Coronavirus update – Part 17 (March 2022)

Dr John Ling continues to provide us with a monthly review of all things Covid. This, his latest offering, was published a few days ago on his personal website, which is well worth a look for many other resources and information. Thank you John!

Covid-19 numbers

It was 2 years ago, on 23 March 2020, that prime minister Boris Johnson announced the first UK national lockdown, ordering people to ‘stay at home’.  In this drastic bid to stem the spread of Covid-19, they would only be allowed to leave their homes for limited reasons.  By then, according to the Department of Health and Social Care, 6,650 people had tested Covid-19 positive and 335 patients had died.  Remember that?  Two years on, there have been 21,000,000 confirmed Covid-19 cases and 165,000 deaths in the UK.  The numbers tell a cheerless story.

Currently, the UK key metrics – cases, hospitalisations and deaths – are all showing gentle, but concerted, upswings.  In early March, there were about 45,000 daily cases.  By late March, there were about 85,000.  Numbers of Covid-19 patients in hospital have risen slightly during March.  In February, there were about 17,000 admissions with 300 on ventilators.  The equivalent March figures were 17,500 and 330.  Covid-19-related deaths have also increased somewhat.  March started with 130 daily deaths and ended with about 150.  The UK total sum of deaths throughout the pandemic has now reached 165,000.

The only metrics in decline have been the vaccination rates.  The numbers for first, second and boosters administered have slowed to only about 8,000 each day.  The totals of people jabbed are now reported to be 52.8, 48.9 and 38.1 million respectively.  Overall, 77.4% of the UK population have received at least one dose.

March has generally been a month of Covid-19 contrariness – the above trends of UK data are going the wrong way.  Perhaps this was inevitable.  With the loosening of restrictions, more social mixing, less mask-wearing and so on, the case numbers were bound to increase.  Moreover, as the more transmissible Omicron BA.2 variant became more dominant, more cases were certain to occur.  And even though BA.2 is less severe, hospital admissions were up, though deaths were more limited.

Globally, the picture remains mixed.  While Covid-19 news is now rarely top TV news, infection and death figures are lessening in many rich countries, though citizens of poorer countries are still suffering greatly.  And there have been astonishing surges of Covid-19 cases in places, such as, for example, Hong Kong and China.  So far, total global cases stand at 500 million, total deaths are at 6.2 million and total vaccinations administered are at 10,900 million.

South Korea has taken the top spot of the infection table with a daily average in late March of 324,000 cases, followed by Vietnam with 208,000 and Germany with 164,000.  The UK is in seventh position with 85,000.  But the USA still dominates the total death table at 980,000, followed by Brazil (660,000) and India (521,000) with the UK in seventh place at 165,000.

What to conclude?  For the umpteenth time, the constant refrain is still, this Covid-19 pandemic is not over – much of the world is still in its grip.

Where are we now?

What is happening with Covid-19 in the UK?  The government reckons the pandemic is on the run.  It has announced that most restrictions are over.  The mantra is now, ‘It is time to learn to live with Covid-19.’  After all, high rates of immunity from antibodies derived from both infections and vaccinations mean that many of the earlier restrictions designed to thwart the spread of Covid-19 are now unnecessary – herd immunity is close at hand.

On the other hand, numerous scientists, statisticians and other experts say the policy change to lift restrictions governing travel, socialising, mask-wearing, testing and self-isolation is premature – Covid-19 still has verve.  And many of these newly-restored freedoms and health-monitoring cutbacks are not based on scientific evidence – they are politically-based, driven in particular by fears that the national economy will suffer if restrictions remain in place.

Is the world heading for more Omicron surges?  Almost certainly, yes.  Look at current data from Hong Kong and China.  In the UK, cases and hospital admissions, which had been falling since the Omicron peak in January, are now increasing.  Indeed, during late March, the Office for National Statistics (ONS) revealed that Covid-19 cases had climbed by a million a week in the UK – up to 4.3 million from 3.3 million the previous week.  The cause is at least three-fold – recent easing of restrictions, waning immunity from vaccines and the high transmissibility of the Omicron variant BA.2.  Swab tests have shown that BA.2 has continued to spread so that around 1 in every 16 UK people in late March were infected.  All age groups have been affected, including especially the 75s and over.  Youngsters have not escaped either.  Covid-19-related school absences tripled during March from about 58,000 in early March to about 202,000 in late March.

