Novel Strategies to Profile SARS-CoV-2 and Human Lung Proteome: Inflammatory Pathways in the Spotlight

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has caused widespread morbidity and mortality worldwide. SARS-CoV-2 infection triggers innate and adaptive immune responses, but excessive cytokine release can drive hyperinflammation, acute respiratory distress syndrome and poor clinical outcomes. Although serological and molecular assays, such as ELISA and RT-qPCR, remain central to COVID-19 diagnostics, they have limited capacity to reveal host-pathogen interactions at the tissue level. Therefore, profiling the human lung proteome offers a powerful strategy to identify molecular signatures associated with viral pathogenesis and disease severity. This review emphasises emerging technologies that advance lung proteome profiling during SARS-CoV-2 infection. Novel strategies include phage display for high-throughput identification of antibody-antigen interactions, yeast two-hybrid for mapping virus-host protein interactions and lateral flow immunoassays for rapid, point-of-care detection. Conversely, omics-based technologies such as single-cell RNA sequencing, microarrays and mass spectrometry are transforming our understanding of the lung proteome by revealing patterns of gene expression, protein abundance and immune heterogeneity. Therefore, comparing these conventional diagnostic assays with innovative approaches, we highlight their unique contributions to lung proteome research. These tools not only improve diagnostic precision but also hold the potential to uncover biomarkers for early risk stratification and therapeutic targeting. Prioritising integrative proteome-focused strategies may ultimately guide personalised interventions and enhance preparedness for future viral outbreaks.