Three members of the South African soccer team staying in the Olympic Village have tested positive for COVID just days before the Olympic opening ceremonies. They are also the first Olympic athletes who tested positive in the tightly-monitored athletes’ enclave along a Tokyo waterfront.
The South African team said in a July 17 statement that defender Thabiso Monyane, midfielder Kamohelo Mahlatsi, and Mario Masha, a video analyst on the coaching staff, had tested positive on the weekend. All South African players had tested negative when they departed for Tokyo on July 13. The entire South African football team is now under quarantine, raising doubts whether they’ll be cleared for their July 22 match against Japan.
Since the announcement, South African rugby Sevens coach Neil Powell as well as an unnamed member of the female US gymnastics team have also tested positive. Outside the athlete’s complex, positive results have been reported for South Korean IOC official Ryu Seung, an unnamed member of the Nigerian delegation, and an unnamed athlete.
Despite the country’s best efforts to contain the virus, COVID remains a big concern in Tokyo at the world’s largest sporting event, expected to draw about 11 000 athletes from 200 nations. The Tokyo Olympic Committee has introduced measures such as banning spectators at games, daily COVID screening for athletes, and limiting stays at the Olympic Village to seven days.
With Japan still under a state of emergency and the COVID delta variant spreading rapidly, many continue to appeal to the International Olympic Committee to cancel the games. But some experts said that at this point a cancellation would cost Japan $16.4 billion. It would also run the risk of being sued by the IOC for breach of contract.
Addressing the outbreaks in an effort to rally local support for the events, IOC president Thomas Bach said, “We are well aware of the skepticism a number of people have here in Japan,” he said. “My appeal to the Japanese people is to welcome the athletes for their competitions.”
Researchers suggest that nutritional supplements such as Vitamin C do play a role in reinforcing the immune system against SARS-CoV-2.
An article in Advances in Experimental Medicine and Biology lays out the scientific rationale and possible benefits — as well as possible drawbacks — of several dietary supplements currently in clinical trials related to COVID-19 treatment. The article was written by Johns Hopkins Medicine gastroenterologist Gerard Mullin, MD, and colleagues.
Dr Mullin, associate professor of medicine at the Johns Hopkins University School of Medicine, and his colleagues shine a light on melatonin, vitamin C, vitamin D, zinc and several plant-based compounds, such as green tea and curcumin. For instance, the authors explained that vitamin C (ascorbic acid), “contributes to immune defense by supporting cell functions of both the innate and adaptive immune systems.”
The authors discuss in the journal article the mechanism of action of each of the supplements works, how each could benefit a patient with COVID.
Zinc is well tolerated, and well known for its antioxidant, anti-inflammatory, immunomodulatory, and antiviral activities, the latter possibly mediated by its ability to inhibit RNA virus replication, thereby protecting cells from viral infection, oxidative damage, and dysfunction. It has been shown “to inhibit coronavirus RNA replication.” They also noted that, when administered at symptom onset, zinc “can reduce the duration of symptoms from illness attributed to more innocuous coronavirus infections, such as the common cold.”
Finally, Dr Mullin and colleagues gave short summaries of the clinical trials underway to test each supplement’s effectiveness in fighting COVID.
Regarding Vitamin D, which has received a lot of attention with regard to COVID outcomes, Dr Mullin said that, “to date, there are abundant data associating low vitamin D status to higher vulnerability to COVID-19 and poor clinical outcomes.”
The authors however struck a note of caution in that “any benefit of dietary supplements against COVID-19 depends on results of randomised controlled trials” and peer-reviewed literature.
Immunotherapy company ImmunityBio has been authorised by the South Africa Health Products Regulatory Authority (SAHPRA) to proceed with the South Africa Sisonke T-Cell Universal Boost trial.
The Phase 1/2/3 study, starting in the second third quarter of 2021, is designed to evaluate hAd5 Spike + Nucleocapsid (S+N) as a boost for South African healthcare workers previously vaccinated with an S (Spike)-only vaccine.
