Aerial footage shows the extent of the incident on the M53 on the Wirral.
A 15-year-old schoolgirl and a coach driver have died following a motorway crash involving a school bus.
Merseyside Police said a 14-year-old boy has suffered life-changing injuries in the crash on the M53 in Wirral on Friday 29 September.
A major incident was declared following the incident, which involved pupils from Calday Grange Grammar School, and West Kirby Grammar School for Girls.
The crash happened between J4 and J5 near Hooton on the M53 on the Wirral shortly after 8am. The bus was carrying 58 people, including the driver.
A further two patients were taken to Alder Hey Children’s Hospital with serious injuries, while a number of other patients were taken to surrounding hospitals for treatment to minor injuries, North West Ambulance Service said.
A total of 52 children were transported to a casualty clearing centre at the emergency services training centre in Wallasey.
Of those, 39 have now been discharged while the remainder have been taken to the Countess of Chester and Arrowe Park hospitals.
Alder Hey Children's Hospital, declared a major incident at its hospital at around 11:30am but have de-escalated two hours later.
It is still urging parents to only bring children to its emergency department if it is urgent, as its Accident and Emergency department "remains extremely busy".
Taking to social media earlier, the Liverpool hospital said: "Our Emergency Department is currently extremely busy and we would ask parents to only bring their children to the Department if it is urgent."
It later added it was treating “a number of patients”.
A statement on its website read: “We can confirm that we are treating a number of patients following the incident this morning.
“We will continue to support and liaise with families directly and are unable to share any further details of individual patients at this time.”
North West Ambulance Service says it has taken one female patient to hospital with "major trauma-related injuries", while a further 50 other patients are being assessed at the scene.
Drivers in Merseyside are advised the M53 between junctions 5 (Hooton) and 4 (Clatterbridge) is expected to remain closed into the evening with roads remaining closed in both directions.
National Highways traffic officers remain on scene, aiding with traffic management. Once complex investigation work has been completed, recovery of the coach and clear-up work can begin.
Calday Grange Grammar School released a statement on its social media saying: "We are aware of a situation involving one of our school buses on the motorway earlier today.
"We're actively gathering details and assisting affected students and their families."
West Kirby Grammar School has also released a statement on its social media saying: "We are aware of a situation involving one of our school buses on the motorway earlier today.
"We're actively gathering details and assisting affected students and their families.
"Support is available. If you need to talk or seek guidance, please contact the school office."
Local Councillor Sherin Akhtar, confirmed he was 'aware children are being taken to hospital as a precaution'.
He said: "I can confirm and am aware of an accident on the M53 this morning going towards the Wirral/ Birkenhead.
"It involves a Carvers coach ( W3) travelling to Calday Grange Grammar School and West Kirby Grammar school for girls.
"Whilst this is a live situation, I would like to assure residents that I am working on their behalf and offer support and will endeavour to update, as soon as possible.
"I am aware that children are being taken to Arrowe Park as precautionary."
Clinical Support Workers striking outside Arrowe Park on the Wirral "have immediately returned to work to help".
Posting on the UNISON North West social media, they said: "We dispersed our picket and members are returning home to be on-call to help.
"Our thoughts are with everyone impacted by this terrible incident."
Mayor of Liverpool City Region, Steve Rotheram, says he's "deeply concerned" and his "thoughts are with those affected and their loved ones".
Mr Rotheram adds: "the Combined Authority and Merseytravel have offered our full support and assistance."
All emergency services are on the scene along with North West Air Ambulance Services.
Merseyside Police said it was called to the incident shortly after 8am.
In a statement the force said: "We can confirm that emergency services are on the M53 in Hooton following a collision involving a bus on the motorway.
"Just after 8am we received a report that a bus had struck a reservation on Junction 5 of the M53.
"Junctions 3-5 of the M53 are closed in both directions. Merseyside Fire and Rescue Service is currently ensuring the safe removal of passengers and the driver, and North West Ambulance Service are at the scene attending to anyone requiring treatment
"Police and National Highways are advising people to avoid the area as all traffic is being temporarily held, and the road is likely to remain closed for 'some time'."
A spokesperson for Merseyside Fire & Rescue Service said: "Fire crews have been called to the scene of a road traffic collision between junctions 5 and 4 of the M53 on the northbound carriageway this morning.
"Two fire engines and the Search and Rescue Team are in attendance.
"Crews were alerted at 8.05am and on scene at 8.16am. Crews arrived at the scene to find an overturned bus with a number of casualties.
"North West Ambulance and Merseyside Police are also in attendance. The incident is ongoing and the carriageway will remain closed for some time."
Northbound traffic is advised to follow the solid circle diversion symbol.
Exit the M53 northbound at J5
At the roundabout, take the 1st exit onto the A41 southbound (New Chester Road)
At the B5133 junction, turn right onto the B5133 westbound (Hooton Road)
At the junction with the B5151, turn right and join the B5151 northbound (Birkenhead Road)
Continue to then re-join the M53 at J4
Southbound traffic is advised to follow the hollow diamond diversion symbol.
Exit the M53 southbound at J4
Take the 3rd exit at the roundabout onto the B5151 southbound (Mount Road)
At the junction with the B5133, turn left onto the B5133 eastbound (Neston Road)
Continue onward and then at the junction with the A41, turn right and join the A41 New Chester Road northbound
Continue to then re-join the M53 southbound at J5
The Birkenhead Tunnel will not close as scheduled at 9pm tonight (Friday) and will remain open while the M53 is closed.