May 5, 2020

Plasma cytokines associated with COVID-19 severity and progression, radiographic severity index of COVID-19 in relation to age and sex, and neonatal late onset infection with SARS-CoV-2

By Denise Baez

NEW YORK -- May 5, 2020 -- In today’s DG Alert, we cover the association between expression levels of plasma cytokines and coronavirus disease 2019 (COVID-19) severity, radiographic severity index of COVID-19 in relation to age and sex, and neonatal late onset infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),

According to a study published in the Journal of Allergy and Clinical Immunology, continuously high levels of IP-10, MCP-3, HGF, MIG, and MIP-1α are associated with deterioration and adverse outcomes in patients with COVID-19.

Yang Yang, MD, Shenzhen Third People's Hospital, Shenzhen, China, and colleagues analysed plasma samples of 11 critically ill patients with COVID-19, 25 patients with severe disease, and 14 patients with moderate disease. Eight healthy controls were also included for comparison.

Patients were aged 22 to 78 years, but most (81.8%) patients who were critically ill were aged 60 years and older, as were 68% of the patients in the severe group. Moderate cases were mainly (64.3%) in the 16- to 59-year age group.

Plasma was collected at the earliest possible time-point after hospitalisation and thereafter. The concentrations of 48 cytokines were measured using Bio-Plex Pro Human Cytokine Screening Panel (Bio-Rad).

A total of 14 cytokines were found to be significantly elevated in COVID-19 cases and showed different expression profiles in patients with different disease severity. Expression levels of IP-10, MCP-3, HGF, MIG, and MIP-1α were significantly higher in critically ill patients, than in patients with severe or moderate disease. Serial detection of these 5 cytokines in 16 cases showed that continuously high levels were associated with deteriorated progression of disease and fatal outcome.

Furthermore, IP-10 and MCP-3 were excellent predictors for the progression of COVID-19, and the combination of the 2 cytokines showed the biggest area under the curve of the receiver-operating characteristics calculations with a value of 0.99.

“In this study, we report biomarkers that are highly associated with disease severity and progression of COVID-19,” the authors wrote. “These findings add to our understanding of the immunopathologic mechanisms of SARS-CoV-2 infection, and provide potential therapeutic targets and strategies.”

Another study, published in Chest Radiology, showed that, among patients with SARS-CoV-2, males aged 50 years or older and females aged 80 years or older showed the highest risk of developing severe lung disease.

Andrea Borghesi, MD, University of Brescia, Brescia, Italy, and colleagues evaluated correlations between an experimental chest x-ray (CXR) scoring system for quantifying lung abnormalities, and the age or sex of patients with SARS-CoV-2.

“The CXR scoring system for quantifying the severity and progression of lung abnormalities in COVID-19 pneumonia was introduced in our Diagnostic Imaging Department,” the authors explained. “The CXR scoring system ranks pulmonary involvement on an 18-point severity scale according to extent and characteristics of lung abnormalities.”

Dr. Borghesi and colleagues analysed CXR reports from 783 patients (67.9% male) hospitalised with SARS-CoV-2 between March 4, 2020, and March 18, 2020. There were no patients aged younger than 20 years in the study and only 15.2% were aged younger than 50 years.

The CXR score was significantly higher in males than in females only in groups aged 50 to 79 years. A significant correlation was observed between the CXR score and age in both males and females. Males aged 50 years or older and females aged 80 years or older with COVID-19 showed the highest CXR score (median ≥8).

Limitations included the retrospective nature of the study and lack of comparison between CXR score and patient comorbidities or final outcome (recovery versus death).

“To the best of our knowledge, this study is the first to examine the relationship between the severity of lung disease and the age or sex in European (Italians) patients,” the authors wrote. “In addition, no published study used a radiographic severity index to analyse these correlations. We believe that the results of our study make a significant contribution to clinicians because they could help to identify at an early stage the highest-risk patients and to know who require specific treatment strategies and which people need to be protected from becoming infected.”

Lastly, in a study published in the American Journal of Perinatology, Danilo Buonsenso, MD, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy, and colleagues describe the case of a newborn born to a mother with SARS-COV-2 who tested negative at birth and 3 days after birth, but tested positive at the 2-week follow-up.

“To date, no information on late-onset infection in newborns to mothers with SARS-CoV-2 contracted in pregnancy are available,” the authors wrote. “This study aimed to evaluate post-discharge SARS-CoV-2 status of newborns to mothers with COVID-19 in pregnancy that, at birth, were negative to SARS-CoV-2.”

The case series included 7 pregnant women with laboratory-confirmed SARS-CoV-2 infection. One woman had a spontaneous abortion at 8 weeks of gestational age, 4 women recovered and are still in follow-up and 2 women delivered. The 2 newborns tested negative for SARS-CoV-2 at birth and 3 days of life. However, at a 2-week follow-up, one newborn tested positive with no symptoms.

“Our findings highlight the importance of follow-up of newborns to mothers with COVID-19 in pregnancy, since they remain at risk of contracting the infection in the early period of life and long-term consequences are still unknown,” the authors concluded.

SOURCE: Journal of Allergy and Clinical Immunology, Chest Radiology, and American Journal of Perinatology