The World Health Organization said on Monday that a SARS-CoV-2 variant circulating in India is of global concern.
“We classify it as a variant of concern at a global level,” Maria Van Kerkhove, WHO technical lead on COVID, told a briefing. “There is some available information to suggest increased transmissibility.”
India’s daily COVID statistics are down slightly but remain high. The health ministry said Monday there were 366 161 new cases and 3754 deaths from the virus in the previous 24-hour period. Public health experts believe the new cases and deaths to be an underestimate of the true picture.
India has 22.6 million COVID cases so far, according to the Johns Hopkins Coronavirus Resource Center. India’s case load is surpassed only by the US, with 32.7 million COVID cases.
There is also growing concern in India about ‘black fungus’ or mucormycosis, an opportunistic fungal infection which is affecting COVID patients and also those who have recovered from the disease. It typically only appears in immunocompromised patients. COVID patients with diabetes are particularly susceptible to mucormycosis, medical experts said. Meanwhile, struggling to contain its own COVID outbreak, Nepal is running short of oxygen and oxygen tanks and has asked Mount Everest climbers and guides not to abandon their oxygen cylinders on the mountain, rather bringing them back down so that medical facilities can fill them to give to COVID patients.
Kul Bahadur Gurung, a senior official with the Nepal Mountaineering Association, told Reuters, “We appeal to climbers and Sherpas [Himalayan people living around Nepal and Tibet, well known for climbing mountains] to bring back their empty bottles wherever possible as they can be refilled and used for the treatment of the coronavirus patients who are in dire needs.”
A Nepal health ministry official speaking to Reuters said the country needs 25 000 oxygen tanks immediately.
While COVID has been long known to be more dangerous in men than women, research which is still in its early stages shows that some of this increased risk could be from having a gene for male balding.
A team of researchers in the US first suspected the link when they noticed that men with a common form of hormone-sensitive hair loss, known as androgenetic alopecia, were also more likely to be hospitalised with COVID. They presented their findings May 6 at the virtual spring meeting of the European Academy of Dermatology and Venereology (EADV).
“Among hospitalized men with COVID-19, 79% presented with androgenetic alopecia compared to 31%-53% that would be expected in a similar aged match population,” said researchers led by Dr Andy Goren, chief medical officer at Applied Biology Inc in California.
The researchers noted that androgenetic alopecia is due to the activity of the androgen receptor (AR) gene, which can lead to balding in some men. An enzyme called TMPRSS2, key to COVID infection, is also androgen-sensitive, and might be affected by the AR gene as well, explained Dr Goren’s group.
One key segment on the AR gene seems to affect both COVID severity and male balding.
In the new study, the Irvine group enrolled 65 men hospitalised with COVID, and conducted a genetic analysis on them. The results showed that participants with certain structural differences in the AR gene were at greater risk of developing severe COVID. Speaking in a meeting press release, Goren said the AR gene anomaly “could be used as a biomarker to help identify male COVID-19 patients most at risk for ICU admissions.”
He added that he believes that “the identification of a biomarker connected with the androgen receptor is another piece of evidence highlighting the important role of androgens [male hormones] in COVID-19 disease severity.”
Dr Teresa Murray Amato has seen many severe cases of COVID. She is chair of emergency medicine at Long Island Jewish Forest Hills in New York City. Though not connected to the new research, but said it “did show a significant correlation between a higher number of androgen receptors and a higher incidence of ICU admissions for patients infected with COVID-19.”
Dr Amato added that, “While the study is small and the exact association is not completely understood, it may show at least one answer to why men were more likely to be admitted to ICU and have overall higher morality with COVID-19 infections.”
According to Amato, further investigations are necessary to determine whether “medications that block androgen receptors will be useful in treating a subset of [COVID-19] patients.”
Since the findings were presented at a medical meeting, they should be considered preliminary until published in a peer-reviewed journal.
A comprehensive review of what is so far known about the coronavirus its functions suggests the virus has a unique infectious profile, explaining why COVID is so difficult to treat and often leaves survivors with debilitating ‘long COVID’ symptoms.
In a review recently published in The Lancet Respiratory Medicine, the authors review what is currently known about COVID, and find that it works differently to most pathogens.
