Tag: covid

Viral RNA Levels Can Predict COVID Mortality

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Viral RNA levels in the blood is a reliable indicator in predicting COVID mortality, according to a study published in Science Advances.

“In our study, we were able to determine which biomarkers are predictors of mortality in the 60 days following the onset of symptoms,” said Université de Montréal medical professor Dr. Daniel Kaufmann, the study’s co-lead author alongside colleagues Nicolas Chomont and Andrés Finzi.

“Thanks to our data, we have successfully developed and validated a statistical model based on one blood biomarker,” viral RNA, Prof Kaufmann said.

Despite advances in COVID management, identifying patients at greater risk of dying of the disease has been difficult. Other studies identified various biomarkers, but assessing so many parameters is not possible in a clinical setting and gets in the way of doctors’ quick clinical decision-making ability.

Using blood samples from 279 patients hospitalised for COVID of differing severity, Kaufmann’s team measured amounts of inflammatory proteins, looking for any that stood out.

At the same time, Chomont’s team measured the amounts of viral RNA and in Finzi’s the levels of antibodies targeting the virus. Samples were collected 11 days after the onset of symptoms and patients were monitored for a minimum of 60 days after that.

The goal: to test the hypothesis that immunological indicators were associated with increased mortality.

“Among all of the biomarkers we evaluated, we showed that the amount of viral RNA in the blood was directly associated with mortality and provided the best predictive response, once our model was adjusted for the age and sex of the patient,” said Elsa Brunet-Ratnasingham, a doctoral student in Kaufmann’s lab and co-first author of the study.

“We even found that including additional biomarkers did not improve predictive quality,” she added.

Prof Kaufmann and Brunet-Ratnasingham tested the model on two independent cohorts of infected patients from Montreal’s Jewish General Hospital (recruited during the first wave of the pandemic) and the CHUM (recruited during the second and third waves).

No matter which hospital the patients were treated at, nor which period of the pandemic they fell into: in all cases, the predictive model worked. Now Prof Kaufmann and his colleagues want to put it to practical use.

“It would be interesting to use the model to monitor patients,” he said, “with the following question in mind: when you administer new treatments that have proven effective, is viral load still a predictive marker of mortality?” 

Source: University of Montreal

NICD Issues COVID Increase Warning

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Over the past week, an increase in the 7-day moving average for new COVID cases and the percentage testing positive in Gauteng has been observed by the National Institute for Communicable Diseases (NICD), particularly in Tshwane amongst 10–29 year olds.

Additionally, the NICD has recently identified a cluster amongst the 20–44 age group at an institute of higher education in Tshwane. “We are monitoring these trends to see if these increases persist,” comments NICD Acting Executive Director, Prof Adrian Puren. He continued, “Localised increases in case numbers (clusters) are not unexpected, however, it is hard to say whether the increases indicate the start of a widespread resurgence.”

The emergence of new SARS-CoV-2 variants to a large extent drove previous waves: Beta in the second wave and Delta in the third wave. “Genomic sequencing in South Africa has, to date, not yet detected the emergence of any new variants which are making up an increasing proportion of the sequences,” Dr Puren added. Molecular sequencing has some inherent delays in processing, due to transport of samples and the time taken to process them. In spite of any possible new variants emerging in the future, the importance of non-pharmaceutical interventions remains unchanged and individuals are encouraged to wear masks, practice hand hygiene, maintain social distancing and to gather in well ventilated spaces.

At present the National Department of Health reports that 41% of adults in South Africa have received at least one dose of a COVID vaccine, with 35% fully vaccinated. “It is difficult to predict the magnitude and timing of a potential COVID resurgence, however, we implore the unvaccinated to get the COVID vaccine, especially the elderly and those with comorbidities,” urged Dr Michelle Groome, Head of the Division of Public Health Surveillance and Response. She added that vaccination and prior infection confer good protection against developing severe disease, and while there might be an increase in future case numbers, the number of hospitalisations and deaths are expected to be less severe compared to prior waves.

“As the endemic endures, I would like to reassure the public that the NICD continues to acutely monitor trends in case numbers, positivity rates and hospitalisations,” Dr Puren concluded.

