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.