Tag: covid

Vitamin D Deficiency Shown to Increase COVID Severity and Mortality

Photo by Julian Jagtenberg from Pexels

A new study conducted by the Azrieli Faculty of Medicine of Bar-Ilan University and its affiliate Galilee Medical Center (GMC) is one of the first to show that vitamin D deficiency before infection is associated with increased COVID severity and mortality. The study is available on the medRxiv preprint server, awaiting peer review.

Vitamin D has attracted attention in prevention of severe COVID as its levels are known to be related to risks of influenza and respiratory tract infections. It also has direct antiviral effects primarily against enveloped viruses, which include coronaviruses.

Previous studies that examined the link between vitamin D levels and SARS-CoV-2 infection had mixed results. Most measured vitamin D levels once patients were already sick, making interpretation of the results difficult. The new study assessed this correlation using low levels of vitamin D measured prior to infection and also focused on disease severity.

The researchers searched for vitamin D levels measured 14 to 730 days prior to positive PCR tests in the records of individuals admitted between April 2020 and February 2021 to GMC in Nahariya, Israel.

Of 1176 patients admitted, 253 had vitamin D levels recorded prior to COVID infection. Compared to mildly or moderately diseased patients, those with severe or critical COVID disease were more likely to have severe pre-infection vitamin D deficiency with levels less than 20 ng/mL.

“This study can highlight the risks of vitamin D deficiency in terms of COVID-19,” said Dr Amiel Dror, of GMC and the Azrieli Faculty of Medicine of Bar-Ilan University, who led the study. “Vitamin D is often associated with bone health. We’ve shown that it may also play an important role in other disease processes, such as infection.”

Prof Michael Edelstein, of the Azrieli Faculty of Medicine of Bar-Ilan University said, “It is still unclear why certain individuals suffer severe consequences of COVID-19 infection while others don’t. Our finding adds a new dimension to solving this lingering puzzle. In Israel, where vitamin D deficiency is common in certain population groups, this finding is particularly important.”

The authors said that the link between low pre-infection vitamin D levels and severe COVID does not necessarily imply that giving vitamin D to COVID patients will decrease the risk of severe disease. However, it does highlight the need to better manage vitamin D deficiency.

Source: Bar-Ilan University

Epsilon and Delta Variant Mutations Allow Immune Evasion

Researchers found that the L452R mutation of the SARS-CoV-2 spike protein, common to two mutant strains, the Epsilon and Delta, can evade cellular immunity through the human leukocyte (HLA) A24 and can increase viral infectivity.

The study, by researchers at the Kumamoto University and Weizmann Institute of Science, was published in the journal Cell Host & Microbe. It showed emerging mutations L452R and Y453F in the SARS-CoV-2 spike receptor-binding motif evade (HLA) A24-restricted cellular immunity. The L452R mutation also enhances spike stability, viral fusogenicity, and viral infectivity. Hence, the findings suggest that HLA-restricted cellular immunity potentially affects the evolution of viral phenotypes.

Emerging variants of concern (VOC) may escape immune responses induced by vaccination or natural infection, threatening global vaccination efforts.

The first reported and well-studied mutant contains a D614G substitution in the spike (S) protein. The D614G mutation has recently been shown to enhance the binding affinity of SARS-CoV-2 to the ACE2 receptor. It is also more infectious and easily transmissible. However, there is no evidence suggesting that the D614G variant is tied to increased lethality.

At the end of 2020, the emergence of new variants was reported – the B.1.1.7 (Alpha), the B.1.351 (Beta), and the P.1 (Gamma) in the United Kingdom, South Africa, and Brazil, respectively. At the end of 2020, another lineage, the B.1.427 also called the CAL.20C, occurred in California, United States.

The Delta variant is becoming dominant globally, and has been linked to increased infectivity, transmissibility, severe illness, and even death.

Interestingly, mutated viruses are mainly due to error-prone viral replication, and the spread of new variants is linked to their escape from immune responses. SARS-CoV-2 mutants may resist neutralising mediated antibodies from COVID patients and vaccinated individuals.