Evidence increasingly points to the virus infecting both the upper and lower respiratory tracts. In contrast, ‘low pathogenic’ human coronavirus sub-species typically settle in the upper respiratory tract, causing cold-like symptoms, while ‘high pathogenic’ viruses, such as those that cause SARS and ARDS, typically settle in the lower respiratory tract.
Additionally, COVID has evolved a uniquely challenging set of characteristics as evidenced by more frequent multi-organ impacts, blood clots, and an unusual immune-inflammatory response not commonly associated with other similar viruses.
While animal and experimental models imply an overly aggressive immune-inflammation response is a key driver, it seems things work differently in humans: Although inflammation is a factor, it is a unique dysregulation of the immune response that causes our bodies to mismanage the way they fight the virus.
This could explain the ‘long COVID’ phenomenon that some people experience after infection, struggling with significant health issues months after infection. Long COVID is characterised by symptoms of fatigue, headache, difficulty breathing and loss of sense of smell. It is more likely with increasing age, body mass index and female sex
“The emergence of severe acute respiratory syndrome coronavirus two (SARS-CoV-2), which causes COVID-19, has resulted in a health crisis not witnessed since the 1918 Spanish flu pandemic. Tragically, millions around the world have died already,” said co-author Ignacio Martin-Loeches, Clinical Professor in Trinity College Dublin’s School of Medicine, and Consultant in Intensive Care Medicine at St James’s Hospital.
“Despite international focus on the virus, we are only just beginning to understand its intricacies. Based on growing evidence we propose that COVID-19 should be perceived as a new entity with a previously unknown infectious profile. It has its own characteristics and distinct pathophysiology and we need to be aware of this when treating people.
“That doesn’t mean we should abandon existing best-practice treatments that are based on our knowledge of other human coronaviruses, but an unbiased, gradual assembly of the key COVID-19 puzzle pieces for different patient cohorts—based on sex, age, ethnicity, pre-existing comorbidities—is what is needed to modify the existing treatment guidelines, subsequently providing the most adequate care to COVID-19 patients.”
Journal information: Marcin F Osuchowski et al, The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity, The Lancet Respiratory Medicine (2021). DOI: 10.1016/S2213-2600(21)00218-6
Experts such as epidemiologists and statisticians made much more accurate predictions about COVID than the public, but both groups substantially underestimated the true extent of the pandemic, a study from the University of Cambridge has found.
Researchers from the Winton Centre for Risk and Evidence Communication surveyed 140 UK experts and 2086 UK laypersons in April 2020 and asked them to make predictions about the impact of COVID by the end of 2020. Participants were also asked to assign confidence in their predictions by providing upper and lower bounds of where they were 75% sure that the true answer would fall—for example, a participant would say they were 75% sure that the total number of infections would be between 300 000 and 800 000.
While only 44% of predictions from the expert group fell within their own 75% confidence ranges, only 12% of predictions from the non-experts fell within their ranges, though more numerate individuals performed a little better. The results were published in the journal PLOS ONE.
“Experts perhaps didn’t predict as accurately as we hoped they might, but the fact that they were far more accurate than the non-expert group reminds us that they have expertise that’s worth listening to,” said lead author Dr Gabriel Recchia from the Winton Centre for Risk and Evidence Communication,. “Predicting the course of a brand-new disease like COVID-19 just a few months after it had first been identified is incredibly difficult, but the important thing is for experts to be able to acknowledge uncertainty and adapt their predictions as more data become available.”
Expert opinion is important for those making decisions at any level from individual to policy. The quality of expert intuition can vary greatly depending on the field of expertise and the type of judgment required, so it is important to determine how good expert predictions really are, especially in where they could shape public opinion or government policy.
“People mean different things by ‘expert’: these are not necessarily people working on COVID-19 or developing the models to inform the response,” said Dr Recchia. “Many of the people approached to provide comment or make predictions have relevant expertise, but not necessarily the most relevant.” Dr Recchia noted that in the early stages of the pandemic, clinicians, epidemiologists, statisticians, and other individuals seen as experts by the media and the general public, were often asked to give off-the-cuff answers to questions about how bad the pandemic might get. “We wanted to test how accurate some of these predictions from people with this kind of expertise were, and importantly, see how they compared to the public.”
