Re: Virology, transmission, and pathogenesis of SARS-CoV-2; focus on immunology
Dear Editor,
COVID-19 is a worldwide emergency, with many scientists working towards drug discovery. After reading carefully the article published by Cevik et al [1], one understands that there are many unanswered questions regarding the pathophysiology of COVID-19, especially regarding immunology. Indeed, severe disease seems to be associated with a detrimental immune response, leading to cytokine storm that even resembles secondary hemophagocytic lymphohistiocytosis, with increased TNF-α, IFN-γ, and IL-2 among others [2]. Interestingly, the immunologic response produced by patients that necessitated hospitalization but not ICU care, included production of TNF-α, IL-2 and IL-10 among others, but in lower levels that those who were hospitalized in the ICU [3]. Surprisingly, however, it seems that having a mild disease is not associated with production of cytokines such as TNF, IFN-γ, IFN-α, IL-1β and IL-6 [4]. Given the relative lack of immunology studies with SARS-CoV-2 and its similarity with SARS-CoV [5], it is tempting to correlate the abovementioned data with the work of Channappanavar et al [6], where late type I IFN production is associated with lethal SARS disease in mice via inflammatory monocyte recruitment, while either no or early type I IFN production is associated with mild disease. This implies that there may be different types of immune responses in COVID-19 disease leading to different clinical phenotypes [7]. Better understanding of those immune responses, could allow for early risk stratification and appropriate treatment by altering the host immune response.
Conflict of Interest
The authors declare no competing interests.
References
1 Cevik M, Kuppalli K, Kindrachuk J, et al. Virology, transmission, and pathogenesis of SARS-CoV-2. BMJ 2020;371:m3862. doi:10.1136/bmj.m3862
2 Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020;395:1033–4. doi:10.1016/S0140-6736(20)30628-0
3 Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497–506. doi:10.1016/S0140-6736(20)30183-5
4 Thevarajan I, Nguyen THO, Koutsakos M, et al. Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19. Nat Med 2020;26:453–5. doi:10.1038/s41591-020-0819-2
5 Zhou P, Yang X-L, Wang X-G, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020;579:270–3. doi:10.1038/s41586-020-2012-7
6 Channappanavar R, Fehr AR, Vijay R, et al. Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice. Cell Host & Microbe 2016;19:181–93. doi:10.1016/j.chom.2016.01.007
7 Mathew D, Giles JR, Baxter AE, et al. Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science 2020;369. doi:10.1126/science.abc8511
Rapid Response:
Re: Virology, transmission, and pathogenesis of SARS-CoV-2; focus on immunology
Dear Editor,
COVID-19 is a worldwide emergency, with many scientists working towards drug discovery. After reading carefully the article published by Cevik et al [1], one understands that there are many unanswered questions regarding the pathophysiology of COVID-19, especially regarding immunology. Indeed, severe disease seems to be associated with a detrimental immune response, leading to cytokine storm that even resembles secondary hemophagocytic lymphohistiocytosis, with increased TNF-α, IFN-γ, and IL-2 among others [2]. Interestingly, the immunologic response produced by patients that necessitated hospitalization but not ICU care, included production of TNF-α, IL-2 and IL-10 among others, but in lower levels that those who were hospitalized in the ICU [3]. Surprisingly, however, it seems that having a mild disease is not associated with production of cytokines such as TNF, IFN-γ, IFN-α, IL-1β and IL-6 [4]. Given the relative lack of immunology studies with SARS-CoV-2 and its similarity with SARS-CoV [5], it is tempting to correlate the abovementioned data with the work of Channappanavar et al [6], where late type I IFN production is associated with lethal SARS disease in mice via inflammatory monocyte recruitment, while either no or early type I IFN production is associated with mild disease. This implies that there may be different types of immune responses in COVID-19 disease leading to different clinical phenotypes [7]. Better understanding of those immune responses, could allow for early risk stratification and appropriate treatment by altering the host immune response.
Conflict of Interest
The authors declare no competing interests.
References
1 Cevik M, Kuppalli K, Kindrachuk J, et al. Virology, transmission, and pathogenesis of SARS-CoV-2. BMJ 2020;371:m3862. doi:10.1136/bmj.m3862
2 Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020;395:1033–4. doi:10.1016/S0140-6736(20)30628-0
3 Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497–506. doi:10.1016/S0140-6736(20)30183-5
4 Thevarajan I, Nguyen THO, Koutsakos M, et al. Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19. Nat Med 2020;26:453–5. doi:10.1038/s41591-020-0819-2
5 Zhou P, Yang X-L, Wang X-G, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020;579:270–3. doi:10.1038/s41586-020-2012-7
6 Channappanavar R, Fehr AR, Vijay R, et al. Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice. Cell Host & Microbe 2016;19:181–93. doi:10.1016/j.chom.2016.01.007
7 Mathew D, Giles JR, Baxter AE, et al. Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science 2020;369. doi:10.1126/science.abc8511
Competing interests: No competing interests