Category: COVID

Categories : COVIDTags :

Immunity to Other Coronaviruses Confers COVID Protection

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Transmission electron micrograph of SARS-CoV-2 virus particles (gold) within endosomes of a heavily infected nasal Olfactory Epithelial Cell. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

Researchers have discovered another component beside previous infection or vaccination that contributes to SARS-CoV-2 immunity – previous antibody responses to other, harmless coronaviruses. “People who have had strong immune responses to other human coronaviruses also have some protection against SARS-CoV-2 infection,” said Alexandra Trkola, head of the Institute of Medical Virology at University of Zurich.

The study, published in Nature Communication, used a specially developed assay to analyse antibody levels against four other human coronaviruses in 825 serum samples taken before  the emergence of SARS-CoV-2, as well as 389 samples from donors infected with the virus. Combining these analyses with computer-based models enabled the team to precisely predict how well the antibodies would bind to and neutralise invading viruses.

The researchers were able to demonstrate that people who caught SARS-CoV-2 had lower levels of antibodies against coronaviruses that cause common colds compared to uninfected people. In addition, people with high levels of antibodies against harmless coronaviruses were less likely to have been hospitalized after catching SARS-CoV-2. “Our study shows that a strong antibody response to human coronaviruses increases the level of antibodies against SARS-CoV-2. So someone who has gained immunity to harmless coronaviruses is therefore also better protected against severe SARS-CoV-2 infections,” says Trkola. This type of immune response is referred to as cross-reactivity, and it also occurs with T cell responses,  the additional line of the immune system in the defense against infections.

People are only fully protected against SARS-CoV-2 shortly after they have recovered from an infection or have received an effective vaccination. This is when antibody levels against the virus are still very high. As these levels drop over time, infection is no longer prevented, but the immunological memory quickly reactivates the body’s defenses, the production of antibodies as well as the T cell defense. “Of course, immune responses targeting SARS-CoV-2 that are mounted by the memory cells are far more effective than cross-reactive responses. But even though the protection isn’t absolute, cross-reactive immune responses shorten the infection and reduce its severity. And this is exactly what is also achieved through vaccination, just much, much more efficiently,” said Trkola.

Whether cross-reactivity also works in the opposite direction is not yet known. “If SARS-CoV-2 immunity also offers some degree of protection from infection with other coronaviruses, we would be a significant step closer to achieving comprehensive protection against other coronaviruses, including any new variants,” the virologist explains. This idea is also supported by the fact that cross-reactive protection is not only based on antibodies, but very likely also on T cells.

Source: University of Zurich

Categories : COVIDTags :

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

Categories : COVID Diseases, Syndromes and ConditionsTags :

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

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Mosquito
Photo by Егор Камелев on Unsplash

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

Categories : Cancer COVIDTags :

Vaccine Hesitancy Among Caregivers of Childhood Cancer Survivors

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In a study published in Pediatric Blood & Cancer, researchers reported that caregivers of childhood cancer survivors expressed high rates of vaccine hesitancy, especially if they lacked confidence in governmental COVID response.

The researchers conducted a survey of 130 caregivers of childhood cancer survivors, 21% of caregivers expressed hesitancy to vaccinate themselves and 29% expressed hesitancy to vaccinate their children who had survived cancer.  

Caregivers who expressed confidence in the US government’s response to COVID were six times more likely to express willingness to self-vaccinate and were three times more likely to express willingness to vaccinate their children.  

Caregivers who reported that they were hesitant to vaccinate cited concerns about the speed of COVID vaccine development and a lack of safety and efficacy data in children, particularly children with cancer.

“Results suggest that COVID vaccination outreach to hesitant caregivers might be more effective when delivered by non-governmental organisations, including paediatric oncology care teams,” said senior author Kyle Walsh, PhD, of the Duke Cancer Institute. “Such providers are well-positioned to discuss potential risks and benefits of vaccination and to update families as longer-term outcomes data emerge from vaccine trials and registries.”

Source: Wiley

Categories : COVIDTags :

A Smaller Fourth Wave Predicted for South Africa as Flu Cases Spike

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A fourth wave of infections is likely for South Africa but its impact probably won’t be as severe as during earlier surges, as shown by new modelling, according to BusinessTech.

Factoring in sero-prevalence surveys and other data, it appears that an estimated 60% to 70% of the population has already contracted COVID, which along with vaccinations will provide protection from severe disease, the South African COVID-19 Modelling Consortium said in an online presentation on Wednesday.

Even in its worst-case scenario, deaths and hospitalisations during a fourth wave were projected to be substantially lower than during previous surges.

