A recent study posted to the medRxiv* preprint server assessed neutrophil extracellular trap (NET) formation and antiviral host response in high-risk coronavirus disease 2019 (COVID-19) patients.

Study: Proteome reveals antiviral host response and NETosis during acute COVID-19 in high-risk patients. Image Credit: solar22/Shutterstock

To date, COVID-19 has affected over 448 million people worldwide, including 6 million deaths. Several studies conducted worldwide have aimed to understand the pathophysiology and symptoms of mild to severe infections. While there is sufficient data concerning the same for the general population, extensive research is needed for individuals at a higher risk of COVID-19.

About the study

The present study assessed the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteome to identify NET formation, pro-coagulatory response, and protein regulation of SARS-CoV-2-specific symptoms. The study involved 65 patients with SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) between March 2020 and August 2020 in Germany, prior to the routine prescription of steroid against COVID-19. Patients were enrolled before or after symptom onset.

The study groups were classified into PCR-positive patients (C19 group), PCR-positive patients requiring oxygen supply (C19-ox), PCR-positive patients with no need for oxygen supply (C19-nonox), an inflammatory control group (Ctrl-infl), and a healthy control group (Ctrl-noninfl).

Demographic data of all the participants, including age, sex, comorbidities, and past medications, were collected. The researchers also obtained clinical data including biomedical indices, inflammation markers like C-reactive protein (CRP), ferritin, or interleukin-6 (IL-6), coagulation markers such as partial thromboplastin time (PTT) or platelet count, past treatments received, and any adverse events.

The ordinal scale developed by the World Health Organization (WHO) to assess the clinical progress of COVID-19 patients was used to classify patients in this study. The patients were sorted into two sub-groups based on disease severity, that is, the patient’s requirement for oxygen supply. Based on the levels of inflammation markers in each patient, three disease phases were determined, namely, COVID-19-acute-early, COVID-19-acute-late, and COVID-19-recovery phase.

The team collected 129 samples from all participants over the different disease phases and performed proteomic analysis. Also, the analysis of plasma proteomics and routine biochemical indices was conducted via the comparison of the three disease phases with the control groups, the three phases among each other, and the groups with severe COVID-19 with each other in each of the three disease phases.


The study results showed that 27 patients from the C19-ox group had a WHO score of 4 or higher, while 37 patients from the C19-nonox group had a WHO score of 3 or lower. In the C19-ox and C19-nonox groups, disease severity was observed in patients aged 70 and 57 years, on average, respectively.

Furthermore, 37% and 32.4% of females suffered higher disease severity in the C19-ox and C19-nonox groups, respectively. Also, while there was no difference in the time passed between the onset of COVID-19 symptoms and related hospitalization, C19-ox patients spent significantly longer in the hospitals than the C19-nonox patients.

Among the C19-ox and C19-nonox groups, 59.3% and 37.8% of patients had dyspnea. Nearly 52% and about 54% of patients had a fever, 51.9% and 29.7% of patients had fatigue, while 48.2% and 48.7% of patients had a dry cough, respectively. With respect to comorbidities in the C19-ox and C19-nonox groups, 66.7% and 64.9% of patients had cardiovascular disease, 33.3% and 13.5% of patients had a pre-existing lung disease, 37.0%, and 24.3% had a compromised immune system, 33.3% and 18.9% patients had diabetes, and 22.2% and 18.9% of patients had hyperlipidemia. 

Analysis of the course of the disease showed that the acute-early phase of disease in the C19 patients had lowered lymphocyte counts, which were found to increase in the acute-late and recovery phases. Also, monocyte levels were similarly elevated in the acute-early and acute-late phases in both C19-ox and Ctrl-infl groups, while in the C19-non ox patients, monocyte levels in the acute-early phase were lower than in the acute-late phase. Likewise, a significant elevation of neutrophil proportions was found in C19 patients in the acute-early phase compared to the levels in the acute-late phase.     


The study findings showed that the identification of a COVID-related protein signature helped assess the antiviral response and the activation of NET in patients with severe disease manifestations. The protein regulation in patients with less severe symptoms, on the other hand, had a type-2 centered immune response. The researchers believe that this study helps identify new proteins, which could serve as potential indicators of COVID-19 disease severity. 

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.


Leave a Reply

Your email address will not be published.