“With the virus continuing to spread, moving forward with this boost trial is crucial,” said Leonard Sender, MD, Chief Operating Officer of ImmunityBio. “We are encouraged by the preliminary safety findings in our ongoing Phase 1 studies in both the U.S. and South Africa. In addition, our U.S. data show that just a single prime subcutaneous vaccination with our COVID-19 vaccine candidate induces a 10-fold increase in T cell response—equivalent to T cell responses from patients previously infected with SARS-CoV-2. We have also shown that the T-cell responses are maintained against variants, which is critical to providing protection against this ever-changing virus.”
In the trial, the effect of combining vaccination by subcutaneous (SC) and sublingual (SL) routes will be assessed. This combination has the potential to deliver protection from the virus with a single injection followed by droplets placed under the tongue. Methods that do not require injection such as SL, intranasal, and oral capsule offer potential advantages depending on the participant’s needs or situation. Sublingual administration offers the most rapid absorption, while nasal spray or oral capsule delivery have the potential to provide mucosal immunity, which could reduce both the chance of infection and potential spread of the virus via the respiratory tract. The three non-injection formulations do not need a trained healthcare worker to administer them and are easier to transport and store. The SL and nasal routes of administration are also currently being tested in a separate Phase 1 trial in South Africa.
“The number of new cases in South Africa is frightening, particularly when you consider recent data suggesting currently available COVID-19 vaccines may not provide the immune memory needed to fend off infection from future variants. This highlights an urgent need for a boost dose that confers long-term protection by activating both antibodies and T cells, ” said Patrick Soon-Shiong, MD, Founder and Executive Chairman of ImmunityBio.
“Several peer-reviewed studies demonstrate that patients who have recovered from SARS-CoV in the 2003 outbreak possess long lasting memory T cells reactive to the nucleocapsid protein of SARS-CoV 17 years after infection. While antibodies block infection when present, T cells are vital for long-term immune memory. We are excited to begin this controlled, randomized trial of boosting a previously administered DNA-based viral vector vaccine with our own Ad5 dual-antigen S plus N vaccine to see if it can augment protection in participants who have received the S-based vaccine alone,” added Dr Soon-Shiong.
Unlike other population-level stressful events such as natural disasters, COVID has not resulted in a net increase in smoking, according to a new study from the International Tobacco Control (ITC) Project, at the University of Waterloo.
However, the researchers also found that although nearly half of smokers reported that COVID caused them to consider quitting, the vast majority of smokers did not change their smoking habits during the early phase of the COVID pandemic.
Stress is known to be a significant risk factor for smoking, especially in females. The study surveyed 6870 smokers and vapers in Australia, Canada, England, and the United States between April and June 2020. The team investigated the association between COVID and thoughts about quitting smoking, changes in smoking, and factors related to positive changes such as attempting to quit or reducing smoking.
Only 1.1 per cent of smokers in the four countries attempted to quit and 14.2 percent reduced smoking, but this was offset by the 14.6 percent who increased smoking, with 70.2 percent reported no change.
“It is important to note that population-level stressful events, such as 9/11 and natural disasters, have often led to increased smoking,” said Geoffrey Fong, professor of psychology at Waterloo and principal investigator of the ITC Project. “So, our findings that there was no net increase in smoking in response to COVID may actually represent a positive result for public health.”
The study found that those who considered quitting smoking due to COVID were mostly females, ethnic minorities, those under financial stress, current vapers, less dependent smokers, those with greater concern about personal susceptibility of infection, and those who believed COVID is more severe for smokers.
According to study co-author Fong, this latter finding may explain why a significant uptick in smoking was seen in the COVID pandemic, compared to past tragedies.
“Unlike other population stressors such as earthquakes, which are unrelated to smoking, COVID severity is indeed linked to smoking,” Fong said. “Public health officials have mentioned the link as yet another reason for smokers to quit, and over 80 percent of smokers across the four countries believed that smoking made COVID more severe. And this led to the lack of an increase in smoking, unlike what we have seen after other tragedies.”