Though current caseload for the country is “incredibly low”, it is still “very hard to commit to say South Africa is over the worst” of the COVID pandemic, said Harry Moultrie, a senior epidemiologist at the National Institute for Communicable Diseases, which coordinated the modelling.

“It’s going to be a bumpy ride,” he said. “We don’t know where this virus is going to take us. We will still be seeing hospital admissions and deaths related to Covid for years to come.”

South Africa;s seven-day rolling average of new infections has fallen below 300, much reduced from a third-wave peak which hit nearly 20 000 in July.

To date, South Africa has had 2.93 million confirmed cases of COVID, with 89 504 deaths, although excess death numbers indicate the true toll may be much higher. About 34% of the nation’s 39.8 million adults have been fully vaccinated.

While some countries in the northern hemisphere such as Germany are seeing severe fourth and even fifth waves of infection driven by the spread of the delta variant, that’s not a good indicator South Africa will follow a similar path because the strain has already spread widely in the country, explained Gesine Meyer-Rath, a member of the modelling consortium.
“We have paid in a way with high deaths and a lot of destruction” during previous waves, Meyer-Rath said. “We don’t think we will have a super-fast case increase again” unless a highly transmissible new variant emerges, she said.

While the outlook for the fourth wave is brighter, the past few weeks has seen a sharp rise of influenza cases, the National Institute for Communicable Diseases (NICD) reported.

A high number of cases had been seen from the beginning of the month, including influenza-like illness and pneumonia hospitalised cases at surveillance sentinel sites.

The NICD added that there had been clusters of influenza cases reported in schools and workplaces.

The NICD’s Cheryl Cohen said: “The increase in influenza this summer, which is not the typical time for the influenza season in South Africa, is likely the result of the relaxation of non-pharmaceutical interventions to control COVID combined with other factors such as reduced immunity because flu has not circulated since 2020 and 2021.”

Sources: Eyewitness News; BusinessTech

Categories : COVID ImmunologyTags :

Immune Cells Persist 6 Months after COVID Vaccination

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Image of a syring for vaccination
Photo by Mika Baumeister on Unsplash

A recent study shows that T helper cells produced by people who received either of the two available messenger RNA (mRNA) vaccines for COVID persist six months after vaccination, at only slightly reduced levels from two weeks after vaccination. They are also at significantly higher levels than in unvaccinated individuals.

In the study, published in Clinical Infectious Diseases, the researchers also found that the T cells they studied recognise and help protect against the highly infectious delta variant of SARS-CoV-2.

“Previous research has suggested that humoral immune response – where the immune system circulates virus-neutralising antibodies – can drop off at six months after vaccination, whereas our study indicates that cellular immunity – where the immune system directly attacks infected cells – remains strong,” said Professor Joel Blankson, MD, PhD, study senior author. “The persistence of these vaccine-elicited T cells, along with the fact that they’re active against the delta variant, has important implications for guiding COVID vaccine development and determining the need for COVID boosters in the future.”

The researchers sampled blood from 15 study participants at three times: prior to vaccination, between seven and 14 days after their second Pfizer/BioNTech or Moderna vaccine dose, and six months after vaccination. The median age of the participants was 41 and none had evidence of prior SARS-CoV-2 infection.

CD4+ T lymphocytes are nicknamed helper T cells because they assist another type of immune system cell, the B lymphocyte (B cell), to respond to antigens on viruses such as SARS-CoV-2. Activated by the CD4+ T cells, immature B cells become either plasma cells that produce antibodies to mark infected cells for disposal from the body or memory cells that ‘remember’ the antigen’s biochemical structure for a faster response to future infections. Therefore, a CD4+ T cell response can serve as a measure of how well the immune system responds to a vaccine and yields humoral immunity.

The researchers found that the number of helper T cells recognising SARS-CoV-2 spike proteins was very low pre-vaccination, with a median of 2.7 spot-forming units (SFUs, the level of which is a measure of T cell frequency) per million peripheral blood mononuclear cells (PBMCs, identified as any blood cell with a round nucleus, including lymphocytes). Between 7 and 14 days after vaccination, the T cell frequency rose to a median of 237 SFUs per million PBMCs. At six months after vaccination, the level dropped slightly to a median of 122 SFUs per million PBMCs – a T cell frequency still significantly higher than before vaccination.

Six months after vaccination, the number of T cells recognising the delta variant spike protein was not significantly different from that of T cells attuned to the original virus strain’s protein.

