This is a pretty complex question, but I'll try my best to answer it. The Northern States have generally been wealthier than the South since the 1600s, likely due to the early start in industrialization. There is also an economic theory, the environmental theory of economic growth, which suggests that tropical climates where more diseases exist (and other factors) require additional financial support in order to compete economically. I'm sure there are also political reasons that these states have failed to grow. The recent drop in coal mining has hit the Appalachian states (WV and KY) pretty hard, and Alabama, Mississippi and Arkansas still have huge farming economies with little modern industry. The Civil War probably set these states pretty far behind the rest of the United States, but it is by no means the reason these states have failed to catch up.

Native West Virginian here, speaking for West Virginia: Most of the state of West virginia has seen very little economic development, literally ever. The land itself is not good for farming and the rugged, hilly landscape means that some parts of the state are very isolated even today. Back when West Virginia was a part of Virginia the Eastern portion of the state disfranchised Western portions, providing them with little representation and not investing in their infrastructure compared to Eastern Virginia. I've seen West Virginians wanting a state of their own in newspapers as early as 1830s and their biggest beef with eastern virginia was that they pursue policies that kept Western Virginia's economy down

That's not the biggest problem, though. The part of West Virginia where the state developed industrialization and a reasonably paid workforce were in extractive industries that tend to despoil the state's environment. In the early 19th century salt production was a major part of the state's economy and in the process of mining salt, coal and natural gas industries were developed which eventually became major employers.

The coal industry was a famously awful industry in terms of labor relations and paying its workers. Mine company owners literally fought armed battles against mass numbers of miners over the course of several decades in order to earn the right to organize unions. At the worst times for workers, many miners were paid in company currencies known as 'scrip' only redeemable at company-owned stores with limited selection and extortionist pricing.

Coal began its decline in employment in the seventies, but it was never a good economic base for building wealth in the first place. Lack of opportunities have caused at least 1,000,000 people to leave the state in the past five decades, leading to a stagnant/declining and aging population. The extraction industries that continue in the state have benefitted from a lax regulatory environment and there have been noticeable incidents of environmental devastation (last year's public water poisoning, for instance or the buffalo creek mine disaster) that makes West Virginia an unattractive place for businesses to relocate.

These trends are unlikely to reverse anytime soon, and the state is expected to lose population and grow poorer and older than the rest of America for the foreseeable future