Participants in the survey were asked to predict how many people living in their country would have died and would have been infected by the end of 2020; they were also asked to predict infection fatality rates both for their country and worldwide.
The expert group and the non-expert group both underestimated the total number of deaths and infections in the UK. The official UK death toll at 31 December was 75 346. The median prediction of the expert group was 30 000, while that of the the non-expert group was 25 000.
For COVID fatality rates, the median expert prediction was that 10 out of every 1000 people with the virus worldwide would die from it, and 9.5 out of 1000 people with the virus in the UK would die from it. The median non-expert response to the same questions was 50 out of 1000 and 40 out of 1000. The true infection fatality rate at the end of 2020—as best could be estimated—was nearer to 4.55 out of 1000 worldwide and 11.8 out of 1000 in the UK.
“There’s a temptation to look at any results that says experts are less accurate than we might hope and say we shouldn’t listen to them, but the fact that non-experts did so much worse shows that it remains important to listen to experts, as long as we keep in mind that what happens in the real world can surprise you,” said Dr Recchia.
The researchers cautioned that it is important to differentiate between research on evaluating the forecasts of ‘experts’—individuals involved in relevant fields, such as epidemiologists and statisticians—and research on evaluating specific epidemiological models, though the models may inform experts. Many COVID prediction models have proved accurate in the short term, but rapidly become less accurate for later predictions.
One of the first doctors to warn of COVID’s disproportionate effect on ethnic minorities has been named on the Forbes 30 Under 30 list.
Dr Daniel Pan in Leicester, UK, was part of a group to treat the first cases in the city and noticed some of the sickest patients were minority ethnic.
The Forbes 30 Under 30 list celebrates young innovators in their respective fields, such as science and healthcare.
Dr Pan, who is a clinical fellow at the National Institute for Health Research (NIHR) at the University of Leicester, said: “It’s a great honour and I think the best thing about it is it helps advertise the research we’ve been doing, because it’s important work.”
He was one of the first to treat COVID patients in Leicester, and noticed the differences among the patients.
Dr Pan said: “Leicester has a very multi-ethnic diverse population so when the pandemic first hit the UK, I was working on the clinical wards.
“It became immediately clear to myself and my colleagues that a lot of these patients were from ethnic minority backgrounds – especially the ones who were very sick.
“We probably noticed that slightly earlier than a lot of other places, for example Italy, and we felt a need to get that out there.”
As part of a group of researchers led by Dr Manish Pareek, he contributed to work that demonstrated that COVID’s disproportionate impact on UK ethnic minority groups was largely a result of a greater risk of being infected, due to societal and health inequalities.
NIHR Leicester Biomedical Research Centre director Professor Melanie Davies remarked that Dr Pan had made a “significant contribution to research efforts”, adding he had “a bright future in clinical research ahead of him”.
He is now working alongside his colleagues on a face mask that could determine whether the wearer has COVID, and possibly how infectious they are.
Dr Pan said: “We can probably find out when a person is most infectious, because we can find the time of day and the period of their illness where they breathe out the most virus.
“If it’s effective it can be rolled out, for example, everyone in A&E could wear a mask while they’re waiting to see a doctor and those who are mask positive can then go into isolation bays.”
‘Vaccine shedding’ is the new disinformation being circulated among anti-vaxxers.
When a school in Florida, US announced that it wouldn’t allow vaccinated teachers in its classrooms, its founder said “vaccine shedding” was her main concern.
Paediatrician Nicole Baldwin, MD, said the anti-vaxx community is buzzing with this latest bit of disinformation.
“It’s amazing, and sad, what people will believe,” Dr Baldwin told MedPage Today.
This piece of disinformation follows that vaccinated people can somehow shed the spike protein, supposedly causing menstrual cycle irregularities, miscarriages, and sterility in women, merely by being in proximity.
“This is a new low, from the delusional wing of the anti-vaxx cult,” said Zubin Damania, MD, aka ZDoggMD, in a video he recently posted to bust vaccine shedding myths.
Damania explained that the misinformation arises from a previous claim that syncytin, a protein involved in placental formation, has some structural similarity SARS-CoV-2 spike protein, and so vaccination would interfere with women’s reproductive systems. Numerous fact checks have shown that vaccines don’t target the protein.
