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The question is fairly simple: when did Europeans come to a general knowledge that the Native Americans had weak immunity specifically to Old World diseases?

I'm looking for the first person to notice this as well as when this knowledge was known to at a large group of Europeans.

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    Is there evidence that they ever realized that? What research have you already done? Can you edit the question to indicate the sources you have already checked?
    – MCW ♦
    Commented Oct 2, 2019 at 14:15
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    It would also be useful to be clearer about what you mean by "come to a general knowledge". For one thing, I'd bet that a majority of people today have never thought about the subject. But perhaps more important, the realization that immunity existed at all came only gradually. There was immunization or sorts long before there was any clear concept of immunity and the idea of an Old vs. New World disease was likewise not initially obvious. The framing of your question may make it hard to give a good answer. (Does someone writing a book that said "Those Indians sure get sick easily" count?)
    – Mark Olson
    Commented Oct 2, 2019 at 15:20
  • I don't think you can expect a reasonable answer to this. Some Europeans might have noticed something, as in Pieter Geerkens' answer, but it's not really understandable at least until you develop the germ theory of disease, and probably not until you start to understand the immune system. So probably mid-20th century? And an important point: it's not just the American Indians who were susceptible to unfamiliar diseases, it's everyone. E.g. the Black Death and other European plagues that came from Asia and/or Africa, or syphilis fro m the Americas.
    – jamesqf
    Commented Oct 3, 2019 at 3:26
  • @jamesqf: See my update below. I believe you conflate cause with symptom - the symptom was widely understood even though the cause - and the distinction between Old World and New World diseases - was unknown.
    – Pieter Geerkens
    Commented Oct 4, 2019 at 18:22
  • @Pieter Geerkens: Yes, that's my point. Without knowing about immunity &c, the observations could easily be attributed to racism &c.
    – jamesqf
    Commented Oct 5, 2019 at 2:29

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The Spanish and Portuguese noticed early in the 16th century that the native peoples of the Caribbean and South and Central America were sickly to the point of being unsuitable (in general) for slave labour. From this the First Atlantic System develops into South and Central America:

Regarding the Atlantic slave trade

[The First Atlantic System] started (on a significant scale) in about 1502 and lasted until 1580 when Portugal was temporarily united with Spain.

...

Native peoples were at first utilized as slave labour by Europeans until a large number died from overwork and Old World diseases.

So to answer your specific question - By 1502, just one decade after Columbus' arrival in the New World

A comment on the original question states:

I don't think you can expect a reasonable answer to this. Some Europeans might have noticed something, as in Pieter Geerkens' answer, but it's not really understandable at least until you develop the germ theory of disease, and probably not until you start to understand the immune system.

I believe this conflates cause - viral and bacterial agents unknown until modern germ theory - with effect - that the indigenous people of North America were at (greatly) increased risk of sickness. That the effect was known - and widely so - is evidenced by the rapid adoption of race-based slavery around importation of black slaves. Employing native labour would have been more convenient and less expensive - except that the native peoples were too sickly to be so employed.

However - the distinction between Old World and New World diseases was meaningless until modern germ theory. Prior to that realization diseases were classified solely by symptoms and not cause - as the causes were both unknown and misattributed.

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