“The robust expansion of T cells in response to stimulation with spike proteins is certainly indicated, supporting the need for more study to show booster shots do successfully increase the frequency of SARS-CoV-2-specific T cells circulating in the blood,” said Prof Blankson. “The added bonus is finding that this response also is likely strong for the delta variant.”

Source: John Hopkins Medicine

Categories : COVIDTags :

Automated Messaging System Saved Lives in Early Pandemic

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During the early days of the COVID pandemic, an automated text messaging system saved two lives a week, and, overall, the patients who enrolled in that system had a 68% lower mortality rate than those not on it.

These insights about Penn Medicine’s COVID Watch – a system designed to monitor COVID outpatients using automated texts and then escalate those with concerning conditions to a small team of health care providers – were published in the Annals of Internal Medicine.

“At the beginning of the pandemic, we instinctually thought patients needed extra support at home, even if they weren’t sick enough or ill yet. And if they were to get very sick, we wanted to help them get to the emergency department earlier, so COVID Watch was our solution,” said a co-primary investigator of the study, Krisda Chaiyachati, MD, the medical director of Penn Medicine OnDemand and an assistant professor of Medicine. “Our evaluation found that a small team of five or six nurses staffing the program during some of the most hectic days of the pandemic directly saved a life every three to four days.”

COVID Watch was rapidly developed and designed to help patients with the virus recover safely at home and keep hospital capacity available. The system uses algorithmically guided text message conversations with patients to assess their conditions. It sent out twice-daily routine questions to patients, such as “How are you feeling compared to 12 hours ago?” and “Is it harder than usual for you to breathe?” If a patient indicated a worsening condition, follow-up questions were asked and they were elevated to the human members of a centralised team – headed by co-author Nancy Mannion, DNP, COVID Watch’s nurse manager – who would call to check in and recommend hospitalisation, if needed.

Since the start of COVID Watch, nearly 20 000 patients have been enrolled in it.

“We did an early analysis of the system and determined that we could safely monitor more than 1,000 patients simultaneously, 24/7, with a small, well-trained team of registered nurses,” said Anna Morgan, MD, COVID Watch’s medical director and an assistant professor of Internal Medicine. “On top of that, those same nurses could often also take care of other COVID-related tasks such as helping patients arrange COVID testing and discussing their results, which is important during surges.”

To further assess COVID Watch’s effect on patients, researchers analysed data from every adult who received outpatient care from Penn Medicine, starting the day COVID Watch launched until Nov. 30, 2020. 
Only three out of 3448 patients in COVID Watch died within 30 days of their enrollment, compared to 12 of the 4337 otherwise equivalent patients outside of the program: a three times higher mortality rate. At 60 days after enrollment, five people within COVID Watch died compared to 16 not using the system.

This amounted to a 68 percent reduction mortality risk with COVID Watch. Additionally, COVID Watch was credited with saving 1.8 lives per 1000 patients at 30 days, and 2.5 per 1000 at 60 days.

The study’s lead author and co-primary investigator, M. Kit Delgado, MD, an assistant professor of Emergency Medicine and Epidemiology, believes that the benefits seen by COVID Watch patients could be explained by: Increased access to and use of telemedicine, and more frequent and earlier trips to the hospital – an average of two days earlier for COVID Watch patients – when symptoms worsened.

Importantly, the study found that COVID Watch was equally accessible and effective for everyone.

“We saw a higher proportion of higher-risk patients and also low-income and Black patients enrolled in COVID Watch, but the fact that we measured a significant benefit associated with enrollment in the program is a good indicator that there truly is a treatment benefit for everyone,” Prof Delgado said. “It’s crucial that we found all major racial and ethnic groups benefited because non-white and low-income communities have had disproportionately higher infection rates, lower access to care, and higher death rates. This implies that this model of care could have reduced disparities in COVID outcomes if it was scaled up more broadly to these communities.”

The COVID Watch team plans to see if the approach, which had originally been built off a system for keeping tabs on chronic obstructive pulmonary disease (COPD) patients, can be applied to helping people with other conditions manage their health at home. They see the system as a lasting technology that will play an important part in future care.

Source: Penn Medicine

Categories : COVIDTags :

Heparin’s Beneficial Impact on COVID Outcomes

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Researchers at the Medical University of Vienna have now shown that the anticoagulant heparin not only has a beneficial effect on survival of COVID patients, but also influences the duration of active infection with the SARS-CoV-2 coronavirus. The results were published in the journal Cardiovascular Research.

