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I'm not a medical professional either, but...
Except in the specific cases of microbes that target the immune response, wouldn't you expect to see things like an elevated white blood cell count in patients suffering from a pathogen, even if the specific pathogen was not well recognized or understood? In other words, you would see the symptom in a blood test even if you didn't know exactly how to look for the pathogen.
If the pathogen reproduces slowly (the pathogen that causes TB might be one such) or has some way of hiding from the immune system or is one of those viruses (e.g., the herpes family) that get into cells and tend to remain dormant for long intervals, then they can be very hard to detect and will certainly not show up in a WBC. I saw news reports earlier this year about evidence that some cases of obesity are caused by gut microbes not previously regarded by, e.g., doctors and society as being pathogenic.