Source: NICD

Is Malaria Behind Low COVID Burden in Sub-Saharan Africa?

Mosquito
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In both rural and urban areas of Mali, there was a high seroprevalence of COVID, but a low burden of symptomatic disease, a researcher said in a presentation at the American Society of Tropical Medicine & Hygiene (ASTMH) virtual meeting. This could be tentatively attributable to the prevalence of malaria.

From spring to autumn (northern hemisphere) 2020, the seropositivity rate among those with self-reported symptoms jumped from 20.8% to 48.6%, while those reporting symptoms but were seronegative also increased from 9.8% to 49.3% in the cohort, reported John Woodford, MD, of the National Institute of Allergy and Infectious Diseases (NIAID).

However, he said that during March to July, the COVID-attributable fraction was 11%, and from August to December, the COVID-attributable fraction was 0%.

In addition, the percentage of seropositive people with symptomatic illness over the background illness reporting rate was 0%-11%, well below the age-adjusted 33% of cases expected, based on the US case rate.

Only three hospitalisations occurred throughout spring and autumn 2020, also far below the expected 11-30 hospitalisations, and no deaths.

Dr Woodford pointed to “a lot of anecdotal reports that there was a limited disease burden in Mali.”

“It was repeated over and over again for a variety of sub-Saharan African settings, but there’s very limited data to back this up,” he clarified.

His group performed a serosurvey of urban and rural areas of Mali, using two-antigen ELISA qualified for use in that country. Participants were also given a questionnaire asking about self-reported symptoms, medical, and social history.

Overall, they obtained serosurvey data from 3671 participants at four sites, who were a median age of 15. They noted the dates of the symptom questionnaires were March to July 2020 and August to December 2020.

No symptoms were independently associated with seropositivity, Dr Woodford said. There was no greater change of seropositive people being absent from work, seeking medical care, or being hospitalised compared to seronegative people in the cohort during spring. However they were more likely to seek medical care in the autumn than seronegative people (63.4% vs 45.9%, respectively).
The second follow-up visit was during the malaria season, when there was a high percentage of seropositivity, but the proportion of those with self-reported symptoms was comparable with background illness. MedPage Today asked Dr Woodford as to whether malaria infection might have a protective effect, to which he responded: “That is a question much larger than me, and much larger than COVID.” He added that the rural areas in their study had higher rates of malaria than the urban sites, while the reverse was true for COVID.

“What that means, I’m not sure, but there’s certainly a blunt association there,” Dr Woodford noted.

He referenced a recent study of hospitalised patients in Uganda, which found that patients with low previous malaria exposure had higher risk of severe or critical COVID clinical presentation compared to those with high previous exposure, even among patients with no comorbidities.

However, Dr Woodford explained that without a much larger sample size and more accurate tests such as PCR, there was no way to tease out asymptomatic versus symptomatic infections.
“You’d need a very large population to look at symptomatic versus asymptomatic in seropositive patients,” he said. “Logistically, it’s a very challenging study to put together.”

Source: MedPage Today

Previously Infected Older People Have More COVID Antibodies

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In a recent study published in Scientific Reports, researchers found that older people previously infected with COVID, when vaccinated, had higher antibody levels than previously infected individuals. These antibodies were also effective against the Delta variant, which wasn’t present in Canada when the samples were taken  in 2020.

Joelle Pelletier and Jean-François Masson, both professors in Université de Montréal’s Department of Chemistry, wanted to find out whether natural infection or vaccination led to more protective antibodies being generated. The focussed on an understudied group: people who have been infected but not hospitalised by SARS-CoV-2.

Consequently, 32 non-hospitalised COVID positive adults were recruited 14 to 21 days after being diagnosed through PCR testing. This was in 2020, before the Beta, Delta and Gamma variants emerged.

“Everyone who had been infected produced antibodies, but older people produced more than adults under 50 years of age,” said Prof Masson. “In addition, antibodies were still present in their bloodstream 16 weeks after their diagnosis.”

Antibodies produced after an infection by the original, “native” strain of the virus also reacted to SARS-CoV-2 variants that emerged in subsequent waves, namely Beta (South Africa), Delta (India) and Gamma (Brazil), but to a lesser extent: a reduction of 30 to 50%.

