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“How can I possibly admit an infirmity in the one sense which ought to be more perfect in me than in others, a sense which I once possessed in the highest perfection,’’ Beethoven lamented in 1802, calling his life “hopelessly afflicted.’’

Hopeless is not a word to describe a composer whose internal struggle with deafness rendered such resounding masterpieces as the late piano sonatas and string quartets, the Missa Solemnis, and improbably, the Ninth Symphony.

This juxtaposition – isolation and creativity – took flight in TFO’s Masterworks program this past weekend, an imaginative pairing of works that gave us both the intimate and grandiose sides of Beethoven.

Even with Covid still with us, the performance at Mahaffey Theater on Saturday was sold out, with lines at the box office and many masked people coming late to their seats in a darkened hall. (The concert also was performed at the Straz Center and Ruth Eckerd Hall.) After a pause for everyone to settle in, the concert opened with the Master Chorale of Tampa Bay in A Silence Haunts Me by Jake Runestad, a Minneapolis-based musician who found inspiration in the Beethoven diary known as the Heiligenstadt Testament.

Composed in 2019, the music unfolds as a dramatic choral monologue, using Beethoven’s own anguished words against echoes of the Moonlight Sonata, the Eroica Symphony, and the finale of the Ninth.

“It quotes from Beethoven symphonies, and toward the end the musicians play but without making any sound, so it reflects Beethoven’s loss of hearing,’’ said Brett Karlin, artistic director of the chorus, who conducted the work in precise sonic blocks.

The music is stark and piercing, and delivers its impact near the end, when the conductor continues to lead a choir in silence – symbolic of a composer who could not hear.

Before the concert, TFO Music Director Michael Francis set up the piece and asked the audience to withhold applause afterward. He didn’t want to break the mood. As the piece neared the end, Francis slowly walked on stage to take the podium from Karlin, and without a break dove into the opening of the Ninth Symphony, Beethoven’s grand opus for orchestra, chorus and soloists. The musicians embraced the roiling D-minor introduction and its complex development with spasms of tension and release, and conveyed the feverish counterpoint of the scherzo.

The tender adagio – one of the composer’s most sublime creations – set up what most listeners come to hear: the famed Ode to Joy theme, a giant vocal coda that shines out from chaos and turbulence like a ray of light. At one point during the finale, Frances turned slightly and smiled at the audience, which at evening’s end offered a long standing ovation.

“It’s such a huge and important piece, and there’s always a sense of wanting to go deeper into the music,’’ Francis said about the symphony as a whole. “It’s the Sistine Chapel of music, and it’s hugely important today because people instinctively understand it.’’

A Silence Haunts Me and the Ninth can stand alone on any orchestra program, but as a pairing they serve as prelude and fugue into the workings of a creative mind. They also make us wonder how Beethoven’s last symphony was born at all – sketched out by a composer who never heard a single note of it – but manages to resonate like nothing that came before or will ever follow.