Curiously, and ominously, several countries, the UK included, are starting to curtail the surveillance and reporting of the virus’s movements.  Polymerase chain reaction (PCR) and lateral flow test (LFT) monitoring are no longer regarded as essential.  Is this foolish?  How will we know whether the virus is increasing or decreasing?  How will we discover and treat infection hot spots?  How will we uncover new variants?  Is complacency in the air?  The UK government’s world-leading Covid-19 dashboard has stopped reporting data at weekends.  At least two data collection programmes, REACT-1 and ZOE, have lost government funding.  And from 1 April, free LFTs will no longer be available to most groups.  If the government’s strategy of ‘living with Covid’ places the emphasis on vaccination and personal responsibility, how can citizens consider and then exercise their choice without the necessary numerical tools?  Is the ‘new normal’ to be characterised by ignorance?

Where are we now?  Good question.  It seems like the world of Covid-19 is in limbo.  Part is busy learning to live with Covid-19.  And the other part is busy fighting a raging pandemic.

A fourth jab

On 21 March, it was announced that all 75-year olds and over, around 600,000 people in England, will be invited to book a fourth Covid-19 jab.  This will also include residents in care homes and those aged over 12 who are immunosuppressed.  Similar Spring boosters are already being rolled out in Wales and Scotland.

This new strategy comes after the Joint Committee on Vaccination and Immunisation (JCVI) recommended an additional Spring booster dose for the most vulnerable individuals in the population.  Immunity derived from vaccination is known to wane over time and many of the oldest adults received their most recent vaccine in September or October 2021.  A fourth dose is advised around 6 months after their last jab.

On offer will be 50mcg Moderna (Spikevax) vaccine, or 30mcg Pfizer-BioNTech (Comirnaty) vaccine for those eligible adults over 18 years old and for those immunocompromised aged 12 to 18 years, 30mcg Pfizer-BioNTech (Comirnaty) vaccine.  Another sleeve-rolling up session is on its way.

While it is too early to predict how the pandemic will develop during the Summer months, the JCVI considers that the coming Winter will see the greatest threat from Covid-19.  As such, provisional precautionary plans are being made for an Autumn 2022 vaccination programme for, at least, the most vulnerable and maybe for other groups too, including perhaps the over 50s.

Long Covid revisited

This topic was first considered in Coronavirus – Part 8 (June 2021).  It is time for a revisit and an update.  Long Covid has been variously described as ‘the long-term adverse sequelae after an infection of SARS-CoV-2’ (the posh name for the virus), or as ‘a poorly-defined syndrome that exhibits at least one lingering symptom after an infection of Covid-19’, or as ‘the prolonged symptoms experienced by some patients, following a multi-organ dysfunction after a Covid-19 infection, termed Post-Acute Sequelae of Covid-19 (PASC)’.

Long Covid is still surrounded by numerous unknowns – how many patients, why some patients, symptom differences, symptom persistence, and so on.  Uncertainty rules.  According to the World Health Organization (WHO), long Covid may affect between 10% and 20% of Covid-19 patients with symptoms lingering for up to five months after the initial infection.  Yet despite the effectiveness of Covid-19 vaccines, the emergence of new treatments and the relative mildness of the Omicron variant, there is one certitude – long Covid can distress, even ravage, the human body for months, perhaps even years, after an infection.

Two recent studies have shone some light on this topic.  The first is the result of a collaboration of over 30 scientists associated with the National Institutes of Health at Bethesda, Maryland in the USA.  It is entitled, ‘SARS-CoV-2 infection and persistence throughout the human body and brain’ by Daniel Chertow et al., and it was published in Research Square, on 20 December 2021.

Chertow and his colleagues performed extensive autopsies on 44 patients who died with or from Covid-19 in order to map and quantify viral distribution, replication, and cell-type specificity across the human body, including the brain, from acute infection to seven months after symptom onset.  In other words, they studied the movement of the virus particularly from its customary location, the lungs, to the potentially-dangerous location, the brain.

They showed that the virus was widely distributed throughout the human body tissues from early after infection and for months afterwards, even in those who died with no or mild Covid-19 symptoms.  Evidence of the virus, in the form of viral RNA, was detected in numerous sites, including the brain.  However, inflammation and virally-mediated injuries, as typically seen in the respiratory tract and lungs of Covid-19 patients, were rarely detected elsewhere.

In summary, the Covid-19 virus can infect most human tissues including the brain.  It can also replicate and persist in these locations.  While our aetiology of long Covid is inadequate, these findings, that the virus can replicate, move and persist in the body post-infection, are valuable results.  Whether, and how, they might be instrumental in the emergence of long Covid is another issue and one that is essential to our understanding and treatment of this damaging condition.

The second study examined a key question – can vaccination prevent long Covid?  Entitled, ‘Association between vaccination status and reported incidence of post-acute COVID-19 symptoms in Israel: a cross-sectional study of patients tested between March 2020 and November 2021’ by Paul Kuodi et al., it was published as a prior to peer review pre-print in MedRxiv on 17 January 2022.