“But the result that surprised us the most was that antibodies produced by naturally infected individuals 50 and older provided a greater degree of protection than adults below 50, ” said Prof Pelletier.

“This was determined by measuring the antibodies’ capacity to inhibit the interaction of the Delta variant’s spike protein with the ACE-2 receptor in human cells, which is how we become infected,” he added. “We didn’t observe the same phenomenon with the other variants.”

When someone who has had a mild case of COVID is vaccinated, the antibody level in their blood doubles compared to an unvaccinated person who has been infected by the virus. Their antibodies are also better able to prevent spike-ACE-2 interaction.

“But what’s even more interesting,” said Prof Masson, “is that we have samples from an individual younger than 49 whose infection didn’t produce antibodies inhibiting spike-ACE-2 interaction, unlike vaccination. This suggests that vaccination increases protection against the Delta variant among people previously infected by the native strain.”

Both scientists believe more research should be conducted to determine the best combination for maintaining the most effective level of antibodies reactive to all variants of the virus.

Source: University of Montreal

Cats and Dogs Develop Myocarditis from COVID

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A new study reveals that pets can be infected with the Alpha variant of SARS-CoV-2. Due to its increased transmissibility and infectivity, this variant rapidly outcompeted pre-existing variants in England, before being replaced by the Delta variant.

The study, which was published in Veterinary Record, describes the first identification of the SARS-CoV-2 Alpha variant in domestic pets; two cats and one dog were positive on PCR test, while two additional cats and one dog displayed antibodies two to six weeks after they developed signs of cardiac disease. Many owners of these pets had themselves developed respiratory symptoms several weeks before their pets became ill and had also tested positive for COVID.  

These pets all had experienced an acute onset of cardiac disease, including severe myocarditis. Humans also have a slight risk for myocarditis from COVID, particularly in children, for whom the risk is 37 times higher than without having contracted COVID, according to the US Centers for Disease Control.

“Our study reports the first cases of cats and dogs affected by the COVID alpha variant and highlights, more than ever, the risk that companion animals can become infected with SARS-CoV-2,” said lead author Luca Ferasin, DVM, PhD, of The Ralph Veterinary Referral Centre, in the UK. “We also reported the atypical clinical manifestations characterised by severe heart abnormalities, which is a well-recognised complication in people affected by COVID but has never described in pets before. However, COVID infection in pets remains a relatively rare condition and, based on our observations, it seems that the transmission occurs from humans to pets, rather than vice versa.”

Source: Wiley

Over 28 Million More Years of Life Lost in 2020

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Over 28 million more years of life were lost than expected in 2020 in 31 upper-middle and high-income countries, according to a University of Oxford-led study published in the BMJ.

Save for a handful of exceptions, 37 countries examined including the US had more premature deaths than expected in 2020, with a higher rate in men than women.

Understanding the full impact of the COVID pandemic requires counting excess deaths, and analysing how premature those deaths are. Years of life lost (YLL) is a more detailed assessment of COVID’s impact on populations as it measures both the number of deaths and the age at which death occurs.

Researchers used this measure to estimate the changes in life expectancy and excess years of life lost from all causes in 2020. They compared the observed life expectancy and years of life lost in 2020 with historical trends in 2005-19 in 37 upper-middle and high-income countries.

Between 2005 and 2019, life expectancy at birth rose for both men and women in all the countries studied. In 2020, a drop in life expectancy was seen in both men and women in all countries save New Zealand, Taiwan, and Norway, where there was a life expectancy gain and Denmark, Iceland, and South Korea saw no change.

The biggest life expectancy drop was in Russia (−2.33 years in men and −2.14 in women), the US (−2.27 and 1.61), Bulgaria (−1.96 and −1.37), Lithuania (−1.83 and −1.21), Chile (−1.64 in men), and Spain (−1.11 in women). Years of life lost declined in most countries in both men and women between 2005 and 2019, except Canada, Greece, Scotland, Taiwan, and the US.  