Journal information: Gravely, S., et al. (2021) Smokers’ cognitive and behavioural reactions during the early phase of the COVID-19 pandemic: Findings from the 2020 ITC Four Country Smoking and Vaping Survey. PLOS ONE. doi.org/10.1371/journal.pone.0252427.
New trial results show that early administration of the blood thinner heparin to moderately ill hospitalised COVID patients with could halt the thrombo-inflammation process, reducing the risk of severe disease and death.
COVID is characterised by inflammation and abnormal clotting in the blood vessels, especially the lungs, and is believed to contribute to progression to severe disease and death.
The study is available as a preprint on MedRxiv and was led by investigators at St. Michael’s Hospital, a site of Unity Health Toronto, and the University of Vermont’s Larner College of Medicine.
Heparin, an anticoagulant, is indicated for both the prevention and treatment of thrombotic events such as deep vein thrombosis (DVT) and pulmonary embolism as well as atrial fibrillation. Heparin is also used to prevent excess coagulation during procedures such as cardiac surgery, extracorporeal circulation or dialysis. Heparin also has a wide range of off-label uses in hospitals. “This study was designed to detect a difference in the primary outcome that included ICU transfer, mechanical ventilation or death,” said study co-principal investigator Mary Cushman, MD, MSc, professor of medicine at the UVM Larner College of Medicine. The open-label randomised international multi-centre clinical RAPID Trial (also known as the RAPID COVID COAG – RAPID Trial) examined the benefits of administering a therapeutic full dose of heparin versus a prophylactic low dose to hospitalised patients with moderate COVID.
The primary outcome was a composite of ICU admission, mechanical ventilation, or death up to 28 days. Safety outcomes included major bleeding. Primary outcome occurred in 16.2% of patients with therapeutic full dose heparin, and 21.9% with low dose heparin (odds ratio [OR], 0.69). Four patients (1.8%) with therapeutic heparin died vs 7.6% with prophylactic heparin (OR, 0.22).
“While we found that therapeutic heparin didn’t statistically significantly lower incidence of the primary composite of death, mechanical ventilation or ICU admission compared with low dose heparin, the odds of all-cause death were significantly reduced by 78 percent with therapeutic heparin,” said first author and co-principal investigator Michelle Sholzberg, MDCM, MSc, Head of Division of Hematology-Oncology, medical director of the Coagulation Laboratory at St. Michael’s Hospital of Unity Health Toronto, and assistant professor at the University of Toronto.
Co-principal investigator Peter Jüni, MD, director of the Applied Health Research Centre (AHRC) at St. Michael’s, and professor of medicine at the University of Toronto, said that the researchers also presented a meta-analysis of randomised evidence (including data from a large multiplatform trial of ATTACC, ACTIV-4a and REMAP-CAP), which clearly indicated that therapeutic heparin is beneficial in moderately ill hospitalised COVID patients. He added that an additional meta-analysis presented in the preprint showed that therapeutic heparin is beneficial in moderately ill hospitalised patients but not in severely ill ICU patients.
Unusually, the RAPID Trial was funded through grassroots efforts from various institutions, grants and even a GoFundMe campaign.
“We called this trial ‘The Little Engine that Could,’ because of the sheer will of investigators around the world to conduct it,” said Cushman.
Sholzberg said, “We believe that the findings of our trial and the multiplatform trial taken together should result in a change in clinical practice for moderately ill ward patients with COVID.”
A study of COVID transmission in a US university indicates that at least a fifth of asymptomatic COVID cases passed the infection on, suggesting that containing the SARS-CoV-2 virus is more difficult than previously thought.
Even as multiple resurgences of the COVID pandemic occur in many countries, the risk posed by various degrees of infection, from asymptomatic through presymptomatic to symptomatic SARS-CoV-2 infection is still undefined.