The authors, from the Bar-Ilan University at Safed, Israel, used the answers to health questionnaires completed by 951 Covid-19 infected and 2,437 uninfected patients at participating hospitals.  Among the Covid-19 infected, 637 (67%) had been vaccinated.  The most commonly reported symptoms were fatigue (22%), headache (20%), weakness (13%) and persistent muscle pain (10%).  Those who had received two doses of vaccine were significantly less likely than the unvaccinated individuals to report any of these symptoms by 64%, 54%, 57%, and 68% respectively.  Those who received two doses were also no more likely to report any of these symptoms than individuals who had no previous Covid-19 infections.

The authors concluded, ‘Vaccination with at least two doses of COVID-19 vaccine was associated with a substantial decrease in reporting the most common post-acute COVID-19 symptoms, bringing it back to baseline.  Our results suggest that, in addition to reducing the risk of acute illness, COVID-19 vaccination may have a protective effect against long COVID.’  In other words, the jabbed are seemingly less likely to suffer from long Covid.

Covid-19 and the brain

In the early days of the pandemic, the world was focused on detecting and treating infected individuals.  Besides physiological symptoms, such as fatigue and persistent coughs, numerous neurological symptoms were being reported, including lost senses of smell and taste, headaches, memory problems and more.

Now, after two years of Covid-19 coping, aspects of this neurological aftermath are being more earnestly considered.  In particular, concerns have centred on long Covid and mental health.  Such concerns inevitably lead to questions about Covid-19 and the brain.  And a growing number of studies are providing strong evidence that brain-related abnormalities have been caused by Covid-19 infections.

One such study has been recently published.  It is entitled, ‘SARS-CoV-2 is associated with changes in brain structure in UK Biobank’ by Gwenaëlle Douaud et al., and it was published in Nature on 7 March 2022.

These researchers, from the University of Oxford and in conjunction with data from the UK Biobank, used magnetic resonance imaging (MRI) to scan the brains of 785 people, both before and after Covid-19 infections.  The participants were aged between 51 and 81.  A total of 401 had tested positive for Covid-19 and 384 had not.  The scans were conducted before the emergence of the Omicron variant.  Nevertheless, this ‘before’ and ‘after’ experimental design should provide powerful evidence for any neurological consequences of Covid-19 infections.

Douaud and her colleagues found subtle, but significant, differences between the brains of the infected and the non-infected groups.  For instance, those in the infected group exhibited a decrease in thickness and tissue contrast in some areas of the brain cortex compared with those in the non-infected group.  Such changes are often associated with a worsening well-being of the brain.  The infected group also displayed increases in markers of tissue damage in brain regions connected to the smell and taste systems.  Diffuse atrophy in other brain regions was also detected.  Overall, people who have been infected with Covid-19 had slightly reduced brain volume and performed less well on cognitive tasks – these effects were more marked the older the participants were.

This repeat-imaging study is ongoing.  Eventually it is expected that 2,000 participant scans will be reported.  There is much to do.  To unpack the link between neurological symptoms and brain changes will hopefully lead to prevention and better treatment of Covid-19 sufferers.

The second study was by Barbara Hanson et al., and entitled, ‘Plasma Biomarkers of Neuropathogenesis in Hospitalized Patients With COVID-19 and Those With Postacute Sequelae of SARS-CoV-2 Infection’ was published in Neurology, Neuroimmunology & Neuroinflammation on 7 March 2022.

These researchers, from Northwestern Medicine, Chicago, recruited 64 Covid-19 patients who were hospitalised, post-hospitalised, or non-hospitalised.  Rather than use MRI scans, they employed numerous biomarkers, or molecular signatures, for evidence of brain injury.  In particular, two such markers were used to detect either direct damage to nerve cells, or for increased inflammation in the central nervous system of the brain itself.

Results found evidence that Covid-19 infections damaged neurons and glial cells, which are fundamental to brain function.  In addition, evidence of brain inflammation correlated with symptoms of anxiety/depression reported by Covid-19 long-term sufferers.  According to Hanson, about a third of people with Covid-19 develop some form of long Covid symptoms – many of them neurological symptoms like decreased memory, headaches and dizziness.
Hanson also predicted that Covid-19-related neurological symptoms could become even more widespread in the decade to come.

So here is the big question – will the symptoms of long Covid brain-related damage wither or persist?  It is neurological studies like these recent two that will lead the way to better understanding and treatment of these severe sequelae.  In other words, the science needs to move on to combine structure and function.

