Paper and Threads

Clinical vaccine trials are rarely done in pregnant women, or children, until there are substantial safety data.  This week a prospective cohort study of pregnant women was reported in a preprint from two of the Harvard hospitals.  There were 84 pregnant patients, 31 lactating patients. and 16 non pregnant reproductive age controls.  Titers of SARS-CoV-2 antibodies were measured in serum samples and breast milk at 4 times, including at delivery.  Umbilical cord sera were also collected at delivery.  Antibody measurements were compared to pregnant women 4-12 weeks after they had Covid-19.

Patients in this study had antibody titers in serum and breast milk after vaccination that were comparable to the antibody titers measured in non-pregnant vaccinated patients and all of the titers were higher than those induced by Covid-19 infection. Antibodies were also present in the umbilical cord samples at the time of delivery.  The Pfizer-BioNTech and Moderna vaccines were known to be safe in pregnant women, but this study demonstrates that the immune response is as robust as in non-pregnant patients and the babies are probably protected for some period of time due to the antibodies passed to them from the mother during the pregnancy and in breast milk. This is the largest study to date of vaccinated pregnant women.  See Below

 It would be wonderful to have this type of data earlier during an epidemic or pandemic, but pregnant women aren't studied until the safety of the vaccines is known - when millions have been vaccinated.  The number of pregnancy complications in these vaccinated patients, like miscarriage and gestational diabetes, were comparable to those in non-vaccinated patients.  Thousands of pregnant women were already vaccinated, safely, but this trial confirmed the excellent immune response in pregnant women and newborn babies. Pfizer has started a clinical trial of their vaccine in 4000 pregnant women so more data will be available later this year.  But at least physicians now have trial data to reassure their pregnant patients about the benefits of the vaccine. 

Posted by Shirley at 7:45 AM | Permalink | Comments (0)

Although both Moderna and Pfizer vaccines both had efficacy of 94-95% in their clinical trials, people aren't protected fully until at least 2 weeks after their 2nd vaccine dose.  Now we are getting reports of the vaccine performance in the real world in millions of patients.  In California (UC LosAngeles and UC SanDiego) and Texas (Univ of Texas Southwestern Medical Center) health care workers were vaccinated and then tested regularly to detect Covid-19.  The number of cases decreased beginning 2 weeks after the first dose and most importantly maximal protection occurred at 2 weeks after the second dose.  

The incidence was reduced to 0.05% (of approximately 10,000 HCW) in both studies and with both vaccines.  There is a 3rd recent report from Hadassah Medical Center in Jerusalem with similar results with the Pfizer vaccine,  and at that time the B.1.1.7 variant (UK) was 80% of infections locally.  Read More Below

Breakthrough cases can occur in people who have an immune deficiency disorder or because their bodies cannot produce a robust immune reaction, which can be seen in elderly patients.  Examination of virus samples from breakthrough patients will give us information about the current vaccines ability to prevent infection with the new variants.  In order to analyze that data virus samples need to be saved for genomic sequencing, a complex process.   There is no current evidence that the breakthrough cases are due to the circulating variants, but the CDC has ramped up genomic testing of coronavirus patient samples to map the spread of the variants and especially those in breakthrough cases.

I've been following the SARS-CoV-2 variants present locally.  This week, ending March 23rd, a subset of 1481 patient samples from the NYC Health and Hospital facilities (inpatients and outpatients)  were analyzed in the NYC Pandemic Response Lab.  Variants present included UK Variant (141), California variants (15), Brazilian variant (1) and New York City variant (481).  There were no S. African variants detected.  I hope this information will be helpful for my friends that live in this area.  I'm still following the CDC mitigation guidelines for vaccinated people. 

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On Monday I thought I would be reviewing the Covid-19 US data from the Phase 3 Clinical Trial in preparation for the FDA request for an EUA.  It was one of the first vaccines I learned about.  Oxford University developed the platform for the Viral Vector vaccine using a Chimp adenovirus to carry the DNA for the SARS-CoV-2 spike protein into the cells - leading to spike protein production to stimulate the human immune response.  The vaccine was produced in concert with AstraZeneca, and was selected as part of Operation Warp Speed by the US.  For approval here vaccine makers had to conduct a Phase 3 Clinical Trial with at least 30,000 US volunteers - with a full range of ages, races, and ethnicity.  As soon as more than 50% of the volunteers were followed for side effects for more than 2 months, an application could be made to the FDA for EAU. 

