Optimism is the faith that leads to achievement. Nothing can be done without hope and confidence.
--Helen Keller
Two vaccines are in the final stages of getting EUA approval for distribution to the public to combat the COVID -19 virus. Pfizer and its German partner, BioNTech, released additional data Wednesday following the completion of their Phase 3 trial. The companies announced that their vaccine was 95 percent effective at preventing symptomatic Covid-19, an improvement over the 90 percent efficacy that Pfizer reported in a preliminary analysis a week earlier. Pfizer applied for its Emergency Use Authorization (EUA) on Friday.
Moderna said Monday that early results of its Phase 3 trial show that the company’s experimental vaccine is 94.5 percent effective at reducing infection. Its application for an EUA with the FDA is pending some additional data results.
How the process works: The FDA requires that vaccine developers submit two months of follow-up safety data as part of the application for emergency use. This is a critical step to ensure that drug makers can monitor trial participants for any serious safety issues after vaccination.
Typically, most side effects from vaccines appear within 60 days of receiving the shot, according to Dr. Grace Lee, a professor of pediatrics at the Stanford University School of Medicine. But it’s possible for rare issues to crop up later, which means the FDA will need to weigh the potential benefits over the known risks before granting emergency use authorization.
There is a system in place to review vaccine data before it is granted approval and made available to the public. An application for emergency use authorization will be reviewed by an independent group of advisers to the FDA known as the Vaccines and Related Biological Products Advisory Committee. Members of this committee include physicians, scientists, infectious disease specialists and a consumer representative, but the group is not employed by the FDA or associated with any of the vaccine developers
After the committee makes its recommendations, the FDA will decide whether to grant authorization for emergency use. Then, the Advisory Committee on Immunization Practices will craft guidance for the CDC about how to prioritize who gets the vaccine first.
How these vaccines work: Both vaccines are messenger RNA (mRNA) vaccines and will be the first mRNA vaccines to ever come to market. Most vaccines are protein-based: we inject a protein from a virus into the body and hope the immune system generates protective antibodies. This is how a flu or hepatitis vaccine works. An mRNA vaccine is a gene-based approach that injects the genetic code of a protein from SARS-CoV-2 into your body so you produce the viral protein and generate an immune response.
There are two major theoretical advantages to having your body produce the antigen directly as opposed to injecting the antigen: mRNA vaccines may stimulate a more effective immune response
Manufacturing mRNA vaccines is cheaper and more scalable than protein-based vaccines.
Challenges with the vaccine: The most notable difference has less to do with science and more to do with shipping and logistics. The Pfizer vaccine must be kept at -70°C, which will require dry ice, whereas the Moderna vaccine can be shipped at -20°C and, according to a recent update, stored for up to a month at ordinary refrigerator temperatures. Thus, the Moderna vaccine has a simpler distribution and storage protocol as compared to Pfizer's vaccine. The reason that both vaccines require cold temperatures is because RNA is an unstable molecule and prone to degrading. Higher temperatures mean more breakdown and thus lower efficacy.
Both vaccines will require two doses with the Moderna vaccine given 28 days apart, and the Pfizer vaccine given 21 days apart.
Other than the differences noted above, the two vaccines appear more similar than different. Both appear to be highly effective based on the initial data, but this may change as more data becomes available. But, the difference in storage temperatures as described above could prove to be an important differentiator moving forward.
Dr. Fauci’s thoughts on the quick development of these vaccines: “The process of the speed did not compromise at all safety nor did it compromise scientific integrity,” Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said. “It was a reflection of the extraordinary scientific advances in these types of vaccines which allow us to do things in months that took us years before.”
Facts about the new surge of COVID -19: Healthcare workers are now seeing unprecedented increases in COVID-19 diagnoses and hospitalizations -- but there hasn't been a congruent rise in mortality rates even as case counts set records.
In fact, the COVID-19 mortality rate in the U.S. has fallen since the start of the pandemic.
That decline has no single, clear explanation, but experts have pointed to a host of contributing factors, including a higher proportion of cases among the young, increased knowledge of how to treat COVID patients, better therapies, and less overcrowding in hospitals.
Healthcare workers are now seeing unprecedented increases in COVID-19 diagnoses and hospitalizations -- but there hasn't been a congruent rise in mortality rates even as case counts set records.
In fact, the COVID-19 mortality rate in the U.S. has fallen since the start of the pandemic.
That decline has no single, clear explanation, but experts have pointed to a host of contributing factors, including a higher proportion of cases among the young, increased knowledge of how to treat COVID patients, better therapies, and less overcrowding in hospitals.
