Billions are spent, the globe is scoured, data banks are sifted and the best-laid plans of football men can still go awry.

A rush of blood – a moment of unpunished thuggery – has tilted the tectonic plates at the top of the English Premier League.

Invincibles suddenly look vulnerable. Challengers have a new lease of life and the landscape takes on a different hue.

Liverpool have been shaken more by Virgil van Dijk’s injury than their 7-2 defeat at Aston Villa. That was cast dismissively into the bin of freak results and normal service was resumed.

But this is something they have to live with for the entire season. They are far from a one-man team but the giant Dutchman is their best player, their talisman, their rock.

Once the injury was confirmed as an anterior cruciate ligament (ACL), the bookies made Manchester City odds-on title favourites.

Perhaps, they saw parallels with how City had struggled without Vincent Kompany.

Or maybe they remembered Arsenal after the Eduardo injury in 2008. The Gunners led the table by eight points and were on a 10-game unbeaten run when Birmingham City’s Matt Taylor sank his studs into the Croatian’s shin bone.

Eduardo suffered a broken leg and dislocated ankle and was never the same again. Nor were Arsenal.

Their young side was visibly shaken, skipper William Gallas completely lost the plot and Arsene Wenger called for Taylor to be banned for life.

They never did shut up about it and many feel their constant whingeing played into the hands of wily old fox, Alex Ferguson: Manchester United caught them and became champions.

Arsenal picked up only one point in their next four games and bowed out in the Champions League to Liverpool. It remains one of football’s most dramatic season-changing injuries.

Pickford’s clumsiness was not in the same league as Taylor’s, but if it’s not handled right, it could be just as damaging.

Liverpool have to rejig the defence where they have few options. They must also be careful not to follow Arsenal and wallow in self-pity.

One or two players have had their say and social media has been predictably incandescent, but generally, they are older and made of sterner stuff than Wenger’s flimsy young guns.

Klopp is also a more rational leader than the famously one-eyed Frenchman.

At least the loss has removed any last vestige of complacency Liverpool might have been harbouring.

It looked to have already gone by the way they started the game, and now, with so many people writing them off, it won’t be returning.

But they, too, have a keeper who can be described as dodgy – albeit for very different reasons.

Adrian had his ‘moments’ in that game and against Ajax in midweek. It is the simultaneous loss of the two players who transformed Klopp’s side and took it to the next level that is causing such angst among Kopites.

Alisson and Van Dijk brought instant solidity and confidence that oozed through the team, and to lose both at the start of a new campaign is a devastating double blow.

Keeping Klopp awake at night is that centreback is the last place the Reds could afford to lose anyone.

While they bolstered their midfield and attacking ranks impressively with Thiago Alcantara and Diogo Jota, Dejan Lovren was allowed to leave and not replaced.

Most likely candidates Joe Gomez and Joel Matip can be very good on their day, especially when they have Van Dijk alongside, but without him they are not quite the same players. And both have a chequered history of injuries.

The versatile Brazilian Fabinho was immense against Ajax but was missed in midfield. We could see glimpses of the youngsters as Klopp has to weigh up whether to plunge into the transfer market when the window opens in January.

Liverpool will have a list of options, top of which must be RB Leipzig’s Dayot Upamecano. A full France International at 21, he not only ticks many boxes as a powerful, ball-playing defender, he would be a steal: his release clause is just €42m but cannot be triggered until next summer.

Does Klopp find a stop gap or wait and risk another injury? He may just change the formation and in Amsterdam we did not see the normal high line.

Games against Sheffield United and Midtjylland next up may allow for more experimentation.

Despite the gloom that has descended on the red half of Merseyside (in sharp contrast to the sunshine in the blue half) there are plenty of reasons to believe Liverpool can still retain their title.

None of their challengers – including City – really convince. Guardiola’s side are still porous at the back and now have lost Fernandinho to a long-term injury.

Chelsea still don’t know their best team and nor do United. Arsenal and Spurs are also work in progress.

All opponents will now be emboldened and come at the champions without fear. But even without their best player, Liverpool are a formidable unit with the best manager in the game.

The once-irresistible red machine will still take some stopping.

The views expressed as those of the author and do not necessarily reflect those of FMT.