If treated with therapeutic-dose anticoagulation, moderately ill patients hospitalised with COVID have better odds of survival, according to an international study published in The New England Journal of Medicine.
COVID patients frequently develop a pro-coagulative state caused by virus-induced endothelial dysfunction, cytokine storm and complement cascade hyperactivation. Thrombotic risk appears directly related to disease severity and worsens patients’ prognosis.
Moderately ill COVID patients treated with therapeutic-dose anticoagulation with unfractionated or low molecular-weight heparin were 27% less likely to need cardiovascular respiratory organ support such as intubation, said Ambarish Pandey, MD, Assistant Professor of Internal Medicine at UT Southwestern, who served as site investigator and . Moderately ill patients had a 4% increased chance of survival until discharge without requiring organ support with anticoagulants, according to the study involving 2200 patients.
“The 4% increase in survival to discharge without needing organ support represents a very meaningful clinical improvement in these patients,” said Dr Pandey, a Texas Health Resources Clinical Scholar specialising in preventive cardiology and heart failure with preserved ejection fraction. “If we treat 1,000 patients who are hospitalized with COVID with moderate illness, an additional 40 patients would have meaningful improvement in clinical status.”
Moderately ill patients were defined as those who did not need intensive care unit-level support. The participating platforms for the study, included Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC); A Multicenter, Adaptive, Randomized Controlled Platform Trial of the Safety and Efficacy of Antithrombotic Strategies in Hospitalized Adults with COVID-19 (ACTIV-4a); and Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP).
A parallel study reported in The New England Journal of Medicine found however that therapeutic-dose anticoagulation did not help severely ill patients.
After a group of anti-vaxxer demonstrators gathered outside Groote Schuur Hospital (GSH), Western Cape Health authorities have slammed anti-vaxxers for inflaming vaccine hesitancy. Even so, there was a record vaccination turnout on Friday when inoculations were offered to over 18s.
“I just don’t understand why people don’t believe us when we say that the vaccines are safe,” Western Cape Health Department’s Dr Saadiq Kariem said, warning of the damage that misinformation can do.
“There’s no 3G in the vaccine. There’s certainly no conspiracy theory. All we’re trying to do is help by making sure that the population is as protected as possible against coronavirus,” Dr Kariem said, adding that it was even more dangerous when medical professionals were against the shots.
“It just baffles my mind how other medical professionals can, in fact, be anti-vaccination because people will believe professionals, you know, and take their word as they’ve studied this field,” he added. Some of the protesters were carrying signs in support of controversial anti-vaxxer doctors.
IOL reports that one man who was employed by the hospital and chose not to be named, stood alone in the street and faced down the protesters with a sign saying “Covidiots”. He said the pandemic had been happening for 18 months, and that the ignorance of the crowd was disgraceful.
Just before the protests got underway, the University of Cape Town had released a statement in support of GSH. “The Faculty stands in solidarity with the staff (including cleaners, security, admin staff, drivers etc) of GSH. We stand in support of their work and the herculean efforts they have taken across the era of this pandemic under extremely challenging circumstances and often at personal risk. We salute the work of our partners in delivering the best possible care in responding to the world’s greatest human tragedy.”
Only 21 percent of patients with severe pneumonia caused by SARS-CoV-2 have a documented bacterial superinfection at the time of intubation, resulting in potential overuse of antibiotics, according to new research.
Superinfection occurs when another, usually different, infection is superimposed on the initial infection. In this case, it is bacterial pneumonia during severe viral pneumonia.
Dr Wunderink and co-authors reported their findings in a study published online in the Journal of Respiratory and Critical Care Medicine, which shows that the usual clinical criteria used to diagnose bacterial pneumonia could not distinguish between those with bacterial superinfection and those with severe SARS-CoV-2 infection only.
According to the authors, there is weak evidence behind current guidelines recommending that patients with SARS-CoV-2 pneumonia receive empirical antibiotics on hospital admission for suspected bacterial superinfection. In other published clinical trials of patients with SARS-CoV-2 pneumonia, rates of superinfection pneumonia are unexpectedly low. “More accurate assessment other than just reviewing clinical parameters is needed to enable clinicians to avoid using antibiotics in the majority of these patients, but appropriately use antibiotics in the 20-25 percent who have a bacterial infection as well,” said Dr Wunderink.
