Category: COVID

An Estimated 70% of South Africans Have Had COVID

Image by Quicknews

Writing for GroundUp, Dr Alex Welte unpacks the results of the latest blood donor survey, which suggests that some 70% of South Africans have had a COVID infection.

The South African National Blood Service (which handles the blood supply for eight provinces) and the Western Cape Blood Service have been testing some donors for Covid antibodies over the last year or so. This has contributed to our understanding of how many people have been infected by SARS-CoV-2 (the virus that causes Covid), and what proportion of infections lead to death. It may help us plan for future waves, though exactly how is complicated.

On the assumption that another wave towards the end of 2021 was nearly inevitable – but before we all heard about omicron – it was decided to perform more such testing in early November. The numbers are now out.

The headline results are:

  • Overall about 80% of black donors had previously had Covid, and 40% of white donors.
  • There is no meaningful variation between age groups and sexes.
  • This latest survey did not include Western Cape data.
  • The test used does not detect the antibodies produced in response to vaccination, so this really is an estimate of people who have been infected.

While blood donors are not perfectly representative of the country’s population, we can take into account differences between the racial breakdown of the donor population and the racial breakdown of the general population. This means that our face-value national estimate is that about 70% of people had been infected before the omicron wave hit.

Since then we’ve had the omicron wave. We would very much like to know how many people are infected now, but there’s really no simple way to derive this number. Researchers are now updating their models with this additional piece of data, and we may see some estimates soon.

With that caution, here is my back-of-the-envelope estimate:

  • Omicron seems to have little trouble infecting people who have been infected by other variants, though there is some protection from prior infection and vaccination.
  • By late last year, quite a bit more than half the population had already had a prior infection.
  • Hence, I estimate that about half of the omicron wave infections were in previously uninfected individuals.
  • Given the infection detection rate estimates from previous waves, and a number of plausible sources of possible variation in this rate, I estimate the detection rate at about 1 in 10.
  • Given the roughly 700 000 cases reported between mid November and mid February, we get an estimate of 7 million cases, and therefore 3.5 million new infections.
  • Given our population of about 60 million, this is roughly an additional 6%.
  • Bottom line: it’s not crazy to estimate that about three-quarters of South Africans have by now been infected. But I would not be surprised if serious models come up with even higher estimates.

A troubling result of the survey is that once more it shows the serious racial disparities in South Africa. I don’t know if this carried over to the omicron wave. Estimating the racial breakdown of infection after omicron depends in a complicated way on variations in housing, lifestyle, access to vaccination, and all the usual factors that shape daily life in our country.

Dr Welte helped design and implement the blood donor survey.

Source: GroundUp

High COVID Mortality Rate Found in African Children and Adolescents

Photo by Roman Nguyen on Unsplash

African children and adolescents hospitalised with COVID experience much higher mortality rates than Europeans or North Americans of the same age, according to a recent six-country study which included South Africa.

The study, published in JAMA Pediatrics. was conducted by researchers from the Institute of Human Virology (IHV) at the University of Maryland School of Medicine (UMSOM) and the Institute of Human Virology Nigeria (IHVN). Both organisations are members of the Global Virus Network (GVN).

“This study provides important information about COVID among African children, which was not previously available at this scale. We now have evidence from multiple countries to show that African children also experience severe COVID; they experience multisystem inflammatory syndrome; some require intensive care; some also die, and at much higher rates than outside Africa,” said co-first author Nadia Sam-Agudu, MD, Associate Professor of Pediatrics at the UMSOM’s Institute of Human Virology.

The AFREhealth study collected data from 25 health facilities across Nigeria, Ghana, Democratic Republic of the Congo, Kenya, South Africa, and Uganda. The study included 469 African children and adolescents aged three months to 19 years hospitalised with COVID between March and December 2020. The team reported a high overall mortality rate of 8.3%, compared with 1% or less totaled from Europe and North America. Furthermore, African children less than a year old and with pre-existing, non-communicable diseases were more likely to have poorer outcomes.

Eighteen participants had suspected or confirmed multisystem inflammatory syndrome (also known as MIS-C), and four of these children died.