Researchers in a new study found that at least a third of infected individuals were asymptomatic, and a fifth of them successfully passed on the virus to others. In comparison, about a quarter of symptomatic cases did so, especially when the symptoms included fever, cough and shortness of breath. In these instances, up to 30% of them transmitted the virus. The findings of the study are available on the medRxiv preprint server, and are not yet peer reviewed.
Asymptomatic carriage has been suspected and reported since the pandemic’s outset, though the exact proportion has been described to be anywhere between 40% and 77%. Such differences in ascertainment could be from varying demographic, testing, and interaction patterns.
Most systematic reviews have quoted figures of 30-45% as asymptomatic, which are considered to be much less transmissible. Secondary attack rates (SAR) of as low as 0.7% are reported in these cases, compared to 21% for symptomatic cases. Most of these studies had a lack of follow-up, meaningthat asymptomatic and presymptomatic cases could have been combined or misclassified.
The study was based on a campus population at a Midwestern university in the USA, during the northern hemisphere autumn of 2020. The study included about 13 000 students and 1600 confirmed cases.
The researchers found not only that SAR differed when patients were classified by symptom presence or absence, but the nature of the symptoms also determined the SAR. This could hamper containment efforts, especially as economic activity is burgeoning after a long hiatus.
Moreover, daily checks on individuals such as employees and students which are meant to help define transmission risk, may not yield the desired results when the wide difference in symptom types and timing in relation to infection, as well as the SAR, are taken into account.
The college campus in this study had a set of measures in place to reduce the risk of viral spread. In particular, this included a daily requirement to assess one’s own health and report on any issues; testing for the virus; contact tracing; case isolation and contact quarantine; and surveillance testing to monitor the spread of the virus.
In August, students began to come back to campus, and this was associated with 151 positive tests for the virus by reverse transcriptase polymerase chain reaction (RT PCR). This led to the suspension of in-person classes, with all teaching being online until August 24.
At this point, graduate and professional students again had in-person classes, while the others continued with online classes until September 2. The number of cases detected by a positive PCR test went down, from just over 600 in August to approximately 150 by September.
A second rise was seen in the middle of October, and by the end of the semester, on November 20, over 1500 students were positive. Of these, daily health data was present for at least half the days for about 1200 students.
Testing was administered by a rapid antigen test if a student had symptoms suggestive of SARS-CoV-2 infection or had a history of exposure to someone with COVID. Negative results were validated by a PCR, with the result coming within 1-2 days during which time they were quarantined.
Positive rapid antigen tests led to 14 days isolation, along with contact tracing and quarantine. The quarantined students were also advised to do an antigen test, which, if positive, necessitated a PCR test. They were also expected to quarantine until tests on days four and seven were also negative, at which point they were released. The university also conducted surveillance monitoring to hopefully catch asymptomatic or presymptomatic cases.
The scientists found that nasal congestion, headache and dry cough was higher among those who tested positive within five days, with fever and sensory disturbances (anosmia/dysgeusia/ageusia) were higher among positives only three and two days previous to testing positive. Loss of taste and smell occurred in the greatest proportion of cases by day four after testing positive.
The SAR was 19% vs 25% for asymptomatic vs symptomatic index cases on day 14 after virus exposure. In the four days immediately following exposure, symptomatic cases showed a higher SAR, with presymptomatic cases showing lower SAR and asymptomatic cases the lowest.
Perhaps this was because symptomatic cases have delayed testing, indicating that they had more time to transmit the virus before testing positive.
After this period, presymptomatic COVID had the highest SAR, but symptomatic case SAR began to rise, becoming almost identical thereafter. At seven days post-exposure, the SAR in all categories flattened, therefore making it the quarantine limit for contacts.
Symptoms varied in their predictive capacity, but fever, shortness of breath and a dry cough at the onset of infection were found to be associated with an SAR of 30%, provided body aches and/or chills were also reported. The investigators suggest this could be owing to higher viral loads, and therefore greater ability to shed and spread the virus.