The team conducted an observational study to determine the prevalence and cause of bacterial superinfection at the time of initial intubation and the incidence and cause of subsequent bacterial ventilator-associated pneumonia (VAP) in 179 patients with severe SARS-CoV-2 pneumonia which required mechanical ventilation.
The researchers analysed 386 bronchoscopic bronchoalveolar lavage fluid samples from patients, and actual antibiotic use was compared with guideline-recommended therapy. Bacterial superinfection within 48 hours of intubation was detected in 21 percent of patients; 72 patients (44.4 percent) developed at least one VAP episode; and 15 (20.8 percent) of initial VAPs were caused by difficult-to-treat bacteria.
The authors found that in patients with severe SARS-CoV-2 pneumonia, bacterial superinfection at the time of intubation occurred in less than 25 percent of patients. Guideline-based empirical antibiotic management at the time of intubation would have resulted in antibiotic overuse.
The researchers believe that their findings have multiple implications for antibiotic guidelines: “Rapid diagnostic tests are important for helping identify suspected pneumonia in intubated patients. This can have major clinical implications because the current approach of using clinically defined risk factors for suspected methicillin-resistant staphylococcus aureus (MRSA) or pseudomonas bacteria as the cause of pneumonia still grossly overestimate the true incidence of these pathogens. In addition, the recommendation for empirical antibiotic treatment of worsening viral community-acquired pneumonia (now requiring intubation) may need to be revisited. This is not only true for SARS-CoV-2 but potentially for severe influenza as well.”
“An accurate diagnosis of suspected pneumonia allows clinicians to safely avoid or use narrow spectrum antibiotics for many patients,” Dr Wunderink added. “While multiple interventions impact mortality in these critically ill patients, the low mortality in our study with more limited antibiotic treatment suggests that our approach was safe.”
A COVID prophylactic cocktail of long-acting antibodies cut the risk of developing symptomatic disease in a high-risk unvaccinated patient population, AstraZeneca announced on Friday.
Initial phase III trial data showed that AZD7442 (tixagevimab and cilgavimab) as pre-exposure prophylaxis significantly reduced the risk of developing COVID symptoms by 77% versus placebo, meeting the trial’s primary endpoint. AstraZeneca further noted there were no cases of severe COVID or COVID-related deaths in the intervention group, while there were three cases of severe COVID and two deaths in the placebo group.
No safety concerns were noted by the manufacturer, as the treatment was well-tolerated and adverse events were balanced between groups.
A key feature of the trial was that 75% of participants had comorbidities, including being “at risk of an inadequate response to active [immunisation],” such as older adults and those with immunosuppressive disease or on immunosuppressive medication.
“With these exciting results, AZD7442 could be an important tool in our arsenal to help people who may need more than a vaccine to return to their normal lives,” the trial’s principal investigator, Myron Levin, MD, of the University of Colorado School of Medicine, said in a statement.
AZD7442 was derived from the B cells of convalescent patients. PROVENT was a phase III randomised trial conducted in the US and Europe. Participants were 5197 adults “who would benefit from prevention” with the long-acting antibody, were unvaccinated at the time of enrollment, and tested negative for SARS-CoV-2. Participants were randomised 2:1 to receive a single 300 mg dose of AZD7442 or placebo. AstraZeneca noted that 43% of participants were ages 60 and older. The company noted that the drug is active in lab studies against emerging strains, including the Delta variant.
Patients were followed for 183 days, though subjects are slated to be followed for 15 months, AstraZeneca said. Data will be submitted for peer-reviewed publication while the company seeks approval for AZD7442.
A study found that antibiotic prescriptions for non-respiratory ailments were unchanged by COVID lockdown in Australia, which had comparatively few COVID cases.
In regions with high levels of COVID transmission, such as Europe and the United States, prescriptions for antibiotics in the community fell dramatically after COVID restrictions were introduced in early 2020. A study published in the British Journal of Clinical Pharmacology looked at antibiotic prescribing in Australia, which has so far had low COVID rates.
Analysing national claims data, researchers observed that COVID restrictions in Australia were associated with substantial reductions in community dispensing of antibiotics primarily used to treat respiratory infections, but found that antibiotics for non-respiratory infections did not change.
