Starting a riot

Among last year’s many stories about influenza (Flu) deaths during the 1918 pandemic, we often heard about the secondary impact of bacteria; they complicate Flu virus infections, causing pneumonia and death. But it’s worth remembering that Flu viruses can sometimes, by themselves, cause viral pneumonia, thanks to their ability to start a riot through the immune response to their presence.

Flu viruses in patients with pneumonia but no sign of bacteria

Viral pneumonia due to Flu virus infection – not because of bacteria that take advantge of th virus infection – is not common but having it can mean severe illness.

Studies such as this one, this one and this one have shown that even when bacteria cannot be grown from sputum or bronchial samples or the blood, pneumonia can still develop.[1,3,6]

Pneumonia due to infection results from damage of the lungs leading to inflammation and fluid build-up that reduces the entry of oxygen into the blood. Seasonal and novel H1N1 Flu virus-infected patients can develop pneumonia.

Start a riot in the blood

We know a lot about what drives the host body’s response to infection; the immune system.[5] Sometimes our own defences can get a little too defensive and end up creating the sort of collateral damage you’d expect to see in a DC superhero movie.

This hyper-excited response is called a “cytokine storm”,[2] or hypercytokinemia, and involves the actions of a highly complex network of chemical messenger proteins, called cytokines, in the blood. They call in a wider arsenal of cells to combat infections, they calm that response down, they have roles in cell death and viral clearance. there are many cytokines; some make inflammation more likely, some less likely….and so on.

When looking at avian Flu virus infection of humans we tend to see such responses occur. These viruses are very “alien” to our human immune system and often very trigger a very aggressive reposnse. With seasonal (human-adapted) Flu virus infection, it doesn’t tend to be the same degree of over-excited response.[3]

Initial responses to infection aim to contain the virus. And at this level, we see a lot of success in virus shutdown. If we didn’t, we’d be sick due to virus infections… ALL. THE. TIME.

These initial responses are die to our innate immunity. It’s not highly specific to a particular strain of the virus, but is still complex and is the director of a moderated inflammatory response.

Cloudy bu no cytokine storm?

Pure viral pneumonia is caused by cytokine storm, but the term and research are mostly limited to cases of infection by the more exotic viruses; animal Flu viruses that only rarely spillover and infect humans. These zoonotic infections result from A/H5N1 or A/H7N9 or the swine A/H1N1, for example.

Cytokine storm doesn’t usually refer to pneumonia that results from infection with every day, seasonally circulating human H3N2 or B/Yamagata of FluB for example.[2] Nonetheless, cytokine storm may be a relevant term to explain what happens when viral pneumonia results from seasonal Flu virus infection as well. Perhaps the lingo will evolve further.

There are also other driving factors that cause inflammation in the lungs like the presence of the optimal virus receptors on cells, how well a virus strain replicates within the cells int infects, an underlying health condition in the host or the nature of any pre-existing host immunity.[4]

The fallout from the riot is real

Bacterial pneumonia as a complication of a Flu virus infection is what we usually read about.[7] But don’t overlook the ability of some Flu viruses to cause pneumonia directly and by themselves. It may not always be labelled something headline-grabbing like “cytokine storm”, but the host immune response and the invading Flu virus can together make a potent and occasionally highly destructive team.

References

  1. Influenza pneumonia: a comparison between seasonal influenza virus and the H1N1 pandemic
    https://erj.ersjournals.com/content/38/1/106
  2. The advent of the cytokine storm
    https://www.ncbi.nlm.nih.gov/pubmed/17551531
  3. Influenza pneumonia among adolescents and adults: a concurrent comparison between influenza A (H1N1) pdm09 and A (H3N2) in the post-pandemic period
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4204512/#b19
  4. The Role of Cytokine Storm in Influenza Pathogenesis
    https://nccid.ca/wp-content/uploads/sites/2/2015/04/PP_23_EN.pdf
  5. New fronts emerge in the influenza cytokine storm
    https://www.ncbi.nlm.nih.gov/pubmed/28555383
  6. Clinical Characteristics of Influenza-Associated Pneumonia of Adults: Clinical Features and Factors Contributing to Severity and Mortality
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482296/pdf/yjbm_90_2_165.pdf
  7. Mechanisms of Severe Mortality-Associated Bacterial Co-infections Following Influenza Virus Infection
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5540941/

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1 thought on “Starting a riot”

  1. Regarding the absence of growth in sputum from influenza patients, I would suggest only that it is not said that bacteria are indeed out of question in these circumstances. The strong inflmmatory response might have killed a lot of germs so that cultures return a false negative results. Or the same germs could have been ‘entrenched’ making biofilms then releasing cells in lesser number. The pathology examination on formalin-fixed brain tissues from 1918-19 deceased patients failed also to produce conclusive evidences about neuroinvasion by the virus or other pathogens despite the clinical spectrum of the Spanish flu included encephalitis. The societal impact of 1918 pandemic was tragic even when seen decades later. Some of the survivors suffered from long-lasting conditions, such as neuro-psychiatric disorders. It was suggested that the large number of inmates in Italian insane asylums – for example – was result of the development of brain damages after the acute phase of infection by H1N1: some of these patients passed their entire life in these institutions, as well as the World War I veterans. So the concentration camps idea born ahead the horrors of the WWII and ended well beyond 1945.

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