Friday, 25 September 2020

Differences between pneumonitis occurring with immunotherapy and COVID-19

I've recently took some new training courses as part of my professional role as a medical information specialist, and in one of these I was lucky to be clarified on a current and important aspect related to COVID-19:

On the differences between pneumonitis occurring with immunotherapy and that of COVID-19

The information we were provided relates to what was known by then and might not be the most up-to-date at the time you might be reading this post, so please keep that in mind before assuming the details hereby shared with you are still actual.

Why is it important to understand such differences?

Because as for any chronic patient and due to the impact on the immune system of cancer patients (especially lung cancer ones), their risk of developing lung complications is much higher than for regular patients. In addition, COVID-19 also has the potential to trigger pneumonitis, and therefore a clear diagnosis must be conducted to differentiate.

What are the symptoms of pneumonitis in these groups?

Typical symptoms reported by cohorts from China and Europe refer dyspnoea (difficult breathing), pain, and other symptoms like cutaneous, gastrointestinal or endocrine ones (related to hormonal release); but it is cough, the pain profile and pyrexia (increased body temperature above what is believed to be the expected normal) that sees increased incidence in COVID-19 patients (in comparison to the other group). 

Timing and onset of symptoms is a very important aspect to retain!

Even though, times are not to be taken as absolute indicators for any of the groups, cancer patients reveal peak points with the highest toxicity grade (namely, colitis and pneumonitis) at about 6 and 12 weeks, respectively), whereas for COVID-19 patients the incubation times sits at an average of 4 days.

What other differences have clinicians observed?

In immune-related pneumonitis, the radiological aspect is of peripheral ground glass shadowing that tends to affect the lower lobe specifically; and is almost universally bilateral. This scenario evolves as disease progresses to a more severe condition. Because there is no specific test to scrutinise for a immune-related pneumonitis it might be relevant to associate to all the reported differences a few other relevant tests, such as, a lymphocyte count expected to be normal or higher than normal values in immune-related pneumonitis; also the presence of more than normally expected values of C-reactive protein (CRP) (a protein produced by the liver in response to inflammation), and even more than normal values of sedimentation rates for erythrocytes (usually these red blood cells sediment quite slowly in a normal subject, but for a body fighting with inflammation the sedimentation rate would be faster than expected). Finally, cancer patients undergoing pneumonitis would present with a bronchiolar lavage displaying prominence of eosinophils and lymphocytes.

As to pneumonitis in COVID-19 patients the first line of testing would immediately be the genetic/antibody recognition of the presence of the virus, by means of PCR, after a nasopharyngeal test. But at best this recognises the virus up to a sensitivity of 70-80%. In case of a negative test, a false-negative cannot be ruled out, so subsequent tests are then applied in order to positively affirm of the presence of the virus in patients suffering of pneumonitis, namely, a battery of tests known as liver function tests:

- the LDH test that is typically used to determine in a more accurate fashion where a certain damage is organ-located and the severity of the disease progression, 

- the creatinine kinase test to assed whether the pathology is of a cardiac or skeletal muscle nature (that in association with the troponin test provides a better understanding as to whether damage of the cardiac tissue has taken place); 

- by also checking the aforementioned inflammatory markers described in the paragraph below (especially when considering that clinicians recognise typical values around 100-150 mg/L, 

- a D-dimer test to check on the occurrence of blood clots (where they have noticed that in severely sick patients this indicator is quite elevated - even though such is not specific of thromboembolic disease, but can indicate severe inflammation);

But be sure that the variety of tests available for diagnosis is large and I cannot immediately discuss them all in detail hereby. However, I'd like to add to the pool of exams yet another one the clinicians mentioned, the Beta-D-glucan test that helps them rule out (or not!) pneumocystis infection with fluid buildup in the patients lung.

In summary

Differences and similarities exist between pneumonitis in these two populations of patients, but clinicians have plenty of biochemical options to scrutinise the profile of a immune-related pneumonitis from that of a pneumonitis caused by the new corona-virus.

Photo by CDC on Unsplash

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