The authors concluded that daily virus surveillance does not by itself help in containing transmission. The only way out may be rigorous face mask use until sufficient vaccine coverage is reached, along with social distancing, testing and quarantine. Both asymptomatic and presymptomatic viral transmission are significant contributors to viral spread, impeding efforts to stop the virus, especially with novel emerging SARS-CoV-2 strains.
The flu vaccine may provide a level of protection against COVID, a new study concludes.
An analysis of patient data from around the world strongly suggests that the annual flu shot reduces the risk of stroke, sepsis and DVT in patients with COVID. Flu-vaccinated COVID patients were also less likely to visit the emergency department and be admitted to the intensive care unit (ICU). The research was presented online at research being presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID).
Global COVID vaccination is a daunting challenge and, although production and distribution of vaccines increases daily, some countries are not expected to vaccinate large numbers of their population until the start of 2023.
Recently, several modestly-sized studies suggested that the flu vaccine may provide some measure of protection against COVID.
Ms Susan Taghioff, of the University of Miami Miller School of Medicine, and colleagues carried out a retrospective analysis of data on tens of thousands of patients from around the world to find out more.
In the largest study of its kind, the team screened de-identified electronic health records held on the TriNetX research database of more than 70 million patients to identify two groups of 37 377 patients, from countries including the US, UK, Germany, Italy, Israel and Singapore.
The two groups were matched for factors that could affect their risk of severe COVID-19, including age, gender, ethnicity, smoking and health problems such as diabetes, obesity and chronic obstructive pulmonary disease.
The first group had received the flu vaccine between two weeks and six months before COVID diagnoses. The second group also had COVID but were not vaccinated against flu.
The incidence of 15 adverse outcomes, including sepsis and death, within 120 days of testing positive for COVID was then compared between the two groups. Analysis showed that those not vaccinated for flu were significantly more likely (up to 20%) to have been admitted to ICU.
They were also significantly more likely to visit the Emergency Department (up to 58%), to develop sepsis (up to 45%), to have a stroke (up to 58%) and a deep vein thrombosis (up to 40%). However, the risk of death was not reduced.
It isn’t known exactly how the flu jab provides protection against COVID but most theories centre around it boosting the innate immune system.
The results strongly suggest that the flu vaccine protects against several severe effects of COVID, according to the study authors. Further research is needed to prove this possible link but, in the future, the flu shot could be used to help bolster protection in countries short of COVID vaccine doses.
Senior author Dr Devinder Singh, professor of plastic surgery at the University of Miami Miller School of Medicine, said: “Only a small fraction of the world has been fully vaccinated against COVID to date and, with all the devastation that has occurred due to the pandemic, the global community still needs to find solutions to reduce morbidity and mortality.
“Having access to real-time data of millions of patients is a powerful research tool. Together with asking important questions it has allowed my team to observe an association between the flu vaccine and lower morbidity in COVID patients.
“This finding is particularly significant because the pandemic is straining resources in many parts of the world. Therefore, our research – if validated by prospective randomised clinical trials – has the potential to reduce the worldwide burden of disease.”
Ms Taghioff added: “Influenza vaccination may even benefit individuals hesitant to receive a COVID vaccine due to the newness of the technology.
“Despite this, the influenza vaccine is by no means a replacement for the COVID vaccine and we advocate for everyone to receive their COVID vaccine if able to.
“Continued promotion of the influenza vaccine also has the potential to help the global population avoid a possible ‘twindemic’ – a simultaneous outbreak of both influenza and coronavirus.
“Regardless of the degree of protection afforded by the influenza vaccine against adverse outcomes associated with COVID, simply being able to conserve global healthcare resources by keeping the number of influenza cases under control is reason enough to champion continued efforts to promote influenza vaccination.”
Researchers in Belgium report on the case of a 90-year-old woman who was simultaneously infected with two different COVID variants.
On March 3 2021, the woman, with an unremarkable medical history, was admitted to a Belgian hospital after a spate of falls. She tested positive for COVID on the same day. She received nursing care at home, where she lived alone, and had not received a COVID vaccination.