Further, the new emerging variants may escape the cellular immunity conferred by cytotoxic T lymphocytes (CTLs), which recognise non-self epitopes present on virus-infected cells through the HLA class I molecules. This is called CTL-mediated antiviral immunity.

Human CTLs were recently shown to be able to recognise HLA-restricted SARS-CoV-2-derived epitopes. Also, the functionality of virus-specific cellular immunity correlates inversely with COVID-19 severity. Thus, CTLs play pivotal roles in controlling SARS-CoV-2 infection.

The team explored the potential emergence of SARS-CoV-2 mutants that can evade HLA-restricted cellular immunity in the current study.

The team used immunological experiments to show that an antigen to the SARS-CoV-2 spike protein is strongly recognised by the HLA-A24-restricted cellular immunity, which is often seen in Japanese people.

The team also conducted a large-scale sequence analysis of SARS-CoV-2 strains and demonstrated that HLA-A24 could recognize mutations in the spike protein region.

The team found that at least two naturally occurring substitutions in the receptor-binding motif of the SARS-CoV-2 spike protein, the L452R and Y453F identified in the B.1.427 and B1.1.298, can be resistant to the HLA-A24 cellular immunity.

The mutants also increase ACE2 binding affinity. Pseudovirus experiments show that L452R also enhances viral infectivity. The L452R mutation does so by stabilising the S protein, enhancing viral replication.

“These data suggest that HLA-restricted cellular immunity potentially affects the evolution of viral phenotypes and that a further threat of the SARS-CoV-2 pandemic is its ability to escape cellular immunity,” the team concluded in the study.

Investigating the L452R mutation further should be a priority since it is borne by the highly infectious Delta variant. 

Source: News-Medical.Net

True COVID Toll in India Likely in the Millions

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Excess deaths in India during the pandemic could be as much as 10 times the official COVID toll, likely making it modern India’s worst human tragedy, according to a new report.

report published by Arvind Subramanian, the Indian government’s former chief economic adviser, and two other researchers at the Center for Global Development and Harvard University, estimates that between 3.4 million and 4.7 million excess deaths have occurred in the country from January 2020 to June 2021.

The report said that the true toll was likely “an order of magnitude higher”, and the official count could have missed deaths with overwhelmed and disrupted healthcare systems, particularly during the devastating virus surge earlier this year. It also has recently come to light that the Indian government did not count any deaths due to a lack of oxygen.

The researchers from used three different data sources to estimate India’s excess all-cause mortality. They extrapolated death registrations from seven states, accounting for half of India’s population, but published data for annual mortality surveys are only available up to 2019. Second, the researchers applied international estimates of age-specific infection fatality rates to data from two countrywide antibody tests, also called sero surveys. Third, they looked at India’s thrice yearly consumer survey of 900 000 individuals, which also records deaths in households.

Taken together, the researchers arrived at an estimate of of 3.4 million to 4.7 million – about 10 times higher than India’s official COVID death toll of 414 000. This was also considerably higher than other estimates by epidemiologists, who estimated excess deaths were between five and seven times higher. Not all these deaths were caused by COVID and an estimation of the actual death toll by the disease would be difficult to give, said Subramanian. 

The data implied that four million people had died in the pandemic in India, according to Dr Subramanian.

“Two of our three estimates measure all-cause mortality and not COVID deaths. Our second measure is a bit closer to a number of [actual] COVID deaths, but it is only one of three estimates,” Dr Subramanian told the BBC.

The researchers also said that the first wave last year appeared to have been more lethal than what was popularly believed. Mortality only seemed to be moderate because it was “spread out in time and space”.

Dr Subramanian said one of the conclusions might be that “India has not been an outlier” and has had “mortality not dissimilar from countries of comparable size and infections”.

The researchers said the most “critical take-away, regardless of the sources and estimates”, was that actual deaths during the pandemic were “likely to be far greater than the official count”.

“The true deaths are likely to be in several millions, not hundreds of thousands, making this arguably India’s worst human tragedy since the partition and independence.” The 1947 Partition of the British-ruled Indian subcontinent into independent India and Pakistan resulted in up to 1 million people being killed in violence between Hindu and Muslim gangs.

