2020-09-16 11:53
by Lisa Keilhofer
  Last edited: 2020-09-22 10:48

What happens when a (THE!) virus infects your lung – and which circumstances lead to a mild course?

lung microbiome
Until not long ago, the lung was considered more or less sterile. (Picture: © sewcream - stock.adobe.com)

It has been about nine months now, that the new Corona virus is on its conquest around the globe. It forwards from host to host, efficiently spreading on every continent. Proud of being a serious and independent platform, we refrained from publishing any news on the matter in the first months of insecurity. The virus was simply too new and any statement would have been pure speculation. This is why we came up with only one article with general advice on how to best prepare for an(y) infection.

Recommendation: Corona everywhere? Take a deep breath!

As of today, middle of September 2020, we collected a reasonable amount of data and are happy to be able to point out especially one very profound study: The US National Library of Medicine’s National Institutes of Health published a concise summary of all studies published so far. 

The study analyzed all entries on the databases PubMed and Scopus for the keywords (SARS-CoV-2) OR (coronavirus disease 2019) OR (COVID-19) AND (microbiome) until July 20, 2020. The evaluation focused on a possible correlation between a healthy vs. impaired microbiome and the severity level of the Covid-19 illness. The underlying databases list scientific articles.

What does a healthy microbiome look like?

Until not long ago, the lung was considered more or less sterile. (Article recommendation: The unexplored lung microbiome.)

In fact, a healthy lung is not very densely populated, but with a high diversity. A normal, healthy lung microbiome is home to Firmicutes, Bacteroidetes and Proteobacteria at phylum level, and Prevotella, Veillonella, and Streptococcus at genus level. In cases of lung disease, it is just the other way round: the diversity is reduced, but eventually the density of microbes will predominate. So, a healthy microbiome is constantly keeping its own balance. Inflammations and infections are prevented, and a stable immunity is kept by active immune cells.

What if the lung microbiome is out of balance?

Numerous studies verified specific miss-populations that are typical for certain illnesses. Patients suffering from asthma or bronchitis, for instance, show a prevalence in Haemophilus, Neisseria, Fusobacterium and Porphyromonas. Mucoviscidosis is commonly associated with an abundance of Pseudomonas, Staphylococcus, Stenotrophomonas, Achromobacter, and Streptococcus. Pneumonia is reported to come along with Streptococcus pneumoniae and Haemophilus influenzae type b, as well as the respiratory syncytial virus (RSV). Even courses that require ventilation are precisely described regarding the involved density of bacilli compared to groups with mild courses without ventilation. The first show an increased prevalence in Pseudomonas, Corynebacterium, and Rothia, whereas theshare of Streptococcus and Prevotella is low, compared to mild courses without pneumonia.

Even different cases of pneumonia are associated with different bacteria in the lung microbiome. Rhinovirus, Adenovirus, Influenza and Parainfluenza, as well as RSV are amongst the most common viruses to dwell in our lungs and cause illnesses. This profound database proves diversity and density of the microbiome to be very dynamic, in any case.

Structure of the lung and immunity from pathogens

Naturally, the lung is constantly exposed to environmental impacts and can cope with most of them fairly well by its structure. The lungs are covered by a layer of mucus containing enzymes, proteins and lysozymes. Those are able to kill intruding and potentially deadly viruses. Furthermore, the lung cells are in constant contact with immune cells and can trigger a quick immune response if needed. Macrophages, lymphocytes, lymphoid cells, and neutrophils support the body’s immune response. So, in many cases, harmful invasions can be defanged before entering the body further.

Usually, we absorb pathogens like SARS-CoV-2 via the respiratory tract. When the germs reach the lungs, they bind to the so-called ACE2 (angiotensin-converting enzyme). Next step is the endocytosis, which means the process of the virus conquering a body cell. After that, the virus begins to reproduce and attack further lung cells. The damaged cells die and trigger a series of immune reactions and inflammatory processes. This is also documented pretty well for infections of SARS-CoV-2.

If the immune processes cannot stop the reproduction of the virus, it proliferates and causes serious damage to the lung. The body releases a great amount of cytokines and chemokines as an immune response. This state of hyperinflammation is called “cytokine storm” and results in ARDS (acute respiratory distress syndrome) which is the worst-case scenario of that illness with potentially deadly course. Furthermore, a shift in lung microbiome is documented for SARS-CoV-2 infections. An increase in specific bacteria is described.

The new corona virus comes with a number of smart mechanisms, one of those being a kind of “cap of invisibility”. It forms double-membrane vesicles lacking PRRs (Pattern Recognition Receptors) and making it more difficult for the immune system to detect the intruder. All in all, an infection manifests mainly in the lungs, so it is obvious that an intact or impaired lung microbiome can change the course of an infection for the better or worse.

Correlation between lung microbiome and healthy immune response

It takes a healthy lung microbiome for the lung to trigger an adequate immune response. Research proved especially IL-17-producing γδT cells important and that regular contact to pathogens is important for a proper development of the microbiome with sufficient abundance in those cells. Newborn babies in contact with certain strains of bacteria turned out to be more resilient to inflammatory airway diseases. Also, children who grow up in an environment rich in microbes (meaning in contact with animals, house dust, flower pollen, and other natural impacts) are less prone for allergies and asthma.

Article redommendation: Old friends from the dirt make you happy and healthy

Regarding Covid-19 patients, the number of examined cases is still too little to be able to conclude definite causal links. But still – especially taking into account what we know from the lung microbiome and viral infections, in general – there are hints for severe courses and an impaired lung microbiome. Compared to a healthy control group, patients show a clearly reduced diversity of lung microbes. At the same time, an abundance in opportunistic pathogens like Streptococcus, Rothia, Veillonella, and Actinomyces is reported, while symbionts with immune supportive function are of reduced prevalence.

Another study identified Clostridium hathewayi, Actinomyces viscosus, and Bacteroides nordii as pathogens and a deficiency in the supportive bacteria Eubacterium ventriosum, Faecalibacterium prausnitzii, Roseburia, and Lachnospiraceaetaxa. The same study postulates a direct causal link between the amount of the pathogens Clostridium ramosum and Clostridium hathewayi and the severity of the illness. Also, the fungi Candida albicans, Candida auris, and Aspergillus flavus were identified as indicators for a severe course.

Until today, only two studies (study 1 und study 2) have examined the correlation between lung microbiome and the course of a SARS-CoV-2 infection, so as mentioned in the beginning, it is a bit too early to draw general conclusions (that pandemic came with an overload of premature conclusions, anyway, and we want to provide you with real facts and information, instead). Still, the results we have so far, are interesting and comparable studies show similar results: The lung microbiome and the severity of a course are in causal correlation.

Conclusively, we can say that an intact lung microbiome is generally more capable of fending intruding pathogens. Also, the lung microbiome is the basis for a functioning immune response. The proposition resulting from both studies is therefore that an impaired lung microbiome fosters severe courses with ARDS.

Future studies should focus on that correlation. A possible further research interest would be the effect of probiotic cures, or microbiome transplants. The authors of the study encourage taking as many bronchoalveolar samples from Covid-19 patients as possible and sequence those in order to be able to create a database on which decisions for or against the above-mentioned therapies can be drawn.

Lisa Keilhofer
Lisa Keilhofer
Author

Lisa Keilhofer studied at the University of Regensburg. She works in internationalization and as a freelance editor.

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