# COVID-19 Lung Injury: Unique and Familiar Aspects of Pathophysiology
## 5 Therapeutic and Supportive Strategies for COVID-19  
The COVID-19 pandemic stimulated a concerted global effort to develop novel therapeutics, repurpose approved medications, define optimal supportive strategies, and create effective vaccines to reduce disease burden. Many drugs have shown promise either conceptually or pre-clinically, only to fall short in large-scale clinical trials. Other treatments have demonstrated success, with the caveat that ARDS has been and remains associated with extremely high mortality rates. Recently, our increasing understanding of COVID-19 has provided rationale for the outcomes of some of these trials and has emphasized the importance of timing and patient factors in selecting appropriate therapies. This section provides a brief overview of supportive measures and relevant drug therapies which have been recommended and trialed in COVID-19 patients.  
\begin{table}
\begin{tabular}{p{56.9 pt} p{113.8 pt} p{113.8 pt} p{113.8 pt} p{113.8 pt}} \hline \hline
**Etiology** & **Virulence Profile** & **Immune Profile** & **Microvascular Profile** & **Clinical Profile** \\ \hline COVID-19 & S protein & Inflammasome & Thrombocytopenia & Viral pneumonia, DAD Main infiltrates: monocyte-derived \\
[46; 52; 60; 80; 89; 142] & ACE2-mediated entry & Hypercytokinemia (IL-19, IL-6, IL-8, TNF) & REMS/microthrombi & macrophages, lymphocytes \\  & Strong IFN-I inhibition & Lymphopenia & Reduced vasoconstrativity & Lymphocytes \\ \hline Severe Acute & S protein & Inflammasome & & Viral pneumonia, DAD Main infiltrates: monocyte-derived \\ Respiratory Syndrome & ACE2-mediated entry & Hypercytokinemia (IL-19, IL-6, IL-8, TNF) & Thrombocytopenia NETosis/microthrombi & Diffuse lung injury \\
[132; 133; 134; 136] & IFN-I inhibition & IFN-I inhibition & (IL-19, IL-6, IL-8, TNF) & Lymphopenia & —tumorocytes-derived macrophages, lymphocytes \\ \hline Middle East & S protein & Inflammasome & & Viral pneumonia, DAD Main infiltrates: monocyte-derived \\ Respiratory Syndrome & DPP4-mediated cell entry & Hypercytokinemia (IL-19, IL-6, IL-8, TNF) & Thrombocytopenia NETosis/microthrombi & Diffuse-derived macrophages, neutrophils \\
[132; 133; 134; 137] & IFN-I inhibition & Lymphopenia & —tumorocytes-derived macrophages, neutrophils \\ \hline Influenza A Virus & Hemagglutinin & Inflammasome & & Viral pneumonia, DAD Main infiltrates: naïve \\
[134; 135; 138; 139] & Sialic acid-mediated cell entry & Hypercytokinemia (IL-19, IL-6, IL-8, TNF) & Thrombocytopenia (lesser than COVID-19) & Viral pneumonia, DAD Main infiltrates: neutrophils, lymphocytes \\ Respiratory Syncrytial & F/G glycoproteins & CY3 CR1-mediated cell entry & Varying cytokine responses & Not pathogenomic & Bronchioliitis, viral pneumonia Main infiltrates: neutrophils, eosinophils \\
[143; 144; 145] & IFN-I inhibition & Syncytia formation & & & \\ \hline Bacterial Pneumonia & Biofilm formation & Inflammasome & & Various phenotypes of lung injury \\
[146; 147; 148] & Pore-forming toxins & Hypercytokinemia (IL-19, IL-6, IL-8, TNF) & & & \\ \hline Fungal Pneumonia & Biofilm formation & Varying cytokine responses & Not pathogenomic & Various phenotypes of lung injury \\
[159; 160; 165] & Tissue invasion by hyphae & Varying responses & Not pathogenomic & Main infiltrates: neutrophils \\ \hline Non-Pulmonary Sepsis & Various & Hypercytokinemia (IL-19, IL-6, IL-8, TNF) & Thromocytopenia NETosis/microthrombi & Diffuse lung injury \\
[38; 166; 167] & Various & Lymphopenia & Reduced shear stress (shock) & neutrophils \\ \hline \hline \end{tabular}
\end{table}
Table 2: Comparison of COVID-19 to other etiologies of ALI.