On injection, mRNA and viral vector vaccines prompt cells to make the spike protein, but it’s usually cleared in 24 to 48 hours, leaving little opportunity for “shedding,” even if it was possible, which it isn’t, underscored Dr Damania.
He pointed out another logical fallacy: “Why, then, wouldn’t natural spike protein do the same thing? Wouldn’t you be more scared of natural coronavirus infection? Oh, but it’s ‘natural.'”
There are legitimate questions about and research on whether the coronavirus itself and vaccines affect women’s menstrual cycles, he added. Since the beginning of the pandemic, women who’ve had COVID reported changes to their menstrual cycle, and Dr Damania said that researchers are examining reports of menstrual cycle changes after vaccination.
Regarding the potential relationship to vaccination, “we don’t understand, first, if it’s true, and if it were true, what is the mechanism?” he said. “Anything that causes stress, inflammation, and an immune response may have an effect on the menstrual cycle. […] Could it be that the vaccine causes a temporary change in menses? Sure, it’s possible, and it’s being looked at.”
India postponed exams for trainee doctors and nurses on Monday, freeing them up to fight the world’s biggest surge in COVID infections, as the health system buckles under the weight of new cases, and a lack of beds and oxygen.
The total number of infections so far rose to just short of 20 million, propelled by a 12th straight day of more than 300 000 new cases.
Actual numbers in India could be five to 10 times higher than those reported, according to medical exports.
Hospitals have been overloaded, oxygen has run short, and morgues and crematoriums have struggled with the number of corpses. “Every time we have to struggle to get our quota of our oxygen cylinders,” said BH Narayan Rao, a district official in the southern town of Chamarajanagar, where 24 COVID patients died, some suspected from lack of oxygen.
“It’s a day-to-day fight,” added Rao, describing the struggle for supplies.
In many cases, volunteer groups have come to the rescue. Outside a temple in India’s capital, New Delhi, Sikh volunteers provided oxygen to patients lying on benches inside makeshift tents, hooked up to a giant cylinder. A new patient would come in every 20 minutes.
“No one should die because of a lack of oxygen. It’s a small thing otherwise, but nowadays, it is the one thing every one needs,” Gurpreet Singh Rummy, who runs the service, told Reuters.
Offering a glimmer of hope, the country’s health ministry said that positive cases relative to the number of tests fell on Monday for the first time since at least April 15, and modelling shows that the virus could peak on Wednesday.
While 11 states and regions have put movement curbs in place to stem transmissions, Prime Minister Narendra Modi’s government, widely criticised for allowing the crisis to spin out of control, is reluctant to announce a national lockdown, concerned about the economic impact.
“In my opinion, only a national stay at home order and declaring medical emergency will help to address the current healthcare needs,” Bhramar Mukherjee, an epidemiologist with the University of Michigan, said on Twitter.
As medical facilities near collapse, the government postponed an exam for doctors and nurses to free up some to join in the COVID fight, it said in a statement.
Prime Minister Modi has provoked criticism for not acting earlier to limit the spread and for allowing millions of people, mostly without masks, to attend religious festivals and political rallies during March and April.
In early March, a forum of government scientific advisers warned officials of a new and more contagious variant of the coronavirus taking hold, five of its members told Reuters.
Four of the scientists said in spite of the warning, the federal government did not try and impose strict curbs.
Meanwhile, in response to India’s crisis, aid has poured in. On Sunday, the UK government said it will send another 1000 ventilators to India.
Several nations have shut their borders to Indian arrival as the Indian COVID variant has now reached at least 17 countries including the UK, Iran and Switzerland.
Although long hours in the lab are standard, some young cancer researchers have told BBC’s Radio 1 Newsbeat that, in order to continue their work, the pandemic is forcing them to work longer, harder days with no pay.
Many relished the easing of COVID rules in the UK at the beginning of the summer months. However Dr Alba Rodriguez-Meira, 28, said that those sunny weeks were like an “extended lockdown”.
At the time, labs had been shut for nearly four months and Dr Rodriguez-Meira worked more than 90 hours a week – equivalent to 13 hours a day, 7 days a week – to catch up her leukaemia research at the University of Oxford.
