There seems little doubt that Keats is indeed referring to his dying, consumptive brother, Tom. At the same time, Keats is making a general point, exploring the distinction between the occasional harshness of the material world in which we all must live and die, and the world of the imaginary sublime, as symbolized by the nightingale. Keats veers back and forth between the two worlds throughout the poem, keeping them in constant tension until, at last, he comes round from his intense, hazy reverie and realizes that he must somehow live in this world of the senses.
It is this world, after all, which allows Keats in this poem and elsewhere to indulge in the most luscious, sensuous descriptions of nature and her inexhaustible bounties. Yet this is also a world of immense suffering, illness and death. But, as a poet Keats embraces the full range of human experience, both...
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good and bad; and this is one of the main reasons why Ode to aNightingale,as with Keats's other great odes, lives on as one of the true glories of the English language.
References
There is a definite reference to his brother. I think that at the time of writing the poem, Keats was already profoundly occupied with his brother's predicament and wrestling with the issue of death, in general. However, another read on the poem could be involved in the entire stanza, where he discusses how the issue of age is something that plagues mortals. The third stanza opens with an allusion to a world where death and issues connected to mortality do not exist. His transition from this elusive world into the world in which we, including he, exist is where he talks about the withering of youth, or the "youth grows pale." Perhaps, Keats is making a statement on the cursed condition of growing old, something that impacts everyone. This reading makes the poem more of an elegy to youth, impacting all mortals, as opposed to something that is only intrinsic to him and the passing of his brother.