Preliminary results find COVID-19 vaccine candidate based on inactivated SARS-CoV-2 virus is safe

A Chinese COVID-19 vaccine candidate based on the inactivated whole SARS-CoV-2 virus (BBIBP-CorV) is safe and elicits an antibody response, findings from a small early-phase randomised clinical trial published today in The Lancet Infectious Diseases journal have found.

A previous clinical trial reported similar results for a different vaccine that is also based on inactivated whole SARS-CoV-2 virus, but in that study the vaccine was only tested in people aged under 60 years.

The latest study included participants aged between 18 and 80 years, and found that antibody responses were induced in all recipients. Participants aged 60 and over were slower to respond, taking 42 days before antibodies were detected in all recipients compared with 28 days for participants aged 18-59. Antibody levels were also lower in those aged 60-80 years compared with those aged 18-59 (Mean neutralising antibody titre 42 days after receiving a 8μg vaccine dose was 228.7 for people aged 18-59, and 170.9 for those aged 60-80).

The trial was not designed to assess efficacy of the vaccine, so it is not possible to say whether the antibody responses induced by the vaccine, called BBIBP-CorV, are sufficient to protect from SARS-CoV-2 infection.

Professor Xiaoming Yang, one of the authors of the study, from the Beijing Institute of Biological Products Company Limited, Beijing, China, said: “Protecting older people is a key aim of a successful COVID-19 vaccine as this age group is at greater risk of severe illness from the disease. However, vaccines are sometimes less effective in this group because the immune system weakens with age. It is therefore encouraging to see that BBIBP-CorV induces antibody responses in people aged 60 and older, and we believe this justifies further investigation.”

There are currently 42 vaccines for COVID-19 in clinical trials. These vary in type and include DNA plasmid vaccines, inactivated virus vaccines, adenovirus-vectored vaccines, RNA vaccines, protein subunit vaccines and virus-like particle vaccines. Some of these have already been shown to be safe and to elicit immune responses in early phase clinical trials.

The BBIBP-CorV vaccine used in the study reported here is based on a sample of the virus that was isolated from a patient in China. Stocks of the virus were grown in the lab using cell lines and then inactivated using a chemical called beta-proprionolactone. BBIBP-CorV includes the killed virus mixed with another component, aluminium hydroxide, which is called an adjuvant because it is known to boost immune responses.

The first phase of the study was designed to find the optimal safe dose for BBIBP-CorV. It involved 96 healthy volunteers aged between 18 and 59 years and a second group of 96 participants aged between 60 years and 80 years. Within each group, the vaccine was tested at three different dose levels (2μg, 4μg and 8μg, 24 participants per group), with two vaccinations administered on day 0 and 28. A fourth group within each age group (24 participants in each age group) were given two doses of a placebo vaccine. In total, in phase 1 of the study, 144 participants received the vaccine and 48 received the placebo.

The second phase of the study was designed to identify the optimal timing schedule for vaccination. 448 participants aged between 18 and 59 years were randomly assigned to receive either one 8?g shot of vaccine or placebo, or two shots of 4μg vaccine or placebo (at 0 and 14 days, 0 and 21 days or 0 and 28 days). In this second phase, there were 112 participants per group, with 336 receiving the vaccine, and 112 receiving the placebo.

Participants were asked to report any adverse events for the first seven days after each vaccination and these were verified by the research team. Thereafter, participants recorded any adverse events using paper cards for the following 4 weeks. During phase 1, laboratory tests were carried out after the first and second vaccinations to assess kidney function, liver function and other organ functions. Blood samples were taken to test antibody levels for SARS-CoV-2 before and after vaccination.

No serious adverse events were reported within 28 days of the final vaccination. The most common side effect was pain at the injection site (phase 1 results: 24% [34/144] of vaccine recipients, vs 6% [3/48] of placebo recipients). A small number of participants reported experiencing a fever (phase 1 results: 4% [5/144] of vaccine recipients, vs 6% [3/48] of placebo recipients). There were no instances of clinically significant changes in organ functions detected in laboratory tests in any of the groups.

The greatest antibody responses were elicited by two 4μg doses of the vaccine at either days 0 and 21 or 0 and 28 (Mean neutralising antibody titres 28 days after second vaccination were 282.7 for two 4μg injections at day 0 and 21, and 218.0 for two 4μg injections at day 0 and 28).

Professor Xiaoming Yang said: “Our findings indicate that a booster shot is necessary to achieve the greatest antibody responses against SARS-CoV-2 and could be important for protection. This provides useful information for a phase 3 trial.”