Dr Sam-Agudu, who led the West Africa team for the study, urged health authorities and policymakers in Nigeria and other African countries to act upon the study findings “to protect children by expanding vaccine approvals and procurements for children specifically, as the variants emerging since our study’s completion have either caused more severe disease and/or more cases overall. We cannot leave children behind in the pandemic response.”

Source: University of Maryland

Higher Oestrogen Levels Protect Older Women Against Severe COVID

Photo by Ravi Patel on Unsplash

An older woman’s oestrogen levels may be linked to her chances of dying from COVID, with higher levels of the hormone seemingly protective against severe infection, according to a study published in BMJ Open.

Supplemental hormone treatment to curb the severity of COVID infection in post-menopausal women could be investigated, the researchers suggested.

Even after accounting for other factors, women seem to have a lower risk of severe COVID infection than men. This holds true for other serious recent viral infections, such as MERS (Middle East Respiratory Syndrome).

Oestrogen may have a role in this gender discrepancy, so to invesitgate the researchers compared the potential effects of boosting and reducing oestrogen levels on COVID infection severity.

They drew on Swedish national data, and the study sample included 14 685 women in total: 227 (2%) had been previously diagnosed with breast cancer and were on oestrogen blocker drugs (adjuvant therapy) to curb the risk of cancer recurrence; and 2535 (17%) were taking hormone replacement therapy (HRT) to boost their oestrogen levels in a bid to relieve menopausal symptoms.

Some 11,923 (81%) women acted as the comparison group as they weren’t on any type of treatment, either to enhance or reduce their systemic oestrogen levels.

Analysis of all the data showed that compared with no oestrogen treatment, the crude odds of dying from COVID were twice as high among women on oestrogen blockers but 54% lower among women on HRT.

After accounting for potentially influential factors, COVID mortality risk remained significantly lower (53%) for women on HRT.

Unsurprisingly, age was significantly associated with COVID mortality risk, with each extra year associated with 15% greater odds, while every additional coexisting condition increased the odds of death by 13%.

And those with the lowest household incomes were nearly 3 times as likely to die as those with the highest.

As an observational study, it cannot establish cause. There were no data on the precise doses of HRT or oestrogen blocker drugs, or their duration, nor on weight or smoking, while the number of women on adjuvant therapy was relatively small.

These factors may have been influential. But the researchers conclude: “This study shows an association between oestrogen levels and COVID death. Consequently, drugs increasing oestrogen levels may have a role in therapeutic efforts to alleviate COVID severity in postmenopausal women and could be studied in randomised control trials.”

Source: EurekAlert!

Almost a Third of Older Adults Develop New Condition after COVID

Image from Pixabay

Almost a third of older adults infected with COVID in 2020 developed at least one new condition requiring medical attention in the months after initial infection, compared to only a fifth who were not infected, according to a study published by The BMJ.

Conditions involved a range of major organs and systems, including the heart, kidneys, lungs and liver as well as mental health complications. Some studies now examine the frequency and severity of sequelae after COVID infection, but few have described the excess risk of new conditions triggered by COVID infection in adults 65 and older.

Researchers used US health insurance records to identify 133 366 individuals aged 65 or older in 2020 who were diagnosed with COVID before 1 April 2020. Three (non-COVID) comparison groups were matched: from 2020, 2019, and a group diagnosed with viral lower respiratory tract illness.

The researchers then recorded any persistent or new conditions starting 21 days after a COVID diagnosis (the post-acute period) and calculated the excess risk for conditions triggered by COVID over several months based on age, race, sex, and whether patients were hospitalised with COVID.

The results show that among individuals diagnosed with COVID9 in 2020, 32% sought medical attention in the post-acute period for one or more new or persistent conditions, which was 11% higher than the 2020 comparison group.

Compared with the 2020 comparison group, COVID patients were at increased risk of developing a range of conditions including respiratory failure (an extra 7.55 per 100 people), fatigue (+5.66 per 100), high blood pressure (+4.43 per 100), and mental health diagnoses (+2.5 per 100). Similar findings were found for the 2019 comparison group.

However, compared with the group with viral lower respiratory tract illness, only respiratory failure, dementia, and fatigue showed increased risk differences of 2.39, 0.71, and 0.18 per 100 people with COVID, respectively.