At first, no signs of respiratory distress were seen, and oxygen saturation was good. However, she went on to develop rapidly worsening respiratory symptoms, and died five days later.
PCR testing revealed that she had been infected by two different strains of the virus — one which originated in the UK, known as B.1.1.7 (Alpha), and another that was first detected in South Africa (B.1.351; Beta).
“This is one of the first documented cases of co-infection with two SARS-CoV-2 variants of concern”, says lead author and molecular biologist Dr. Anne Vankeerberghen from the OLV Hospital in Aalst, Belgium. “Both these variants were circulating in Belgium at the time, so it is likely that the lady was co-infected with different viruses from two different people. Unfortunately, we don’t know how she became infected.”
The Alpha variant had been detected in the south east of England in December and within weeks, this variant displaced the viral strains circulating there. Since then, it has spread to more than 50 countries, including Belgium. The Beta variant was reported on December 18, 2020, and has since spread to 40 countries, which also includes Belgium. Scientists in Brazil reported in January 2021 that two people had been simultaneously infected with two different strains of the coronavirus—the Brazilian variant known as B.1.1.28 (E484K) and a novel variant VUI-NP13L, which had previously been discovered in Rio Grande do Sul. However, this study has yet to be published in a scientific journal.
“Whether the co-infection of the two variants of concern played a role in the fast deterioration of the patient is difficult to say”, said Vankeerberghen. “Up to now, there have been no other published cases. However, the global occurrence of this phenomenon is probably underestimated due to limited testing for variants of concern and the lack of a simple way to identify co-infections with whole genome sequencing.”
She continued, “Since co-infections with variants of concern can only be detected by VOC-analysis of positive samples, we would encourage scientists to perform fast, easy and cheap VOC-analysis by PCR on a large proportion of their positive samples, rather than just whole genome sequencing on a small proportion. Independent of the technique used, being alert to co-infections remains crucial.”
Progress against the COVID pandemic has been impeded by the emergence of new variants of concern (VOC), and new ones may further worsen and prolong it.
VOCs increase the transmissibility of the SARS-CoV-2 virus and hence raise the reproduction number. Furthermore, they enhance the immune escape capabilities of the virus and blunt the effectiveness of available vaccines. Finally, they increase the pathogenicity of the infection.
Alpha, Beta, and Gamma VOCs with the N501Y mutation replaced the initial wild-type SARS-CoV-2 strains in Ontario, Canada, and then the Delta variant dominated during the period between February to June 2021. While enhanced virulence of VOCs having the N501Y mutation has been reported, there is a lack of comprehensive analyses that demonstrate increased virulence of the Delta variant.
Researchers from Toronto University, Canada, recently showed that these emerging VOCs were linked to increased virulence, as determined by hospitalisation risk, ICU admission, and mortality. This study is currently available on the medRxiv preprint server.
The researchers created a retrospective cohort of patients testing positive for SARS-CoV-2 in Ontario and screening for VOCs between February 3 and July 1, 2021. Case data was gathered from the Ontario provincial Case and Contact Management (CCM) database. All PCR positive COVID-19 specimens with a cycle threshold (Ct) ≤ 35 were screened for the N501Y mutation using the real-time PCR assay from the Public Health Ontario Laboratory. Whole genome sequencing (WGS) was performed on 5% of specimens regardless of the presence of mutations.
Results show that infection by VOCs with the N501Y mutation significantly elevated risk of hospitalization, ICU admission, and death in patients in Ontario.
Compared to non-VOC strains of SARS-CoV-2, the increase in risk associated with N501Y-positive variants was 138% (105-176%) for ICU admission; 74% (62-86%) for hospitalisation; and 83% (57-114%) for death, after adjusting for age, sex, and comorbidity. Increase in risks associated with the delta variant was even higher- 241% (163-344%) for ICU admission; 105% (80-133%) for hospitalisation; and 121% (57-211%) for death.
