COVID-19 pandemic was heralded by the 2003 SARS epidemic which led to the discovery of human and civet SARS-CoV-1, bat SARS-related-CoVs, Middle East respiratory syndrome (MERS)-related bat CoV HKU4 and HKU5, and other novel animal coronaviruses. The suspected animal-to-human jumping of 4 betacoronaviruses including the human coronaviruses OC43(1890), SARS-CoV-1 (2003), MERS-CoV(2012), and SARS-CoV-2(2019) indicates their significant pandemic potential. The presence of a large reservoir of coronaviruses in bats and other wild mammals, culture of mixing and selling them in urban markets with suboptimal hygiene, the relatively long duration of environmental survival in environment, habit of eating exotic mammals in highly populated areas, and the rapid and frequent air travels from these areas are perfect ingredients for brewing rapidly exploding epidemics. Nasopharyngeal swab and deep throat secretions are better samples than nasal or throat swabs for routine laboratory testing. Sputum though seldom produced and bronchoalveolar lavage can be useful in those with predominant lower respiratory tract involvement. Stool and urine are generally less useful during the early stage of COVID-19. RT-PCR and viral load study are the tests of choice for rapid case identification and clinical management, while enzyme immunoassay (EIA) for Spike receptor binding domain is useful for retrospective diagnosis of recovery from past exposure. Antigen detection by EIA has a markedly lower sensitivity and can only catch those with higher viral load. Many SARS-CoV-2 proteins including Nsp1, Nsp3, Nsp12, Nsp13,Nsp14, Nsp15, ORF3b, ORF6, ORF8 and ORF9b are found to antagonize interferon response which explain the mild symptoms, the peaking of viral load at the time of clinical presentation, the difficulty in epidemic control by contact tracing, case isolation and quarantine of contacts. Thus injectable or inhaled interferons are reported in randomized control treatment trials. However Nsp10 can interact with NF-kB repressing factor to induce IL8 which potentially induce overexuberant host inflammation at some stage of COVID-19. Thus in addition to antivirals, medium dose steroid and even IL6 antagonist are often given in severe COVID-19. Antivirals including remdesivir, neutralizing antibodies or convalescent plasma are unlikely to be useful if not given during the early stage of the disease. Mutations at the receptor binding domain of the surface spike protein can improve transmissibility and some degree of resistance to passive and perhaps active immunization. Thus these virus variants of concern should be continuously monitored. Admission screening and precautions against airborne, droplet and contact transmission should always be stringently enforced for hospitalized COVID-19 patients.