“The issue is that antibiotics should rarely be prescribed for common viral respiratory infections in the first place. These big reductions show how low general practitioners’ antibiotic prescribing could go if guidelines were followed more closely,” said co–senior Helga Zoega, PhD, of UNSW Sydney, in Australia.
In the UK’s first wave, more than one in ten COVID hospitalised patients acquired the disease in a hospital according to researchers conducting the world’s largest study of severe COVID.
Dr Jonathan Read from Lancaster University with colleagues from other UK universities led the research into hospital-acquired infections (HAIs) which was published in The Lancet.
For the study, researchers analysed records of COVID patients in UK hospitals enrolled in the International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) Clinical Characterisation Protocol UK (CCP-UK) study, who became ill before 1st August 2020.
The researchers found that at least 11.1% of COVID patients in 314 UK hospitals were infected after admission. The proportion of hospital-acquired infections also rose to between 16% and 20% in mid-May 2020, well after the first wave’s peak in admissions.
“We estimate between 5699 and 11 862 patients admitted in the first wave were infected during their stay in hospital. This is, unfortunately, likely to be an underestimate, as we did not include patients who may have been infected but discharged before they could be diagnosed,” the researchers said.
“Controlling viruses like SARS-CoV-2 has been difficult in the past, so the situation could have been much worse. However, infection control should remain a priority in hospitals and care facilities,” said Dr Read.
Dr Chris Green, University of Birmingham, said: “There are likely to be a number of reasons why many patients were infected in these care settings. These include the large numbers of patients admitted to hospitals with limited facilities for case isolation, limited access to rapid and reliable diagnostic testing in the early stages of the outbreak, the challenges around access to and best use of PPE, our understanding of when patients are most infectious in their illness, some misclassification of cases due to presentation with atypical symptoms, and an under-appreciation of the role of airborne transmission.”
According to the type of care provided, there were notable differences in infections. Lower proportions of hospital-acquired infection were seen in hospitals providing acute and general care (9.7%) than residential community care hospitals (61.9%) and mental health hospitals (67.5%). Professor Calum Semple, University of Liverpool, said: “The reasons for the variation between settings that provide the same type of care requires urgent investigation to identify and promote best infection control practice. Research has now been commissioned to find out what was done well and what lessons need to be learned to improve patient safety.”
In a digital media briefing, Western Cape Premiere Alan Winde said that the province had still not exited its third wave of COVID infections.
With an R value of 0.9, this was the first time in the third wave that the value was below 1. However, this could be due to testing delays caused by the long weekend. Indeed, a sharp daily increase in national COVID cases has been recorded as of Thursday’s latest data, with the NICD reporting a 90% jump to 14 271. Overall case positivity still hovers above the 20% mark at 22.52%.
Cases continue to spike While overall cases in the Western Cape are plateauing, spikes in certain areas are seeing higher case rates than in the peak of the second wave. Oxygen is still being used as fast as it can be produced in the province, being supplemented by an additional 22 tonnes per day by truck deliveries from other provinces. A total of 3665 patients are in acute hospitals, with 99% occupancy in Metro areas. The Metro area is seeing a week-on-week case rise of 7%, which points to a plateau.
Vaccines proving effective – even against beta The Johnson & Johnson vaccine however is proving effective, with 91-95% protection against death and 65-66% protection against hospitalisation. With regard to variants, the vaccine confers 67% protection against hospitalisation when beta is dominant and 71% where delta is dominant.
The Western Cape’s vaccination programme remains on track, with 287 000 doses of Pfizer and 28 800 J&J doses to arrive today, Friday 13th.
Elsewhere, with 31.2 new cases per 100 000 people, KwaZulu-Natal may be becoming a COVID hotspot.
A further 473 people have died from COVID, bringing the official death toll to 76 247.
In an article published in the South African Medical Journal, Shabir Madhi, Professor of Vaccinology at Wits, argues that COVID variants have made the initial goal of attaining herd immunity no longer feasible, even for well-resourced countries. However, vaccine protection against severe COVID seems a more realistic path to normalcy.