Individuals hospitalised with COVID had a markedly increased risk for nearly all conditions. The risk of several conditions was also increased for men, for those of black race, and for those aged 75 and older.

Limitations include being an observational study – however, the authors warn that the number survivors with sequelae will continue to grow.

“These findings further highlight the wide range of important sequelae after acute infection with the SARS-CoV-2 virus,” they write. “Understanding the magnitude of risk for the most important clinical sequelae might enhance their diagnosis and the management of individuals with sequelae after acute SARS-CoV-2 infection.”

“Also, our results can help providers and other key stakeholders anticipate the scale of future health complications and improve planning for the use of healthcare resources,” they conclude.

Source: The BMJ

Is it Possible to Detect COVID in Exhaled Breaths?

Source: CDC

In a study published in Influenza and Other Respiratory Viruses, researchers were able to detect SARS-CoV-2 viral RNA in droplets from the exhaled breaths and coughs of COVID patients.

COVID is assumed to be transmitted mainly by respiratory droplets. However, probable aerosol transmission has been reported to occur under certain conditions. The researchers sought to address the lack of information on viral load in exhaled breath samples,as well as the size and concentration of exhaled endogenously generated droplets in relation to viral load. Additionally, the relationship between the viral load in upper airway diagnostic samples and aerosol samples needed to diagnose.
For the study, researchers analysed exhalations by two different methods during 20 normal breaths, 10 airway opening breaths (which involves deep inhalation followed by relaxed exhalation), and 3 coughs.

PCR detection of SARS-CoV-2 RNA in aerosols was possible in 10 out of 25 participants. Viral RNA presence in aerosol was mainly detected in cough samples (8 samples), but also in normal breaths (4 samples) and in airway opening breaths (3 samples).  

“Our data confirm findings from other researchers that SARS-CoV-2 can be detected in aerosol particles < 5µm and highlight the small amount of exhaled aerosol needed for detection. Of specific interest were findings from the airway opening maneuver, which is thought to generate particles mainly from the small airways,” said lead author Emilia Viklund, PhD student at the University of Gothenburg, in Sweden. “COVID causes a lot of damage in this region, and it would be of great interest to further explore the amount of exhaled virus and the course of disease, as well as the infectious potential of exhaled virus.”

Source: Wiley

South African Biotech Company Replicates Moderna Vaccine

Photo by Mat Napo on Unsplash

Afrigen Biologics and Vaccines, a South African biotechnology company, has nearly created a copy of Moderna’s COVID mRNA vaccine, without Moderna’s involvement, Nature reports.

The Cape Town-based company has so far made only microlitres of the vaccine, based on Moderna’s publicly available development data. This nevertheless is a success for a major initiative launched by the World Health Organization (WHO): a technology transfer hub meant to build vaccine manufacturing capacity in low- and middle-income countries.

During the COVID pandemic, the developers of mRNA vaccines, Moderna and Pfizer/BioNTech have sent more than 70% of their doses to wealthy nations. Meanwhile, millions of vaccine orders for southern hemisphere countries have been delayed. “Moderna and Pfizer-BioNTech’s vaccines are mainly still going to just the richest countries,” says Martin Friede, the WHO official coordinating the hub. “Our objective is to empower other countries to make their own.”

Much work needs to be done before Afrigen’s mRNA vaccine mimic can be distributed. But the WHO hopes that the process of creating it will lay the foundation for a more globally distributed mRNA vaccine industry in the future.

Gerhardt Boukes, chief scientist at Afrigen is proud to have helped complete this first step of the plan. Afrigen and its collaborators completed the process, beginning with mRNA encoding a modified portion of the SARS-CoV-2 coronavirus, and finishing by encapsulating it in a lipid nanoparticle that delivers the vaccine to cells. “We didn’t have help from the major COVID vaccine producers,” he says, “so we did it ourselves to show the world that it can be done, and be done here, on the African continent.”

When the mRNA hub was launched by the WHO in June 2021, Moderna, Pfizer and BioNTech did not respond to requests to help make their vaccines, so the WHO proceeded without their help. The Moderna vaccine was chosen to copy because there is more freely available data on it, and it has not vowed to enforce its patents.