“That was fine during the first month but it becomes a bit disruptive in terms of life quality if you try to do it for much longer,” Dr Rodriguez-Meira said.
Her weekly hours are slowly returning to her usual 60 a week – but she’s still feeling the pressure.
“I’ve lost a lot of productivity – sometimes I think I’ve not been as happy or as passionate as I used to be.
“Working under these circumstances has made me lose a bit of that. And I am sometimes so, so, absolutely tired.”
Social distancing rules mean that even though labs have reopened, not everyone can be there at the same time.
This is affecting the work of PhD student Laurien van de Weijer, 24, who is studying meningioma, a kind of tumour which makes up over a third of primary central nervous system tumours.
An important experiment she was running at her lab at the University of Plymouth over Easter weekend in April failed because she could not get in to provide nutrients to the tumour cells, which subsequently died. She is apprehensive about the 18 months she has left to finish her doctorate.
“I’ll be so overloaded… because I lost lots of time in the early stage, I really have to catch up, so I probably will do crazy hours.
“I really don’t look forward to being in the lab in the middle of the night.”
Laurien is also concerned that the longer she takes to get her research done, “the longer there won’t be any good drugs” for people with meningiomas.
The Institute of Cancer Research (ICR) says the COVID pandemic will add on an extra two years to the lag time between new treatments being discovered and cancer patients being able to use them.
“We don’t have the luxury of time – that’s the truth – to wait for two extra years,” says Amani Liaquat, 23, who has an aggressive cancerous brain tumour known as a glioblastoma multiforme, and according to doctors has between 12 and 18 months to live.
Amani is now trying a new drug called ONC201 which is still in trials, after chemotherapy and radiotherapy have both failed to shrink the tumour
Amani says she “can’t really put into words” how grateful she is to researchers going into labs during the pandemic, “risking their own health to try and help others”.
“The fact that people are still out there, trying their best in such difficult circumstances is really important,” she says.
Spurred on by stories like Amani’s, some groups of so-called “wet lab” researchers, whose work is experiment-heavy, have come up with shifts that allow them in to labs while observing social distancing.
It’s often after midnight when Beshara Sheehan begins her cycle home from the ICR lab in Sutton, south London.
Beshara Sheehan, 28, whose research is on improving prostate cancer therapy, works a lot of late shifts, often cycling home at midnight. She finds it “difficult to switch off” from work, having to still communicate with on-shift colleagues..
Fiona Want, 25, works at the same site as Beshara, albeit in a different research team, but prefers early morning shifts over late ones.
“It took a bit of getting used to having that real jumble of routine,” said Fiona, who has walked half her day at the lab and half at home.
Her research is on bladder cancer, and works up to 55 hours a week, 10 hours more than pre-COVID. She is driven on by the death of her fiance’s dad from cancer at the end of last year.
“That’s been a real source of motivation for me to keep working hard and a reminder that everyone’s life is, in some way, impacted by cancer,” she said.
“It is so important that we don’t let research slow down and keep pushing forward with discoveries that ultimately save lives.”
The treatment of pain in recovered COVID patients poses unique challenges, said a pain expert presenting at the American Academy of Pain Medicine virtual meeting.
“A lot of these patients are going to need rehabilitation” or physical therapy, noted Natalie Strand, MD, of the Mayo Clinic in Scottsdale, Arizona, at the meeting. “There can be quite a bit of deconditioning that occurs, especially after a prolonged ICU stay. Neuropathic pain is also quite common.”
Post-COVID neuropathy may be viral or else possibly related to patient positioning, including prone positioning. Some patients “may need short-term opioids or gabapentinoids and they may experience aggravation of prior underlying pain, either due to direct physical causes or to the increase in anxiety and depression that can accompany a COVID infection,” Dr Strand said.
A study that followed 143 patients two months after acute COVID showed a high proportion reported persistent symptoms — including fatigue (53%), joint pain, (27%) and chest pain (22%) — that often results in patients going to a pain clinic for care, she noted.
Persistent pain remains prevalent, following any ICU admission, ranging from 28% to 77%, according to Dr Strand.
