Identification of Serum Prognostic Biomarkers of Severe COVID-19 by Quantitative Proteomic Approach (preprint)

The COVID-19 pandemic is an unprecedented threat to humanity provoking global health concerns. Since the etio-pathogenesis of this illness is not fully characterized, the prognostic factors enabling treatment decisions have not been well documented. An accurate prediction of the disease progression can aid in appropriate patient categorization to determine the best treatment option. Here, we have introduced a proteomic approach utilizing data-independent acquisition mass spectrometry (DIA-MS) to identify the serum proteins closely associated with the prognosis of COVID-19. We observed 27 proteins to be differentially expressed between the cohorts of severely ill COVID-19 patients with adverse and favorable prognosis. Ingenuity pathway analysis revealed that 15 out of the 27 proteins might be regulated by cytokine signalling relevant to interleukin (IL)-1b, IL-6 and tumor necrosis factor (TNF), and their differential expression was possibly implicated in the systemic inflammatory response and cardiovascular disorders. We further evaluated the practical prognosticators for the clinical prognosis of severe COVID-19 patients. Subsequent ELISA analyses further uncovered that CHI3L1 and IGFALS could be potent prognostic markers with a high sensitivity. Our findings can help in formulating a diagnostic approach for accurately discriminating severe COVID-19 patients and provide appropriate treatment based on their predicted prognosis.

Corticosteroids for hospitalized patients with mild to critically-ill COVID-19: A multicenter, retrospective, propensity score–matched study (preprint)

Background: Corticosteroids use in coronavirus disease 2019 (COVID-19) is controversial, especially in mild to severe patients who do not require invasive/noninvasive ventilation. Moreover, many factors remain unclear regarding the appropriate use of corticosteroids for COVID-19. In this context, this multicenter, retrospective, propensity score–matched study was launched to evaluate the efficacy of systemic corticosteroid administration for hospitalized patients with COVID-19 ranging in the degree of severity from mild to critically-ill disease.Methods: This multicenter, retrospective study enrolled consecutive hospitalized COVID-19 patients diagnosed January–April 2020 across 30 institutions in Japan. Clinical outcomes were compared for COVID-19 patients who received or did not receive corticosteroids, after adjusting for propensity scores. The primary endpoint was the odds ratio (OR) for improvement on a 7-point ordinal score on Day 15.Results: Of 1092 COVID-19 patients analyzed, 118 patients were assigned to either the corticosteroid and non-corticosteroid group, after propensity score matching. At baseline, most patients did not require invasive/noninvasive ventilation (85.6% corticosteroid group vs. 89.8% non-corticosteroid group). The odds of improvement in a 7-point ordinal score on Day 15 was significantly lower for the corticosteroid versus non-corticosteroid group (OR, 0.611; 95% confidence interval [CI], 0.388–0.962; p = 0.034). The time to improvement in radiological findings was significantly shorter in the corticosteroid versus non-corticosteroid group (hazard ratio [HR], 1.758; 95% CI, 1.323–2.337; p < 0.001), regardless of baseline clinical status. The duration of invasive mechanical ventilation was shorter in corticosteroid versus non-corticosteroid group (HR, 1.466; 95% CI, 0.841–2.554; p = 0.177). Of the 106 patients who received methylprednisolone, the duration of invasive mechanical ventilation was significantly shorter in the pulse/semi-pulse versus standard dose group (HR, 2.831; 95% CI, 1.347–5.950; p = 0.006).Conclusions: Corticosteroids for hospitalized patients with COVID-19 did not improve clinical status on Day 15, but reduced the time to improvement in radiological findings for all patients regardless of disease severity and also reduced the duration of invasive mechanical ventilation in patients who required intubation.Trial registration: This study was registered in the University hospital Medical Information Network Clinical Trials Registry on April 21, 2020 (ID: UMIN000040211).

Identification of Serum Prognostic Biomarkers of Severe COVID-19 by Multi-Layered Quantitative Proteomic Approach (preprint)

The COVID-19 is an unprecedented threat to humanity provoking global health concerns. Since the etio-pathogenesis of this illness is not fully characterized, the prognostic factors enabling treatment decisions have not been well documented. An accurate prediction of the disease progression can aid in appropriate patient categorization to determine the best treatment option. Here, we introduced an innovative approach utilizing data-independent acquisition (DIA) mass spectrometry to identify the serum proteins closely associated with the COVID-19 severity. We observed 23 proteins to be differentially expressed between the cohorts of critically ill COVID-19 patients with adverse and favorable prognosis. Myoglobin (MB), CHI3L1 and IGFALS were found to have a high sensitivity and specificity for their possible use as independent biomarkers to provide information on the disease prognosis. Our findings can help in formulating a diagnostic approach for accurately discriminating severe COVID-19 patients and provide appropriate treatment based on their predicted prognosis.Funding: This work was in part supported by grants from the Japan Agency for Medical Research and Development (JP19fk0108169 to YK and JP19fk0108110/JP20he0522001 to AR).Conflict of Interest: The authors declare no competing interests.Ethical Approval: This research plan and protocol was approved by the Clinical Ethics Committee of Yokohama City University Hospital (B2002000048). This study was also performed with the approval of the Clinical Ethics Committee in each of the medical facilities. Informed consent was obtained from all patients and/or their guardians before serum samples collection.