The project started in late September, with a Wits University team spearheading the first step: making a DNA molecule that would serve as a template to synthesise the mRNA needed in the vaccine. While Moderna controversially patented this sequence, Stanford University researchers had deposited it into the online database Virological.org in March last year.

Patrick Arbuthnot, director of gene therapy research at Wits says, “We were not intimidated, because mRNA synthesis is a fairly generic procedure.” Despite delays in the shipment of raw materials, the team completed this process in ten weeks and sent vials of mRNA to Afrigen in early December.

Around this time, scientists worldwide emailed offers of assistance. Some were researchers at the US National Institutes of Health who had conducted foundational work on mRNA vaccines. Petro Terblanche, Afrigen’s managing director, said that it was “extraordinary”. “I think a lot of scientists were disillusioned with what had happened with vaccine distribution, and they wanted to help get the world out of this dilemma.”

On 5 January, Afrigen’s researchers accomplished another tricky part of the process: They encapsulated the mRNA in a fatty nanoparticle made of a mixture of lipids. Boukes says they haven’t yet used Moderna’s specific lipid mixture, but rather another one that was immediately available from the manufacturer of the machine that the laboratory uses to create lipid nanoparticles. They plan to use Moderna’s lipid mixture in the coming days, as soon as one last analytical instrument arrives. After that, the team will analyse the formulation to ensure that it is truly a near copy of Moderna’s vaccine.

Once a reliable copy is made, the next step is increasing production. Jason McLellan, a structural biologist at the University of Texas at Austin whose work was foundational to the development of several COVID vaccines, says he is not surprised that SA scientists seem to have copied Moderna’s vaccine, but he adds that scaling up production of that original shot required a lot of additional innovation by manufacturers.

For the next phase of the project, several southern hemisphere companies will learn from Afrigen and attempt to create batches of vaccines themselves, in preparation for animal testing. By end November, the WHO expects a Moderna clone to be ready for phase I trials in humans.

What happens beyond that is unclear. Moderna might choose to license its patent (lab research is usually not subject to patent rules), or alternatives may become available, such as next-generation mRNA vaccines that do not require ultracold storage.

Source: Nature

SA Doctors Report SARS-CoV-2 Mutations in a Patient with HIV

HIV Infecting a T9 Cell. Credit: NIH

In an article awaiting peer review, doctors in South Africa report on the case of a 22-year-old female with uncontrolled advanced HIV infection and a SARS-CoV-2 infection that lasted 9 months, during which time the virus accumulated more than 20 additional mutations. Antiretroviral therapy suppressed HIV and cleared the coronavirus within 6–9 weeks. 

One hypothesis for novel variants is that they arise in severely immunocompromised individuals. Being unable to clear the virus because of a weakened immune response results in a persistent infection, letting mutations accumulate – some of which may allow immune evasion. In one case, SARS-CoV-2 in a female leukaemia patient developed seven mutations over three months of infection.

The authors describe a case of persistent SARS-CoV-2 infection, lasting for at least 9 months, in a severely immunocompromised woman with HIV that had challenges with adherence to antiretroviral therapy.

In mid-September 2021, a female in her 20s was admitted to a tertiary hospital in Cape Town with a one-week history of sore throat, malaise, poor appetite and dysphagia. The patient was infected with HIV at birth. In January 2021, her antiretroviral therapy (ART) regimen had been changed to tenofovir, emtricitabine and efavirenz, but she had difficulty adhering. In August 2021 she moved from rural KwaZulu-Natal to Cape Town. She stated that she had not received a COVID vaccination.

“On physical examination, the patient was wasted but had no palpable lymph nodes,” the authors report. “She was awake and lucid, with no focal neurological deficits. She was not in respiratory distress with an oxygen saturation of 98% on room air. The cardiovascular and abdominal examinations, renal function, white cell count and liver enzymes were without abnormalities. Her CD4 count was 9 cells/μL and her plasma HIV viral load 4.60 log10 viral RNA copies/mL, indicating advanced HIV infection, poorly controlled by ART.

“During a prolonged hospital stay the patient experienced multiple complications requiring treatment. Following adherence counselling, antiretroviral therapy was reinitiated with a new regimen of tenofovir/efavirenz/dolutegravir a week after admission.” 