Source: BBC News

Child Mask Study Which Reported High CO2 Levels Retracted

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A study which generated controversy by suggesting that masks may harm children through exposure to high carbon dioxide levels was retracted on Friday.

The research letter released in JAMA Pediatrics on June 30 had reported finding in a lab environment unacceptably high levels of CO2 by German standards in air inside masks worn by children.

The journal editors cited “numerous scientific issues” in the retraction notice, which also included questions over the applicability of the CO2 measurement device and the validity of the study’s conclusions.

“In their invited responses to these and other concerns, the authors did not provide sufficiently convincing evidence to resolve these issues, as determined by editorial evaluation and additional scientific review,” the notice read. “Given fundamental concerns about the study methodology, uncertainty regarding the validity of the findings and conclusions, and the potential public health implications, the editors have retracted this Research Letter.”

The study drew prompt criticism following its publication. Joseph Allen, MPH, DSc, who studies the impact of carbon dioxide on human health at Harvard School of Public Health in Boston, described the study as “terribly flawed”, predicting its retraction on Twitter. He pointed out that the study made no account of the flood of air taken in when children inhale, his key complaint.

The US Centers for Disease Control do not list any known risk wearing facing masks poses to children, and in fact, recently recommended that unvaccinated children wear masks when school reopen later this year. A previous study with adult volunteers had shown short-term but acceptable rises in CO2 when wearing masks,

While many areas of the US have dropped mask mandates, Los Angeles is reinstating its indoor mask mandate regardless of vaccination status as COVID cases and hospitalisations rise, presumably due to the spread of the Delta variant.

Source: MedPage Today

First Olympic COVID Cases Among SA Soccer Team

Photo by Bryan Turner on Unsplash
Photo by Bryan Turner on Unsplash

Three members of the South African soccer team staying in the Olympic Village have tested positive for COVID just days before the Olympic opening ceremonies. They are also the first Olympic athletes who tested positive in the tightly-monitored athletes’ enclave along a Tokyo waterfront.

The South African team said in a July 17 statement that defender Thabiso Monyane, midfielder Kamohelo Mahlatsi, and Mario Masha, a video analyst on the coaching staff, had tested positive on the weekend. All South African players had tested negative when they departed for Tokyo on July 13. The entire South African football team is now under quarantine, raising doubts whether they’ll be cleared for their July 22 match against Japan.

Since the announcement, South African rugby Sevens coach Neil Powell as well as an unnamed member of the female US gymnastics team have also tested positive. Outside the athlete’s complex, positive results have been reported for South Korean IOC official Ryu Seung, an unnamed member of the Nigerian delegation, and an unnamed athlete.

Despite the country’s best efforts to contain the virus, COVID remains a big concern in Tokyo at the world’s largest sporting event, expected to draw about 11 000 athletes from 200 nations. The Tokyo Olympic Committee has introduced measures such as banning spectators at games, daily COVID screening for athletes, and limiting stays at the Olympic Village to seven days.

With Japan still under a state of emergency and the COVID delta variant spreading rapidly, many continue to appeal to the International Olympic Committee to cancel the games. But some experts said that at this point a cancellation would cost Japan $16.4 billion. It would also run the risk of being sued by the IOC for breach of contract.

Addressing the outbreaks in an effort to rally local support for the events, IOC president Thomas Bach said, “We are well aware of the skepticism a number of people have here in Japan,” he said. “My appeal to the Japanese people is to welcome the athletes for their competitions.”

Source: Quartz

Vaccination Setbacks and Medical Supply Shortages from Riots

Photo by Jilbert Ebrahimi on Unsplash
Photo by Jilbert Ebrahimi on Unsplash

Speaking to Bheksisa, deputy director-general at the health department Dr Nicholas Crisp described the vaccination programme’s setbacks and medical supply shortages resulting from the recent violence and looting.

The vaccination programme has been set back due to damage at vaccination sites such as pharmacies, and others such as clinics being unable to operate except for some in KwaZulu Natal’s outer rural regions. The programme is unlikely to reach its 250 000 vaccinations per day, he said, rather, 200 000 is a more likely goal. Currently, “going flat out”, the programme is vaccinating 140 000 people per day elsewhere in the country.

