammatory effects and exacerbate the extent of the allergic
inflammatory response[43]. Therefore, it is hypothesized that MALAT1
silencing miR-146a-5 and NEAT1 targeting miR-21 may serve as targets for
COVID-19 therapeutic targeting.