In 2020, years of life lost were higher than expected in all countries except Taiwan and New Zealand, where there was a reduction in years of life lost, and Iceland, South Korea, Denmark, and Norway, where there was no evidence of a change in years of life lost. In the remaining 31 countries, more than 222 million years of life were lost in 2020, which is 28.1 million more than expected (17.3 million in men and 10.8 million in women).  

The highest excess years of life lost (per 100 000) were in Russia (7020 in men and 4760 in women), Bulgaria (7260 and 3730), Lithuania (5,430 in men and 2,640 in women), and the US (4,350 in men and 2,430 in women).

Overall, excess years of life lost in 2020 were over five times greater (2510 per 100 000) than those associated with the seasonal influenza epidemic in 2015 (458 per 100 000).

The excess years of life lost were relatively low in people under 65 years, except in Russia, Bulgaria, Lithuania, and the US where the excess years of life lost was more than 2 000 per 100 000.

Most countries in Asia, Africa, and Latin America were excluded due to insufficient data, and researchers could not account for other factors, such as socioeconomic status, regional disparities, and race or ethnicity. However, the findings are largely in line with previous studies, and the use of authoritative national mortality data, together with a validated analytical approach, suggests that the results are robust.

“Our findings of a comparable or lower than expected YLL in Taiwan, New Zealand, Denmark, Iceland, Norway, and South Korea underscore the importance of successful viral suppression and elimination policies, including targeted and population based public health policy interventions,” the researchers wrote. “As many of the effects of the pandemic might take a longer time frame to have a measurable effect on human lives, continuous and timely monitoring of excess YLL would help identify the sources of excess mortality and excess YLL in population subgroups.”

Source: University of Oxford

A Case of Three Teens with COVID and Psychiatric Symptoms

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A case study details three teenagers with mild or asymptomatic COVID presented with suicidal thoughts, “paranoia-like fears,” delusions and “foggy brain”, which could be explained by anti-neural antibodies – ‘turncoat’ antibodies that may attack brain tissue.

Mounting evidence points to neurological and psychiatric effects of COVID, with a UK study finding a 13% risk of a first-time diagnosis after COVID. The study, published in JAMA Neurology, is the first to look at anti-neural antibodies in paediatric patients previously infected with SARS-CoV-2.

Over five months in 2020, 18 children and teens were hospitalised with confirmed COVID at UCSF Benioff Children’s Hospital San Francisco, three of whom were the patients in the study who underwent neurological evaluations.

The researchers examined the patients’ cerebrospinal fluid (CSF) and found that two of the patients, both of whom had histories of unspecified depression and/or anxiety, had antibodies indicating that SARS-CoV-2 may have invaded the central nervous system. They also had anti-neural antibodies in their CSF, suggesting a rampant immune system accidentally targeting the brain.

The research follows a previous UCSF study that also found a high level of autoantibodies in the cerebrospinal fluid of adult patients with acute COVID, who experienced neurological symptoms, including intractable headaches, seizures and loss of smell.

“It is way too soon to know whether COVID is a common trigger for neuropsychiatric illnesses, but it does seem to be a potent trigger for the development of autoantibodies,” said co-corresponding author Samuel Pleasure, MD, PhD. “It is currently totally unknown whether patients predisposed to neuropsychiatric illnesses are more likely to develop worsened symptoms after COVID, or whether COVID infection can act as an independent trigger.”

Unlike most psychiatric presentations, the three patients in the UCSF study had symptoms with sudden onset and rapid progression, representing a marked change from their baselines, said co-first author Claire Johns, MD. “The patients had significant neuropsychiatric manifestations despite mild respiratory symptoms, suggesting potential short and long-term effects of COVID.”

After hospitalisations lasting weeks and ongoing psychiatric medications, the two UCSF patients, whose cerebrospinal fluid tested positive for SARS-CoV-2 antibodies and anti-neural antibodies, were treated with intravenous immunoglobulin, an immunomodulatory therapy that curbs inflammation in autoimmune disorders. After five days, the first patient had “more organised thoughts, decreased paranoia and improved insight.”