The authors noted some limitations with the study, including the short duration of follow up at just 42 days. They also highlighted that the study did not include children and adolescents aged under 18. Trials with these groups will be carried out when the full analysis of data from adult groups is completed, the researchers say.

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Results from COMBINE (OCT-FFR) reported at TCT Connect

Data from COMBINE (OCT-FFR) found that the use of FFR combined with OCT imaging can help improve the accuracy of high-risk lesion identification in patients with diabetes.

Findings were reported today at TCT Connect, the 32nd annual scientific symposium of the Cardiovascular Research Foundation (CRF). TCT is the world’s premier educational meeting specializing in interventional cardiovascular medicine.

Fractional flow reserve (FFR) is widely used to guide the revascularization strategy in the catheterization lab. The FAME I and FAME II trials have shown that stable ischemic heart disease lesions with FFR >0.80 can be safely treated medically, while PCI of lesions with FFR<0.80 may benefit from revascularization.

However, recent evidence has shown that in some patient subgroups such as diabetes mellitus (DM) and/or acute coronary syndrome (ACS), lesions with FFR>0.80 can have worse outcomes than in patients without DM or ACS, most likely due to plaque instability or rapid progression of atherosclerotic plaque.

Previous studies have shown that lipid-rich plaques with a thin cap fibroatheroma (TCFA) have unfavorable clinical outcomes compared to non-TCFA lesions particularly in DM patients. Optical coherence tomography (OCT) can accurately identify lipid-rich and TCFA lesions. Whether OCT can identify lesions with future unfavorable clinical events despite lack of ischemia has not been studied previously.

The COMBINE (OCT-FFR) trial was a prospective international, natural history study. Patients with DM and with stable or acute coronary syndromes who had one or more non-culprit target lesion(s), with a 40-80% diameter stenosis, underwent FFR assessment. FFR-negative patients underwent OCT assessment and were further medically treated. Depending on the presence or absence of TCFA, patients were divided in two groups: TCFA negative (group A) and TCFA positive (group B). Patients with target lesions with FFR<0.80 were revascularized (group C).

The primary endpoint was the incidence of target lesion related MACE defined as cardiac death, target vessel myocardial infarction (MI), clinically-driven target lesion revascularization (TLR), or hospitalization due to unstable or progressive angina at 18 months in the medically treated patients with FFR>0.80 and TCFA patients (Group B) compared with medically treated patients with FFR>0.80 and no-TCFA (Group A). The secondary endpoint was the incidence of MACE between patients with FFR>0.80 and TCFA (Group B) vs. revascularized lesions that had FFR<0.80 (Group C).

The primary endpoint occurred in 13.3% of Group B compared with 3.1% of Group A [HR 4.7 95%CI (2.0-10.9) P=0.0004], suggesting that the presence of TCFA even in the absence of an abnormal FFR was predictive of future events. This rate of adverse events was even higher than the rate of events among the revascularized lesions with abnormal FFR at baseline (Group C) [HR 1.25 95%CI (0.28-5.59) P=0.77].

“In patients with diabetes, COMBINE (OCT-FFR) showed that the presence of a high-risk plaque (TCFA) is a strong predictor of future MACE, despite lack of ischemia,” said Elvin Kedhi, MD, Ph.D. Dr. Kedhi is Professor of Cardiology, working in ULB (Liberal University Brussel) Hopital Erasme and Silesian Medical University, Katowice, Poland

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Most physicians have seen false-negative COVID-19 test results

(HealthDay)—Most physicians believe they have seen false-negative results for a COVID-19 diagnostic test, according to the results of a recent survey.

Sermo, a social platform for physicians, has been conducting a weekly international poll. In week 7, conducted from May 3 to 5, 2020, 4,476 physicians offered their perspectives regarding false negatives and reinfection rates.

According to the results of the recent poll, more than eight in 10 physicians report they have seen some degree of false-negative test results, including 96 percent of “supertreaters” in an intensive care unit setting (physicians who have treated more than 20 COVID-19 patients) who believe they have seen COVID-19 tests produce a false negative. Just over one-third of hospital-based respondents believe that more than 20 percent of the tests have produced false negatives. Relatedly, four in 10 physicians report seeing at least one false positive. Nearly one in 10 physicians believe they have seen a patient with a reinfection, with higher rates among physicians working internationally (5 percent saw reinfections in the United States versus 15 percent in Italy and Spain and 14 percent in China).

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