The rise of the highly lethal severe acute respiratory syndrome-2 (SARS-2) as corona virus 2019 (COVID-19) reminded us of the history of other pandemics that happened in the last century (Spanish flu) and stayed in the current century, which include Severe-Acute-Respiratory-Syndrome (SARS), Middle-East-Respiratory-Syndrome (MERS), Corona Virus 2019 (COVID-19). We review in this report the newest findings and data on the origin of pandemic respiratory viral diseases, reservoirs, and transmission modes. We analyzed viral adaption needed for host switch and determinants of pathogenicity, causative factors of pandemic viruses, and symptoms and clinical manifestations. After that, we concluded the host factors associated with pandemics morbidity and mortality (immune responses and immunopathology, ages, and effect of pandemics on pregnancy). Additionally, we focused on the burdens of COVID-19, non-pharmaceutical interventions (quarantine, mass gatherings, facemasks, and hygiene), and medical interventions (antiviral therapies and vaccines). Finally, we investigated the nanotechnology between COVID-19 analysis and immune system boosting (Nanoparticles (NPs), antimicrobial NPs as antivirals and immune cytokines). This review presents insights about using nanomaterials to treat COVID-19, improve the bioavailability of the abused drugs, diminish their toxicity, and improve their performance. Graphical Abstract