In the immortal words of Ned Stark, 'Winter is coming'. And by the looks of things, the state of the pandemic that has dominated 2020 indicates it is indeed kicking into gear to ensure a nightmarish end to the year as well - not all that far-removed from the danger and treachery lurking in an episode of Game of Thrones. This is despite the good news on the vaccine front, where a slew of late-stage trial reports have all tended towards success, even if the ones that have reported so far, may not do the majority of the world's population much good.

In fact, the vaccine candidates are outperforming expectations in clinical trials. But the virus isn't running away. The vaccine news has lifted spirits, not least in the market, and there's probably more good news about vaccines and new, easier testing methods to come. But all the data points to a long, dark winter (in the northern hemisphere) that is already here.

The United States crossed 250,000 deaths from the virus this week. It has had well over 11 million confirmed infections - the last million took just 6 days in November. Both counts are probably low, given all the testing woes. Hospitals are bursting. Health care workers are exhausted. Some are quitting.

Europe made up almost half of the world's 4 million new coronavirus cases last week but recorded a nearly 10% fall in infections compared to the week before, thanks in part to strict government lockdown measures that have fanned some discontent, the World Health Organization reported.

In the same week, Bangladesh started reporting over 2,000 infections a day again, the number of daily deaths reported reached a 2-month high on November 18, and the positivity rate - the percentage of tests coming back positive - also started nudging up again into the teens.

The word of warning came right from the top, as Prime Minister Sheikh Hasina herself asked citizens to be vigilant from the floor of parliament.

"Although the incidence of Covid-19 in Bangladesh has decreased a bit at this moment, experts opined that it may increase again in the coming winter. The second wave of Covid-19 has already started in Europe and America," Hasina said.

The premier also said a tripartite agreement has been signed with the government, Serum Institute of India and Beximco Pharma to import three crore vaccine doses. This is the 'Oxford vaccine' that hasn't yet reported phase-III results. (See later section.)

The prime minister also acknowledged that it is becoming difficult for children to continue staying at home but her government cannot put them at risk of death by opening educational institutions in the coronavirus pandemic. She noted that the US, and several countries in the EU as well as England had opened up their educational institutions, but in the face of increasing Covid-19 infection, were forced to shut their schools again.

As has been her wont, the PM urged everyone to wear masks when they go outside and follow hygiene rules. Noting that extensive preparations have been taken to deal with the second wave of Covid-19 and the fear of an increase in infections in the winter, the prime minister said the government has given instructions to implement "no-mask, no-service" policy to contain the expansion of Covid-19 infection in the upcoming winter season.

Also during her deliberations in the JS this week, the prime minister informed the House that during the Covid-19 period, the government has been able to arrange emergency financing from development partners on an emergency basis.

PM informed parliament that Bangladesh is receiving financial assistance of Tk 2,720 crore as emergency assistance from Japan to combat the coronavirus.

The Asian Development Bank (ADB) is providing US$ 800 million to deal with prevention of Covid-19 and the ADB is providing another US$ 30 million to procure coronavirus vaccines and medical equipment, Sheikh Hasina added.

She also said the World Bank has provided US$ 105 million for employment during the Covid-19 period.

"We have also received €110 million from the European Union for the garment sector. Germany and the European Union have pledged to provide € 113 million for the garment and leather industries."

No letting up

The promise of a vaccine being imminent can cut both ways. It can make people feel the pandemic is just about over, that it's safe to race back to normal. But public health experts keep insisting, that will just prolong the crisis and cost more lives. People still have to do all the things they've gotten weary of doing: wearing masks, social distancing, staying home when they can.

The WHO's Michael Ryan said vaccines should not be seen as a "unicorn" magic solution -- and countries battling a resurgence of the virus would once again have to "climb this mountain" without them.

"I think it's at least four to six months before we have significant levels of vaccination going on anywhere," he said, during a public question and answer session live on social media.

Despite recent promising announcements from final-phase candidate vaccine trials, "We're not there with vaccines yet," said Ryan.

"Many countries are going through this wave, and they're going to go through this wave, and continue through this wave, without vaccines.

"We need to understand and internalise that, and realise: we have got to climb this mountain this time, without vaccines."

Ryan warned against slackening off individual vigilance against the virus in the mistaken belief that vaccines would now solve the problem instead.

The US government's top infectious disease expert, Dr Tony Fauci, has said his daughters won't be coming home for Thanksgiving this year. Speaking Tuesday to CNN, he urged the public to stay patient - and careful.

"The fact that we have a vaccine coming means we should double down and hang in there," he said. "Help is on the way."

Pfizer followed up this week with an announcement that a completed study of its experimental vaccine showed it was 95 percent effective, while fellow US firm Moderna said this week that its own candidate was 94.5 percent effective. Russia claims its candidate is more than 90 percent effective.

But if you're in Bangladesh, chances are none of those three are for you.

Dude, where's my vaccine?

Following the breakthroughs in the race to deliver a coronavirus vaccine reported by Pfizer-BioNTech and then Moderna, the University of Oxford is expected to release data on the efficacy of its own candidate in the coming weeks, with the latest trial results published in The Lancet suggesting it produces a strong immune response in older adults.

