Significant knowledge about COVID-19

The COVID-19 pandemic, which has been going on for a year and a half, has triggered an unprecedented race for scientific knowledge on how to reverse the high infection numbers and limit the consequences of the disease. The resulting flood of scientific data can hardly be kept track of, even by experts. It is becoming increasingly difficult to distinguish between well-founded results, preliminary findings, and hypotheses. This has noticeable consequences, also with regard to the public’s trust in science. While measures to prevent infection became well-known quickly and vaccinations were developed at record speed, important questions about the disease mechanisms of different courses of the disease – asymptomatic to critically ill – remain unanswered. One reason for this is that the body’s own defense reaction triggered by SARS-CoV-2 is extremely complex and inconsistent. As a result, important prerequisites for the development of evidence-based treatment strategies against COVID-19 are missing.

International, interdisciplinary cooperation for reliable COVID-19 knowledge

Scientists from the European Group on Immunology of Sepsis, EGIS for short, have now reviewed and evaluated the bulk of publications. In an overview article published in The Lancet Respiratory Medicine, the group from Vienna – Göttingen and Jena – summarizes the most important findings on the clinical picture of COVID-19 and its different courses of disease. Established as a scientific discussion platform, the network offers the best conditions for viewing and critically examining the overflowing amount of COVID data thanks to its interdisciplinary nature. EGIS is made up of 27 scientists from ten countries, including Priv.-Doz. Dr. Marcin Osuchowski, head of intensive care research at the Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, research center of the AUVA.

“The unconditional cooperation across disciplines and national borders is crucial, especially in the current situation,” emphasizes EGIS coordinator Prof. Dr. Ignacio Rubio from the Jena University Hospital. “Only by pooling scientific expertise as much as possible can we make progress in our quest for reliable COVID-19 knowledge.”

In contrast to other corona viruses, which often only cause mild to moderate cold symptoms, SARS-CoV-2 multiplies in the lower respiratory tract and thus triggers severe pneumonia and even acute lung failure. An essential “infectious advantage” of Sars-CoV-2 is its long-lasting colonization and multiplication in the upper respiratory tract.

SARS-CoV-2 damages the vascular endothelium

“It is astounding to find out that in a certain phase of the disease we see patients whose oxygen content in the blood is reduced to a critical extent, but who initially oftentimes don’t show restrictions in pulmonary ventilation. It is not uncommon for patients to breathe many times more than is normal, even when they are at rest. This is new to us! It is probably a reflection of the fact that the viral infection initially affects the blood vessels rather than the ventilated areas of the lungs, thereby causing severe oxygen deprivation. Virus-related damage to the innermost cell layer of blood vessels, the endothelium, also explains other common COVID-19-typical organ complications such as thrombosis or coagulation disorders,” says Priv.-Doz. Dr. med. Martin Winkler from the University Medical Center Göttingen.

In addition, there is an atypical immune response. In comparison to influenza and other serious infections, pro-inflammatory messengers called cytokines are produced for a longer time in COVID-19, but at much lower levels. This atypical inflammatory profile distinguishes COVID-19 from other septic diseases and may complicate the immune response and thus the efficient elimination of the virus. In fact, a high viral load is associated with disease severity.

COVID-19: a novel severe lung infection

Combined with a dysregulated inflammatory response, damage to the endothelium can affect not only the lungs but also organs such as the brain, heart, kidneys, intestines and liver. Compared to Influenza or SARS, complications such as multi-organ failure and severe coagulation disorders are more common with COVID-19.

Priv.-Doz. Dr. Marcin Osuchowski explains: “SARS-CoV-2 is a new infectious pathogen that poses a new challenge to our immune system. It is therefore understandable that our approach must not be one of simply transferring known and previously represented concepts to COVID-19. It is becoming increasingly clear that the severity of the COVID-19 disease is associated with a dysregulated immune system response that differs from previously known mechanisms and causes of sepsis. We caution against the widespread notion of a systemic cytokine storm as the leading reason for the observed multi-organ responses. The data on this is not yet clear.”

In its summary, the EGIS group formulates research questions that are to be answered with high priority. These include, among other things, the more precise characterisation of the prognostic markers for the course and long-term consequences of the disease, as well as high-quality clinical studies to optimize anticoagulant and immunomodulatory therapies.

Original publication:
Osuchowski MF, Winkler MS, et al.: The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity. Lancet Respir Med 2021 May 6