Then I woke up Tuesday to several online news alerts: "AstraZeneca's US trial data may have been outdated and incomplete NIH says" (Washington Post). The Data and Safety Monitoring Board, is a group of 11 independent scientists appointed by NIH to oversee the clinical trials with each of the companies.  They suggested that AstraZeneca should include data on all of the volunteers that were beyond 2 months before publishing their efficacy data.  They didn't.  The DSMB has that data and when more volunteers were included, efficacy dropped.  It is highly unusual for the FDA/NIH to make an announcement like this and no further details were given in the first newspaper articles.  Read More Below

Later Tuesday afternoon this was the NYT Breaking News Headline, "In a two-page letter to AstraZeneca and federal authorities, an independent panel of medical experts that was helping to oversee the vaccine's clinical trial in the United States said that the company had essentially cherry-picked data that was most favorable for the study as opposed to the most recent and most complete."  This is a problem with transparency.

The main issue, as written in the news, is that the data up to February 17 was the final data used to determine an efficacy of 79%.  But when the advisory board included data collected after Feb 17, there were more Covid-19 patients diagnosed and they were in the vaccinated group thereby reducing efficacy to 69-74%.  AstraZeneca in their initial Phase 3 Clinical Trial in Europe used two dose regimens in an error, and those volunteers that received half of the planned dose had fewer cases of Covid-19 than the full dose volunteers.  That was difficult to explain and now there are more questions. 

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Covid-19 case numbers were falling in most parts of the world after the Christmas surge, but now 15 states are demonstrating an increase and the total number of cases per day are still at least 50,000.  Dr. Tony Fauci said that we would need to see the case number fall below 10,000 in order to control the spread of the SARS-CoV-2 virus.  Europe saw the case numbers fall when they implemented lockdowns and other public health measures.  But the variant B.1.1.7 is now quickly spreading across Europe. Yesterday Paris was locked down again!  Critics say the new restrictions in Europe have come too late and can be traced back to the speed of reopening.

Scientists predict that unless each state maintains control of the virus, and reinstitutes masks mandates, social distancing, limited group sizes, and more gradual reopenings, we will follow Europe in the next 4-6 weeks.  This estimate is based on the sequence of virus spread from Europe to the US that already occurred earlier in the pandemic.  Dr. Ashish Jha, Dean of Brown School of Public Health, reported yesterday that the B.1.1.7 variant is already 40-50% of virus cases in the US and is now present in every state. This variant has greater transmission and some reported increase in case severity.  Fortunately preliminary studies demonstrated that the current vaccines are still effective against this variant. See Below.

The other variants of concern are also already in the US and the home grown NYC (B.1.526) variant is increasing in frequency in the genomic surveillance tests on New York and each week the percent is higher.  Last week they tested 712 cases in the NY Pandemic Response Lab and the NYC variant accounted for 45.1% of the samples - up from 29.2% 4 weeks earlier. 

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Many drugs were tested in randomized, placebo-controlled trials in 2020-21 and most drugs were no better than placebo.  Remdesivir is the exception.  Dexamethasone was already an FDA approved drug for many years.

SaNOtize Research and Development Corp in Vancouver, Canada:  This week there were several online reports of a Nitric Acid Nasal Spray (NONS) that was tested in a Phase 2 trial in the UK (79 NHS patients) and in over 7000 patients in Canada.  The primary outcome measure in the UK trial was the difference in nasal SARS-CoV-2 RNA load from baseline through day 6.  The nasal spray accelerated clearance of the virus by a factor of 16-fold vs placebo.   NONS reduced the virus by more than 95% in infected participants within 24 hours of treatment and by more than 99% in 72 hours, including the B.1.1.7 variant.  No adverse effects were seen in the treated patients and there are decades of experience with nitric acid as an anti-microbial agent. The spray was designed to kill the virus in the upper respiratory tract, preventing the virus from spreading to the lungs.  The news articles say that they are applying for emergency approval in the UK and Canada, and will begin clinical trials to see if the nasal spray can also prevent disease after a Covid-19 contact.  See Below.   

NOTE:  The collage nasal sprays were magnified for effect.  I also verified the reports of the safe antimicrobial activity of nitric acid against bacteria, viruses, and fungi using multiple methods to deliver the nitric acid.  And searched for data from a Phase 3 trial, but couldn't find any.  Maybe the UK and Canada can use Phase 2 Randomized Placebo Controlled Trial (RCT) data for an EUA application, I'm not familiar with their drug approval process. This is an exciting report that would be a much needed drug therapy for Covid-19!

Posted by Shirley at 6:56 AM | Permalink | Comments (1)