Autoantibodies targeting the protein TCF4 were also found, which has genetic links in some schizophrenia cases. However, “we don’t know that the antibodies are actually interfering with the protein’s function,” said co-corresponding author, Michael R. Wilson, MD, noting that the diagnosis of schizophrenia is based on a constellation of symptoms, not a biomarker.
The second patient partially responded to immunotherapy with improved cognition and working memory, but continued to have “impaired mood and cognitive symptoms” six months later. The third patient, with no psychiatric history and without SARS-CoV-2 antibodies or anti-neural antibodies in their cerebrospinal fluid, recovered with psychiatric medications. Their symptoms were attributed to recreational drug use.

In another case study, a 30-year-old patient with mildly symptomatic COVID who presented at a hospital emergency department with delusions, violent outbursts, hyper-anxiety and paranoia was unresponsive to antipsychotic medication but after being diagnosed with possible “autoimmune-mediated psychosis”, responded to intravenous immunoglobulin.

Nonetheless, the researchers agree it’s unlikely that there were pre-existing autoantibodies, and they point to other disorders with psychiatric symptoms, like anti-NMDAR encephalitis syndrome, that are caused by anti-neural antibodies and respond to treatment directed at these rogue antibodies.

The researchers agree that more study is warranted, although Dr Pleasure noted that the rarity of cerebrospinal fluid samples from paediatric patients is a challenge, as they rarely have severe enough COVID to warrant a lumbar puncture.

Source: University of California San Francisco

Up to 180 000 Health Workers may Have Died from COVID

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Between 80 000 and 180 000 health and care workers (HCWs) are estimated to have died from COVID between January 2020 and May 2021, the World Health Organization (WHO) said on Thursday.

That grim estimate features in a new WHO working paper based on the 3.45 million coronavirus-related deaths reported globally to the UN health agency up to May. The WHO warns it may well be an underestimate of 60%. To highlight the need for better protection, WHO was joined by global partners working to end the pandemic, to issue an urgent call for concrete action on behalf of workers in the sector.  

WHO Director-General, Dr Tedros Adhanom Ghebreyesus, said that “the backbone of every health system is its workforce.”

“COVID-19 is a powerful demonstration of just how much we rely on these men and women, and how vulnerable we all are when the people who protect our health are themselves unprotected”, he added.  

WHO and partners said that besides the deaths, more and more HCWs are suffering from burnout, stress, anxiety and fatigue. They are urging  equitable access to vaccines so that HCWs are prioritised.  

By the end of last month, on average, two in five HCWs were fully vaccinated, but with considerable differences across regions.

“In Africa, less than one in ten health workers have been fully vaccinated. Meanwhile, in most high-income countries, more than 80% of health workers are fully vaccinated”, Dr Ghebreyesus pointed out.  

For him, over 10 months since the approval of the first vaccines, “the fact that millions of health workers still haven’t been vaccinated is an indictment on the countries and companies that control the global supply of vaccines”.

Currently, 82 nations risk missing the target of vaccinating 40% of their population by year end, and 75% of those countries are faced with insufficient supply. The remainder have some limitations that WHO is helping solve.

Speaking to journalists via videolink, Gordon Brown, former UK Prime Minister and currently WHO’s Ambassador for Global Health Financing, said it would be a “moral catastrophe of historic proportions” if G20 countries cannot act quickly.

These nations have pledged to donate more than 1.2 billion vaccine doses to COVAX. According to WHO, so far, only 150 million have been delivered.  

With wealthy countries stockpiling millions of unused doses, close to expiration, Brown said they should start an “immediate, massive, concerted” airlift of vaccines to low income countries.  

If they do not, he argued, they will be guilty of an “economic dereliction of duty that will shame us all.”  

Brown also warned that “the longer vaccine inequity exists, the longer the virus will be present.”

Source: UN News

Inquiry Accuses Brazilian President of ‘Crimes Against Humanity’

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A draft of a major inquiry into the Brazilian government’s handling of the COVID pandemic has recommended that the country’s President Bolsonaro should be charged with several serious crimes over his actions.

The report will be the culmination of a six-month inquiry that has revealed scandals and corruption in the country’s government.