In low and middle income countries (LMICs), the official COVID case estimates are likely grossly underestimated, Prof Madhi writes, due to a lack of testing coverage. Even in South Africa, the true number of COVID cases is likely in the region of 10 times the 2.39 million recorded through testing. The true number of COVID-related deaths in India is also estimated as 3.4–3.9 million, again 10 times the official count, and in South Africa it is likely three times the official figure of 70 388 in July 2021.
While New Zealand researchers have suggested that COVID eradication is feasible, it is likely a very long term goal if at all attainable. The herd immunity goal can be considered with the equation (p1 = 1 – 1/R0), where p1 is the proportion of immune individuals who will also no longer transmit the virus, and R0 is the reproduction rate, ie the number of susceptible individuals a single infected person can further infect. However, this ignores key aspects of the virus.
The problem is that the proportion of people that would need to be immunised to achieve herd immunity was initially calculated at 67%, based on an assumed R0 of 3, derived from the Wuhan strain’s R0 of 2.5 to 4. However, the Delta variant has an R0 of 6, meaning that to reach herd immunity, 84% of the population would need to be vaccinated. In South Africa, this would be 100% of the population aged over 12.
The emergence of SARS-CoV-2 variants, especially the Beta variant with the E484K mutation, showed that existing vaccine protection, including the Pfizer variant, can be degraded to an extent.
Studies have strongly suggested that neutralising and antibody titers are associated with mild to moderate COVID protection, while protection from severe COVID may be mediated by T-cell immunity.
Real world data showed that in Israel, with a world best immunisation of 61.6% using the Pfizer vaccine which produces the greatest antibody response, herd immunity appeared to be successful until an outbreak of the more transmissible Delta variant combined with waning vaccine effectiveness.
However, in the UK, excess death data showed that, even with a resurgence of cases caused by the Delta variant, there was a significant decoupling of deaths from cases. This points to the effectiveness of vaccines in preventing severe illness, as opposed to reaching herd immunity.
Vaccine rollouts have therefore not interrupted COVID transmission. Prof Madhi concludes that, based on an estimated R0 of 6 for the Delta variant, “it is unlikely that any country could have a sustainable strategy for durable high level of protection against infection by the delta variant. Mutations of the SARS-CoV-2 genome are likely to continue resulting in enhanced transmissibility, infectiousness and resistance to neutralising activity.”
He observes that the “UK approach seemingly concedes that the goal of herd immunity, even in a highly resourced setting, is unattainable.”
He adds that aspiring to reach herd immunity by wealthy countries comes at the cost of exacerbating vaccine inequality, which he says “is immoral.” Antibody dynamics modelling suggests that a booster would be required every 2–3 years to protect against severe COVID, and every 6–9 months to protect against moderate disease. This is a challenging goal, and likely unattainable for most LMICs, especially given the slow rate of vaccination in those settings.
A new analysis shows that the global eradication of COVID is tough but theoretically more feasible than for polio and less so than it was for smallpox.
The article in BMJ Global Healthranked the feasibility of eradicating the three diseases based on technical, socio-political and economic factors.
Smallpox, which was declared eradicated in 1980, had the highest average score for eradication feasibility. It had an average score of 2.7 on a three-point scale across 17 variables. COVID had an average score of 1.6 which was close to polio’s average score of 1.5.
Professor Nick Wilson from the University of Otago said that their analysis shows COVID’s eradication is feasible.
Vaccination programmes, public health measures and the global interest in combating the disease together contribute to making eradication possible.
“Elimination of COVID-19 at the country level has been achieved and sustained for long periods in various parts of the Asia Pacific region, which suggests that global eradication is possible.”
Vaccination programmes eradicated smallpox and two of the three serotypes of poliovirus, while other diseases are close to eradication. China recently became the 40th country to be certified malaria-free.
In ranking the feasibility of eradication for the three diseases, the researchers incorporated factors including the availability of safe and effective vaccines, the possibility of lifelong immunity, the impact of public health measures, effective infection control messaging by governments, political and public concern about the infection and public acceptance of infection control measures.
While there has been a focus on the need to reach herd immunity to overcome COVID, population immunity may not be essential to combat the disease, as smallpox was eradicated through ring-vaccination programmes which target the contacts of those infected.
