The current COVID-19 pandemic caused by the SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2), has already nearly 4.8 million confirmed cases and more than 318,000 deaths.
One of the distressing features of the epidemic is the progression of a significant percentage of patients to acute respiratory distress syndrome (ARDS), requiring invasive mechanical ventilation. The reason behind this severe clinical deterioration is thought to be related to a phenomenon called a ‘cytokine storm.’
What is a Cytokine Storm?
The chief characteristics of this condition include a hyperinflammatory reaction to the infection, with high blood levels of pro-inflammatory cytokines and chemokines like IL-6. This latter chemokine, in particular, causes more severe disruption of blood-gas exchange between the alveoli and capillaries of the lungs.
Many clinical reports from both China and Italy indicate that this condition is closely linked to the development of severe or critical COVID-19 illness. In other words, a more significant proportion of patients with high cytokine levels develop cardiovascular collapse, multi-organ dysfunction, and death.
This finding makes it vital to identify patients with cytokine storms, as well as to treat them and to prevent its occurrence in other patients, if necessary. For this reason, the researchers advise the use of such drugs that have already been approved for clinical use and to reduce the hyperinflammation and thus the number of deaths due to this virus. It is necessary to compile information about how far tocilizumab, for instance, helps to prevent and treat cytokine storms in these patients.
SARS-CoV-2 viruses binding to ACE-2 receptors on a human cell, the initial stage of COVID-19 infection. Image Credit: Kateryna Kon / Shutterstock
What Does Tocilizumab Do?
The drug tocilizumab has recently come into the spotlight due to its ability to inhibit cellular signal transduction via the IL-6 mediated pathway. Its safety has been established in phase III trials for patients with rheumatoid arthritis. There were no complications linked to its use, or deaths, neither any features of disease progression.
Moreover, the drug is not associated with an excessive risk of secondary infection as a result of immunosuppression.
At present, a small trial in China has demonstrated the drug to be effective in COVID-19 patients. Within a few days of commencement of treatment, patients showed improvement of the clinical symptoms, while the fever vanished. The need for oxygen supplementation reduced over time, while lung healing was confirmed by the slow. Still, steady improvement in the ground glass opacities and lung infiltrates on chest CT scanning.
Corresponding improvements in laboratory tests of inflammation confirm that this drug could effectively help COVID-19 patients. Also, a larger randomized controlled trial is being conducted over multiple centers, to assess the effectiveness and safety of tocilizumab in the treatment of new cases of COVID-19 pneumonia.
A related syndrome is secondary haemophagocytic lymphohistiocytosis (sHLH), an often-missed but explosive and lethal increase in cytokine levels that culminates in multi-organ failure. The characteristic cytokine profile of sHLH, when seen in COVID-19 patients, predicts a severe course of the disease.
For this reason, a panel of inflammatory markers like rising ferritin, falling platelet counts, and C-reactive protein is recommended for screening COVID-19 patients with severe disease, to detect the presence of hyperinflammation. This panel, along with an HScore over 169, is useful in picking up the group of patients for whom the death rate could be reduced by immunosuppression. At this threshold, the HScore has a sensitivity of 93% and a specificity of 80%.
The Current Study
The current study published on the preprint server medRxiv* included 94 patients aged 18 years or more who were hospitalized between March 15, 2020, and April 20, 2020. All cases were positive for the RT-PCR (real-time polymerase chain reaction) on a nasopharyngeal swab specimen.
For this study, 44 patients were recruited for the study group and 50 in the control group. Both were matched for age, sex, body mass index, and HScore for inflammatory markers like ferritin, AST, fibrinogen, and triglycerides. The median age was 56 and 66 years in the study and control groups.
The researchers found that the mean HScore was 114 in the group on tocilizumab vs. 92 in the control group. The levels of pro-inflammatory markers were higher in the first group, who also had a more extended period of hospitalization, at almost 18 days.
The rate of survival was much higher in the tocilizumab group, at 61% compared to 48% in the control group. However, the incidence of severe sickness and of survival among male patients who got the drug was higher and lower, respectively, compared to the females who were treated for the infection.
Acknowledging the need for caution in interpreting the findings too broadly, the researchers say,” We await the results of ongoing randomized controlled trials to definitely answer the question of whether Tocilizumab improves survival in COVID-19 ARDS patients.
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.