All of the available vaccines will be used including those Johnson & Johnson vaccines left over from innoculating teachers and other critical workers.

Those receiving Pfizer vaccines needn’t be too concerned about missing their second dose appointment, as research shows that the immunity conferred is as strong or even stronger at 42 days as compared to the standard 21 days.

However, he said that “the biggest disaster with the looting of medicine isn’t vaccines; it’s the looting of chronic medicine. For close to half of patients in KwaZulu-Natal, it’s gone. So much of the insulin for diabetes patients, the morphine, the antiretroviral drugs for HIV patients, are gone.”

The other challenge, he said, is getting oxygen to COVID patients via blocked roads, and delivering food supplies to hospitals, warning that there are patients who are without food. 

Afrox has confirmed that its facilities in Durban have not been affected by rioting, and their deliveries of medical oxygen continue though often under police escort.

Source: Bheksisa

No Smoking Uptick in COVID Pandemic – Unlike Other Disasters

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Unlike other population-level stressful events such as natural disasters, COVID has not resulted in a net increase in smoking, according to a new study from the International Tobacco Control (ITC) Project, at the University of Waterloo.

However, the researchers also found that although nearly half of smokers reported that COVID caused them to consider quitting, the vast majority of smokers did not change their smoking habits during the early phase of the COVID pandemic.

Stress is known to be a significant risk factor for smoking, especially in females. The study surveyed 6870 smokers and vapers in  Australia, Canada, England, and the United States between April and June 2020. The team investigated the association between COVID and thoughts about quitting smoking, changes in smoking, and factors related to positive changes such as attempting to quit or reducing smoking.

Only 1.1 per cent of smokers in the four countries attempted to quit and 14.2 percent reduced smoking, but this was offset by the 14.6 percent who increased smoking, with 70.2 percent reported no change.

“It is important to note that population-level stressful events, such as 9/11 and natural disasters, have often led to increased smoking,” said Geoffrey Fong, professor of psychology at Waterloo and principal investigator of the ITC Project. “So, our findings that there was no net increase in smoking in response to COVID may actually represent a positive result for public health.”

The study found that those who considered quitting smoking due to COVID were mostly females, ethnic minorities, those under financial stress, current vapers, less dependent smokers, those with greater concern about personal susceptibility of infection, and those who believed COVID is more severe for smokers.

According to study co-author Fong, this latter finding may explain why a significant uptick in smoking was seen in the COVID pandemic, compared to past tragedies.

“Unlike other population stressors such as earthquakes, which are unrelated to smoking, COVID severity is indeed linked to smoking,” Fong said. “Public health officials have mentioned the link as yet another reason for smokers to quit, and over 80 percent of smokers across the four countries believed that smoking made COVID more severe. And this led to the lack of an increase in smoking, unlike what we have seen after other tragedies.”

Source: EurekAlert!

Journal information: Gravely, S., et al. (2021) Smokers’ cognitive and behavioural reactions during the early phase of the COVID-19 pandemic: Findings from the 2020 ITC Four Country Smoking and Vaping Survey. PLOS ONE. doi.org/10.1371/journal.pone.0252427.

Flu Shots May Offer Some COVID Protection

Photo by Raghavendra V. Konkathi on Unsplash
Photo by Raghavendra V. Konkathi on Unsplash

The flu vaccine may provide a level of protection against COVID, a new study concludes.

An analysis of patient data from around the world strongly suggests that the annual flu shot reduces the risk of stroke, sepsis and DVT in patients with COVID. Flu-vaccinated COVID patients were also less likely to visit the emergency department and be admitted to the intensive care unit (ICU). The research was presented online at research being presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID).

Global COVID vaccination is a daunting challenge and, although production and distribution of vaccines increases daily, some countries are not expected to vaccinate large numbers of their population until the start of 2023.

Recently, several modestly-sized studies suggested that the flu vaccine may provide some measure of protection against COVID.

Ms Susan Taghioff, of the University of Miami Miller School of Medicine, and colleagues carried out a retrospective analysis of data on tens of thousands of patients from around the world to find out more.