Chronic neuropathic pain after a COVID patient’s ICU stay can include muscle pain related to joint contractures or muscle atrophy, and pain due to critical illness myopathy or polyneuropathy. In addition, peripheral nerve injuries have been associated with prone positioning for COVID–related acute respiratory distress syndrome, Dr Strand added. Complications from traumatic procedures like placement of chest tubes or tracheotomy can also cause chronic neuropathic pain.
Dr Strand noted that pain can persist after discharge of COVID patients, as indicated by follow-ups. In China, three-quarters of patients previously hospitalised with COVID continued to report at least one symptom 6 months later, with fatigue or muscle weakness by far the most common symptoms (63%). “Compared with 2-month follow up, 6 months later we see the same trends,” she pointed out.
In that study, “13% of the patients who did not develop an acute renal injury during their hospital stay and presented with normal renal function exhibited a decline in GFR at follow up,” Dr Strand noted. This may signal caution about using NSAIDS to manage pain in some patients, she said: “Normal renal function at discharge does not necessarily mean it will remain this way 6 months afterwards.”
There may be a relationship with the SARS-CoV-2 virus and chronic neuropathic pain, Strand observed. In a recent article in Pain Reports, “the authors concluded it could be direct or indirect effects of the virus on the nervous system that can cause neuropathic pain,” she noted. “We know that there are neuropathic symptoms involved with the famous loss of taste and loss of smell with presentation,” she continued. “But also in the acute phase, we commonly see headache, dizziness, muscle pain, ataxia, and in hospitalized patients we see stroke, meningitis, encephalitis, and autoimmune disorders like Guillain-Barré syndrome and acute disseminated encephalomyelitis.”
Psychological stressors can also be related to the emergence of chronic pain, added Dr Strand. “Anxiety and depression often follows COVID-19 infection,” she said. “It may be wise to screen our patients for anxiety and depression after infection to see if we can further control these components to help manage their pain overall.”
Researchers have developed an entirely new treatment for COVID: ‘Nanotraps’ that capture the viruses inside the body, allowing the immune systems to destroy them
The “Nanotraps” mimick the human cells the virus normally attaches to, and bind it to their surface, keeping the virus from reaching other cells and target it for destruction by the immune system. It is possible that Nanotraps could be used on SARS-CoV-2 variants, and could be administered as a nasal spray.
“Since the pandemic began, our research team has been developing this new way to treat COVID-19,” said Assistant Professor Jun Huang, whose lab led the research. “We have done rigorous testing to prove that these Nanotraps work, and we are excited about their potential.”
Postdoc Min Chen and graduate student Jill Rosenberg targeted the spike mechanism that SARS-CoV-2 uses to lock onto ACE2 proteins on human cells.
To create a trap that would bind to the virus in the same way, they designed nanoparticles with a high density of ACE2 proteins on their surface. Other nanoparticles were designed with neutralising antibodies on their surfaces.
ACE2 proteins and neutralising antibodies have both been used in COVID treatments, but by mounting them onto nanoparticles, a much more effective and robust means for trapping the virus was created.
The nanoparticles are smaller than cells, 500 nanometres in diameter, allowing them to reach deep inside tissue and trap the virus.
No evidence of toxicity was seen in tests with mice, and they then tested the Nanotraps against a non-replicating virus called a pseudovirus in human lung cells in tissue culture plates and saw that they completely prevented viral entry into the cells.
When the nanoparticle binds to the virus (about 10 minutes after injection), it chemically signalled macrophages to engulf and destroy the nanoparticle and the attached virus. Macrophages normally engulf nanoparticles, so this merely sped up the process.
Testing the Nanotraps on a pair of donated lungs kept alive with a ventilator, they found that they completely prevented infection.
They also collaborated with researchers at Argonne National Laboratory to test the Nanotraps with a live virus (rather than a pseudovirus) in an in vitro system. They found a 10 times better performance than with neutralising antibodies or ACE2 inhibitor.
The researchers plan further tests, including live virus and its variants.
“That’s what is so powerful about this Nanotrap,” Rosenberg said. “It’s easily modulated. We can switch out different antibodies or proteins or target different immune cells, based on what we need with new variants.”
Storage is simple, as the Nanotraps can be kept in a standard freezer, and administration is simple, using a nasal spray. The researchers said it is also possible to serve as a vaccine by optimisation of the Nanotrap formulation.