VOCs with the N501Y mutation were found to be associated with a significantly higher risk of hospitalisation, ICU admission, and death in infected individuals in Ontario, Canada. They also reveal that the Delta variant, becoming dominant in Ontario, has increased these risks even further.
“Individuals infected with VOCs were, on average, younger and less likely to have comorbid conditions than those infected with non-VOC, but nonetheless had higher crude risks of hospitalisation and ICU admission,” the authors found.
According to the authors, the clear and significant elevation of risks of even delayed outcomes such as death visible in their analysis is remarkable given the relatively small number of delta variant infections in the time period of this study. The fact that Canada is one of the leading countries in the world in terms of COVID vaccination rates has certainly mitigated the impact of these VOCs.
In summary, the researchers showed that despite excellent vaccination rates in Ontario, Canada, and VOCs infecting predominantly younger and healthier individuals, these VOCs are associated with an increase in virulence and risk of death. In particular, the Delta variant is more virulent compared to previously dominant VOCs possessing the N501Y mutation. It is the authors’ view that the progressive increase in transmissibility, immune escape and virulence of emerging VOCs could result in the pandemic being more drawn out and deadly.
An eagerly awaited review and meta-analysis on ivermectin for COVID has arrived, however while it seems positive there are many shortcomings and unanswered questions.
The findings of the study, led by Andrew Hill, PhD, of the University of Liverpool, were published in Open Forum Infectious Diseases. The review and meta-analysis was conducted as part of the International Ivermectin Project Team from December 2020 to May 2021. Ivermectin proponents alleged that Dr Hill was conducting the analysis for the WHO, but MedPage Today was not able to make a confirmation of this. A separate review published on June 28 in the journal Clinical Infectious Diseases found no benefits for ivermectin use in COVID.
Dr Hill and colleagues assessed 24 randomised trials enrolling a total of 3328 patients that involved some type of control, whether it was standard of care or some other therapy. Sample sizes ranged from 24 to 400 participants. Of these, eight were published studies.
In the 11 trials with 2127 patients that focused on moderate or severe infection, a 56% reduction in mortality was seen (P=0.004), with 3% of patients on ivermectin dying compared with 9% of controls.
However, the researchers noted that the total number of deaths was small (128) and in the subgroup with severe disease, there was no difference between ivermectin and controls. As for moderate disease, they reported a 70% improvement in survival with ivermectin (P=0.0004). Compared with controls, ivermectin use was also associated with a reduction in time to recovery of 1.58 days (P=0.01) and with a shorter duration of hospitalisation of 4.27 days (P=0.05).
However, the drug was not associated with a lower risk of hospitalisation, though a sensitivity analysis that included any hospitalizations within 12 hours of taking the drug did show a reduction with ivermectin (RR 0.32, 95% CI 0.13-0.80, P=0.01).
A key limitation was the lack of peer review for many studies included in the analysis; there was also wide variation in terms of dosage, treatment duration, and inclusion criteria. There were also many different comparators, including hydroxychloroquine, lopinavir/ritonavir, standard of care, and placebo.
The authors concluded that their results “need to be validated in larger confirmatory trials”. David Boulware, MD, MPH, of the University of Minnesota, agreed with this. Dr Boulware has been interested in evaluating ivermectin for COVID outpatients, agreed with. On Twitter, he noted that no mention was made of whether patients used steroids, which could seriously confound results.
Only two of seven trials showed a reduction in symptom duration in outpatient trials. No analysis was done to see if early treatment cut hospitalisation risk.
He tweeted that there was a need for phase III randomised clinical trials “in order to delineate what is the clinical benefit of early treatment”, such as quicker resolution and fewer symptoms. He would have also liked to see more distinction between outpatient and in-hospital therapy.
“Of course, rolling out vaccination as quickly and widespread as possible would negate the need to use ivermectin as a treatment,” he added. “So big picture, vaccines are the better solution.”
There are multiple ongoing phase III randomised controlled trials “which will provide definitive results,” Boulware noted. These include the UK-based PRINCIPLE outpatient trial which has a target of 1500 patients for its ivermectin arm.