In the largest study of its kind, the team screened de-identified electronic health records held on the TriNetX research database of more than 70 million patients to identify two groups of 37 377 patients, from countries including the US, UK, Germany, Italy, Israel and Singapore.

The two groups were matched for factors that could affect their risk of severe COVID-19, including age, gender, ethnicity, smoking and health problems such as diabetes, obesity and chronic obstructive pulmonary disease.

The first group had received the flu vaccine between two weeks and six months before COVID diagnoses. The second group also had COVID but were not vaccinated against flu. 

The incidence of 15 adverse outcomes, including sepsis and death, within 120 days of testing positive for COVID was then compared between the two groups. Analysis showed that those not vaccinated for flu were significantly more likely (up to 20%) to have been admitted to ICU.

They were also significantly more likely to visit the Emergency Department (up to 58%), to develop sepsis (up to 45%), to have a stroke (up to 58%) and a deep vein thrombosis (up to 40%). However, the risk of death was not reduced.

It isn’t known exactly how the flu jab provides protection against COVID but most theories centre around it boosting the innate immune system.

The results strongly suggest that the flu vaccine protects against several severe effects of COVID, according to the study authors. Further research is needed to prove this possible link but, in the future, the flu shot could be used to help bolster protection in countries short of COVID vaccine doses.

Senior author Dr Devinder Singh, professor of plastic surgery at the University of Miami Miller School of Medicine, said: “Only a small fraction of the world has been fully vaccinated against COVID to date and, with all the devastation that has occurred due to the pandemic, the global community still needs to find solutions to reduce morbidity and mortality.

“Having access to real-time data of millions of patients is a powerful research tool. Together with asking important questions it has allowed my team to observe an association between the flu vaccine and lower morbidity in COVID patients.

“This finding is particularly significant because the pandemic is straining resources in many parts of the world. Therefore, our research – if validated by prospective randomised clinical trials – has the potential to reduce the worldwide burden of disease.”

Ms Taghioff added: “Influenza vaccination may even benefit individuals hesitant to receive a COVID vaccine due to the newness of the technology.

“Despite this, the influenza vaccine is by no means a replacement for the COVID vaccine and we advocate for everyone to receive their COVID vaccine if able to.

“Continued promotion of the influenza vaccine also has the potential to help the global population avoid a possible ‘twindemic’ – a simultaneous outbreak of both influenza and coronavirus.

“Regardless of the degree of protection afforded by the influenza vaccine against adverse outcomes associated with COVID, simply being able to conserve global healthcare resources by keeping the number of influenza cases under control is reason enough to champion continued efforts to promote influenza vaccination.”

Source: EurekAlert!

Woman, 90, Succumbs to Double COVID Variant Infection

Double COVID Variant Infection

Researchers in Belgium report on the case of a 90-year-old woman who was simultaneously infected with two different COVID variants.

On March 3 2021, the woman, with an unremarkable medical history, was admitted to a Belgian hospital after a spate of falls. She tested positive for COVID on the same day. She received nursing care at home, where she lived alone, and had not received a COVID vaccination.

At first, no signs of respiratory distress were seen, and oxygen saturation was good. However, she went on to develop rapidly worsening respiratory symptoms, and died five days later.

PCR testing revealed that she had been infected by two different strains of the virus — one which originated in the UK, known as B.1.1.7 (Alpha), and another that was first detected in South Africa (B.1.351; Beta).

“This is one of the first documented cases of co-infection with two SARS-CoV-2 variants of concern”, says lead author and molecular biologist Dr. Anne Vankeerberghen from the OLV Hospital in Aalst, Belgium. “Both these variants were circulating in Belgium at the time, so it is likely that the lady was co-infected with different viruses from two different people. Unfortunately, we don’t know how she became infected.”

The Alpha variant had been detected in the south east of England in December and within weeks, this variant displaced the viral strains circulating there. Since then, it has spread to more than 50 countries, including Belgium. The Beta variant was reported on December 18, 2020, and has since spread to 40 countries, which also includes Belgium.
Scientists in Brazil reported in January 2021 that two people had been simultaneously infected with two different strains of the coronavirus—the Brazilian variant known as B.1.1.28 (E484K) and a novel variant VUI-NP13L, which had previously been discovered in Rio Grande do Sul. However, this study has yet to be published in a scientific journal.

