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SARS-CoV-2 impairs human immune defences

Natalia Reoutova
20 Aug 2020
From left: Dr Li Liu, Dr Kelvin To, Prof Zhiwei Chen, Prof Kwok-Yung Yuen, Dr Runhong Zhou, Mr Biao Zhou

A Hong Kong study in 41 patients with coronavirus disease 2019 (COVID-19) shows that acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in a reduction in the number of immune cells, including T, natural killer (NK), monocyte and dendritic cells (DCs).

Researchers at the AIDS Institute, Department of Microbiology and State Key Laboratory of Emerging Infectious Diseases, University of Hong Kong (HKU), in collaboration with clinicians at Queen Mary Hospital, Pamela Youde Nethersole Eastern Hospital and Princess Margaret Hospital, evaluated the immune cell profiles of 17 acute patients (APs) and 24 convalescent patients (CPs) with COVID-19, and compared them with those of healthy donors (HDs). [Immunity 2020, doi: 10.1016/j.immuni.2020.07.026]

“The major challenge for COVID-19 vaccine development is not knowing what kind of vaccine-induced immune responses are needed for protection. Therefore, we aimed to learn from patients naturally infected by SARS-CoV-2,” explained lead investigator, Professor Zhiwei Chen, Director of the AIDS Institute.

Significantly reduced frequencies of broad immune cell types, including T cells, NK cells, DCs and classical monocytes, were observed in APs vs HDs. In contrast, the frequency of monocytic myeloid-derived suppressive cells (M-MDSCs) was significantly higher in APs vs HDs. “Since the majority of AP samples were tested within 3 weeks of symptom onset, our results indicate that acute SARS-CoV-2 infection leads to broad immune cell reduction during the early phase of infection,” highlighted the researchers.

Of note, while many CPs had increased frequencies of lymphocytes, including T and NK cells, their DC and monocyte frequencies remained significantly lower compared with HDs. “These observations suggest that there is likely a broad suppression of monocyte and DC populations, with shorter-term effect on NK and T cells in COVID-19 patients,” wrote the researchers.

Although few APs included in the study received even a low dose of steroid treatment, the frequency and functionality of their peripheral DC subsets reduced significantly and rapidly upon symptom onset. “Plasmacytoid DCs [pDC] are potent and major type-I interferon producers in response to viral infection. Therefore, the significant loss of these cells, coupled with the reduction of NK cell numbers among severe cases, may lead to immediate abolishment of innate immunity against SARS-CoV-2,” commented the researchers. “These findings may explain the significant efficacy of our early interferon beta-1b cocktail treatment.” [Lancet 2020;395:1695-1704]

APs were divided into mild (n=11) and severe (n=6) cases to evaluate the impact of disease severity on patients’ immune cell profiles. Results showed that the frequency of M-MDSCs and the ratio of conventional DCs (cDC) to pDCs were significantly higher in severe vs mild patients. “Our results suggest that a high cDC:pDC ratio of about 50-fold may serve as a potential biomarker for severe sickness,” they proposed.

In addition, 39 percent of CPs did not develop measurable Spike protein receptor-binding domain–specific T cell responses. While these findings may have been affected by the method used to measure T cell response, lacking specific T cell responses was proposed by the researchers as one of the potential mechanisms allowing SARS-CoV-2 to evade immune control as well as the reason for prolonged viral shedding vs SARS-CoV.

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