Covid-19 and diabetes

There is growing evidence suggesting that beyond the acute phase of infection, people with Covid-19 can experience a wide range of post-acute sequelae, including diabetes.  However, the specific risks and burdens of diabetes in the post-acute phase of the disease have not yet been comprehensively characterised.  The data are accumulating.  In other words, is there an association between Covid-19 cases and the subsequent diagnosis of type 2 diabetes?  Two recent studies are enlightening.

The first study is entitled, ‘Incidence of newly diagnosed diabetes after Covid-19’ by Wolfgang Rathmann et al., and was published in Diabetologia on 16 March 2022.

These scientists analysed health records from 1,171 medical practices across Germany.  In total, they documented 35,865 patients with Covid-19 who were matched with a cohort of individuals with acute upper respiratory tract infections as a control group.  The foremost outcome was that individuals with Covid-19 showed a subsequent increase in the occurrence of newly-diagnosed type 2 diabetes – the incidence rate ratio was 1.28.  The authors suggest that these results support the practise of actively monitoring blood glucose concentrations in patients after recovery from mild forms of Covid-19 infections.

The second study is entitled, ‘Risks and burdens of incident diabetes in long Covid: a cohort study’ by Yan Xie and Ziyad Al-Aly and was published in The Lancet, Diabetes & Endocrinology on 21 March 2022.

The authors used a cohort of 181,280 participants, derived from a national US database, who had had a positive Covid-19 test.  A non-infected group was used as a control.  All had been previously free from diabetes.  The numbers of new diabetes cases were compared between the two groups.  The results showed that Covid-19 infection was linked to a 46% increased risk of type 2 diabetes.

Both studies demonstrate that patients who have contracted mild forms of Covid-19 are more at risk, by between 28% and 46%, of developing type 2 diabetes for the first time.  It would therefore be prudent to monitor the blood glucose of Covid-19 recoverees – they may require blood-sugar-lowering medication.  Why?  It may be that a Covid-19 infection can adversely affect the pancreas so that its beta insulin-producing cells decrease production of the hormone to such an extent that type 2 diabetes is established.

Covid-19 in Hong Kong

What is going on in Hong Kong?  The territory has long been lauded for its ambition of becoming zero-Covid with its stringent public policy of confining every infected person.  However, the strategy to keep Covid-19 out is now in tatters thanks mainly to the more contagious Omicron variant.  By early March, Hong Kong was reporting the highest Covid-19 case rate in the world.

Hong Kong has a population of 7.4 million.  At the start of February, there had been only about 100 new Covid-19 cases each day and virtually no deaths for the previous two years.  But by mid-February, the virus had begun to surge.  By early March, as many as 75,000 new infections and 300 deaths were being reported daily.  The authorities called it the ‘fifth wave’.

The upshot has been staggering.  The health system has been close to collapse.  The surge in Covid-19 deaths overwhelmed hospital mortuaries and coffins became unobtainable.  New refrigeration units for storing bodies were requisitioned.  Patients have been lined up in beds and waiting days to be seen by medical staff before being admitted to wards.

The city, officially known as the Special Administrative Region of the People’s Republic of China, had lost its way.  Food and drug supplies were being rationed.  Some supermarkets limited shoppers to five items per customer for goods, such as rice and canned foods.  Pharmacies restricted common medications.  Hong Kong’s executive leader, Carrie Lam, tried to calm fears over shortages of food and daily necessities by promised assistance from Beijing.

In addition, Lam resisted calls for a complete lockdown and instead brought in inflatable laboratories as part of compulsory testing plans to try to control the virus.  Anyone testing positive was admitted to a hospital or isolation facility, depending on the severity of symptoms.  However, it soon dawned on the authorities that with few available hospital beds and isolation units, an alternative strategy was needed.  Lam then insisted that residents would each have to undergo three lots of mandatory Covid-19 testing during March.  That plan is currently ‘on hold’, possibly until April.  And by the end of April it is reckoned that infections will have fallen to just 200 each day.  Maybe.

So, what has caused this ‘fifth wave’ surge?  Hong Kong’s focus on border closures rather than vaccinating has been blamed.  While other parts of the world were prioritised vaccinations, especially among their elderly, because of their vulnerability to the virus, Hong Kong pressed ahead with its policy of controlling its border in order to keep the virus out.  Its vaccination uptake had been slow and low.  Only 78% of the population had received two doses of a Covid-19 vaccine compared with, for example, 92% in nearby Singapore and more than 80% in mainland China.  Hong Kong’s elderly have been a particular problem – by early February less than half of those aged over 70 had had two doses and only a third of over 80s were fully vaccinated.  Typically, 90% of deaths were of people who were not fully vaccinated.  Apparently, people had begun to think that the virus could be excluded from the territory for ever and that the adverse risks of vaccination were greater than the adverse risks of Covid-19 infections.  As Karen Grépin, an associate professor at the School of Public Health at the University of Hong Kong, said at the time, ‘We are paying for that complacency.’