The patient tested positive for COVID on 25 September 2021, with genomic sequencing indicating the Beta variant. However, in October, the patient later revealed that she had tested positive for COVID in January 2021. On 25 November 2021, the patient’s HIV viral load was <50 copies/ml and a PCR test was negative for COVID. While there was no CD4 count performed, suppressed HIV replication and clearance of the SARS-CoV-2 infection suggest her immune system had recovered to some degree.

Phylogenetic analysis showed that the samples indicated an ongoing infection instead of re-infections. During the 9 months of infection, the virus acquired at least 10 mutations in the spike glycoprotein and 11 other mutations over and above the lineage-defining mutations for Beta.

The authors consider it unlikely that the novel variant described spread into the general population, and stress that it does not prove that any of the other novel variants originated from an immunocompromised host in this fashion.

Increased vigilance is warranted to benefit affected individuals and prevent the emergence of novel SARS-CoV-2 variants. They ascribed the detection of the case to good connections between sequencing laboratories, routine diagnostic laboratories and frontline clinicians.

The authors concluded that their experience “reinforces previous reports that effective ART is the key to controlling such events. Once HIV replication is brought under control and immune reconstitution commences, rapid clearance of SARS-CoV-2 is achieved, probably even before full immune reconstitution occurs. This underscores the broader point that gaps in the HIV care cascade need to be closed which will benefit other conditions and public health problems, too, including COVID.”

Bleeding from Full-dose Anticoagulants in COVID ICU Patients

Photo by Mufid Majnun on Unsplash

COVID patients in intensive care units (ICU) receiving full-dose anticoagulants are significantly more likely to experience heavy bleeding than patients prescribed a smaller yet equally effective dose, according to a recent study.

The research, which compared the safety and effectiveness of blood clot treatment strategies for more than 150 critically ill COVID patients at two hospitals, found that almost all patients who experienced significant bleeding were on mechanically ventilation and receiving full-dose anticoagulants.

The results, published last month in Hospital Pharmacy, may inform treatment guidelines for blood clots in hospitalised COVID patients, who are at an increased risk for both blood clots and severe bleeding. Previous reports have found that 17% of hospitalised COVID patients experience blood clots, said first author Maya Chilbert, PharmD, clinical assistant professor in the UB School of Pharmacy and Pharmaceutical Sciences.

“A wide variety of practice exists when it comes to approaching blood clots in hospitalized patients with COVID, and there is little data to suggest improved outcomes using one strategy versus another,” said Chilbert. “Caution should be used in mechanically ventilated patients with COVID when selecting a regimen to treat blood clots, and the decision to use full-dose blood thinners should be based on a compelling indication rather than lab markers alone.”

The study analysed the outcome of blood clot treatments and the rate of bleeding events for more than 150 patients with COVID-19 who received either of two blood thinner regimens: a full-dose based on patient levels of D-dimer, and the other a smaller but higher-than-standard dosage.

Patients’ average age was 58, and all experienced elevated levels of D-dimer, fibrinogen, and prothrombin time.

Significant bleeding events were experienced by almost 14% of patients receiving full-dose anticoagulants, compared to only 3% of patients who received a higher-than-standard dosage. All patients who experienced bleeding events were on mechanical ventilation. No difference was reported in the regimens’ effectiveness at treating blood clots.
Further investigation is needed to determine the optimal strategy for treating blood clots and bleeding in hospitalised COVID patients, said Asst Prof Chilbert.

Source: University at Buffalo

Nitazoxanide Flops in South African COVID Trial

Photo by Artem Podrez on Pexels

Interim analysis of a South African clinical trial has revealed that nitazoxanide, an oral antiparasitic agent with antiviral properties, was ineffective in improving outcomes in ambulatory patients with mild-to-moderate COVID.

Funded by the South African Medical Research Council (SAMRC), the study was performed at four sites in South Africa. The primary goal of the trial was to evaluate the effectiveness of nitazoxanide (1g twice daily for 7 days) in reducing the progression from mild to severe COVID in ambulatory patients. Progression to severe disease was defined as hospitalisation or death. The trial underwent an interim analysis at 67% of the recruitment target (290 participants), and the data was reviewed by an independent data and safety monitoring board (DSMB). Following the interim analysis, the DSMB recommended halting recruitment of the trial on the grounds of futility.