COVID is now known to be a multifaceted infectious disease, which affects several functional systems in the human body following infection with the pathogen SARS-CoV-2. One of these functional systems is blood clotting. COVID patients are at greater risk of thromboses and embolisms, such as strokes, pulmonary or myocardial infarctions, and even deep vein thromboses. The use of drugs that inhibit blood clotting has been part of the treatment guidelines for COVID since July 2020. “These complications during hospitalisation have a direct impact on the well-being of patients and increased the risk of dying from COVID,” said first author David Pereyra from MedUni Vienna’s Department of General Surgery. The underlying coagulopathy is still not fully understood.

“The coagulopathy observed in COVID patients is novel and differs in many respects from previously known coagulation problems,” said senior author Alice Assinger, group leader at the Institute of Vascular Biology and Thrombosis Research at the Medical University of Vienna. “COVID-associated coagulopathy displays characteristics that, although partially comparable with other coagulation diseases, cannot be fully explained by them.” Alice Assinger’s group therefore started to look for an explanation for this sub-condition of COVID in the spring of 2020, in an early phase of the pandemic.

In a multi-centre analysis of COVID patients, the group saw that COVID-associated coagulopathy occurs almost exclusively in patients requiring intensive care or in patients who die as a result of COVID. While anticoagulant drugs improve the survival of COVID patients, they show no effect on immunological processes related to blood coagulation (immunothrombosis).

However, an analysis of the results showed that the length of active SARS-CoV-2 infection is shortened in patients treated with low-molecular-weight heparin, the most commonly used anticoagulant. “In patients who receive this drug, infection time is an average of four days shorter than in patients who are not treated with low-molecular-weight heparin. We were surprised to see that low-molecular-weight heparin may have a direct effect on coronavirus and its infectivity,” said David Pereyra. Experimental data show that heparin can inhibit the ability of SARS-CoV-2 to bind to cells, thereby preventing them from being infected.

These observations were made in the context of a close collaboration between the three hospitals involved – the Favoriten Hospital in Vienna, the Innsbruck Regional Hospital Innsbruck and the Johannes Kepler University Hospital in Linz – as well as through the active exchange between basic researchers and clinicians,” says Alice Assinger, underscoring the relevance of good cooperation during the COVID pandemic for a better understanding of the disease and its treatment.

Source: Medical University of Vienna

Categories : COVID VaccinesTags :

WHO Predicts Shortfall in Syringe Production

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The World Health Organization has said that with the goal of two COVID vaccine doses for seven billion people between now and 2023, a shortage of at least one billion syringes “could occur”, if manufacturing does not increase. This could endanger other immunisation programmes.

Lisa Hedman, WHO Senior Advisor, from the Access to Medicines and Health Products division, warned that there could be a generation of children who miss scheduled immunisation jabs unless manufacturers come up with a way to make more single-use disposable syringes.

“When you think about the magnitude of the number of injections being given to respond to the pandemic, this is not a place where we can afford shortcuts, shortages or anything short of full safety for patients and healthcare staff,” said the WHO expert.

She told media that more than 6.8 billion doses of COVID vaccines are being administered globally per year – nearly twice the yearly number for routine inoculations.

“A shortage of syringes is unfortunately a real possibility and here’s some more numbers. That [given] the global manufacturing capacity of around six billion a year for immunisation syringes it’s pretty clear that a deficit in 2022 of over a billion could happen if we continue with business as usual.”

Reuse of syringes was inadvisable, also noting that syringes were particularly prone to transport delays because they took up 10 times the space of a vaccine.

Meanwhile, the heads of the International Monetary Fund (IMF), World Bank Group, WHO and the World Trade Organization (WTO) held a follow up session of High-Level Consultations with the CEOs of leading COVID vaccine manufacturing companies on Tuesday.

All participants at the meeting agreed on the urgency of increased vaccine dose delivery to low-income countries, where less than 2.5% of the population has been fully vaccinated.

The meeting’s aim was to identify how to ensure more equitable distribution of vaccines and all participants pledged to continue working together to clarify donations, vaccine swaps and delivery schedules, so that distribution of the life-saving vaccines can be more effectively targeted towards needy countries.

The meeting of the Multilateral Leaders Task Force on COVID-19 built on technical work undertaken by multidisciplinary teams during the months of September and October.

During the consultations, the leaders of the four organisations and the CEOs also examined how best to tackle trade-related bottlenecks; how to improve the donation process; what additional steps are needed to reach the vaccination target of 40% of people in all countries by the end of the year; and how to improve transparency and data sharing with the IMF-WHO Vaccine Supply Forecast Dashboard and the Multilateral Leaders Task Force.

The effort will require close collaboration between manufacturers, governments and the international COVAX initiative, on enhanced delivery schedules, especially for doses that are being donated.

Source: UN News

Categories : Ageing COVIDTags :

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