Developed jointly with pharma giant AstraZeneca, who have enlisted manufacturing partners in different parts of the world, the ChAdOx1 nCov-2019 vaccine - it's a working title - is the one most likely to play a large role in any large or medium-scale vaccination effort in Bangladesh.

Phase 2 data published in The Lancet on Wednesday suggests one of the groups most vulnerable to serious illness and death from Covid-19 could "build immunity" on the 'Oxford vaccine', as it is more fondly known.

The vaccine has been shown to trigger a robust immune response in healthy adults aged 56-69 and over 70.

According to the researchers, the trial demonstrated similar immune responses across all three age groups - 18-55, 56-69, and 70 and over.

Upon closer scrutiny, the study of 560 healthy adults, including 240 over the age of 70, found, interestingly, that the vaccine is better tolerated in older people than in younger adults.

Volunteers received two doses of the vaccine candidate or a placebo meningitis vaccine. No serious adverse health events related to the vaccine were seen in the participants.

Large-scale Phase 3 trials of the vaccine are ongoing, with early efficacy readings possible "in the coming weeks", according to the Press Association.

Three vaccine candidates - from Pfizer-BioNTech, Moderna and Russia's Sputnik- have already reported good preliminary data from phase three trials, each topping 90% in early efficacy readings. Public health experts have been willing to accept efficacy as low as 50%.

The Oxford data is from an earlier stage, which tests the safety of the vaccine and the body's response to it, but in the long run it's likely this vaccine could be easier to roll out because it doesn't need to be stored at very cold temperatures - as has been reported about the Pfizer and Moderna shots.

As reported in these pages before, maintaining the cold chain for coronavirus vaccines won't be easy even in the richest of countries, especially when it comes to those that require ultracold temperatures of around minus 70 degrees Celsius (minus 94 F).

Earlier this month, Bangladesh entered into a deal with the Serum Institute of India (SII) to acquire 30 million doses of the potential vaccine being developed by AstraZeneca for Covid-19.

SII and Bangladesh's own pharmaceutical giant, Beximco Pharma, signed a Memorandum of Understanding (MoU) for "priority delivery of the vaccine doses".

Once the deal is activated following final approval of the vaccine, Beximco will purchase five million doses of the vaccine per month to distribute in Bangladesh - although under what type of scheme is still unclear.

SII will supply the vaccine at a price of around $4 to $5 per dose, a rate similar to what India pays. It partnered with AstraZeneca, the Gates Foundation and the Gavi vaccine alliance to produce over a billion doses of Covid-19 vaccine(s) for supply worldwide.

The latest data

As reported by the UK's state news agency, the Press Association, Dr Maheshi Ramasamy, an investigator in the Oxford Vaccine Group and a consultant physician, said: "Older adults are a priority group for Covid-19 vaccination, because they are at increased risk of severe disease, but we know that they tend to have poorer vaccine responses.

"We were pleased to see that our vaccine was not only well tolerated in older adults, but also stimulated similar immune responses to those seen in younger volunteers. The next step will be to see if this translates into protection from the disease itself."

The study's lead author, Prof Andrew Pollard, from the University of Oxford, is quoted as saying: "Immune responses from vaccines are often lessened in older adults because the immune system gradually deteriorates with age, which also leaves older adults more susceptible to infections. As a result, it is crucial that Covid-19 vaccines are tested in this group who are also a priority group for immunisation."

Researchers say their findings are promising as they show that older people are having a similar immune response to younger adults.

Ramasamy added: "The robust antibody and T-cell responses seen in older people in our study are encouraging. The populations at greatest risk of serious Covid-19 disease include people with existing health conditions and older adults. We hope that this means our vaccine will help to protect some of the most vulnerable people in society, but further research will be needed before we can be sure."

The study also found that the vaccine, being developed with AstraZeneca, was less likely to cause local reactions at the injection site and symptoms on the day of vaccination in older adults than in the younger group.

Adverse reactions were mild - injection-site pain and tenderness, fatigue, headache, feverishness and muscle pain - but more common than seen with the control vaccine.

Thirteen serious adverse events occurred in the six months after the first dose was given, none of which were related to either study vaccine.

The authors note some limitations to their study, including that the participants in the oldest age group had an average age of 73-74 and few underlying health conditions, so they may not be representative of the general older population, including those living in residential care settings or aged over 80.

Climbing a mountain

In an interview Thursday (November 20) with the BBC, Dr Pollard said research was slowed by low infection rates over the summer, but the Phase III trials are now accumulating the data needed to report results as a renewed surge of the pandemic hits countries around the world.

"I think we're getting close, and it's definitely going to be before Christmas based on the progress," he said.

Dr Pollard said there is no competition between the various research teams, because several vaccines will be needed to bring the global pandemic under control and allow life to return to normal.

Despite recent progress, he said the world is still in the early stages of the effort to protect people against COVID-19. Even after vaccines are approved by regulators, drugmakers and public health officials still face the task of producing billions of doses and administering them to people around the world, he said.

Pollard, an amateur mountaineer, compared the task to the work involved in climbing a mountain.

"I think we're still at the bottom of that mountain in some ways," he said. "We've done the route into the bottom of the mountain, the long trek to get to the start. Now we've got to get the data about the vaccines in front of regulators for them to scrutinize it and approve the first vaccines. And then we've got that huge effort to climb up to the top where we've got a vast majority of those who are at risk vaccinated."

That summit though, may finally be visible.