The first 12 months of COVID-19: a timeline of immunological insights

Abstract

Since the initial reports of a cluster of pneumonia cases of unidentified origin in Wuhan, China, in December 2019, the novel coronavirus that causes this disease - severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - has spread throughout the world, igniting the twenty-first century's deadliest pandemic. Over the past 12 months, a dizzying array of information has emerged from numerous laboratories, covering everything from the putative origin of SARS-CoV-2 to the development of numerous candidate vaccines. Many immunologists quickly pivoted from their existing research to focus on coronavirus disease 2019 (COVID-19) and, owing to this unprecedented convergence of efforts on one viral infection, a remarkable body of work has been produced and disseminated, through both preprint servers and peer-reviewed journals. Here, we take readers through the timeline of key discoveries during the first year of the pandemic, which showcases the extraordinary leaps in our understanding of the immune response to SARS-CoV-2 and highlights gaps in our knowledge as well as areas for future investigations.

Fig. 1. Timeline of key discoveries in the immune response to SARS-CoV-2.

In the case of data that were posted as preprints before peer-reviewed publication, the timeline follows the date of the preprint but the reference list details the peer-reviewed journal publication. ACE2, angiotensin-converting enzyme 2; COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Fig. 2. A hypothetical figure showing how the timing of interferon responses might control innate and adaptive immunity to SARS-CoV-2.

a | When the type I interferon response to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is early and robust, the viral load is quickly controlled, resulting in mild disease. This is followed by normal-level T cell and B cell responses. This may occur in young people or after low-dose viral exposure. b | When the type I interferon response is delayed or reduced early during infection with SARS-CoV-2, viral replication and spread occur. Severe coronavirus disease 2019 (COVID-19) is accompanied by T cell lymphopenia. Despite this, strong antibody responses are induced. Type I interferon induced late during infection may be detrimental in driving pathological responses. This may occur in older adults or after high-dose viral exposure. c | In those individuals who are either genetically or serologically deficient in type I interferon, the replication of SARS-CoV-2 occurs unopposed, causing severe to life-threatening COVID-19. T cell lymphopenia is observed. Compensatory activation of antibody responses occurs but is insufficient to control disease. d | Early post-exposure prophylaxis with recombinant type I interferon can reduce the viral load of SARS-CoV-2 and hasten recovery. However, this leads to reduced antigen load and reduced adaptive immune responses.