“Whether the co-infection of the two variants of concern played a role in the fast deterioration of the patient is difficult to say”, said Vankeerberghen. “Up to now, there have been no other published cases. However, the global occurrence of this phenomenon is probably underestimated due to limited testing for variants of concern and the lack of a simple way to identify co-infections with whole genome sequencing.”

She continued, “Since co-infections with variants of concern can only be detected by VOC-analysis of positive samples, we would encourage scientists to perform fast, easy and cheap VOC-analysis by PCR on a large proportion of their positive samples, rather than just whole genome sequencing on a small proportion. Independent of the technique used, being alert to co-infections remains crucial.”

Source: EurekAlert!

Emerging Variants Threaten a Worsening of the Pandemic

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Progress against the COVID pandemic has been impeded by the emergence of new variants of concern (VOC), and new ones may further worsen and prolong it.

VOCs increase the transmissibility of the SARS-CoV-2 virus and hence raise the reproduction number. Furthermore, they enhance the immune escape capabilities of the virus and blunt the effectiveness of available vaccines. Finally, they increase the pathogenicity of the infection.

Alpha, Beta, and Gamma VOCs with the N501Y mutation replaced the initial wild-type SARS-CoV-2 strains in Ontario, Canada, and then the Delta variant dominated during the period between February to June 2021. While enhanced virulence of VOCs having the N501Y mutation has been reported, there is a lack of comprehensive analyses that demonstrate increased virulence of the Delta variant.

Researchers from Toronto University, Canada, recently showed that these emerging VOCs were linked to increased virulence, as determined by hospitalisation risk, ICU admission, and mortality. This study is currently available on the medRxiv preprint server.

The researchers created a retrospective cohort of patients testing positive for SARS-CoV-2 in Ontario and screening for VOCs between February 3 and July 1, 2021. Case data was gathered from the Ontario provincial Case and Contact Management (CCM) database. All PCR positive COVID-19 specimens with a cycle threshold (Ct) ≤ 35 were screened for the N501Y mutation using the real-time PCR assay from the Public Health Ontario Laboratory. Whole genome sequencing (WGS) was performed on 5% of specimens regardless of the presence of mutations.

Results show that infection by VOCs with the N501Y mutation significantly elevated risk of hospitalization, ICU admission, and death in patients in Ontario.

Compared to non-VOC strains of SARS-CoV-2, the increase in risk associated with N501Y-positive variants was 138% (105-176%) for ICU admission; 74% (62-86%) for hospitalisation; and 83% (57-114%) for death, after adjusting for age, sex, and comorbidity. Increase in risks associated with the delta variant was even higher- 241% (163-344%) for ICU admission; 105% (80-133%) for hospitalisation; and 121% (57-211%) for death.

VOCs with the N501Y mutation were found to be associated with a significantly higher risk of hospitalisation, ICU admission, and death in infected individuals in Ontario, Canada. They also reveal that the Delta variant, becoming dominant in Ontario, has increased these risks even further.

“Individuals infected with VOCs were, on average, younger and less likely to have comorbid conditions than those infected with non-VOC, but nonetheless had higher crude risks of hospitalisation and ICU admission,” the authors found.

According to the authors, the clear and significant elevation of risks of even delayed outcomes such as death visible in their analysis is remarkable given the relatively small number of delta variant infections in the time period of this study. The fact that Canada is one of the leading countries in the world in terms of COVID vaccination rates has certainly mitigated the impact of these VOCs.

In summary, the researchers showed that despite excellent vaccination rates in Ontario, Canada, and VOCs infecting predominantly younger and healthier individuals, these VOCs are associated with an increase in virulence and risk of death. In particular, the Delta variant is more virulent compared to previously dominant VOCs possessing the N501Y mutation. It is the authors’ view that the progressive increase in transmissibility, immune escape and virulence of emerging VOCs could result in the pandemic being more drawn out and deadly.

Source: News-Medical.Net