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Liu T. et al., posted on medRxvid on 10th March 2020

SUMMARY

In this study Liu and colleagues analyse clinical manifestations and inflammatory markers in patients with severe and non-severe type COVID-19 in attempt to identify parameters valuable in disease prognosis. They report severe type patients are characterized by abnormalities on chest CT, low lymphocyte counts, increased blood CRP, LDH, D-dimer and ferritin levels, as well as elevated plasma IL-6. Levels of IL-6 positively correlate with elevated inflammatory markers and maximal body temperature during hospitalization. In majority of patients, treatment leads to recovery accompanied by significant reduction in IL-6 concentration and improved chest CT images.

RESEARCH HIGHLIGHTS

  1. Severe type patients were characterized by abnormally low lymphocyte counts, elevated markers of inflammation (LDH, CRP, ferritin, D-dimer) and elevated plasma IL-6.
  2. Levels of most cytokines, neutrophil counts and lymphocyte subsets were within normal range in patients with severe and non-severe disease.
  3. Elevated IL-6 levels positively correlated with levels of inflammation markers in blood and maximal body temperature during hospitalization.
  4. IL-6 levels returned to normal range as disease resolved.
  5. In patients who did not recover despite treatment IL-6 levels were further increased.
  6. Severe patients were more likely to receive intensive therapy including glucocorticoids, human immunoglobulin and oxygen therapy.

RESEARCH IMPACT

  • This study corroborates recent reports on low lymphocyte counts and increased proinflammatory cytokine levels in patients with COVID-19.
  • Published data shows cytokine storms are characteristic in patients suffering from respiratory diseases caused by coronaviruses such as SARS and MERS. Emerging data suggests this might also be true for COVID-19. In this paper increase of IL-6 is shown to be associated with severity of COVID-19.
  • Clinical application - quantifying circulating IL-6 levels in patients at hospital admission may help identify those at risk of severe disease who may require treatments such as oxygen therapy.

METHODOLOGY

Case study (69 severe and 11 non-severe COVID-19 patients)

Real-time RT-PCR assay for SARS-CoV-2 to confirm COVID-19

Clinical laboratory blood tests: whole blood cell count, blood biochemistry, markers of inflammation

Flow cytometry analysis of lymphocyte subsets

ELISA quantification of serum cytokine levels

Chest CT scan

STRENGTHS AND WEAKNESSES OF THE PAPER

Strengths

  • Satisfactory number of severe cases. Simple assays, easy to replicate.

Weaknesses

  • Authors claim there is a correlation between disease severity and IL-6 concentration, however they do not definitively demonstrate this. What they do show is that patients with severe disease are likely to have elevated IL-6 at admission, and this increase will diminish with successful treatment.
  • Much lower number of patients in non-severe control group. Very low number of patients with progressive disease despite treatment.
  • There are discrepancies between patient numbers mentioned in different paragraphs of the paper.