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A study published in Nature looks at respiratory viral infections and breast cancer metastasis to the lungs.
The following statements by experts are provided and translated from German to English by the Science Media Center Germany.
Prof Andreas Bergthaler, Professor of Molecular Immunology, Head of the Institute of Hygiene and Applied immunology, Medical University of Vienna, Austria, and Head of the Viral Pathogenesis and Antiviral Immune Responses Research Group, Research Institute for Molecular Medicine of the Austrian Academy of Sciences (CeMM), said:
“The findings presented are innovative and potentially of great clinical relevance. The study provides mechanistic evidence for how respiratory viral infections reactivate dormant disseminated cancer cells (DCCs) and promote metastasis. Although this possibility has been discussed before, the authors of the current study demonstrate a causal link using several approaches. In animal models in which the inflammatory hormone interleukin 6 (IL-6) was genetically removed, no activation of dormant cancer cells occurred after infection with influenza or SARS-CoV-2. The temporal course of this activation could also be described in the animal model, which appears to be initially IL-6-mediated and subsequently dependent on CD4+ T cells (T helper cells; editor’s note).”
“HER2-positive breast cancer is found in 15 to 20 per cent of cases and is an aggressive but treatable form of breast cancer. The study used two well-established transgenic MMTV-HER2+ mouse models (mouse model with susceptibility to HER2+ breast cancer and up to one year of dormant tumour cells in other organs; editor’s note) and an orthotopic mouse model in which breast cancer cells are transplanted. The transgenic models in particular seem well suited to the questions being investigated, as they have a long dormancy phase (phase of inactive tumour cells; editor’s note) of up to one year, which closely mimics the human situation. The use of multiple models in the present study strengthens the generalisability.”
“I would like to note at this point that my expertise in the field of tumour animal models is limited. Mouse-adapted strains of influenza virus and SARS-CoV-2 are used as infection models, both of which are well established and widely used.”
“There are some indications that the present results could be relevant for humans. These include, for example, the fact that the IL-6 signalling pathways described are highly conserved between mice and humans (largely unchanged over the course of evolution; editor’s note).”
“At the same time, it’s important to note that there are species differences and that results from animal models often can’t be directly transferred to humans. The authors therefore also conducted an epidemiological analysis of human data from two large databases (the UK Biobank and the US Flatiron Health database). They concluded that COVID-19 triggers an increased risk of lung metastases in breast cancer patients. When reviewing this human data, it was not clear to me how valid and robust these data actually are in terms of the selected time periods, different potentially influencing factors, effect size and other factors. This may also be due to the fact that I do not have any specialised epidemiological expertise.”
“The study provides an important explanation for the increased COVID-19 mortality in cancer patients: it describes a direct mechanism by which respiratory viral infections can influence the reactivation of the DCC via inflammatory mediators such as IL-6 and immune cells and ultimately promote metastasis. The combination of experimental data and large epidemiological cohorts provides an important contribution to understanding the consequences of the COVID-19 pandemic in cancer patients. However, I assume that other factors also influence the observed increased mortality of cancer patients after SARS-CoV-2 infection.”
Prof Carsten Watzl, Scientific Director of the Immunology Research Unit of the Leibniz Research Centre for Working Environment and Human Factors Dortmund (IfADo), said:
“It is already known that an inflammatory response caused by a chronic infection (e.g. with the hepatitis C virus) can contribute to the development of cancer. What is new and interesting here is that acute respiratory infections can lead to the development of metastases due to the inflammatory response they cause.”
“To investigate this, the authors of the study used a mouse model in which they were able to demonstrate the proliferation of dormant metastatic cells due to the inflammatory response following influenza or SARS-CoV-2 infection. However, it was not shown whether the mice actually died more frequently or earlier from metastases after the infection. The effect also appears to be 10 to 100 times stronger after influenza infection than after infection with the SARS-CoV-2 virus adapted to mice – but this may also be due to the mouse model.”
“Regarding transferability to humans: The study proves that the general phenomenon can also be observed in humans. Of course, the authors cannot prove that it is the same mechanism, as these are epidemiological data.
“However, two independent cohorts show that breast cancer patients with a documented SARS-CoV-2 infection have a higher risk of dying from cancer or developing lung metastases than non-infected patients. Since only documented SARS-CoV-2 infection is examined as a variable, other factors such as stress or fewer visits to the doctor due to the pandemic can be ruled out, as these would also apply to non-infected patients. However, the effect is fortunately limited (approximately twofold, or a 44 percent increased risk in the other cohort). This means that breast cancer patients do not need to completely isolate themselves to prevent respiratory infection at all costs based on this data.”
“The effect was analysed in the early stages of the pandemic, when there were no vaccines and no Omicron variant. Therefore, the study does not take into account the possible protective effect of vaccination. Vaccination significantly reduces the risk of severe disease and thus of a severe inflammatory response after influenza or SARS-CoV-2 infection. It would therefore be expected that vaccination could also reduce the effect on metastasis formation.”
“Future studies should investigate this using the mouse model or other epidemiological data to gain an impression of how significant the metastasis-promoting effect of a respiratory infection really is in vaccinated breast cancer patients.”
“In general, however, this study also shows that respiratory infections have other far-reaching effects in addition to their acute effect on the lungs. Other studies have already shown that the risk of cardiovascular diseases such as heart attacks is increased after a respiratory infection, and this study shows an effect on metastasis formation. These infections should therefore be taken seriously and people should protect themselves with available vaccinations against the disease and, hopefully, also against the secondary consequences.”
‘Respiratory viral infections awaken metastatic breast cancer cells in lungs’ by Shi B. Chia et al. was published in Nature at 16:00 UK time on Wednesday 30 July 2025.
DOI: 10.1038/s41586-025-09332-0
Declared interests
Prof. Carsten Watzl: No COIs.
Prof Andreas Bergthaler: No COI