The challenges of eradicating COVID relative to smallpox and polio include poor vaccine acceptance in some countries and the emergence of variants of the pandemic virus that may be more transmissible or able to evade the protection from vaccines.
But Professor Wilson said eventually the virus will be reach the limit of more infectious mutations, and so new vaccines will likely be formulated to deal with evolving strains of the disease.
Other obstacles includedthe cost of global vaccination and upgrading health systems, and achieving international cooperation in the face of aggressive anti-science movements and vaccine nationalism.
Professor Wilson says while the virus may infect animal populations, they will note likely hamper eradication.
“Wild animal infections with SARS-CoV-2 appear to be fairly rare to date and when companion animals become infected, they don’t appear to reinfect humans.”
A co-author of the article, Professor Michael Baker from the University’s Department of Public Health, says global concern about the pandemic could be tapped.
“The massive scale of the health, social and economic impacts of COVID-19 in most of the world has generated unprecedented global interest in disease control and massive investment in vaccination programmes.
“Unlike smallpox and polio, control of COVID-19 also benefits from the added impact of public health measures, such as border controls, social distancing, contact tracing and mask wearing, which can be very effective if well deployed.”
Professor Baker says upgrading health systems to target COVID-19 could also help to control other diseases, and could even aid in eradicating measles.
“When all factors are taken into account, it could be that the benefits of eradicating COVID-19 outweigh the costs, even if eradication takes many years and has a significant risk of failure.”
This work is preliminary, the researchers cautioned.
“The World Health Organization or a coalition of national agencies working collaboratively needs to formally review the feasibility and desirability of attempting COVID-19 eradication on a global basis,” Professor Baker says.
The researchers noted it is important to distinguish between eradication of infection, ie the permanent reduction to zero of the worldwide incidence of infection caused by a specific agent as a result of deliberate efforts; and elimination, ie the reduction to zero of the incidence of infection caused by a specific agent in a defined geographical area as a result of deliberate efforts.
COVID elimination has been reached and sustained for long periods in a number of jurisdictions in the Asia-Pacific region (notably China, Hong Kong, Taiwan, Australia and New Zealand), demonstrating that global eradication is technically possible.
Infected cell covered with SARS-CoV-2 viruses. Source: NIAID
In a small study, people with previous COVID infection were observed to have higher antibody levels after a single dose of Pfizer vaccine compared with uninfected people after two doses.
Furthermore, there was no increase in IgG levels after the second dose among those previously infected, possibly indicating that one dose of vaccine may be sufficient for this population, reported James Moy, MD, of Rush University Medical Center in Chicago, and colleagues in aJAMA Network Openresearch letter.
“This study highlights the potential for recommending a single dose for previously infected individuals and may be useful for discussions surrounding vaccination strategy,” the authors wrote.
Whether to offer only a single dose of vaccine to those previously infected with COVID is a hot topic, with some experts conceding that previously infected individuals likely only need one dose, but would be challenging to implement.
Indeed, Dr Moy’s group urged performing “baseline serological testing” for previously infected individuals, but CDC and the agency’s Advisory Committee on Immunization Practices (ACIP) argued that this would be next to impossible to do for the entire country.
At a meeting in March, ACIP Chair José Romero, MD, voiced concern that the one-dose strategy would only work if individuals had sufficiently high antibody titers. If people had no or low antibodies, they may not have “enough memory B-cells to boost to levels that will be protective,” he said.
The researchers recruited adult participants at the team’s academic medical center, sorting them according toinfection status. Prior infection was established by a positive RT-PCR test and/or a positive SARS-CoV-2 antibody result. Overall, 30 participants had no evidence of infection, while 29 did.
The authors measured SARS-CoV-2 spike IgG levels at baseline and then after the first and second doses of the Pfizer vaccine among all participants.
There were no significant IgG differences between the first and second dose in previously infected individuals. Interestingly, four participants reported a previous positive COVID test via RT-PCR, but had no evidence of antibodies.
“Vaccine responses in these four participants resembled infection-naive individuals,” Moy’s group noted, adding that because this group did not develop S-protein antibodies, baseline testing should be required before forgoing a second dose.
The researchers said study limitations included the small sample size and lack of diversity of participants, as well as lack of neutralisation studies and T-cell response studies.
