Authors: Ling Ni et al.

Link to paper: https://doi.org/10.1016/j.immuni.2020.04.023

Journal/ Pre-Print: Immunity

Tags: Immunology/Immunity, Clinical

Research Highlights 

1. Presence of neutralising antibodies in 13 out of 14 hospital discharged COVID-19 patients

2. Antibodies are raised against NP and S-RBD rather than M protease.

3. Positive correlation suggested between strong antibody neutralization and cellular immune response

Summary 

Ling Ni et al. analyse the humoral and cellular immunity in 14 COVID-19 patients with mild symptoms that became virus-free and have been recently discharged from hospital, or two weeks after discharge, and compared to 7 healthy donors. Out of the 14 patient cohort, they observed the presence of SARS-CoV-2 Nucleocapsid (N) and Receptor Binding Domain specific (RBD) IgM and IgG in all patients, with a predominance of IgG1 and IgG3 subclasses. By neutralisation assay using SARS-CoV-2 pseudovirus, they highlight the presence of neutralising antibodies that recognise RBD-S protein in 13 patients. In addition, they measured the presence of SARS-COV2 specific T cells and their ability to secrete IFN-gamma by ELISPOT. They reported a positive correlation between the presence of a high titre of neutralising antibodies and the presence of cellular immunity.

Impact for SARS-CoV2/COVID19 research efforts

A better understanding of the immune response to SARS-CoV2/COVID19 which might help to develop effective strategies for vaccine design and diagnostic tools.

Study Type

· In vitro study

· Clinical Cohort study (14 COVID-19 patients)

Strengths and limitations of the paper

Novelty: The main point and novelty of this study is to follow the neutralising activity of antibodies generated by COVID-19 patients with mild symptoms that became virus-free and were discharged from hospital. The authors try to correlate humoral immunity with the presence of cellular immunity.

Standing in the field:

This study reinforces observations made by other reports concerning the presence of humoral and cellular immunity generated following SARS-COV2 infection. They point out the presence of neutralising antibodies in 13/14 of the patients two weeks after hospital discharge.

Appropriate statistics: The authors use Students t-test for all statistical analyses, despite not testing for normal data distribution, and some data are clearly not normally distributed and so should have been analysed using non-parametric tests.

Viral model used: SARS-COV2 (blood from COVID-19 patients analysed) and SARS-COV2 pseudovirus for neutralization assays.

Translatability: It is not directly translatable but a better understanding of the immune response developed in recovering patients could help with vaccine design.

Main limitations:

- Small cohort size

- The study follows the immunity of recovering patients two weeks after hospital discharge, which is too early after infection to draw conclusions about long-term immunity, which should be assessed at much later time points.

- Figure 2B, one sample doesn’t have dilution data.

- In their figure on cellular immunity (Fig. 3), the example dot plots for the healthy donor provided (Fig. 3A) highlight a lower frequency of T cells in comparison with the two COVID-19 patients that does not correlate with the graph in Fig. 3B. The healthy donor seems to have a higher frequency of CD3-/NK- cells that are not commented on. Their conclusion on the positive correlation between cellular and humoral immunity is overstretched.

- In their patient’s table, they highlight that the data have been measured before treatment; it would be interesting to know what treatment the patients received.