Abstract :In December 2019, the first case of patient with severe acute respiratory syndrome (SARS) caused by the novel coronavirus, SARS-CoV-2, was reported in Wuhan, Hubei Province, Central China. SARS-CoV-2 causes CoronaVirus Disease-2019 (COVID-19 or nCoV-19) disease, which rapidly spread all over the world. In response to this serious situation, on 30 January 2020, the World Health Organization (WHO) declared a global public health emergency of international concern, putting all health organizations on high alert. In mid-March 2020, WHO declared nCoV-19 a pandemic. By the end of September 2020, there were ~33.67 million confirmed cases and ~10.08 lakh deaths worldwide and the trend rising on each passing day. SARS-CoV-2 mainly infects the pulmonary system, but cause damage to other organs such as heart, kidney and intestine. Understanding the cardio-pulmonary issues underpinning of nCOV-19 pathogenesis is key to managing outcomes and mortality. SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease inhibitor TMPRSS2 for S protein priming. Alveolar cells and cardiomyocytes express ACE2 and TMPRSS2. In this Review, we summarize the current understanding of nCOV-19 pandemic from basic mechanisms to clinical perspectives, focusing on the interaction between SARS-CoV-2 and the cardio-pulmonary-immune signatures. The study provides crucial insights into the first step of SARS-CoV-2 infection, and potential targets for antiviral intervention.