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Authors: Bing Liu et al. Link to paper: https://www.medrxiv.org/content/10.1101/2020.03.26.20044768v1.full.pdf

Journal/ Pre-Print: medrxiv

Key Words: COVID-19, persistent SARS-CoV-2, lymphocytes, clinical practice.

RESEARCH HIGHLIGHTS 

1. Non-severe COVID-19 patients (mild and moderate) have dysregulated immune system (lymphocytopenia) at disease onset.

2. Persistent SARS-CoV2 presence (viral RNA detection for more than 20 days) in non-severe recovered COVID-19 patients is associated with reduced numbers of B and T cells.

3. “Abnormalities” in adaptive immune cells (frequencies) but not clinical symptoms and laboratory indicators, were associated with SARS-CoV2 viral RNA detection in non-severe COVID-19 patients.

SUMMARY 

The detection of SARS-CoV2 RNA has several limitations leading to asymptomatic patients discharge who were positively tested for SARS-CoV2 RNA weeks later. In this paper, the authors suggest that assessing the relative frequency of immune cells (especially adaptive immune cells) might be a better or at least a relevant complementary readout for discharge management of non-severe COVID-19 patients.

IMPACT FOR SARS-COV2/COVID19 RESEARCH EFFORTS

Evaluate a potential outcome in discharge management for COVID-19 patients

STUDY TYPE

· Clinical Cohort study – retrospective study.

STRENGTHS AND LIMITATIONS OF THE PAPER

Novelty: They suggest another parameter than viral RNA detection that has technical limitations, to distinguish false-negative recovered patients (still carrying the virus) to the fully recovered negatively tested patients. First analysis of non-severe patients.

Standing in the field: The idea that lymphocyte counts correlates with disease development has been proposed by many researchers. First time analysis of this landscape in non-severe patients, as a clinical management tool.

Appropriate statistics: Yes, the study design is pretty robust as they age- and sex-matched patients to healthy donors.

Viral model used: Community-infected COVID-19 patients from Wuhan hospital.

Translatability: In principle , lymphocyte counts could provide an additional blood marker to indicate persistence of infection despite recovery from disease. However, it would be necessary to perform a prospective randomized multicentre study (with a bigger sample size) to confirm this.

Main limitations:

- The use of “dysregulated” immune response, is somewhat misleading. Since the patients recovered their immune system is clearly functional and is fighting the disease. The low cell numbers at the onset of the disease could be a mere indication of recruitment to the site of infection and draining lymph nodes.

- They did not show the methods and the FACS gating strategy

- They mention themselves other limitations:

o Study made in a single hospital – selection bias

o Small sample size (N=37; + controls)

o Did not have laboratory results and lymphocyte measurement at disease onset- need of baseline reference (they used other patients for that). Thus, the extent to which viral infection has modulated lymphocyte counts in individual patients is unclear.

o Did not perform quantitative viral RNA detection and isolation of live virus (limited resources and not practical for clinical decision making).