Excerpts leaked to the media indicate that the panel wants Bolsonaro to face nine charges, though initial recommendations that the president be charged with homicide and genocide against indigenous groups were dropped on Tuesday.

The massive and highly unusual 1200 page report urges charges of crimes against humanity, forging documents and incitement to crime. It blames Bolsonaro’s policies for the deaths of 300 000 Brazilians, about half of the current COVID death toll in Brazil, which is the world’s second largest. He repeatedly pushed unproven drugs such as hydroxychloroquine long after they had found to be ineffective.

Despite the serious allegations, what this means for Bolsonaro is unclear, according to the BBC’s South America correspondent Katy Watson.

The draft report will still have to be voted on by the Senate commission, where it could be vetoed and altered. Given the political realities of Brazil, it is unclear if these will ever lead to criminal charges.
President Bolsonaro has dismissed the Congressional inquiry as politically motivated, and has frequently spoken out against COVID interventions such as lockdowns, masks and vaccinations.

In March this year, he infamously told Brazilians to “stop whining” about COVID, a day after the country saw a record rise in deaths over a 24-hour period.

However, Mr Bolsonaro’s popularity has already been dented by the pandemic, and this report could make life much harder for him if he wants to run for a second term in Brazil’s 2022 elections.

Speaking to the BBC in advance of the publication of the report, the inquiry rapporteur, Senator Renan Calheiros, said that the panel wanted to punish those who contributed to “this massacre of Brazilians”.

Source: BBC News

Nearly 4 in 10 Swedish COVID Patients in ICUs had Obesity

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People with obesity were overrepresented among adults in Sweden in intensive care for COVID during the first wave of the pandemic, with over twice the proportion as compared to the general population. 

The study, appearing in PLOS One, used  the Swedish Intensive Care Registry (SIR) tp the researchers identified all patients with COVID who were admitted to ICUs in Sweden during the initial wave of the pandemic, in spring and summer 2020. Where height and weight data were missing from SIR, this was supplemented directly from the ICUs and also through the Nationwide Passport Register.

Though people with obesity were identified early on as a risk group that was affected especially severely by COVID, this study contributes to a new, more detailed picture.

A total of 1649 individuals with COVID from ICUs around Sweden were included. All the participants were aged 18 and over; three-quarters were men; and pregnant women were excluded.

The results show that patients with obesity (BMI of 30 kg/m2 or more) were overrepresented among those with COVID receiving intensive care in Sweden, which was 39.4 %, compared to 16% in the general population .

A high BMI increased the risk of both serious illness with long stays in intensive care and of death. A link was found between BMI over 30 and a 50% increase in mortality risk, compared with the normal-weight group. Among those who survived, a BMI over 35 was associated with a more than doubled risk of intensive care for over 14 days. These analyses have been adjusted for age, gender, comorbidity, and state of health at ICU arrival.

“For individuals with COVID who are in intensive care, obesity means an increased risk of death, and among those who survive, obesity boosts the risk of intensive care lasting more than 14 days,” explained first author Lovisa Sjögren, researcher at Sahlgrenska Academy, University of Gothenburg. “Based on our results, obesity should be included as an important risk factor in COVID. Patients with obesity who suffer from COVID should be monitored closely.”

The study is based on the Swedish Intensive Care Register, and Dr Sjögren points out that high-quality registers are a basic precondition for studies of this type to be feasible.

Senior author Jenny M Kindblom, Associate Professor at University of Gothenburg added: “Some international studies have shown a connection between high BMI and the risk of becoming severely ill with COVID. We can now show this in a Swedish context, and with the advantage of having a fully up-to-date BMI value for every patient,” said.

At an early stage during the pandemic, the researchers who conducted the study were in touch with HOBS, a Swedish patient organisation for people living with overweight and obesity. Many members were concerned that a high BMI would elevate the risk of serious illness in COVID.

“At the time, there were no publications in the field, and the study was initiated to enable us to answer patients’ questions. We now hope as many people as possible will take the opportunity to get vaccinated, and that health services include BMI – as a risk factor and perhaps choose to exercise special vigilance in monitoring patients with obesity who are suffering from COVID,” said Prof Kindblom.

Source: University of Gothenburg