Between June and August, 20- to 29-year-olds had the highest incidence of COVID-19 -- a shift from the start of the pandemic, when it was older adults who saw the highest number of infections. The CDC reported that the median age of infected patients dropped from 46 in May to 38 in August.
Researchers found that the age-specific infection fatality rate was extremely low among children and young adults, measuring 0.002% at age 10 and 0.01% at 25. However, the rate progressively increased with age, growing from 0.4% at 55 to around 15% at 85.
"When you compare the fatality rate among people in their 20s and 30s to those in their 70s and 80s, it truly is an order of magnitude difference," said Jeremy Faust, MD, an emergency physician at Brigham and Women's Hospital in Boston. "Small changes in the demographics can make huge differences in mortality."
Some studies show that mortality has decreased among older patients, too. In a cohort of more than 5,000 hospitalized COVID-19 patients at NYU, researchers found that mortality rates dropped 18 percentage points from the start of the pandemic, falling from 26% in March to 8% in August.
Christopher Petrilli, MD, a hospitalist at NYU Langone and co-author of the study, that even after adjusting for age differences, there was a considerable reduction in COVID deaths.
"When we ran our statistical models it was very clear that mortality -- even when you controlled for demographic data, chronic conditions, and even how patients initially presented based on vital signs and laboratory values -- still declined over time, and pretty significantly," Petrilli said.
Lower death rates in older groups raises the question of how much better doctors have gotten at treating COVID-19. Mangala Narasimhan, DO, a critical care specialist from Northwell Health in New York, said that more knowledge about how to care for these patients is a critical reason why the death rates have decreased within her health system.
"We have a standardized approach to these patients now," Narasimhan said. When patients arrive for care, it is easier to decide when to start them on steroids or administer Remdesivir, as opposed to the beginning of the pandemic when doctors had to make educated guesses about what treatments might have some benefit.
Early intubation, for example, was a strategy used early in the pandemic for patients who had low oxygen levels. But proning -- turning patients over onto their stomachs -- seems to play an important role in COVID-19 care.
Dexamethasone was one of the ground-breaking interventions that became more widely used when clinical trial results showed that the steroid slashed deaths by a third in patients on mechanical ventilation, and by a fifth for those on supplemental oxygen.
"But steroids do not explain all of the drops in mortality that we've seen," said Petrilli. Those drops may account for a small percentage of the decrease in deaths. Petrilli added that overburdened hospitals at the start of the pandemic may have contributed to a higher mortality rate.
Hospital concerns: "I think the biggest factor [in the reduction] is that hospitals are not completely overwhelmed," said Narasimhan, who treated patients in New York when it was the epicenter of the crisis. As hospitals in the Midwest experience overcrowding during a third surge of infections, Narasimhan said she is concerned about how healthcare providers will be able to manage care.
"In March and April, we had the luxury that we were the only ones surging and we could borrow doctors from other parts of the country," she said. "All of that now, is not going to be an option, because everyone is surging, in all parts of the country. There aren't spare people to come help, which is also a worry for us."
As cases continue to rise across the country, experts worry that the pandemic will still result in high absolute death tolls among all age groups.
Although age-specific mortality rate for young people is relatively low, they still suffered many excess deaths this year. Faust, an emergency physician from Boston, and colleagues authored a study showing that COVID-19 was likely the leading cause of death in people between the ages of 25 and 44.
"You certainly want to protect the elderly because they are at such higher risk," Faust said. "But the alternative is not to let the virus roam free among the young, because that's when you see this huge increase in deaths that we didn't expect."
Petrilli said it's correct to say that certain patients are at higher risk than others, including the elderly, those with chronic medical conditions, and pregnant women. "But that doesn't mean that the patients who are not in those categories are at low risk. It just means that they are not at as high of a risk."
Until the majority of the population has access to a vaccine, Petrilli said it's important to continue social distancing and mask-wearing -- for one thing, these measures reduce the viral inoculum that an individual may receive, and thus illnesses may be less severe. "This virus didn't change," Petrilli said, warning that it's still "incredibly contagious," and has a much worse death rate than the flu.
"It's going to be a long road," Petrilli added. "While it's good news that the mortality rate is down, the reason that it is down is because everyone is doing a good job with mask-wearing and distancing. We just need to keep it up."
Upcoming Holiday Season: While it may be difficult to not get together for the upcoming Holidays, because we are going to mix our bubble with other family member bubbles or friends bubbles which carries with it the potential of spreading the virus we must do what is right not only for ourselves but for our families, friends and our community.
We are so close to having a solution. We must be diligent and careful for a short while longer so we will be able to enjoy the Holidays with our family and friends next year.
So until next time: Stay Safe, Stay well, Stay distant, Avoid crowds and Wear your Mask
James A Vito, D.M.D.