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Authors: Carsettiet al., (2020) 

Journal/Pre-Print: MedRXiv

Tags:Clinical, Immunology/Immunity, Inflammation 

Research Highlights 

  1. High frequency of peripheral blood NK cellsisassociated with asymptomatic SARS-CoV-2 infection 

  1. IncreasedmonocytetoNK cellratio is associated with disease severity. 

  1. Early and transient increase of specific IgAisassociated withasymptomatic SARS-CoV-2 infection  


In this study, the authorsperformedaanalysisof innate and adaptive immune responses in 36 patients with a spectrum of SARS-CoV-2 infection (20 asymptomatic, 8 mild and severe cases) and 28 healthy SARs-CoV-2 negative contacts. A higher frequency of circulating NK cells and a transient IgA response were associated withasymptomaticinfection. By contrast monocyte expansion and higher levels of IgA and IgG were characteristic of severe disease. This is a small study, that in its current format does not allow for a comprehensive longitudinal analysis of dynamic changes in immune cell populations. It is further limited by the identification of NK cells on the basis of CD7, which restricts apposite interrogation of NK cells and subsets.   

Impactfor SARS-CoV2/COVID19 research efforts 

  • Understand the spectrum of immune responsein relation to SARS-CoV2/COVID19 infection severity 

  • Immunological correlates of protection from severe disease. 

  • Development of prognostic markers of disease severity. 

Study Type 

  • Clinical Cohort study  

  • PatientCase study 

Strengths and limitations of the paper 

Novelty:In this study ananalysis ofthecellular and humoral immunity across the clinical spectrum of COVID-19 disease, includingindividuals with asymptomatic disease and uninfected contacts, was performed. This study provides some early indication of the potential protective role of NK cells in controlling SARS-Cov-2 infection and that the monocyte to NK cell ratio (MNKR) and levels of specific IgA could be early markers of disease progression.  These are interesting findings that merit further investigation in larger cohorts 

Standing in the field:SARS-Cov2 is known to inducelymphocytopeniaand expansion of monocytes. Findings confirm previous observations in severe disease. 

Appropriate statistics:yes 

Viral model used: The authors used PBMC’s from SARS-CoV-2 infected patients.  

Translatability: The study argues in favour of using Monocyte to NK ratio and levels of serum IgA antibody as clinical markers of disease outcome.This should be confirmed in further studies.  

Main limitations:  

There are several limitations with the study in its current format: 

  1. Greater detail in the clinical characteristics of the cohort should be included.  

  1. The availability of samples during longitudinal follow-up from each patient should be made clear and included in the table. 

  1. In addition to cross-sectional comparison of all analysed samples, individual data from longitudinal sampling should be shown for better interpretation of the findings and better assessment of dynamic changes of immune cell populations. This would be a more meaningful way of presenting data. The heatmaps are not particularly informative. 

  1. The authors included a retrospective analysis of 77 patients with severe COVID. The details of these patients are not included. The % of NK cells in these 77 patients was calculated on the basis of CD56+CD3- while in the current study the identified NK cells on the basis of CD3-CD7+Fsclow . The authors should be consistent. 

  1. The identification of NK cells and monocytes is problematic. The phenotypic analysis and flow panels are very basic. In particular, the NK cell panel provided in supplementary material is limited and not sufficient to reliably identify NK cells and subsets on the basis of CD3, CD7 and CD56.  

  1. Given the degree of lymphopenia in patients with severe COVID-19, data should be presented as absolute counts for lymphocyte populations 

  1. The authors do not justify their criteria for patient selection for the data shown in figure 6b,c,d.Longitudinal data on IgA and IgG are shown for only three patients per group that limit any firm conclusions.  

  1. The authors argue that only severe COVID-19 may result in protective adaptive immunityhowever, they have not performed a comprehensive analysis of T cell specific immunity in asymptomatic individuals.