In the meantime, things have been looking up for Hongkongers.  The city is now prioritising efforts to prevent more of its elderly from dying.  In other words, it is concentrating on vaccinating its most vulnerable citizens.  In mid-March, it announced that some restrictions, such as travel rules, quarantine times, mask-wearing, gathering limits and face-to-face classroom teaching, will be phased out, but not until specific dates in April.  It would appear that the policy of zero-Covid is still the aim of the Hong Kong government, or as masterminded by China.

Indeed, China’s so-called ‘dynamic zero-Covid strategy’ is also looking somewhat threadbare as cases there have spiked, much like Hong Kong’s prior Covid-19 troubles.  In early March, lockdowns across China affected tens of millions of people, including inhabitants of Jilin province and the technology hub of Shenzhen.  Yet some cities, such as Beijing, have been kept largely free from the virus.  But in late March, Shanghai for example, the city of 26 million people on the country’s East coast, reported record numbers of new Covid-19 infections.  The city has since been ordered to lockdown in two stages over nine days, during late March and early April, while authorities carry out Covid-19 testing.  Oh yes, the virus is still rampant in its country of origin.

The origin of Covid-19

There is still no definitive evidence – the mystery continues.  Ever since the Covid-19 plague started in January 2020, scientists have argued about its origin.  Seemingly, the only common agreement is that it began somewhere in China.  At the end of February 2022, three new investigative reports, involving almost 100 scientists from around the world, were released.  Two of them traced the outbreak to a Wuhan food market that sold live animals.  The third suggested that the virus spilled over from an animal species to humans at least twice in November or December 2019.  These reports have been published as preprints so have yet to be peer-reviewed.

Nevertheless, these reports strengthen the theory that the virus jumped from animals to humans located at the Huanan Seafood Wholesale Market.  Axiomatically, they weaken the arguments that bats, pangolins or several other proposed animal species, or accidental or deliberate leaks from the Wuhan Institute of Virology, were involved.  Genetic analyses of samples from the Market and from people infected around January 2020, plus geolocation data, certainly point to the Market as the likely disease epicentre.

But what were the spreading animals?  One paper now suggests raccoon dogs, that are used for food and fur across China and were for sale at the Market, were the culprits.  Against this is the suggestion that just one infected person could have been the super spreader and the Market was an incidental location rather than the originating site.

Two years on and these investigations seem slow and detached despite the trail of deaths and destruction that Covid-19 has caused around the world.  The pandemic’s origin has already been the subject of several inconclusive studies, including one by the World Health Organization (WHO) that was reported in March 2021.  That Wuhan was the probable location and an unnamed animal was the possible intermediate are not exactly overwhelmingly convincing outcomes.

In truth, we may never know the origin of Covid-19.  Time has marched on and collected samples have now largely been analysed, although China has been less than cooperative in sharing relevant data.  So what is left to achieve?  Perhaps the best outcome from the Covid-19 saga is to ensure that such a viral pandemic does not occur again, or, at least, to be better readied to detect and defeat it.

Three questions for friends and families

Everybody likes a jolly quiz, especially when they know the answers.  But sometimes such contests are not so entertaining and the answers can shock.  Here are three Covid-19-related questions to ask your family and friends.

First, on average, how many people are now dying of Covid-19 each week around the world?  Few will know that the answer is about 6,000 – the same toll first reached in October 2020, when governments around the world turned to a second round of lockdowns.  At the current rate, that would be more than 3 million Covid-19 deaths a year – more than from any other infectious disease.

Second, Covid-19 is the most recent global pandemic, but in the past four decades, how many dangerous disease outbreaks have been caused by viruses that have jumped from animals to humans?  The correct answer is at least six.  There have been human immunodeficiency virus (HIV), which emerged in the early 1980s; avian influenza A(H5N1 virus (bird flu) in 1997; severe acute respiratory syndrome virus (SARS) in 2003; Middle East respiratory syndrome virus (MERS) in 2012; Ebola virus disease in 2014; and now SARS-CoV-2, the full name of the virus that causes the Covid-19 disease.

Third, what virus will cause the next pandemic?  This is this unanswerable question.  Will it arrive this year, or the next, or the next decade, or ….?  All our answers will be incorrect although the inevitability of another pandemic is unquestionable.