No significant difference was seen in serious adverse events, which included all causes of hospitalisation and death, between the nitazoxanide and the placebo groups [12/144 (8.3%) vs 10/146 (6.8%)]. Hospitalisation and death specifically due to COVID showed the same pattern [7/144 (4.9%) vs 8/146 (5.5%)].

Principal investigator Prof Keertan Dheda from the University of Cape Town (UCT) and the London School of Hygiene and Tropical Medicine, said that the results of the trial, although disappointing, contributes to the growing body of evidence, clarifying what works and what doesn’t for the treatment of COVID. Thus, clarifying what does not work is as important as finding effective therapies so that clinically useful management algorithms can be developed.

Nitazoxanide is a low-cost broad-spectrum antiviral drug with an extensive safety record. Originally developed as antiparasitic, it seemed promising against SARS-CoV-2 in the lab but the real world test did not show any benefit. It is still possible that nitazoxanide may be of benefit at higher doses (greater than the dose used in the trial, which was already twice the normal dose), however this will most likely cause an increase in intolerable gastrointestinal side effects. “The next step will be to focus on formally publishing the data in a peer reviewed journal and to evaluate secondary objectives of the study, including assessing the efficacy of nitazoxanide in reducing the duration of illness, reducing SARS-CoV-2 viral load, and its efficacy, if any, in preventing COVID in close contacts,” said Prof Dheda.

Prof Dheda concluded that nitazoxanide could have a less than 30% benefit which may be detectable in a larger study. However, it is questionable whether such an effect size is clinically relevant given the number needed to treat to prevent disease progression, adverse events, cost and that other therapies have emerged (eg paxlovid) with an efficacy benefit of greater than 80%.

SAMRC President and CEO, Prof Glenda Gray said although the study did not meet its primary endpoint, the results are an important addition into the scientific repository. “COVID and HIV in their very nature are unique and complex viruses which have posed unprecedented challenges for vaccine development, globally – however, the knowledge gained from this trial will help us advance our pursuit of effective therapies and vaccines for both COVID and HIV alike,” said Prof Gray.

Prof Gray, who also has led numerous trials in search of effective HIV and COVID vaccines, said COVID poses substantial challenges for those living with HIV which evades the immune system. “Until an effective vaccine has been found, all people living with HIV should take all recommended preventive measures to minimise their exposure to COVID,” concluded Prof Gray.

Source: South African Medical Research Council

Study Confirms COVID Vaccination does not Affect Fertility in IVF

Photo by Shvets Productions on Pexels

Vaccination against COVID did not affect fertility outcomes in patients undergoing in-vitro fertilisation (IVF), according to a new study. The findings, which were published in Obstetrics & Gynecology, add to the growing body of evidence providing reassurance that COVID vaccination does not affect fertility.

Investigators compared rates of fertilisation, pregnancy, and early miscarriage in IVF patients who had received two doses of vaccines manufactured by Pfizer or Moderna with the same outcomes in unvaccinated patients.

“The study found no significant differences in response to ovarian stimulation, egg quality, embryo development, or pregnancy outcomes between the vaccinated compared to unvaccinated patients.” said first author Devora Aharon, MD.

The study involved patients whose eggs were frozen and then thawed for in vitro fertilisation and womb transfer, and patients who underwent medical treatment to stimulate the development of eggs. The two groups of patients who underwent frozen-thawed embryo transfer (214 vaccinated and 733 unvaccinated) had similar rates of pregnancy and early pregnancy loss. The two groups of patients who underwent ovarian stimulation (222 vaccinated and 983 unvaccinated) had similar rates of eggs retrieved, fertilisation, and embryos with normal numbers of chromosomes, among several other measures.

The authors of the study anticipate that the findings will ease the anxiety of people considering pregnancy. 

Patients undergoing IVF treatment are closely tracked, enabling the researchers to capture early data on the implantation of embryos in addition to pregnancy losses that might be undercounted in other studies.

Previous studies have found that COVID vaccination helped protect pregnant persons (already at greater risk from severe illness and death from COVID) from severe illness, conferred antibodies to their infants, and did not raise the risk of preterm birth or foetal growth problems.

Source: EurekAlert!